{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules [[ gefitinib ]] (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib ([[ Iressa ]], ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, [[ ZD1839 ]]) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and [[ erlotinib ]] (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib ([[ Tarceva ]], OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, [[ OSI-774 ]]), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as [[ cetuximab ]] (IMC-225, Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab ([[ IMC-225 ]], Erbitux).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, [[ Erbitux ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include << CI-1033 >>, an irreversible pan-[[ erbB ]] tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include << CI-1033 >>, an irreversible pan-erbB [[ tyrosine kinase ]] inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and << PKI166 >> and GW572016, both examples of dual [[ kinase ]] inhibitors (inhibiting epidermal growth factor receptor and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and << PKI166 >> and GW572016, both examples of dual kinase inhibitors (inhibiting [[ epidermal growth factor receptor ]] and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and << PKI166 >> and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and [[ Her2 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and << GW572016 >>, both examples of dual [[ kinase ]] inhibitors (inhibiting epidermal growth factor receptor and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and << GW572016 >>, both examples of dual kinase inhibitors (inhibiting [[ epidermal growth factor receptor ]] and Her2).", "label": "INHIBITOR", "metadata": []}
{"text": "Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and << GW572016 >>, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and [[ Her2 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Alprenolol >> and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria.", "label": "ANTAGONIST", "metadata": []}
{"text": "Alprenolol and << bromoacetylalprenololmenthane >> are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Alprenolol >> and BAAM at 10(-7), 3 x 10(-7), and 10(-6) M inhibited the cardiac stimulation response slightly, which is indicative of membrane-stabilizing activity independent of [[ beta-adrenoceptor ]] blockade.", "label": "INHIBITOR", "metadata": []}
{"text": "Alprenolol and << BAAM >> at 10(-7), 3 x 10(-7), and 10(-6) M inhibited the cardiac stimulation response slightly, which is indicative of membrane-stabilizing activity independent of [[ beta-adrenoceptor ]] blockade.", "label": "INHIBITOR", "metadata": []}
{"text": "Alprenolol and BAAM also caused surmountable antagonism of << isoprenaline >> responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible.", "label": "AGONIST", "metadata": []}
{"text": "<< Alprenolol >> and BAAM also caused surmountable antagonism of isoprenaline responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible.", "label": "ANTAGONIST", "metadata": []}
{"text": "Alprenolol and << BAAM >> also caused surmountable antagonism of isoprenaline responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible.", "label": "ANTAGONIST", "metadata": []}
{"text": "We conclude that << alprenolol >> and BAAM are competitive slowly reversible [[ beta 1-adrenoceptor ]] antagonists on rat left atria.", "label": "ANTAGONIST", "metadata": []}
{"text": "We conclude that alprenolol and << BAAM >> are competitive slowly reversible [[ beta 1-adrenoceptor ]] antagonists on rat left atria.", "label": "ANTAGONIST", "metadata": []}
{"text": "Discovery and optimization of << anthranilic acid sulfonamides >> as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of [[ albumin ]] binding.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Adenine phosphoribosyltransferase >> plays a role in purine salvage by catalyzing the direct conversion of adenine to [[ adenosine monophosphate ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Adenine phosphoribosyltransferase >> plays a role in purine salvage by catalyzing the direct conversion of [[ adenine ]] to adenosine monophosphate.", "label": "SUBSTRATE", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, [[ donepezil ]], galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, << donepezil >>, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme [[ acetylcholinesterase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, [[ galantamine ]] and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, << galantamine >> and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme [[ acetylcholinesterase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and [[ rivastigmine ]], to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and << rivastigmine >>, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme [[ acetylcholinesterase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of << acetylcholine >>, an important neurotransmitter associated with memory, by blocking the enzyme [[ acetylcholinesterase ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Mitiglinide (<< KAD-1229 >>), a new anti-diabetic drug, is thought to stimulate [[ insulin ]] secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Mitiglinide >> (KAD-1229), a new anti-diabetic drug, is thought to stimulate [[ insulin ]] secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Mitiglinide (<< KAD-1229 >>), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the [[ ATP-sensitive K+ (K(ATP)) channels ]] in pancreatic beta-cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mitiglinide >> (KAD-1229), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the [[ ATP-sensitive K+ (K(ATP)) channels ]] in pancreatic beta-cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Patch-clamp analysis using inside-out recording configuration showed that << mitiglinide >> inhibits the [[ Kir6.2 ]]/SUR1 channel currents in a dose-dependent manner (IC50 value, 100 nM) but does not significantly inhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Patch-clamp analysis using inside-out recording configuration showed that << mitiglinide >> inhibits the Kir6.2/[[ SUR1 ]] channel currents in a dose-dependent manner (IC50 value, 100 nM) but does not significantly inhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits [[ Kir6.2 ]]/SUR1 and Kir6.2/SUR2B channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits Kir6.2/[[ SUR1 ]] and Kir6.2/SUR2B channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits Kir6.2/SUR1 and [[ Kir6.2 ]]/SUR2B channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits Kir6.2/SUR1 and Kir6.2/[[ SUR2B ]] channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits Kir6.2/SUR1 and Kir6.2/SUR2B channels at 100 nM, and inhibits [[ Kir6.2 ]]/SUR2A channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nateglinide >> inhibits Kir6.2/SUR1 and Kir6.2/SUR2B channels at 100 nM, and inhibits Kir6.2/[[ SUR2A ]] channels at high concentrations (1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "These results indicate that, similar to the sulfonylureas, mitiglinide is highly specific to the Kir6.2/SUR1 complex, i.e., the pancreatic beta-cell << K(ATP) channel >>, and suggest that [[ mitiglinide ]] may be a clinically useful anti-diabetic drug.", "label": "AGONIST", "metadata": []}
{"text": "Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly << telmisartan >>, are partial agonists at [[ peroxisome proliferator-activated receptor-γ ]].", "label": "AGONIST", "metadata": []}
{"text": "Although generally highly specific for << angiotensin II type 1 receptors >>, some ARBs, particularly [[ telmisartan ]], are partial agonists at peroxisome proliferator-activated receptor-γ.", "label": "ANTAGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including [[ Δ(9)-tetrahydrocannabinol ]], WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, [[ WIN 55,212 ]] [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [[[ R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate ]]], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], [[ AM2389 ]] [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [[[ 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol ]]], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and [[ AM4054 ]] [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [[[ 9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol ]]], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.", "label": "AGONIST", "metadata": []}
{"text": "Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist [[ AM1241 ]] [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects.", "label": "AGONIST", "metadata": []}
{"text": "Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [[[ 1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole ]]], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects.", "label": "AGONIST", "metadata": []}
{"text": "Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor [[ AM404 ]], and the CB antagonist rimonabant did not have diuretic effects.", "label": "AGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the << CB1 >> agonist [[ AM4054 ]] were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].", "label": "AGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of << WIN 55,212 >> antagonized by the [[ CB2 ]] antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].", "label": "AGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the << CB1 >> agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with [[ rimonabant ]], but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].", "label": "ANTAGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the << vanilloid receptor type I >> antagonist [[ capsazepine ]], nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].", "label": "ANTAGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist [[ AM630 ]] [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].", "label": "ANTAGONIST", "metadata": []}
{"text": "In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist AM630 [[[ (6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone) ]]].", "label": "ANTAGONIST", "metadata": []}
{"text": "<< N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide >> (NS-398), a selective [[ cyclooxygenase-2 ]] inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (<< NS-398 >>), a selective [[ cyclooxygenase-2 ]] inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I.", "label": "UPREGULATOR", "metadata": []}
{"text": "Beta-1,4-galactosyltransferase I (beta4Gal-T1) normally transfers Gal from UDP-Gal to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from << UDP-Glc >> to GlcNAc ([[ Glc-T ]] activity), albeit at only 0.3% efficiency.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Beta-1,4-galactosyltransferase I >> (beta4Gal-T1) normally transfers Gal from [[ UDP-Gal ]] to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency.", "label": "SUBSTRATE", "metadata": []}
{"text": "Beta-1,4-galactosyltransferase I (beta4Gal-T1) normally transfers Gal from << UDP-Gal >> to GlcNAc in the presence of Mn(2+) ion ([[ Gal-T ]] activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency.", "label": "SUBSTRATE", "metadata": []}
{"text": "Beta-1,4-galactosyltransferase I (<< beta4Gal-T1 >>) normally transfers Gal from [[ UDP-Gal ]] to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency.", "label": "SUBSTRATE", "metadata": []}
{"text": "Discovery of novel << 2-hydroxydiarylamide >> derivatives as [[ TMPRSS4 ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, a novel series of << 2-hydroxydiarylamide >> derivatives were synthesized and evaluated for inhibiting [[ TMPRSS4 ]] serine protease activity and suppressing cancer cell invasion.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, a novel series of << 2-hydroxydiarylamide >> derivatives were synthesized and evaluated for inhibiting TMPRSS4 [[ serine protease ]] activity and suppressing cancer cell invasion.", "label": "INHIBITOR", "metadata": []}
{"text": "The selective << betaAR >> agonist [[ isoproterenol ]] caused an enhancement of hippocampal CA3 network activity, as measured by an increase in frequency of spontaneous burst discharges recorded in the CA3 region.", "label": "AGONIST", "metadata": []}
{"text": "The selective << beta1AR >> antagonists atenolol and metoprolol blocked [[ isoproterenol ]]-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively.", "label": "AGONIST", "metadata": []}
{"text": "The selective << beta1AR >> antagonists [[ atenolol ]] and metoprolol blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively.", "label": "ANTAGONIST", "metadata": []}
{"text": "The selective << beta1AR >> antagonists atenolol and [[ metoprolol ]] blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively.", "label": "ANTAGONIST", "metadata": []}
{"text": "In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively).", "label": "AGONIST", "metadata": []}
{"text": "In contrast, the selective << beta2AR >> antagonists ICI-118,551 and [[ butoxamine ]] inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "In contrast, the selective << beta2AR >> antagonists [[ ICI-118,551 ]] and butoxamine inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, << beta1AR >> activation is responsible for the enhanced hippocampal CA3 network activity initiated by [[ isoproterenol ]].", "label": "AGONIST", "metadata": []}
{"text": "<< P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice.", "label": "AGONIST", "metadata": []}
{"text": "Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons.", "label": "ANTAGONIST", "metadata": []}
{"text": "Selective antagonism of GluR5 << kainate-receptor >>-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons.", "label": "ANTAGONIST", "metadata": []}
{"text": "In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, << topiramate >> at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by [[ kainate receptors ]] containing the GluR5 subunit.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, << topiramate >> at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the [[ GluR5 ]] subunit.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Topiramate >> also partially depressed predominantly [[ AMPA-receptor ]]-mediated EPSCs, but with lower efficacy.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << GluR5 >> kainate receptors could represent a key mechanism underlying the anticonvulsant activity of [[ topiramate ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of GluR5 << kainate receptors >> could represent a key mechanism underlying the anticonvulsant activity of [[ topiramate ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Density functional theory calculations using the hybrid functional B3LYP have been performed to study the << methyl >> transfer step in [[ glycine N-methyltransferase ]] (GNMT).", "label": "SUBSTRATE", "metadata": []}
{"text": "Density functional theory calculations using the hybrid functional B3LYP have been performed to study the << methyl >> transfer step in glycine N-methyltransferase ([[ GNMT ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "The starting point for the calculations is the recent X-ray crystal structure of << GNMT >> complexed with [[ SAM ]] and acetate.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Dasatinib >> (BMS-354825) inhibits [[ KIT ]]D816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dasatinib >> (BMS-354825) inhibits KIT[[ D816V ]], an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Dasatinib (<< BMS-354825 >>) inhibits KIT[[ D816V ]], an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dasatinib >> (BMS-354825) is a novel orally bioavailable [[ SRC ]]/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dasatinib >> (BMS-354825) is a novel orally bioavailable SRC/[[ ABL ]] inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).", "label": "INHIBITOR", "metadata": []}
{"text": "Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable [[ SRC ]]/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).", "label": "INHIBITOR", "metadata": []}
{"text": "Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable SRC/[[ ABL ]] inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type [[ KIT ]] and the KITD816V mutation in the nanomolar range in in vitro and cell-based kinase assays.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type KIT and the [[ KIT ]]D816V mutation in the nanomolar range in in vitro and cell-based kinase assays.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type KIT and the KIT[[ D816V ]] mutation in the nanomolar range in in vitro and cell-based kinase assays.", "label": "INHIBITOR", "metadata": []}
{"text": "Additionally, << dasatinib >> leads to growth inhibition of a [[ KIT ]]D816V-harboring human masto-cytosis cell line.", "label": "INHIBITOR", "metadata": []}
{"text": "Additionally, << dasatinib >> leads to growth inhibition of a KIT[[ D816V ]]-harboring human masto-cytosis cell line.", "label": "INHIBITOR", "metadata": []}
{"text": "Dopamine D(2) receptor-induced << COX-2 >>-mediated production of [[ prostaglandin E(2) ]] in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent.", "label": "SUBSTRATE", "metadata": []}
{"text": "The effect was counteracted by the << D(2) >> antagonist [[ eticlopride ]], pertussis toxin, the inhibitor of intracellular Ca(2+) release TMB-8, incubation in Ca(2+)-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA.", "label": "ANTAGONIST", "metadata": []}
{"text": "It was also antagonized by the non-specific << cyclooxygenase >> (COX) inhibitor, [[ indomethacin ]], and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate.", "label": "INHIBITOR", "metadata": []}
{"text": "It was also antagonized by the non-specific cyclooxygenase (<< COX >>) inhibitor, [[ indomethacin ]], and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate.", "label": "INHIBITOR", "metadata": []}
{"text": "It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective << COX-2 >> inhibitor, [[ NS-398 ]], but not by the specific COX-1 inhibitor, valeryl salicylate.", "label": "INHIBITOR", "metadata": []}
{"text": "It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective COX-2 inhibitor, NS-398, but not by the specific << COX-1 >> inhibitor, [[ valeryl salicylate ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Both the non-specific << phospholipase A(2) >> inhibitor, [[ quinacrine ]], and an inhibitor of cPLA(2) and iPLA(2), AACOF3, counteracted the effect; in contrast, a selective iPLA(2) inhibitor, BEL, and a selective sPLA(2) inhibitor, TAPC, were ineffective.", "label": "INHIBITOR", "metadata": []}
{"text": "The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "A high throughput assay for the glucuronidation of << 7-hydroxy-4-trifluoromethylcoumarin >> by recombinant [[ human UDP-glucuronosyltransferases ]] and liver microsomes.", "label": "SUBSTRATE", "metadata": []}
{"text": "2.  We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of << 7-hydroxy-4-trifluoromethylcoumarin >> (HFC) for several [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "2.  We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of 7-hydroxy-4-trifluoromethylcoumarin (<< HFC >>) for several [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "3.  We have used this method to screen 11 recombinant << human UGTs >> for [[ HFC ]] glucuronidation activity and studied the reaction kinetics with the most active enzymes.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were [[ UGT1A10 ]] followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by [[ UGT1A6 ]] >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >[[ UGT1A7 ]] >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >[[ UGT2A1 ]], whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM [[ UGT1A6 ]] was about 10 times better catalyst than the other recombinant UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "UGT1A6 exhibited a significantly higher Vmax and Km values toward both << HFC >> and UDP-glucuronic acid than the other [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both [[ HFC ]] and UDP-glucuronic acid than the other UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and << UDP >>-glucuronic acid than the other [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both HFC and [[ UDP ]]-glucuronic acid than the other UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-<< glucuronic acid >> than the other [[ UGTs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both HFC and UDP-[[ glucuronic acid ]] than the other UGTs.", "label": "SUBSTRATE", "metadata": []}
{"text": "This inhibition was blocked when mice were pretreated with the selective << H3R >> agonist [[ R-(alpha)-methyl-histamine ]] (10 mg/kg).", "label": "AGONIST", "metadata": []}
{"text": "The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the << 5-HT(1A/1B)-receptor >> antagonist [[ (-)-propranolol ]] and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it.", "label": "ANTAGONIST", "metadata": []}
{"text": "The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the << 5-HT(3/4)-receptor >> antagonist [[ tropisetron ]] did not affect it.", "label": "ANTAGONIST", "metadata": []}
{"text": "The 5-HT(1/2/5/7)-receptor antagonist methysergide and the << 5-HT(2A/2B/2C)-receptor >> antagonist [[ LY 53857 ]] enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it.", "label": "ANTAGONIST", "metadata": []}
{"text": "The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect.", "label": "ANTAGONIST", "metadata": []}
{"text": "The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect.", "label": "ANTAGONIST", "metadata": []}
{"text": "These results suggest that << clomipramine >> induces hyperglycemia in mice by blocking the [[ 5-HT(2B ) ]]and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << clomipramine >> induces hyperglycemia in mice by blocking the 5-HT(2B )and/or [[ 5-HT(2C) ]] receptors, which results in facilitation of adrenaline release.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two [[ PtdSer synthases ]], PSS1 and PSS2.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, [[ PSS1 ]] and PSS2.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, PSS1 and [[ PSS2 ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Moreover, a normal level of expression of << PSS1 >> and/or PSS2 is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by [[ I3A ]] and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and [[ phorbol 12-myristate 13-acetate ]] (PMA) in WEHI-231, HOP-92, and Colo-205 cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate ([[ PMA ]]) in WEHI-231, HOP-92, and Colo-205 cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< I3A >> induced a higher level of secretion of the inflammatory cytokine [[ interleukin 6 ]] compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< I3A >> induced a higher level of secretion of the inflammatory [[ cytokine ]] interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "I3A induced a higher level of secretion of the inflammatory cytokine << interleukin 6 >> compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "I3A induced a higher level of secretion of the inflammatory << cytokine >> interleukin 6 compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The in vitro kinase activity of << PKC-alpha >> induced by [[ I3A ]] was lower than that induced by PMA.", "label": "ACTIVATOR", "metadata": []}
{"text": "The in vitro kinase activity of << PKC-alpha >> induced by I3A was lower than that induced by [[ PMA ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Type I deiodinase >>, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Type I deiodinase, << liver fatty-acid binding protein >> and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Type I deiodinase, liver fatty-acid binding protein and << cytochrome P450 (CYP) 3A37 >> mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced [[ CYP3A37 ]] and CYP2H1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced CYP3A37 and [[ CYP2H1 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of << PPARs >> besides [[ berberine ]].", "label": "AGONIST", "metadata": []}
{"text": "This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific << renin >>-angiotensin-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.", "label": "INHIBITOR", "metadata": []}
{"text": "This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin-<< angiotensin >>-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.", "label": "INHIBITOR", "metadata": []}
{"text": "This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin-angiotensin-aldosterone system (RAAS) blockade by << renin >>-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.", "label": "INHIBITOR", "metadata": []}
{"text": "TREK-1 currents are insensitive to pharmacological agents that block << TWIK-1 >> activity such as [[ quinine ]] and quinidine.", "label": "INHIBITOR", "metadata": []}
{"text": "TREK-1 currents are insensitive to pharmacological agents that block << TWIK-1 >> activity such as quinine and [[ quinidine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< CGP 12177A >> mediates cardiostimulation by activation of the 'putative' [[ beta(4)-adrenoceptor ]]; however, it has recently been reported that disruption of the beta(1)-adrenoceptor gene abolishes this effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< CGP 12177A >> but not isoprenaline initiated arrhythmias at lower concentrations following [[ beta(1)-adrenoceptor ]] overexpression.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< (125)I-Cyanopindolol >> saturation binding in Adv.beta(1) myocytes demonstrated approximately 18-fold increase in [[ beta(1)-adrenoceptors ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "(3)H-CGP 12177A saturation binding, in the presence of << propranolol >>, increased approximately 5-fold following overexpression of [[ beta(1)-adrenoceptors ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< (3)H-CGP 12177A >> saturation binding, in the presence of propranolol, increased approximately 5-fold following overexpression of [[ beta(1)-adrenoceptors ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In contrast, in the presence of << Ca >> UFH accelerated the inhibition of [[ factor Xa ]] by antithrombin 10-fold more efficiently than comparable concentrations of the high affinity fractions of enoxaparin and fragmin.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast, in the presence of << Ca >> UFH accelerated the inhibition of factor Xa by [[ antithrombin ]] 10-fold more efficiently than comparable concentrations of the high affinity fractions of enoxaparin and fragmin.", "label": "INHIBITOR", "metadata": []}
{"text": "INTRODUCTION: The principal aim of this study was to assess the efficacy of << quinidine >> in suppressing [[ IKr ]] in vitro and in modulating the rate dependence of the QT interval in the \"SQT1\" form of the short QT syndrome.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "CONCLUSION: Oral << quinidine >> is effective in suppressing the gain of function in [[ IKr ]] responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence of the QT interval and rendering ventricular tachycardia/ventricular fibrillation noninducible.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The IC50-values obtained for the inhibition of lipopolysaccharide (LPS)-induced release of prostaglandin E2 (PGE2) reflecting << cyclooxygenase (COX)-2 >>-mediated [[ PGE2 ]] release were 47 microg/ml and 0.6 microg/ml, for the Salix extract 1520L and rofecoxib-like research compound L745337, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Our results indicate that Salix extract 1520L inhibits << COX-2 >>-mediated [[ PGE2 ]] release through compounds other than salicin or salicylate.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Follicle-stimulating hormone >> (FSH), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Follicle-stimulating hormone (<< FSH >>), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Humans with << FSH beta >> gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex [[ steroid ]] production occur in both types of mutations.", "label": "PRODUCT-OF", "metadata": []}
{"text": "OBJECTIVES: The aim of the current study was to assess the activity of << rolipram >>, a nonsubtype-selective [[ PDE4 ]] inhibitor, in several animal models predictive of antipsychotic-like efficacy and side-effect liability and to use PDE4B wild-type and knockout mice to begin to understand the subtypes involved in the activity of rolipram.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that PDE4B mediates the antipsychotic effects of rolipram in CAR and that the << PDE4B >>-regulated [[ cyclic adenosine monophosphate ]] signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Cat-1 >>, the transporter for the essential [[ amino acids ]], arginine and lysine, is one of the up-regulated genes.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Cat-1 >>, the transporter for the essential amino acids, [[ arginine ]] and lysine, is one of the up-regulated genes.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Cat-1 >>, the transporter for the essential amino acids, arginine and [[ lysine ]], is one of the up-regulated genes.", "label": "SUBSTRATE", "metadata": []}
{"text": "RESULTS: Fractionated bulb extracts and the two isolated << steroidal glycoalkaloids >> (1) and (2) induced NO production and [[ TGF-β receptor I ]] mRNA expression in fibroblast cell culture.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "A prerequisite for this hypothesis was the unproved assumption that rabbit and human << alpha(2A)-adrenoceptors >> are equally activated by [[ rilmenidine ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Human atrial appendages and rabbit pulmonary arteries were used to determine the potencies of alpha(2)-adrenoceptor agonists in inhibiting the electrically (2 Hz) evoked [(3)H]norepinephrine release and of antagonists in counteracting the << alpha(2)-adrenoceptor >>-mediated inhibition induced by [[ moxonidine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the rabbit pulmonary artery, rilmenidine and << oxymetazoline >> are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, [[ phentolamine ]], and idazoxan.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, phentolamine, and [[ idazoxan ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both rilmenidine and [[ oxymetazoline ]] exhibit different properties (antagonism and agonism, respectively).", "label": "AGONIST", "metadata": []}
{"text": "The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both [[ rilmenidine ]] and oxymetazoline exhibit different properties (antagonism and agonism, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Cetrorelix >> completely blocked the rise of levels of the two most abundant species, 5.0 kb and 4.5 kb, of the [[ GnRH-R ]] mRNA, during both the infantile and the juvenile periods.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Cetrorelix >> also abolished the developmental rise of the [[ gonadotropin beta ]] subunit mRNAs during the two periods of the study.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists [[ terfenadine ]], astemizole, loratadine, and acrivastine are reviewed.", "label": "ANTAGONIST", "metadata": []}
{"text": "The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, [[ astemizole ]], loratadine, and acrivastine are reviewed.", "label": "ANTAGONIST", "metadata": []}
{"text": "The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, [[ loratadine ]], and acrivastine are reviewed.", "label": "ANTAGONIST", "metadata": []}
{"text": "The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, loratadine, and [[ acrivastine ]] are reviewed.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Terfenadine >> and astemizole are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine.", "label": "ANTAGONIST", "metadata": []}
{"text": "Terfenadine and << astemizole >> are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine.", "label": "ANTAGONIST", "metadata": []}
{"text": "Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as [[ diphenhydramine ]] and chlorpheniramine.", "label": "ANTAGONIST", "metadata": []}
{"text": "Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as diphenhydramine and [[ chlorpheniramine ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Anti-inflammatory effect of << prunetin >> via the suppression of [[ NF-κB ]] pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Promoter assay revealed that << prunetin >> inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of [[ iNOS ]] and COX-2 at the transcriptional level.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Promoter assay revealed that << prunetin >> inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of iNOS and [[ COX-2 ]] at the transcriptional level.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << prunetin >> inhibits [[ NF-κB ]]-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signaling.", "label": "INHIBITOR", "metadata": []}
{"text": "Consistent with these results, << prunetin >> significantly reduced serum levels of inflammatory [[ cytokines ]] and mortality in mice challenged with lipopolysaccharide.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "G6PC2: A Negative Regulator of Basal << Glucose >>-Stimulated [[ Insulin ]] Secretion.", "label": "UPREGULATOR", "metadata": []}
{"text": "G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS).", "label": "UPREGULATOR", "metadata": []}
{"text": "These data suggest that << G6pc2 >> represents a novel, negative regulator of basal GSIS that acts by hydrolyzing [[ glucose-6-phosphate ]], thereby reducing glycolytic flux.", "label": "SUBSTRATE", "metadata": []}
{"text": "Using the << mTOR >> inhibitor [[ PP242, ]] we found that TGFβ-induced both early and sustained activation of TORC1 and TORC2 was necessary for deptor suppression.", "label": "INHIBITOR", "metadata": []}
{"text": "<< PP242 >>-induced reversal of [[ deptor ]] suppression by TGFβ was associated with a significant inhibition of TGFβ-stimulated protein synthesis and hypertrophy.", "label": "ACTIVATOR", "metadata": []}
{"text": "METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in [[ human dopamine transporter ]] (DAT) wild-type and mutants with altered conformational equilibria.", "label": "SUBSTRATE", "metadata": []}
{"text": "METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria.", "label": "SUBSTRATE", "metadata": []}
{"text": "METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of [(3)H] dopamine (<< DA >>) uptake and [(3)H]WIN 35428 binding in [[ human dopamine transporter ]] (DAT) wild-type and mutants with altered conformational equilibria.", "label": "SUBSTRATE", "metadata": []}
{"text": "METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of [(3)H] dopamine (<< DA >>) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria.", "label": "SUBSTRATE", "metadata": []}
{"text": "RESULTS: (+/-)-, R-, and S-modafinil bind to the << DAT >> and inhibit [[ DA ]] uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer.", "label": "SUBSTRATE", "metadata": []}
{"text": "Apple << polyphenols >> suppress antigen presentation of [[ ovalbumin ]] by THP-1-derived dendritic cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "A significant decrease in << HLA-DR >> expression was observed in the AP and fractionated [[ procyanidin ]]-treated cells in the presence of ovalbumin (OVA), but no effect on CD86 expression was observed.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, the up-regulation of << IL-12 >> and TNF-α was found in the [[ procyanidin ]] trimers-treated cells in the presence of OVA.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, the up-regulation of IL-12 and << TNF-α >> was found in the [[ procyanidin ]] trimers-treated cells in the presence of OVA.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The acute toxicity of << organophosphorus >> (OP) compounds in mammals is due to their irreversible inhibition of [[ acetylcholinesterase ]] (AChE) in the nervous system, which leads to increased synaptic acetylcholine levels.", "label": "INHIBITOR", "metadata": []}
{"text": "The acute toxicity of << organophosphorus >> (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase ([[ AChE ]]) in the nervous system, which leads to increased synaptic acetylcholine levels.", "label": "INHIBITOR", "metadata": []}
{"text": "The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of << acetylcholinesterase >> (AChE) in the nervous system, which leads to increased synaptic [[ acetylcholine ]] levels.", "label": "SUBSTRATE", "metadata": []}
{"text": "The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of acetylcholinesterase (<< AChE >>) in the nervous system, which leads to increased synaptic [[ acetylcholine ]] levels.", "label": "SUBSTRATE", "metadata": []}
{"text": "In phosphotriesterase and physostigmine-treated mice, a 4- and 2-fold higher << sarin >> dose, respectively, was needed to cause a 50% inhibition of brain [[ AChE ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "The << CYP3A4 >> activity could be induced 2-fold by [[ rifampicin ]], whereas CYP2C9 activity remained equally high.", "label": "ACTIVATOR", "metadata": []}
{"text": "The CYP3A4 activity could be induced 2-fold by << rifampicin >>, whereas [[ CYP2C9 ]] activity remained equally high.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< PF-04859989 >> as a template for structure-based drug design: identification of new pyrazole series of irreversible [[ KAT II ]] inhibitors with improved lipophilic efficiency.", "label": "INHIBITOR", "metadata": []}
{"text": "PF-04859989 as a template for structure-based drug design: identification of new << pyrazole >> series of irreversible [[ KAT II ]] inhibitors with improved lipophilic efficiency.", "label": "INHIBITOR", "metadata": []}
{"text": "The structure-based design, synthesis, and biological evaluation of a new << pyrazole >> series of irreversible [[ KAT II ]] inhibitors are described herein.", "label": "INHIBITOR", "metadata": []}
{"text": "The modification of the inhibitor scaffold of 1 and 2 from a << dihydroquinolinone >> core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent [[ KAT II ]] inhibitors with excellent physicochemical properties.", "label": "INHIBITOR", "metadata": []}
{"text": "The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a << tetrahydropyrazolopyridinone >> core led to discovery of a new series of potent [[ KAT II ]] inhibitors with excellent physicochemical properties.", "label": "INHIBITOR", "metadata": []}
{"text": "The capacity of << acetylcholinesterase >> inhibitors, with the exception of [[ tacrine ]] and ambenonium, to displace bound [3H]-oxotremorine-M in preference to [3H]quinuclinidyl benzilate predicts that the former compounds could act as potential agonists at muscarinic receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "The capacity of << acetylcholinesterase >> inhibitors, with the exception of tacrine and [[ ambenonium ]], to displace bound [3H]-oxotremorine-M in preference to [3H]quinuclinidyl benzilate predicts that the former compounds could act as potential agonists at muscarinic receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>[[ pyridostigmine ]]=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine><< pyridostigmine >>=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=[[ edrophonium ]]=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=<< edrophonium >>=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=[[ galanthamine ]] >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=<< galanthamine >> >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >[[ desoxypeganine ]]>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine ><< desoxypeganine >>>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>[[ parathion ]]>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine><< parathion >>>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>[[ gramine ]]) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion><< gramine >>) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> ([[ ambenonium ]]>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (<< ambenonium >>>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>[[ neostigmine ]]=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium><< neostigmine >>=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=[[ physostigmine ]] =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=<< physostigmine >> =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =[[ tacrine ]]>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =<< tacrine >>>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of pyridoxine and pyridoxal to [[ PLP ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of [[ pyridoxine ]] and pyridoxal to PLP.", "label": "SUBSTRATE", "metadata": []}
{"text": "CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of pyridoxine and [[ pyridoxal ]] to PLP.", "label": "SUBSTRATE", "metadata": []}
{"text": "Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for [[ cholinesterases ]] and Aβ aggregation.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for cholinesterases and [[ Aβ ]] aggregation.", "label": "INHIBITOR", "metadata": []}
{"text": "To develop new drugs for treatment of Alzheimer's disease, a group of << N'-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones >> was designed, synthesized and tested for their ability to inhibit [[ acetylcholinesterase ]], butyrylcholinesterase and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40_1-42).", "label": "INHIBITOR", "metadata": []}
{"text": "To develop new drugs for treatment of Alzheimer's disease, a group of << N'-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones >> was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, [[ butyrylcholinesterase ]] and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40_1-42).", "label": "INHIBITOR", "metadata": []}
{"text": "β-Amyloid aggregation results showed that all compounds exhibited remarkable << Aβ >> fibril aggregation inhibition activity with a nearly similar potential as the reference compound [[ rifampicin ]], which makes them promising anti-Alzheimer drug candidates.", "label": "INHIBITOR", "metadata": []}
{"text": "Here, translocation studies using the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) were performed to aid in identifying the mechanism by which anabolic-androgenic << steroids >> (AAS) were activating [[ hAR ]] and potentially interacting with hGR and how glucocorticoid ligands were interacting with the hGR and hAR.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Licofelone >>, a balanced inhibitor of [[ cyclooxygenase ]] and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a balanced inhibitor of cyclooxygenase and [[ 5-lipoxygenase ]], reduces inflammation in a rabbit model of atherosclerosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to [[ cycloxygenase-1 ]] blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a dual anti-inflammatory drug that inhibits [[ 5-lipoxygenase ]] (LOX) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase ([[ LOX ]]) and cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and [[ cyclooxygenase ]] (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase ([[ COX ]]) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability.", "label": "INHIBITOR", "metadata": []}
{"text": "We examined the anti-inflammatory effect of licofelone on atherosclerotic lesions as well as in isolated neutrophils from whole blood of rabbits compared with a selective inhibitor of << COX-2 >>, [[ rofecoxib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Licofelone >> reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, [[ monocyte chemoattractant protein-1 ]] (MCP-1) gene expression, and the activation of nuclear factor-kappaB in rabbit atheroma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Licofelone >> reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, monocyte chemoattractant protein-1 ([[ MCP-1 ]]) gene expression, and the activation of nuclear factor-kappaB in rabbit atheroma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Licofelone >> reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, monocyte chemoattractant protein-1 (MCP-1) gene expression, and the activation of [[ nuclear factor-kappaB ]] in rabbit atheroma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, << licofelone >> inhibited [[ COX-2 ]] and 5-LOX protein expression in vascular lesions.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, << licofelone >> inhibited COX-2 and [[ 5-LOX ]] protein expression in vascular lesions.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Rofecoxib >> only diminished [[ COX-2 ]] protein expression and MCP-1 gene expression in vascular atheroma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Rofecoxib >> only diminished COX-2 protein expression and [[ MCP-1 ]] gene expression in vascular atheroma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Licofelone >> almost abolished [[ 5-LOX ]] activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood.", "label": "INHIBITOR", "metadata": []}
{"text": "Licofelone almost abolished << 5-LOX >> activity by inhibiting [[ leukotriene B4 ]] generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Licofelone almost abolished << 5-LOX >> activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet [[ thromboxane B2 ]] production from whole blood.", "label": "PRODUCT-OF", "metadata": []}
{"text": "No influence of moderate hepatic impairment on the pharmacokinetics of << lumiracoxib >>, an oral [[ COX-2 ]] selective inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel << cyclooxygenase-2 >> (COX-2) selective inhibitor [[ lumiracoxib ]] (Prexige), so that dose recommendations for clinical use can be provided.", "label": "INHIBITOR", "metadata": []}
{"text": "The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel cyclooxygenase-2 (<< COX-2 >>) selective inhibitor [[ lumiracoxib ]] (Prexige), so that dose recommendations for clinical use can be provided.", "label": "INHIBITOR", "metadata": []}
{"text": "The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel << cyclooxygenase-2 >> (COX-2) selective inhibitor lumiracoxib ([[ Prexige ]]), so that dose recommendations for clinical use can be provided.", "label": "INHIBITOR", "metadata": []}
{"text": "The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel cyclooxygenase-2 (<< COX-2 >>) selective inhibitor lumiracoxib ([[ Prexige ]]), so that dose recommendations for clinical use can be provided.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases ([[ DNMT- ]]1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, [[ DNMT-3a ]], and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and [[ DNMT-3b ]]), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins ([[ MeCP-2 ]], MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, [[ MBD-2 ]] and MBD-3), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and [[ MBD-3 ]]), in MEF cells by the proteasomal pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Comparison of the << monoamine oxidase >> inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors [[ moclobemide ]] and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "Comparison of the monoamine oxidase inhibiting properties of two reversible and selective << monoamine oxidase-A >> inhibitors [[ moclobemide ]] and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "Comparison of the << monoamine oxidase >> inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and [[ toloxatone ]], and assessment of their effect on psychometric performance in healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "Comparison of the monoamine oxidase inhibiting properties of two reversible and selective << monoamine oxidase-A >> inhibitors moclobemide and [[ toloxatone ]], and assessment of their effect on psychometric performance in healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of two reversible, predominantly << monoamine oxidase-A >> (MAO-A) inhibitors, [[ moclobemide ]] (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of two reversible, predominantly << monoamine oxidase-A >> (MAO-A) inhibitors, moclobemide (150 mg three times daily) and [[ toloxatone ]] (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects.", "label": "INHIBITOR", "metadata": []}
{"text": "Before the next drug intake, << MAO-A >> inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with [[ moclobemide ]] but not with toloxatone.", "label": "INHIBITOR", "metadata": []}
{"text": "Before the next drug intake, << MAO-A >> inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with [[ toloxatone ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Previously, we have found that << BRN-103 >>, a nicotinamide derivative, inhibits vascular endothelial growth factor ([[ VEGF ]])-mediated angiogenesis signaling in human endothelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Previously, we have found that << BRN-103 >>, a nicotinamide derivative, inhibits [[ vascular endothelial growth factor ]] (VEGF)-mediated angiogenesis signaling in human endothelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Previously, we have found that BRN-103, a << nicotinamide >> derivative, inhibits vascular endothelial growth factor ([[ VEGF ]])-mediated angiogenesis signaling in human endothelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Previously, we have found that BRN-103, a << nicotinamide >> derivative, inhibits [[ vascular endothelial growth factor ]] (VEGF)-mediated angiogenesis signaling in human endothelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << BRN-250 >> inhibited the [[ VEGF ]]-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular [[ tyrosine kinase ]] activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of [[ VEGF receptor 2 ]] (VEGFR2) and the activation of its downstream AKT pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 ([[ VEGFR2 ]]) and the activation of its downstream AKT pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream [[ AKT ]] pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << gelatinase A >> (MMP-2) by [[ batimastat ]] and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of gelatinase A (<< MMP-2 >>) by [[ batimastat ]] and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << gelatinase A >> (MMP-2) by batimastat and [[ captopril ]] reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of gelatinase A (<< MMP-2 >>) by batimastat and [[ captopril ]] reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effects of the synthetic << matrix metalloproteinase >> inhibitor, [[ batimastat ]] (BB-94) and the angiotensin-converting enzyme inhibitor, captopril, on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effects of the synthetic << matrix metalloproteinase >> inhibitor, batimastat ([[ BB-94 ]]) and the angiotensin-converting enzyme inhibitor, captopril, on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effects of the synthetic matrix metalloproteinase inhibitor, batimastat (BB-94) and the << angiotensin-converting enzyme >> inhibitor, [[ captopril ]], on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice.", "label": "INHIBITOR", "metadata": []}
{"text": "Here we report that << captopril >> treatment resulted in decreased transcription and protein levels of [[ gelatinase A ]] by 3LL cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Both << BB-94 >> and captopril also prevented substrate degradation by [[ gelatinase A and B ]] released in conditioned medium by cultured cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Methionine synthase reductase (<< MTRR >>) is an enzyme involved in the conversion of Hcy to [[ methionine ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of Hcy to [[ methionine ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Methionine synthase reductase (<< MTRR >>) is an enzyme involved in the conversion of [[ Hcy ]] to methionine.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of [[ Hcy ]] to methionine.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< TCDD >> decreased the expression of the [[ glucose transporter ]], SLC2A1, and most of the glycolytic transcripts, followed by decreases in glycolytic intermediates, including pyruvate.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< TCDD >> decreased the expression of the glucose transporter, [[ SLC2A1 ]], and most of the glycolytic transcripts, followed by decreases in glycolytic intermediates, including pyruvate.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Mitochondrial << glutathione (GSH) reductase >> activity and the GSH/glutathione disulfide ratio were decreased by [[ TCDD ]], ultimately leading to mitochondrial dysfunction, characterized by decreased inner mitochondrial membrane potential and ATP production, and increased production of the reactive oxygen species (ROS), hydrogen peroxide.", "label": "INHIBITOR", "metadata": []}
{"text": "<< ATP-binding cassette transporter A1 >> is involved in hepatic [[ alpha-tocopherol ]] secretion.", "label": "PRODUCT-OF", "metadata": []}
{"text": "alpha-Tocopherol transfer protein (<< alpha-TTP >>), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< alpha-Tocopherol transfer protein >> (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "alpha-Tocopherol transfer protein (<< alpha-TTP >>), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma alpha-tocopherol level by mediating the secretion of [[ alpha-tocopherol ]] by the liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< alpha-Tocopherol transfer protein >> (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma alpha-tocopherol level by mediating the secretion of [[ alpha-tocopherol ]] by the liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "First, addition of << apolipoprotein A-I >> (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.", "label": "PRODUCT-OF", "metadata": []}
{"text": "First, addition of apolipoprotein A-I (<< apoA-I >>), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.", "label": "PRODUCT-OF", "metadata": []}
{"text": "First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the << ATP-binding cassette transporter A1 >> (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.", "label": "PRODUCT-OF", "metadata": []}
{"text": "First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (<< ABCA1 >>)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Second, << probucol >>, an antiatherogenic compound reported to be an inactivator of [[ ABCA1 ]] reduced hepatic alpha-tocopherol secretion.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These results strongly suggest that << ABCA1 >> is substantially involved in hepatic [[ alpha-tocopherol ]] secretion.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< 2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid >> (1) is a potent [[ AMPA receptor ]] agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors.", "label": "AGONIST", "metadata": []}
{"text": "<< Pranlukast >>, a leukotriene receptor antagonist, inhibits [[ interleukin-5 ]] production via a mechanism distinct from leukotriene receptor antagonism.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Pranlukast >>, a [[ leukotriene receptor ]] antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.", "label": "ANTAGONIST", "metadata": []}
{"text": "BACKGROUND: << Pranlukast >>, a [[ cysteinyl leukotriene receptor 1 ]] (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation.", "label": "ANTAGONIST", "metadata": []}
{"text": "BACKGROUND: << Pranlukast >>, a cysteinyl leukotriene receptor 1 ([[ CysLTR1 ]]) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation.", "label": "ANTAGONIST", "metadata": []}
{"text": "The aim of this study was to determine the mechanism of << pranlukast >>-induced [[ interleukin-5 ]] (IL-5) inhibition in allergic inflammation.", "label": "INHIBITOR", "metadata": []}
{"text": "The aim of this study was to determine the mechanism of << pranlukast >>-induced interleukin-5 ([[ IL-5 ]]) inhibition in allergic inflammation.", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: Pretreatment of lung tissues with << pranlukast >> alone significantly decreased the amount of [[ IL-5 ]] protein in the culture medium by 40%.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pranlukast >>-induced inhibition of [[ IL-5 ]] mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "CONCLUSION: Our results indicate that << pranlukast >> inhibits [[ IL-5 ]] synthesis via a mechanism distinct from CysLTR1 antagonism.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSION: Our results indicate that << pranlukast >> inhibits IL-5 synthesis via a mechanism distinct from [[ CysLTR1 ]] antagonism.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Thiazolidinediones >> are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of [[ insulin ]]-responsive genes involved in glucose and lipid metabolism.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Thiazolidinediones >> are a new class of anti-diabetic agents which increase [[ insulin ]] sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of insulin-responsive genes involved in glucose and lipid metabolism.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The effect of troglitazone on ENT1 was PPAR(gamma)-independent and kinetic studies revealed that << troglitazone >> was a competitive inhibitor of [[ ENT1 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The difference in structure of << troglitazone >> did not account for its inhibitory effect on [[ ENT1 ]] because Vitamin E did not inhibit [3H]adenosine uptake by HASMCs.", "label": "INHIBITOR", "metadata": []}
{"text": "Using the nucleoside transporter deficient PK15NTD cells stably expressing ENT1 and ENT2, it was found that << troglitazone >> inhibited [[ ENT1 ]] but had no effect on ENT2.", "label": "INHIBITOR", "metadata": []}
{"text": "From these results, it is suggested that << troglitazone >> may enhance the vasodilatory effect of adenosine by inhibiting [[ ENT1 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacologically, << troglitazone >> is a novel inhibitor of [[ ENT1 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Phenytoin >> is principally metabolized by [[ CYP2C9 ]], and both are probable substrates of the drug transporter P-glycoprotein.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Phenytoin >> is principally metabolized by CYP2C9, and both are probable substrates of the [[ drug transporter ]] P-glycoprotein.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Phenytoin >> is principally metabolized by CYP2C9, and both are probable substrates of the drug transporter [[ P-glycoprotein ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Fisetin >> treatment of preadipocytes reduced the phosphorylation of [[ S6K1 ]] and mTORC1 in a time- and concentration-dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Fisetin >> treatment of preadipocytes reduced the phosphorylation of S6K1 and [[ mTORC1 ]] in a time- and concentration-dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "To further our understanding of how << fisetin >> negatively regulates [[ mTORC1 ]] signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results suggested that << fisetin >> treatment inhibits [[ mTORC1 ]] activity in an Akt-dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggested that << fisetin >> treatment inhibits mTORC1 activity in an [[ Akt ]]-dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "We also observed that << fisetin >> efficiently suppressed the phosphorylation of [[ Akt ]], S6K1 and mTORC1 in adipose tissue.", "label": "INHIBITOR", "metadata": []}
{"text": "We also observed that << fisetin >> efficiently suppressed the phosphorylation of Akt, [[ S6K1 ]] and mTORC1 in adipose tissue.", "label": "INHIBITOR", "metadata": []}
{"text": "We also observed that << fisetin >> efficiently suppressed the phosphorylation of Akt, S6K1 and [[ mTORC1 ]] in adipose tissue.", "label": "INHIBITOR", "metadata": []}
{"text": "Collectively, these results suggest that inhibition of << mTORC1 >> signaling by [[ fisetin ]] prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice.", "label": "INHIBITOR", "metadata": []}
{"text": "Cyclin E-cdk2 activation is associated with cell cycle arrest and inhibition of DNA replication induced by the << thymidylate synthase >> inhibitor [[ Tomudex ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Tomudex >> (ZD1694) is a specific antifolate-based [[ thymidylate synthase ]] inhibitor active in a variety of solid tumor malignancies.", "label": "INHIBITOR", "metadata": []}
{"text": "Studies were carried out in vitro to evaluate downstream molecular alterations induced as a consequence of the potent and sustained inhibition of << thymidylate synthase >> by [[ Tomudex ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Tomudex >> treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and cdk2 protein expression and [[ kinase ]] activities 24 h after a 2-h exposure.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Tomudex >> treatment resulted in the decrease in p27(kip1) expression, with an increase in [[ cyclin E ]] and cdk2 protein expression and kinase activities 24 h after a 2-h exposure.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Tomudex >> treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and [[ cdk2 ]] protein expression and kinase activities 24 h after a 2-h exposure.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Tomudex >> treatment resulted in the decrease in [[ p27(kip1) ]] expression, with an increase in cyclin E and cdk2 protein expression and kinase activities 24 h after a 2-h exposure.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The studies with dThyd rescue from cyclin E-<< cdk2 >> protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased [[ cyclin E ]]-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased cyclin E-[[ cdk2 ]] protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INHIBITOR", "metadata": []}
{"text": "The studies with dThyd rescue from cyclin E-<< cdk2 >> protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.", "label": "INHIBITOR", "metadata": []}
{"text": "The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of [[ thymidylate synthase ]] and resultant dNTP pool imbalance.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in [[ cyclin E ]] and cdk2 kinase activities.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and [[ cdk2 ]] kinase activities.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 [[ kinase ]] activities.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of [[ p27(kip1) ]] expression and the increase in cyclin E and cdk2 kinase activities.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of << thymidylate synthase >> by [[ Tomudex ]] and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 kinase activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Cells were also evaluated in the presence of << wortmannin >>, an inhibitor of phosphatidylinositol 3-kinases and thus [[ AKt ]] (0-100 nM).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Cells were also evaluated in the presence of << wortmannin >>, an inhibitor of [[ phosphatidylinositol 3-kinases ]] and thus AKt (0-100 nM).", "label": "INHIBITOR", "metadata": []}
{"text": "Saturated << palmitic and stearic acids >> increased ceramides, up-regulated PTP1B, and had AKt and [[ PTP1B ]] phosphorylation at Ser 50 impaired.", "label": "ACTIVATOR", "metadata": []}
{"text": "Saturated << palmitic and stearic acids >> increased ceramides, up-regulated PTP1B, and had [[ AKt ]] and PTP1B phosphorylation at Ser 50 impaired.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired.", "label": "UPREGULATOR", "metadata": []}
{"text": "Only FFAs that increased << ceramides >> caused impairment of [[ AKt ]] and PTP1B phosphorylation at Ser 50.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Only FFAs that increased << ceramides >> caused impairment of AKt and [[ PTP1B ]] phosphorylation at Ser 50.", "label": "INHIBITOR", "metadata": []}
{"text": "Indoleamine 2,3-dioxygenase (<< IDO >>), a [[ tryptophan ]] catabolizing enzyme, has been implicated in the pathogenesis of various neurological disorders.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Indoleamine 2,3-dioxygenase >> (IDO), a [[ tryptophan ]] catabolizing enzyme, has been implicated in the pathogenesis of various neurological disorders.", "label": "SUBSTRATE", "metadata": []}
{"text": "To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of << SIRT1 >> ([[ nicotinamide ]], sirtinol, EX527) in aorta segments isolated from young Wistar rats.", "label": "INHIBITOR", "metadata": []}
{"text": "To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of << SIRT1 >> (nicotinamide, [[ sirtinol ]], EX527) in aorta segments isolated from young Wistar rats.", "label": "INHIBITOR", "metadata": []}
{"text": "To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of << SIRT1 >> (nicotinamide, sirtinol, [[ EX527 ]]) in aorta segments isolated from young Wistar rats.", "label": "INHIBITOR", "metadata": []}
{"text": "To determine whether dysregulation of SIRT1 promotes << NADPH oxidase >>-dependent production of reactive [[ oxygen ]] species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Endothelial dysfunction induced by SIRT1 inhibition was prevented by treatment of the vessels with the << NADPH oxidase >> inhibitor [[ apocynin ]] or superoxide dismutase.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced << NADPH oxidase >> activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by [[ resveratrol ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced << NADPH oxidase >> activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by [[ resveratrol ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << SIRT1 >> significantly increased vascular [[ superoxide ]] production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by resveratrol.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Peroxisome proliferator-activated receptor-α (PPARα) activation mimicked the effects of << resveratrol >> while PPARα inhibition prevented the effects of this [[ SIRT1 ]] activator.", "label": "ACTIVATOR", "metadata": []}
{"text": "SIRT1 co-precipitated with PPARα and << nicotinamide >> increased the acetylation of the PPARα coactivator [[ PGC-1α ]], which was suppressed by resveratrol.", "label": "ACTIVATOR", "metadata": []}
{"text": "SIRT1 co-precipitated with PPARα and nicotinamide increased the acetylation of the PPARα coactivator << PGC-1α >>, which was suppressed by [[ resveratrol ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< EROD >> activity induction in peripheral blood lymphocytes, liver and brain tissues of rats orally exposed to [[ polycyclic aromatic hydrocarbons ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar [[ halogenated and polycyclic aromatic hydrocarbons ]] (PHH, PAH).", "label": "ACTIVATOR", "metadata": []}
{"text": "Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar halogenated and polycyclic aromatic hydrocarbons (PHH, [[ PAH ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of [[ ApoA-I ]] secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing [[ hApoA-I ]] and cholesterol ester transfer protein transgenes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Repression of << farnesyltransferase >> (FNTA) by siRNA and the enzyme inhibitor [[ manumycin A ]] caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes.", "label": "INHIBITOR", "metadata": []}
{"text": "Repression of farnesyltransferase (<< FNTA >>) by siRNA and the enzyme inhibitor [[ manumycin A ]] caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Estrogens >> are biosynthesised from androgens by the [[ CYP450 ]] enzyme complex called aromatase.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Estrogens >> are biosynthesised from androgens by the CYP450 enzyme complex called [[ aromatase ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Estrogens are biosynthesised from << androgens >> by the CYP450 enzyme complex called [[ aromatase ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "In breast cancer, intratumoural << aromatase >> is the source for local [[ estrogen ]] production in the tissue.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The potent and selective third-generation << aromatase >> inhibitors anastrozole, [[ letrozole ]] and exemestane were introduced to the market as endocrine therapy in postmenopausal patients failing anti-estrogen therapy alone, or multiple hormonal therapies.", "label": "INHIBITOR", "metadata": []}
{"text": "The potent and selective third-generation << aromatase >> inhibitors [[ anastrozole ]], letrozole and exemestane were introduced to the market as endocrine therapy in postmenopausal patients failing anti-estrogen therapy alone, or multiple hormonal therapies.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Anastrozole >> and letrozole are both non-steroidal [[ aromatase ]] inhibitors that compete with the substrate for binding to the enzyme active site.", "label": "INHIBITOR", "metadata": []}
{"text": "Anastrozole and << letrozole >> are both non-steroidal [[ aromatase ]] inhibitors that compete with the substrate for binding to the enzyme active site.", "label": "INHIBITOR", "metadata": []}
{"text": "Identification and synthesis of << N-(thiophen-2-yl) benzamide >> derivatives as [[ BRAF ]](V600E) inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Identification and synthesis of << N-(thiophen-2-yl) benzamide >> derivatives as BRAF([[ V600E ]]) inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we employed virtual screening and chemical synthesis to identify a series of << N-(thiophen-2-yl) benzamide >> derivatives as potent [[ BRAF ]](V600E) inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we employed virtual screening and chemical synthesis to identify a series of << N-(thiophen-2-yl) benzamide >> derivatives as potent BRAF([[ V600E ]]) inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Exposure of cells to 4mM << NaF >> for 24h induced [[ caspase-3 ]] activation, ultrastructural alterations, and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter-membrane space into the cytosol, indicating that fluoride-mediated apoptosis is mitochondria-dependent.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Fluoride >> treatment also increased phosphorylation of [[ JNK ]] and ERK, but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Fluoride >> treatment also increased phosphorylation of JNK and [[ ERK ]], but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Furthermore, the << Panx1 >> channel blockers [[ carbenoxolone ]] and Probenecid were less effective in inhibiting Panx1 currents when Kvbeta3 was co-expressed.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, the << Panx1 >> channel blockers carbenoxolone and [[ Probenecid ]] were less effective in inhibiting Panx1 currents when Kvbeta3 was co-expressed.", "label": "INHIBITOR", "metadata": []}
{"text": "<< (-)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one >> (KCA-1490) exhibits moderate dual [[ PDE3/4 ]]-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent.", "label": "INHIBITOR", "metadata": []}
{"text": "(-)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (<< KCA-1490 >>) exhibits moderate dual [[ PDE3/4 ]]-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent.", "label": "INHIBITOR", "metadata": []}
{"text": "<< N >>-alkylation of the pyridazinone ring markedly enhances potency against [[ PDE4 ]] but suppresses PDE3 inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "<< N >>-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses [[ PDE3 ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "N-alkylation of the << pyridazinone >> ring markedly enhances potency against [[ PDE4 ]] but suppresses PDE3 inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "N-alkylation of the << pyridazinone >> ring markedly enhances potency against PDE4 but suppresses [[ PDE3 ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Addition of a << 6-aryl-4,5-dihydropyridazin-3(2H)-one >> extension to the N-alkyl group facilitates both enhancement of [[ PDE4 ]]-inhibitory activity and restoration of potent PDE3 inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Addition of a << 6-aryl-4,5-dihydropyridazin-3(2H)-one >> extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent [[ PDE3 ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the << N >>-alkyl group facilitates both enhancement of [[ PDE4 ]]-inhibitory activity and restoration of potent PDE3 inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the << N >>-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent [[ PDE3 ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Fumarate reductase (<< FRD >>) is the key enzyme in [[ fumarate ]] respiration induced by anaerobic growth of bacteria.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Fumarate reductase >> (FRD) is the key enzyme in [[ fumarate ]] respiration induced by anaerobic growth of bacteria.", "label": "SUBSTRATE", "metadata": []}
{"text": "The frdA gene coding for subunit A of FRD, and two control genes, << copA >> and copP associated with the export of [[ copper ]] out of H. pylori, were inactivated by insertion of the chloramphenicol acetyltransferase cassette into these individual genes.", "label": "SUBSTRATE", "metadata": []}
{"text": "The frdA gene coding for subunit A of FRD, and two control genes, copA and << copP >> associated with the export of [[ copper ]] out of H. pylori, were inactivated by insertion of the chloramphenicol acetyltransferase cassette into these individual genes.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given that << FRD >>, present in all H. pylori strains, is immunogenic in H. pylori -infected patients and H. pylori growth in vitro can be inhibited by three anthelmintics ([[ morantel ]], oxantel and thiabendazole), this enzyme could potentially be used both as a novel drug target as well as in the development of vaccines for H. pylori prevention and eradication.", "label": "INHIBITOR", "metadata": []}
{"text": "Given that << FRD >>, present in all H. pylori strains, is immunogenic in H. pylori -infected patients and H. pylori growth in vitro can be inhibited by three anthelmintics (morantel, [[ oxantel ]] and thiabendazole), this enzyme could potentially be used both as a novel drug target as well as in the development of vaccines for H. pylori prevention and eradication.", "label": "INHIBITOR", "metadata": []}
{"text": "Given that << FRD >>, present in all H. pylori strains, is immunogenic in H. pylori -infected patients and H. pylori growth in vitro can be inhibited by three anthelmintics (morantel, oxantel and [[ thiabendazole ]]), this enzyme could potentially be used both as a novel drug target as well as in the development of vaccines for H. pylori prevention and eradication.", "label": "INHIBITOR", "metadata": []}
{"text": "To begin to examine whether these changes are mediated by alterations in gene expression for << tryptophan hydroxylase >> (TPH), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR).", "label": "PRODUCT-OF", "metadata": []}
{"text": "To begin to examine whether these changes are mediated by alterations in gene expression for tryptophan hydroxylase (<< TPH >>), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR).", "label": "PRODUCT-OF", "metadata": []}
{"text": "In contrast, there was little change in mRNA levels for << GTP cyclohydrolase I >> (GTPCH), the rate limiting enzyme in synthesis of the [[ tetrahydrobiopterin ]] (BH4), the obligate cofactor for TPH.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the [[ tetrahydrobiopterin ]] (BH4), the obligate cofactor for TPH.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In contrast, there was little change in mRNA levels for << GTP cyclohydrolase I >> (GTPCH), the rate limiting enzyme in synthesis of the tetrahydrobiopterin ([[ BH4 ]]), the obligate cofactor for TPH.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the tetrahydrobiopterin ([[ BH4 ]]), the obligate cofactor for TPH.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In relation to zinc bioavailability, << α-CPPs >>, β-CPPs, α(s1)-CN(64-74)4P and β-CN(1-25)4P increased [[ zinc ]] uptake.", "label": "SUBSTRATE", "metadata": []}
{"text": "In relation to zinc bioavailability, α-CPPs, << β-CPPs >>, α(s1)-CN(64-74)4P and β-CN(1-25)4P increased [[ zinc ]] uptake.", "label": "SUBSTRATE", "metadata": []}
{"text": "In relation to zinc bioavailability, α-CPPs, β-CPPs, << α(s1)-CN >>(64-74)4P and β-CN(1-25)4P increased [[ zinc ]] uptake.", "label": "SUBSTRATE", "metadata": []}
{"text": "In relation to zinc bioavailability, α-CPPs, β-CPPs, α(s1)-CN(64-74)4P and << β-CN >>(1-25)4P increased [[ zinc ]] uptake.", "label": "SUBSTRATE", "metadata": []}
{"text": "In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40h prior to >1 LD50 of aer-<< paraoxon >> (Px) was able to prevent inhibition of circulating [[ cholinesterase ]] in a dose-dependent manner.", "label": "ACTIVATOR", "metadata": []}
{"text": "Next to << Glut-4 >>, the predominant protein influencing [[ glucose ]] metabolism is PPARα and γ whose expressions were also positively modulated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Both the << 5 alpha-reductase >> inhibitor [[ finasteride ]] and alpha 1-adrenoceptor antagonists (e.g. alfuzosin, doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "INHIBITOR", "metadata": []}
{"text": "Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. [[ alfuzosin ]], doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, [[ doxazosin ]], prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, [[ prazosin ]], tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, prazosin, [[ tamsulosin ]] and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, prazosin, tamsulosin and [[ terazosin ]]) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials.", "label": "ANTAGONIST", "metadata": []}
{"text": "Central << 5-HT3 >> receptor stimulation by [[ m-CPBG ]] increases blood glucose in rats.", "label": "ACTIVATOR", "metadata": []}
{"text": "Injections of << m-CPBG >>, a selective [[ 5-HT3 ]] receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states.", "label": "AGONIST", "metadata": []}
{"text": "The hyperglycemic effect of << m-CPBG >> central administration was blocked by pretreatment with ondansetron, a specific [[ 5-HT3 ]] receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors.", "label": "AGONIST", "metadata": []}
{"text": "<< 3'-R/S-Hydroxyvoacamine >>, a potent [[ acetylcholinesterase ]] inhibitor from Tabernaemontana divaricata.", "label": "INHIBITOR", "metadata": []}
{"text": "Guided by the << acetylcholinesterase >> inhibiting activity, the [[ bisindole alkaloid ]] 3'-R/S-hydroxyvoacamine was isolated from a stem extract of Tabernaemontana divaricata, a plant used in Thailand in traditional rejuvenation remedies for improving the memory.", "label": "INHIBITOR", "metadata": []}
{"text": "Guided by the << acetylcholinesterase >> inhibiting activity, the bisindole alkaloid [[ 3'-R/S-hydroxyvoacamine ]] was isolated from a stem extract of Tabernaemontana divaricata, a plant used in Thailand in traditional rejuvenation remedies for improving the memory.", "label": "INHIBITOR", "metadata": []}
{"text": "<< α-Amino-α´-Halomethylketones >>: Synthetic Methodologies and Pharmaceutical Applications as [[ Serine and Cysteine Protease ]] Inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Introduction: 5-Lipoxygenase (<< 5-LO >>) is a crucial enzyme of the [[ arachidonic acid ]] (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein.", "label": "SUBSTRATE", "metadata": []}
{"text": "Introduction: << 5-Lipoxygenase >> (5-LO) is a crucial enzyme of the [[ arachidonic acid ]] (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein.", "label": "SUBSTRATE", "metadata": []}
{"text": "Using a transient heterologous cell expression system, we find that the transport activities of the << short OATP2B1 >> variant towards substrates [[ estrone sulfate ]] and rosuvastatin are similar to the well-characterized full length variant.", "label": "SUBSTRATE", "metadata": []}
{"text": "Using a transient heterologous cell expression system, we find that the transport activities of the << short OATP2B1 >> variant towards substrates estrone sulfate and [[ rosuvastatin ]] are similar to the well-characterized full length variant.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Memantine >> is an uncompetitive (channel blocking) [[ NMDA receptor ]] antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "Like other << NMDA receptor >> antagonists, [[ memantine ]] at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory.", "label": "ANTAGONIST", "metadata": []}
{"text": "Blockade of << NMDA receptors >> by [[ memantine ]] could theoretically confer disease-modifying activity in AD by inhibiting the \"weak\" NMDA receptor-dependent excitotoxicity that has been hypothesized to play a role in the progressive neuronal loss that underlies the evolving dementia.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of NMDA receptors by << memantine >> could theoretically confer disease-modifying activity in AD by inhibiting the \"weak\" [[ NMDA receptor ]]-dependent excitotoxicity that has been hypothesized to play a role in the progressive neuronal loss that underlies the evolving dementia.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, recent in vitro studies suggest that << memantine >> abrogates [[ beta-amyloid ]] (Abeta) toxicity and possibly inhibits Abeta production.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Moreover, recent in vitro studies suggest that << memantine >> abrogates beta-amyloid ([[ Abeta ]]) toxicity and possibly inhibits Abeta production.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Moreover, recent in vitro studies suggest that << memantine >> abrogates beta-amyloid (Abeta) toxicity and possibly inhibits [[ Abeta ]] production.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Considerable attention has focused on the investigation of theories to explain the better tolerability of << memantine >> over other [[ NMDA receptor ]] antagonists, particularly those that act by a similar channel blocking mechanism such as dissociative anesthetic-like agents (phencyclidine, ketamine, MK-801).", "label": "ANTAGONIST", "metadata": []}
{"text": "The concomitantly administered effects of << rifampicin >> on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by [[ p-glycoprotein ]] in the gastrointestinal tract and liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "The concomitantly administered effects of << rifampicin >> on other drugs can result in their altered metabolism or transportation that are metabolised by [[ cytochromes P450 ]] or transported by p-glycoprotein in the gastrointestinal tract and liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "In general, rifampicin can act on a pattern: << rifampicin >> activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.", "label": "ACTIVATOR", "metadata": []}
{"text": "In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "We describe here the isolation and biochemical characterization of the marine natural << sesquiterpene >> palinurin as a [[ GSK-3β ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "We describe here the isolation and biochemical characterization of the marine natural sesquiterpene << palinurin >> as a [[ GSK-3β ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Experimental studies performed for characterizing the inhibitory mechanism indicate that << GSK-3β >> inhibition by [[ palinurin ]] cannot be competed out by ATP nor peptide substrate.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of << palinurin >> leads to [[ GSK-3β ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Cyclooxygenase(COX)-2 >>-derived [[ prostanoids ]] can influence several processes that are linked to carcinogenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of << p21 >>(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(<< WAF1 >>/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/<< CIP1 >>) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of << cyclinB1 >>, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by << rofecoxib >>(a selective [[ COX-2 ]] inhibitor) and rescued by exogenous PGE2.", "label": "INHIBITOR", "metadata": []}
{"text": "Platelet-induced << COX-2 >>-dependent [[ PGE2 ]] synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib(a selective COX-2 inhibitor) and rescued by exogenous PGE2.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Previous studies demonstrated that the << Group III mGlu receptor >>-selective orthosteric agonist, [[ LSP1-2111 ]] produced anxiolytic- but not antidepressant-like effects upon peripheral administration.", "label": "AGONIST", "metadata": []}
{"text": "The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either << 5-HT(1A) >> receptors by [[ WAY100635 ]], or 5-HT(2A/2C) receptors by ritanserin.", "label": "INHIBITOR", "metadata": []}
{"text": "The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either 5-HT(1A) receptors by WAY100635, or << 5-HT(2A/2C) >> receptors by [[ ritanserin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the << benzodiazepine receptor >> antagonist [[ flumazenil ]] (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either 5-HT(1A) receptors by WAY100635, or 5-HT(2A/2C) receptors by ritanserin.", "label": "ANTAGONIST", "metadata": []}
{"text": "Catalytic-site affinities for cGMP, vardenafil, sildenafil, << tadalafil >>, or 3-isobutyl-1-methylxanthine (IBMX) were respectively weakened 14-, 123-, 30-, 51-, and 43-fold for Y612A; 63-, 511-, 43-, 95- and 61-fold for [[ Q817A ]]; and 59-, 448-, 71-, 137-, and 93-fold for F820A.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Allicin >> treatment showed reduced production of pro-inflammatory cytokines and NO and increased [[ HO-1 ]] activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Allicin >> treatment showed reduced production of pro-inflammatory [[ cytokines ]] and NO and increased HO-1 activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Recently, it has been shown that the activation of particular << T2R >> bitter taste receptors is partially involved with the bitter aftertaste sensation of [[ saccharin ]] and acesulfame-K.", "label": "ACTIVATOR", "metadata": []}
{"text": "Recently, it has been shown that the activation of particular << T2R >> bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and [[ acesulfame-K ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "We also found that << TRPV1 >> receptors are activated by [[ CuSO(4) ]], ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation.", "label": "ACTIVATOR", "metadata": []}
{"text": "We also found that << TRPV1 >> receptors are activated by CuSO(4), [[ ZnSO(4) ]], and FeSO(4), three salts known to produce a metallic taste sensation.", "label": "ACTIVATOR", "metadata": []}
{"text": "We also found that << TRPV1 >> receptors are activated by CuSO(4), ZnSO(4), and [[ FeSO(4) ]], three salts known to produce a metallic taste sensation.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 2-Arylpropionic >> CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive [[ CXCL8 ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< (R)-Ketoprofen >> (1) was previously reported to be a potent and specific noncompetitive inhibitor of [[ CXCL8 ]]-induced human PMNs chemotaxis.", "label": "INHIBITOR", "metadata": []}
{"text": "Role of organic cation/carnitine transporter 1 in uptake of << phenformin >> and inhibitory effect on [[ complex I ]] respiration in mitochondria.", "label": "INHIBITOR", "metadata": []}
{"text": "Role of << organic cation/carnitine transporter 1 >> in uptake of [[ phenformin ]] and inhibitory effect on complex I respiration in mitochondria.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Phenformin >> causes lactic acidosis in clinical situations due to inhibition of [[ mitochondrial respiratory chain complex I ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, uptake of phenformin and [(14)C]tetraethylammonium (TEA) and << complex I >> inhibition by [[ phenformin ]] were examined in isolated liver and heart mitochondria.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition by << phenformin >> of oxygen consumption via [[ complex I ]] respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of << phenformin >> on [[ complex I ]] respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.", "label": "INHIBITOR", "metadata": []}
{"text": "These observations suggest that uptake of << phenformin >> into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of [[ complex I ]] respiration.", "label": "INHIBITOR", "metadata": []}
{"text": "These observations suggest that uptake of << phenformin >> into liver mitochondria is at least partly mediated by [[ OCTN1 ]] and functionally relevant to its inhibition potential of complex I respiration.", "label": "SUBSTRATE", "metadata": []}
{"text": "A series of << xanthine >> derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of [[ dipeptidyl peptidase 4 ]] (DPP-4) for the treatment of type 2 diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << xanthine >> derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 ([[ DPP-4 ]]) for the treatment of type 2 diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of xanthine derivatives in which a methylene was inserted at position 8 of << xanthine >> scaffold was synthesized and evaluated as inhibitors of [[ dipeptidyl peptidase 4 ]] (DPP-4) for the treatment of type 2 diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of xanthine derivatives in which a methylene was inserted at position 8 of << xanthine >> scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 ([[ DPP-4 ]]) for the treatment of type 2 diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists << SB224289 >> (300 microg/kg; [[ 5-HT1B ]]), BRL15572 (300 microg/kg; 5-HT1D), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C).", "label": "ANTAGONIST", "metadata": []}
{"text": "The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), << BRL15572 >> (300 microg/kg; [[ 5-HT1D ]]), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C).", "label": "ANTAGONIST", "metadata": []}
{"text": "In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the << dopamine D2 >> agonist [[ apomorphine ]]; however, it is not clear whether both findings share the same biological basis.", "label": "AGONIST", "metadata": []}
{"text": "As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of [[ TES ]]-stimulated superoxide production.", "label": "PRODUCT-OF", "metadata": []}
{"text": "As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Functional and biochemical studies indicated that << TES >> signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the [[ androgen receptor ]] and culminated in enhanced production of cGMP and microvascular vasodilation.", "label": "ACTIVATOR", "metadata": []}
{"text": "These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by << peroxynitrite >> formed from [[ xanthine oxidase ]]-generated superoxide and NO.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from << xanthine oxidase >>-generated [[ superoxide ]] and NO.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from << xanthine oxidase >>-generated superoxide and [[ NO ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Mouse brain serine racemase >> catalyzes specific elimination of [[ L-serine ]] to pyruvate.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< D-Serine >> was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the [[ N-methyl-D-aspartate (NMDA)-type receptors ]].", "label": "AGONIST", "metadata": []}
{"text": "Racemization of << serine >> is catalyzed by [[ serine racemase ]], a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver.", "label": "SUBSTRATE", "metadata": []}
{"text": "Pharmacogenetic analysis of two genes, the << warfarin >> metabolic enzyme [[ CYP2C9 ]] and warfarin target enzyme, vitamin K epoxide reductase complex 1 VKORC1, confirmed their influence on warfarin maintenance dose.", "label": "SUBSTRATE", "metadata": []}
{"text": "Possession of << CYP2C9 >>*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean [[ warfarin ]] dose.", "label": "SUBSTRATE", "metadata": []}
{"text": "Possession of CYP2C9*2 or << CYP2C9 >>*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean [[ warfarin ]] dose.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Pseudoephedrine >> inhibits T-cell activation by targeting [[ NF-kappaB ]], NFAT and AP-1 signaling pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pseudoephedrine >> inhibits T-cell activation by targeting NF-kappaB, [[ NFAT ]] and AP-1 signaling pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pseudoephedrine >> inhibits T-cell activation by targeting NF-kappaB, NFAT and [[ AP-1 ]] signaling pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "We found that << PSE >> inhibits interleukin-2 (IL-2) and [[ tumor necrosis factor (TNF) alpha ]]-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "We found that << PSE >> inhibits [[ interleukin-2 ]] (IL-2) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "We found that << PSE >> inhibits interleukin-2 ([[ IL-2 ]]) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "To further characterize the inhibitory mechanisms of PSE at the transcriptional level, we examined the transcriptional activities of nuclear factor kappa B (NF-kappaB), nuclear factor of activated T cells (NFAT), and activator protein-1 (AP-1) transcription factors and found that << PSE >> inhibited [[ NF-kappaB ]]-dependent transcriptional activity without affecting either the phosphorylation, the degradation of the cytoplasmic NF-kappaB inhibitory protein, IkappaBalpha or the DNA-binding activity.", "label": "INHIBITOR", "metadata": []}
{"text": "However, phosphorylation of the << p65 >>/RelA subunit was clearly inhibited by [[ PSE ]] in stimulated cells.", "label": "INHIBITOR", "metadata": []}
{"text": "However, phosphorylation of the p65/<< RelA >> subunit was clearly inhibited by [[ PSE ]] in stimulated cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, PSE inhibited the transcriptional activity of NFAT without interfering with the << calcium >>-induced [[ NFAT ]] dephosphorylation event, which represents the major signaling pathway for its activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << PSE >> inhibited the transcriptional activity of [[ NFAT ]] without interfering with the calcium-induced NFAT dephosphorylation event, which represents the major signaling pathway for its activation.", "label": "INHIBITOR", "metadata": []}
{"text": "NFAT cooperates with c-Jun, a compound of the AP-1 complex, to activate target genes, and we also found that << PSE >> inhibited both [[ JNK ]] activation and AP-1 transcriptional activity.", "label": "INHIBITOR", "metadata": []}
{"text": "NFAT cooperates with c-Jun, a compound of the AP-1 complex, to activate target genes, and we also found that << PSE >> inhibited both JNK activation and [[ AP-1 ]] transcriptional activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, experiments showed that treatment with << DEC >> results in a reduction in the amount of [[ COX-1 ]] protein in peritoneal exudate cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Micromolar Ntp dose-dependently increased the mean open channel probability in ligand-free solution (P(O(max))) and attenuated the << ATP >> inhibition of [[ K(IR)6.2 ]]/SUR1, but had no effect on homomeric K(IR)6.2 channels.", "label": "INHIBITOR", "metadata": []}
{"text": "Micromolar Ntp dose-dependently increased the mean open channel probability in ligand-free solution (P(O(max))) and attenuated the << ATP >> inhibition of K(IR)6.2/[[ SUR1 ]], but had no effect on homomeric K(IR)6.2 channels.", "label": "INHIBITOR", "metadata": []}
{"text": "These effects resemble those seen with N-terminal deletions (DeltaN) of K(IR)6.0, and application of Ntp to << DeltaNK(ATP) channels >> decreased their P(O(max)) and apparent IC(50) for [[ ATP ]] in the absence of Mg(2+).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of [[ monocarboxylates ]] such as lactate, pyruvate, as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of [[ monocarboxylates ]] such as lactate, pyruvate, as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as [[ lactate ]], pyruvate, as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of monocarboxylates such as [[ lactate ]], pyruvate, as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as [[ ketone ]] bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as [[ ketone ]] bodies.", "label": "SUBSTRATE", "metadata": []}
{"text": "Interestingly, part of << MCT2 >> immunoreactivity is located at postsynaptic sites, suggesting a particular role of [[ monocarboxylates ]] and their transporters in synaptic transmission.", "label": "SUBSTRATE", "metadata": []}
{"text": "Differentiating the roles of mGlu2 and mGlu3 receptors using << LY541850 >>, an [[ mGlu2 ]] agonist/mGlu3 antagonist.", "label": "AGONIST", "metadata": []}
{"text": "Differentiating the roles of mGlu2 and mGlu3 receptors using << LY541850 >>, an mGlu2 agonist/[[ mGlu3 ]] antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< LY541850 >> was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric [[ mGlu2 ]] agonist and mGlu3 antagonist.", "label": "AGONIST", "metadata": []}
{"text": "<< LY541850 >> was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric mGlu2 agonist and [[ mGlu3 ]] antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "These results confirm the selective << mGlu2 >> agonist and mGlu3 antagonist actions of [[ LY541850 ]].", "label": "AGONIST", "metadata": []}
{"text": "These results confirm the selective mGlu2 agonist and << mGlu3 >> antagonist actions of [[ LY541850 ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Selective precipitation of cytosol receptors with 36% << (NH4)2SO4 >> reduced [[ CBG ]] concentrations to negligible levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The activity of the human nasal mucosa microsomes was inhibited by << 8-methoxypsoralen >>, a known [[ CYP2A ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Effects of some mono- and bisquaternary ammonium compounds on the reactivatability of << soman >>-inhibited [[ human acetylcholinesterase ]] in vitro.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetylcholinesterase >> (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by [[ oximes ]] due to dealkylation of the soman-enzyme complex.", "label": "ACTIVATOR", "metadata": []}
{"text": "Acetylcholinesterase (<< AChE >>) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by [[ oximes ]] due to dealkylation of the soman-enzyme complex.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Acetylcholinesterase >> (AChE) inhibited by the [[ organophosphate ]] soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "Acetylcholinesterase (<< AChE >>) inhibited by the [[ organophosphate ]] soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetylcholinesterase >> (AChE) inhibited by the organophosphate [[ soman ]] (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "Acetylcholinesterase (<< AChE >>) inhibited by the organophosphate [[ soman ]] (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetylcholinesterase >> (AChE) inhibited by the organophosphate soman ([[ 1,2,2-trimethyl-propylmethylphosphonofluoridate ]]) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "Acetylcholinesterase (<< AChE >>) inhibited by the organophosphate soman ([[ 1,2,2-trimethyl-propylmethylphosphonofluoridate ]]) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "label": "INHIBITOR", "metadata": []}
{"text": "The effect of the four mono- and bisquaternary ammonium compounds tetramethylammonium (TMA), hexamethonium, decamethonium and suxamethonium on the reactivatability of << soman >>-inhibited, solubilized [[ AChE ]] from human erythrocytes was investigated in vitro.", "label": "INHIBITOR", "metadata": []}
{"text": "If the effectors were added after 5 min of aging they increased the activity of << soman >>-inhibited [[ AChE ]], but to a considerably smaller extent than HI 6.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, << TOP2 >>-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. [[ doxorubicin ]], etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. [[ doxorubicin ]], etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, << TOP2 >>-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, [[ etoposide ]], mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. doxorubicin, [[ etoposide ]], mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, << TOP2 >>-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, [[ mitoxantrone ]], and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. doxorubicin, etoposide, [[ mitoxantrone ]], and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, << TOP2 >>-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, mitoxantrone, and [[ 4'-(9-acridinylamino)methanesulfon-m-anisidide ]]) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. doxorubicin, etoposide, mitoxantrone, and [[ 4'-(9-acridinylamino)methanesulfon-m-anisidide ]]) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive << TOP2 >> poisons (e.g. [[ amonafide ]], batracylin, and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive << TOP2 >> poisons (e.g. amonafide, [[ batracylin ]], and menadione) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive << TOP2 >> poisons (e.g. amonafide, batracylin, and [[ menadione ]]) was only slightly (less than 3-fold) affected.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, ADP was shown to strongly antagonize << TOP2 >>-mediated DNA cleavage induced by [[ ATP ]]-sensitive but not ATP-insensitive TOP2 poisons.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Second, C427A mutant human TOP2alpha, which exhibits reduced << ATPase >> activity, was shown to exhibit cross-resistance to all ATP-sensitive but not [[ ATP ]]-insensitive TOP2 poisons.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Activation of << ALDH2 >> with [[ ethanol ]] attenuates diabetes induced myocardial injury in rats.", "label": "ACTIVATOR", "metadata": []}
{"text": "This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with << ALDH2 >> activator [[ ethanol ]] (EtOH).", "label": "ACTIVATOR", "metadata": []}
{"text": "This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with << ALDH2 >> activator ethanol ([[ EtOH ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "HbA1c level in DM12W group was higher than in DM4W group, << HbA1c >> level in [[ EtOH ]]+DM8W group was lower than in DM8W group.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with DM8W group, << SOD >> and ALDH2 in [[ EtOH ]]+DM8W group was increased, MDA was decreased.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Compared with DM8W group, SOD and << ALDH2 >> in [[ EtOH ]]+DM8W group was increased, MDA was decreased.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Kinetic mechanism of << quinone oxidoreductase 2 >> and its inhibition by the antimalarial [[ quinolines ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< QR2 >> catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or [[ N-ribosylated nicotinamides ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< QR2 >> catalyzes the two-electron reduction of [[ menadione ]] via the oxidation of N-alkylated or N-ribosylated nicotinamides.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< QR2 >> catalyzes the two-electron reduction of menadione via the oxidation of [[ N-alkylated ]] or N-ribosylated nicotinamides.", "label": "SUBSTRATE", "metadata": []}
{"text": "To investigate the mechanism and consequences of inhibition of << QR2 >> by the [[ quinolines ]] further, we have used steady-state and transient-state kinetics to define the mechanism of QR2.", "label": "INHIBITOR", "metadata": []}
{"text": "To investigate the mechanism and consequences of inhibition of QR2 by the << quinolines >> further, we have used steady-state and transient-state kinetics to define the mechanism of [[ QR2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Our studies shed light on the possible in vivo potency of the << quinolines >> and provide a foundation for future studies aimed at creating more potent [[ QR2 ]] inhibitors and at understanding the physiological significance of QR2.", "label": "INHIBITOR", "metadata": []}
{"text": "Methods: Stabilized anaplastic thyroid cancer cell lines (BHT-101 and CAL-62) and primary cultures from patients who underwent thyroidectomy for anaplastic thyroid cancer were treated with the << histone deacetylase >> inhibitor [[ LBH589 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Results: Our results demonstrate that treatment with << LBH589 >> leads to [[ NIS ]] RNA expression as shown by RT-PCR and luciferase assay, and to protein expression as determined by immunofluorescence in vitro and by immunohistochemistry in xenograft tumors.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Pharmacokinetic Interactions between << Monoamine Oxidase A >> Inhibitor [[ Harmaline ]] and 5-Methoxy-N,N-Dimethyltryptamine, and the Impact of CYP2D6 Status.", "label": "INHIBITOR", "metadata": []}
{"text": "Our recent study has demonstrated that coadministration of << monoamine oxidase A >> (MAO-A) inhibitor [[ harmaline ]] (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine.", "label": "INHIBITOR", "metadata": []}
{"text": "Our recent study has demonstrated that coadministration of monoamine oxidase A (<< MAO-A >>) inhibitor [[ harmaline ]] (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine.", "label": "INHIBITOR", "metadata": []}
{"text": "Our data revealed that inhibition of << MAO-A >>-mediated metabolic elimination by [[ harmaline ]] (2, 5, and 15 mg/kg) led to a sharp increase in systemic and cerebral exposure to 5-MeO-DMT (2 and 10 mg/kg) at all dose combinations.", "label": "INHIBITOR", "metadata": []}
{"text": "The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The in vivo inhibitory effect of << harmaline >> on [[ CYP2D6 ]]-catalyzed bufotenine formation was confirmed by in vitro study using purified CYP2D6.", "label": "INHIBITOR", "metadata": []}
{"text": "The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed << bufotenine >> formation was confirmed by in vitro study using purified [[ CYP2D6 ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "The in vivo inhibitory effect of harmaline on << CYP2D6 >>-catalyzed [[ bufotenine ]] formation was confirmed by in vitro study using purified CYP2D6.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of << MAO-A >>- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood [[ harmaline ]], 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood [[ harmaline ]], 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood << harmaline >>, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of << MAO-A >>- and CYP2D6-catalyzed 5-MeO-DMT metabolism by [[ harmaline ]] was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed 5-MeO-DMT metabolism by [[ harmaline ]] was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by << harmaline >> was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models.", "label": "INHIBITOR", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of << MAO-A >>- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, [[ 5-MeO-DMT ]], and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, [[ 5-MeO-DMT ]], and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, << 5-MeO-DMT >>, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of << MAO-A >>- and CYP2D6-catalyzed [[ 5-MeO-DMT ]] metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed [[ 5-MeO-DMT ]] metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed << 5-MeO-DMT >> metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models.", "label": "SUBSTRATE", "metadata": []}
{"text": "Compared pharmacological characteristics in humans of racemic << cetirizine >> and levocetirizine, two [[ histamine H1-receptor ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Compared pharmacological characteristics in humans of racemic cetirizine and << levocetirizine >>, two [[ histamine H1-receptor ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potent << histamine H(1)-receptor >> antagonist [[ cetirizine ]] (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potent << histamine H(1)-receptor >> antagonist cetirizine ([[ Zyrtec ]]) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potent << histamine H(1)-receptor >> antagonist cetirizine (Zyrtec) is a racemic mixture of [[ levocetirizine ]] (now available under the trademark Xyzal and dextrocetirizine.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potent << histamine H(1)-receptor >> antagonist cetirizine (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark [[ Xyzal ]] and dextrocetirizine.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potent << histamine H(1)-receptor >> antagonist cetirizine (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and [[ dextrocetirizine ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Vegfrecine >>, an Inhibitor of [[ VEGF Receptor Tyrosine Kinases ]] Isolated from the Culture Broth of Streptomyces sp.", "label": "INHIBITOR", "metadata": []}
{"text": "A new inhibitor of << VEGF receptor tyrosine kinases >>, [[ vegfrecine ]] (1), was isolated from the culture broth of Streptomyces sp.", "label": "INHIBITOR", "metadata": []}
{"text": "As opposed to the rat and flounder orthologs, << hNaDC-3 >> was hardly inhibited by [[ lithium ]] concentrations up to 5 mM.", "label": "INHIBITOR", "metadata": []}
{"text": "Effects of inhibition of << urokinase-type plasminogen activator >> (u-PA) by [[ amiloride ]] in the cornea and tear fluid of eyes irradiated with UVB.", "label": "INHIBITOR", "metadata": []}
{"text": "Effects of inhibition of urokinase-type plasminogen activator (<< u-PA >>) by [[ amiloride ]] in the cornea and tear fluid of eyes irradiated with UVB.", "label": "INHIBITOR", "metadata": []}
{"text": "The purpose of the present study was to test our hypothesis that << amiloride >>, a specific [[ u-PA ]] inhibitor, effectively decreases u-PA activity in cornea as well as in tear fluid and favourably affects corneal healing.", "label": "INHIBITOR", "metadata": []}
{"text": "The purpose of the present study was to test our hypothesis that << amiloride >>, a specific u-PA inhibitor, effectively decreases [[ u-PA ]] activity in cornea as well as in tear fluid and favourably affects corneal healing.", "label": "INHIBITOR", "metadata": []}
{"text": "Therefore, comparative histochemical and biochemical studies of << u-PA >> and the effects of amiloride were performed on rabbit corneas and tear fluid using the sensitive fluorogenic substrate [[ Z-Gly-Gly-Arg-7-amino-4-trifluoromethylcoumarin ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "When << amiloride >> was dropped on the eye surface on the first day of irradiation and subsequently daily until the end of the experiment, [[ u-PA ]] activity in both cornea and tear fluid was strongly inhibited.", "label": "INHIBITOR", "metadata": []}
{"text": "In conclusion, early application of << amiloride >> inhibited [[ u-PA ]] activity in UVB-irradiated corneas as well as in tear fluid and diminished the development of corneal pathology.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Prednisolone >> also inhibited ACTH and cortisol secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Prednisolone also inhibited ACTH and << cortisol >> secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Pharmacophore identification of << c-Myc >> inhibitor [[ 10074-G5 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A structure-activity relationship (SAR) study of the << c-Myc >> (Myc) inhibitor [[ 10074-G5 ]] (N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine, 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore.", "label": "INHIBITOR", "metadata": []}
{"text": "A structure-activity relationship (SAR) study of the c-Myc (<< Myc >>) inhibitor [[ 10074-G5 ]] (N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine, 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore.", "label": "INHIBITOR", "metadata": []}
{"text": "A structure-activity relationship (SAR) study of the << c-Myc >> (Myc) inhibitor 10074-G5 ([[ N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine ]], 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore.", "label": "INHIBITOR", "metadata": []}
{"text": "A structure-activity relationship (SAR) study of the c-Myc (<< Myc >>) inhibitor 10074-G5 ([[ N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine ]], 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore.", "label": "INHIBITOR", "metadata": []}
{"text": "Importantly, the carboxylic acid of << JY-3-094 >> improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance [[ Myc ]] inhibitory activity further still.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Miglustat >>, a small iminosugar molecule approved for the treatment of Gaucher disease, reversibly inhibits [[ glucosylceramide synthase ]], which catalyses the first committed step in glycosphingolipid synthesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, compared with control groups, the plaque endothelium level of << p75(NTR) >> was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by [[ SFO ]]-HD.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of << p75(NTR) >> was 17.4-fold increased by [[ SFO ]]-HD.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Meanwhile, the serum level of KC (a functional homolog of << IL-8 >> and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in [[ SFO ]]-HD treated group.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory << alpha chemokine >> in mice) in apoE(-/-) mice was up to 357pg/ml in [[ SFO ]]-HD treated group.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating [[ p75(NTR) ]] and IL-8 and cell apoptosis in plaque.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by [[ aromatic-L-amino-acid decarboxylase ]] (AADC) and catechol-O-methyltransferase (COMT).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase ([[ AADC ]]) and catechol-O-methyltransferase (COMT).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and [[ catechol-O-methyltransferase ]] (COMT).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase ([[ COMT ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Because gastric AADC and COMT degrade levodopa, the drug is given with inhibitors of << AADC >> (carbidopa or [[ benserazide ]]), and inhibitors of COMT will also enter clinical use.", "label": "INHIBITOR", "metadata": []}
{"text": "Because gastric AADC and COMT degrade levodopa, the drug is given with inhibitors of << AADC >> ([[ carbidopa ]] or benserazide), and inhibitors of COMT will also enter clinical use.", "label": "INHIBITOR", "metadata": []}
{"text": "Because gastric << AADC >> and COMT degrade [[ levodopa ]], the drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors of COMT will also enter clinical use.", "label": "SUBSTRATE", "metadata": []}
{"text": "Because gastric AADC and << COMT >> degrade [[ levodopa ]], the drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors of COMT will also enter clinical use.", "label": "SUBSTRATE", "metadata": []}
{"text": "Rats were fed experimental diets containing SPI or << casein >> as a [[ nitrogen ]] source.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of << L-arginine >> for [[ aminopeptidase B ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: << 4-methoxy-2-naphthylamide >> of L-alanine for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of << L-alanine >> for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, << 4-methoxy-2-naphthylamide >> of L-leucine for [[ leucine aminopeptidase ]], 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of << L-leucine >> for [[ leucine aminopeptidase ]], 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, << 4-methoxy-2-naphthylamide >> of L-glutamic acid for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of << L-glutamic acid >> for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B.", "label": "SUBSTRATE", "metadata": []}
{"text": "Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and << 4-methoxy-2-naphthylamide >> of L-arginine for [[ aminopeptidase B ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The inhibition of << aminopeptidase >> activity in the presence of [[ bestatin ]] and puromycin inhibitors was also investigated.", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibition of << aminopeptidase >> activity in the presence of bestatin and [[ puromycin ]] inhibitors was also investigated.", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/[[ pThr ]]-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of pSer/[[ pThr ]]-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-[[ Pro ]] moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-[[ Pro ]] moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification.", "label": "SUBSTRATE", "metadata": []}
{"text": "Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to << glutamine >> through the enzyme [[ glutamine synthetase ]] (GS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to << glutamine >> through the enzyme glutamine synthetase ([[ GS ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme [[ glutamine synthetase ]] (GS).", "label": "SUBSTRATE", "metadata": []}
{"text": "Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme glutamine synthetase ([[ GS ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "The protein exhibited modest << H(2)O(2) >>-dependent [[ peroxidase ]] activities with guaiacol, potassium iodide, and 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS).", "label": "ACTIVATOR", "metadata": []}
{"text": "The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with [[ guaiacol ]], potassium iodide, and 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS).", "label": "SUBSTRATE", "metadata": []}
{"text": "The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with guaiacol, [[ potassium iodide ]], and 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS).", "label": "SUBSTRATE", "metadata": []}
{"text": "The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with guaiacol, potassium iodide, and [[ 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid ]] (ABTS).", "label": "SUBSTRATE", "metadata": []}
{"text": "The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with guaiacol, potassium iodide, and 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid ([[ ABTS ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Luciferase reporter assays showed that transcription of << FDX1 >> was synergistically activated by the NR5A family and [[ 8Br-cAMP ]] treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results indicate transcription of << FDX1 >> is regulated by the NR5A family and [[ cAMP ]] signaling, and participates in steroid hormone production in ovarian granulosa cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results indicate transcription of << FDX1 >> is regulated by the NR5A family and cAMP signaling, and participates in [[ steroid ]] hormone production in ovarian granulosa cells.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Flutamide >>, an effective competitive inhibitor of the [[ androgen receptor ]] used orally for palliative treatment of prostatic carcinoma and regulation of prostatic hyperplasia was evaluated for its genotoxic effects in the intact rat and in primary cultures of human hepatocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "In the liver of rats given << flutamide >> as initiating agent at the dose of 500 mg/kg/week for 6 successive weeks, [[ gamma-glutamyltraspeptidase ]]-positive foci were detected only in 3 of 10 rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Cycloxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) has been shown to be important in esophageal tumorigenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Cycloxygenase-2 (<< COX-2 >>)-derived [[ prostaglandin E2 ]] (PGE2) has been shown to be important in esophageal tumorigenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Cycloxygenase-2 >> (COX-2)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Cycloxygenase-2 (<< COX-2 >>)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "We have shown that << COX-2 >> mediates acid-induced [[ PGE2 ]] production.", "label": "PRODUCT-OF", "metadata": []}
{"text": "We conclude that << mPGES1 >> mediates acid-induced increase in [[ PGE2 ]] production and cell proliferation.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Butein >> also increased [[ heme oxygenase-1 ]] (HO-1) protein expression and HO activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Butein >> also increased heme oxygenase-1 ([[ HO-1 ]]) protein expression and HO activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity.", "label": "UPREGULATOR", "metadata": []}
{"text": "Furthermore, << butein >> treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of [[ antioxidant response elements ]] (AREs).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, << butein >> treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements ([[ AREs ]]).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, << butein >> treatment caused nuclear accumulation of [[ nuclear factor-E2-related factor 2 ]] (Nrf2) and increased the promoter activity of antioxidant response elements (AREs).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, << butein >> treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 ([[ Nrf2 ]]) and increased the promoter activity of antioxidant response elements (AREs).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and << butein >> treatment led to increased [[ JNK ]] phosphorylation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced << butein >>-induced [[ HO-1 ]] expression, and butein treatment led to increased JNK phosphorylation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its << proline-42-to-alanine >> mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its proline-42-to-alanine mutant (<< Pro42Ala >>) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact << bovine pancreatic ribonuclease A >> (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (<< RNase A >>) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its << proline-42-to-alanine >> mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate ([[ 2'CMP ]]) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its proline-42-to-alanine mutant (<< Pro42Ala >>) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate ([[ 2'CMP ]]) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact << bovine pancreatic ribonuclease A >> (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate ([[ 2'CMP ]]) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (<< RNase A >>) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and 2'-cytidine monophosphate ([[ 2'CMP ]]) inhibitor binding.", "label": "INHIBITOR", "metadata": []}
{"text": "The folding rate for wild-type << RNase A >> is faster in the presence of the inhibitor [[ 2'CMP ]] than in its absence, indicating that the transition-state structure in the rate-determining step is stabilized by 2'CMP.", "label": "INHIBITOR", "metadata": []}
{"text": "During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce << prostaglandins >> (PG) via [[ PG synthase 2 ]] (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1).", "label": "PRODUCT-OF", "metadata": []}
{"text": "During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce << prostaglandins >> (PG) via PG synthase 2 ([[ PTGS2 ]]) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1).", "label": "PRODUCT-OF", "metadata": []}
{"text": "During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via [[ hydroxysteroid (11-β) dehydrogenase 1 ]] (HSD11B1).", "label": "PRODUCT-OF", "metadata": []}
{"text": "During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via hydroxysteroid (11-β) dehydrogenase 1 ([[ HSD11B1 ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "The primary aim of these studies was to test the hypothesis that << HSD11B1 >>-derived [[ cortisol ]] has a biological role in endometrial function and conceptus development during early pregnancy in sheep.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In study 1, cyclic ewes received vehicle, cortisol, << PF 915275 >> (PF; a selective inhibitor of [[ HSD11B1 ]]), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus.", "label": "INHIBITOR", "metadata": []}
{"text": "In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, << meloxicam >> (a selective inhibitor of [[ PTGS2 ]]), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Cortisol >> and IFNT stimulated endometrial [[ HSD11B1 ]] expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Cortisol >> and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial [[ PTGS2 ]] activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Cortisol >> and IFNT stimulated endometrial [[ HSD11B1 ]] expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery.", "label": "AGONIST", "metadata": []}
{"text": "2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery.", "label": "AGONIST", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the << beta-adrenoceptor >> blocker with high affinity for 5-HT1A and 5-HT1B binding sites [[ (+/-)-pindolol ]] (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the << 5-HT2 receptor >> antagonist [[ ketanserin ]] (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the << 5-HT3 >> and 5-HT4 receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and << 5-HT4 >> receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the << 5-HT1A >> receptor antagonist [[ spiroxatrine ]] (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the << alpha 1-adrenoceptor >> antagonist [[ prazosin ]] (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed [[ 5-HT1-like ]] and 5-HT2 receptor antagonist methiothepin (0.01-1 microM).", "label": "AGONIST", "metadata": []}
{"text": "In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed 5-HT1-like and [[ 5-HT2 receptor ]] antagonist methiothepin (0.01-1 microM).", "label": "AGONIST", "metadata": []}
{"text": "In contrast, the D-1997-induced responses were potently and concentration-dependently antagonized by the mixed << 5-HT1-like >> and 5-HT2 receptor antagonist [[ methiothepin ]] (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "In contrast, the D-1997-induced responses were potently and concentration-dependently antagonized by the mixed 5-HT1-like and << 5-HT2 receptor >> antagonist [[ methiothepin ]] (0.01-1 microM).", "label": "ANTAGONIST", "metadata": []}
{"text": "It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating [[ 5-HT1-like receptors ]] unrelated to either the 5-HT1A or 5-HT1B receptor subtypes.", "label": "ACTIVATOR", "metadata": []}
{"text": "It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the [[ 5-HT1A ]] or 5-HT1B receptor subtypes.", "label": "ACTIVATOR", "metadata": []}
{"text": "It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the 5-HT1A or [[ 5-HT1B ]] receptor subtypes.", "label": "ACTIVATOR", "metadata": []}
{"text": "Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for << VK2 >>-induced [[ cytochrome c ]] (cyt c) release and cell death.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for << VK2 >>-induced cytochrome c ([[ cyt c ]]) release and cell death.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In muscle and liver, << TCDD >> (10 ng/kg/day) induced increases in methylation and decreases in mRNA expression of [[ Igf2r ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Rasagiline >> is a propargylamine and irreversible [[ monoamine oxidase (MAO) B ]] inhibitor used for the treatment of Parkinson's disease (PD).", "label": "INHIBITOR", "metadata": []}
{"text": "Rasagiline is a << propargylamine >> and irreversible [[ monoamine oxidase (MAO) B ]] inhibitor used for the treatment of Parkinson's disease (PD).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Tolvaptan >> is a selective [[ arginine vasopressin (AVP) V(2) receptor ]] blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic hyponatremia.", "label": "INHIBITOR", "metadata": []}
{"text": "Prolonged use of << tolvaptan >> leads to increased endogenous levels of AVP and perhaps over-stimulation of [[ V(1A) receptors ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Prolonged use of << tolvaptan >> leads to increased endogenous levels of [[ AVP ]] and perhaps over-stimulation of V(1A) receptors.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, << tolvaptan >> is metabolized by the [[ CYP3A4 ]] system; thus physicians should be aware of the potential for increased interactions with other medications.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma [[ insulin ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, [[ glycosylated hemoglobin ]] (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin ([[ HbA1c ]]), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), [[ NF-kB ]] p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB [[ p65 ]] unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and [[ IL-1β ]] (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "High-<< glucose >> environment enhanced oxidative stress and increased [[ interleukin-8 ]] secretion from keratinocytes: New insights on impaired diabetic wound healing.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Using cultured human keratinocytes and diabetic rat model, the current study showed that high-<< glucose >> environment enhanced [[ IL-8 ]] production via epidermal growth factor receptor (EGFR) -extracelluar signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In conclusion, << IL-8 >> production and neutrophil infiltration are increased in high-[[ glucose ]] environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased [[ catalase ]] (CAT) activity compared with the control.", "label": "UPREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control.", "label": "UPREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and [[ glutathioneperoxidase ]] (GPx) activities, while increased catalase (CAT) activity compared with the control.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase ([[ GPx ]]) activities, while increased catalase (CAT) activity compared with the control.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and [[ c-jun ]] expression relative to control.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced [[ c-fos ]] and c-jun expression relative to control.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The data indicated that << PhIP >> could cause stomach injury, oxidative stress in rat stomachs as well as the activation of [[ c-fos ]] and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer.", "label": "ACTIVATOR", "metadata": []}
{"text": "The data indicated that << PhIP >> could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and [[ c-jun ]] and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer.", "label": "ACTIVATOR", "metadata": []}
{"text": "The data indicated that << PhIP >> could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of [[ p16 ]], which may play a role in the pathogenesis of PhIP-associated stomach cancer.", "label": "INHIBITOR", "metadata": []}
{"text": "We also shortly discuss the ongoing debate on whether << NO >> is the actual reaction product of [[ NOS ]] catalysis, as well as the phenomenon of NO-mediated autoinhibition.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Prostacyclin >> analogues inhibit [[ tissue factor ]] expression in the human monocytic cell line THP-1 via a cyclic AMP-dependent mechanism.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The present studies were undertaken to determine whether stable analogues of << prostacyclin >>, a potent endothelium-derived platelet inhibitor and vasodilator, could inhibit [[ tissue factor ]] expression by human monocytic cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Preincubation for 30 minutes with << iloprost >>, ciprostene, and carbacyclin led to a dose-dependent inhibition of [[ tissue factor ]] expression induced by all three challenging agents.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Preincubation for 30 minutes with iloprost, << ciprostene >>, and carbacyclin led to a dose-dependent inhibition of [[ tissue factor ]] expression induced by all three challenging agents.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Preincubation for 30 minutes with iloprost, ciprostene, and << carbacyclin >> led to a dose-dependent inhibition of [[ tissue factor ]] expression induced by all three challenging agents.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "This effect was potentiated by << isobutylmethylxanthine >>, an inhibitor of [[ phosphodiesterase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibitory effects of iloprost on << tissue factor >> expression were also potentiated by [[ isobutylmethylxanthine ]] and mimicked by forskolin and dibutyryl cyclic AMP but not dibutyryl cyclic GMP.", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibitory effects of iloprost on << tissue factor >> expression were also potentiated by isobutylmethylxanthine and mimicked by [[ forskolin ]] and dibutyryl cyclic AMP but not dibutyryl cyclic GMP.", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibitory effects of iloprost on << tissue factor >> expression were also potentiated by isobutylmethylxanthine and mimicked by forskolin and d[[ ibutyryl cyclic AMP ]] but not dibutyryl cyclic GMP.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that prostacyclin may play a role in downregulating << tissue factor >> expression in monocytes, at least in part via elevation of intracellular levels of [[ cyclic AMP ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "These results suggest that << prostacyclin >> may play a role in downregulating [[ tissue factor ]] expression in monocytes, at least in part via elevation of intracellular levels of cyclic AMP.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by thymidine phosphorylase ([[ TP ]]) inside target tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by [[ thymidine phosphorylase ]] (TP) inside target tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "PURPOSE: The << fluoropyrimidine carbamate >> (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues.", "label": "SUBSTRATE", "metadata": []}
{"text": "PURPOSE: The << fluoropyrimidine carbamate >> (capecitabine) is converted to 5-fluorouracil (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues.", "label": "SUBSTRATE", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (<< capecitabine >>) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues.", "label": "SUBSTRATE", "metadata": []}
{"text": "PURPOSE: The fluoropyrimidine carbamate (<< capecitabine >>) is converted to 5-fluorouracil (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< 5-FU >> interferes with DNA synthesis by blocking [[ thymidylate synthase ]] (TS) but is inactivated by dihydropyrimidine dehydrogenase (DPD).", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-FU >> interferes with DNA synthesis by blocking thymidylate synthase ([[ TS ]]) but is inactivated by dihydropyrimidine dehydrogenase (DPD).", "label": "INHIBITOR", "metadata": []}
{"text": "Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Favorable enzyme profiles (high TP and low << DPD >>) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Previous studies by this research team proved that vasodilating << prostaglandins >> (PGs) E1, E2 and I2 inhibit [[ carbonic anhydrase ]] (CA) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs.", "label": "INHIBITOR", "metadata": []}
{"text": "Previous studies by this research team proved that vasodilating << prostaglandins >> (PGs) E1, E2 and I2 inhibit carbonic anhydrase ([[ CA ]]) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs.", "label": "INHIBITOR", "metadata": []}
{"text": "Previous studies by this research team proved that vasodilating prostaglandins (<< PGs >>) E1, E2 and I2 inhibit [[ carbonic anhydrase ]] (CA) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs.", "label": "INHIBITOR", "metadata": []}
{"text": "Previous studies by this research team proved that vasodilating prostaglandins (<< PGs >>) E1, E2 and I2 inhibit carbonic anhydrase ([[ CA ]]) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs.", "label": "INHIBITOR", "metadata": []}
{"text": "Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of [[ CA I ]] and CA II.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Indomethacin >> abolished the inhibitory effect of acetazolamide on [[ CA I ]] and CA II.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> abolished the inhibitory effect of acetazolamide on CA I and [[ CA II ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Indomethacin abolished the inhibitory effect of << acetazolamide >> on [[ CA I ]] and CA II.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin abolished the inhibitory effect of << acetazolamide >> on CA I and [[ CA II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< COX-1 >> inhibition was measured as percentage inhibition of serum [[ TXB2 ]] generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100.", "label": "PRODUCT-OF", "metadata": []}
{"text": "CONCLUSIONS: In the maximum registered dosage, << nabumetone >> inhibits thromboxane production much more than meloxicam, signifying less [[ COX-2 ]] selectivity of the former.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Treatment with << diclofenac >> resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated [[ caspase-3 ]] after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade.", "label": "ACTIVATOR", "metadata": []}
{"text": "Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that << diclofenac >> may cause apoptosis of neuronal cells via activation of the [[ caspase ]] cascade.", "label": "ACTIVATOR", "metadata": []}
{"text": "Correlation between activation of << PPARγ >> and resistin downregulation in a mouse adipocyte cell line by a series of [[ thiazolidinediones ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Correlation between activation of PPARγ and << resistin >> downregulation in a mouse adipocyte cell line by a series of [[ thiazolidinediones ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, [[ cinnamic aldehyde ]], and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers (sulforaphane, tert-butylhydroquinone, [[ cinnamic aldehyde ]], and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and [[ hydrogen peroxide ]]) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and [[ hydrogen peroxide ]]) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "label": "ACTIVATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (<< sulforaphane >>, tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, << tert-butylhydroquinone >>, cinnamic aldehyde, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, << cinnamic aldehyde >>, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and << hydrogen peroxide >>) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The treatment of U937 cells with << NRF2 >> inducers including [[ sulforaphane ]] effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3.", "label": "ACTIVATOR", "metadata": []}
{"text": "The treatment of U937 cells with NRF2 inducers including << sulforaphane >> effectively elevated the expression of [[ AKR1B1, 1B10, 1C1, 1C2, and 1C3 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Whereas, the levels of both the basal and << sulforaphane >>-inducible expression of [[ AKR1C1 ]] were significantly reduced in NRF2-silenced stable U937 cells compared to the control cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Human and rat renin >> and angiotensinogen genes were downregulated in dTGR and were increased by [[ losartan ]] and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Human and rat renin and << angiotensinogen >> genes were downregulated in dTGR and were increased by [[ losartan ]] and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Human and rat renin >> and angiotensinogen genes were downregulated in dTGR and were increased by losartan and [[ cilazapril ]] treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Human and rat renin and << angiotensinogen >> genes were downregulated in dTGR and were increased by losartan and [[ cilazapril ]] treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Endothelial NO synthase >> expression was increased by [[ cilazapril ]] but not by losartan.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to this pronounced loss of function, << M1766L >> also showed a 10-fold increase in the persistent late [[ sodium ]] current.", "label": "UPREGULATOR", "metadata": []}
{"text": "Western blot analysis revealed that << OMT >> decreased the expression of [[ Bax ]] and repaired the balance of pro- and anti-apoptotic proteins.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, << OMT >> significantly reversed the up-regulation of [[ NR2B ]] and inhibited the calcium overload in the cultured neurons after challenging the NMDA.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of [[ Bcl-2 ]] family.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing [[ NMDA receptors ]] and up-regulation of Bcl-2 family.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< OMT >> showed partial protection in the cortical neurons via down-regulation of [[ NR2B ]] containing NMDA receptors and up-regulation of Bcl-2 family.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Emodin-6-O-β-D-glucoside >> inhibits [[ HMGB1 ]]-induced inflammatory responses in vitro and in vivo.", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacology of << ramelteon >>, a selective [[ MT1 ]]/MT2 receptor agonist: a novel therapeutic drug for sleep disorders.", "label": "AGONIST", "metadata": []}
{"text": "Pharmacology of << ramelteon >>, a selective MT1/[[ MT2 ]] receptor agonist: a novel therapeutic drug for sleep disorders.", "label": "AGONIST", "metadata": []}
{"text": "<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist.", "label": "AGONIST", "metadata": []}
{"text": "<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT(1)/[[ MT(2) ]] receptor agonist.", "label": "AGONIST", "metadata": []}
{"text": "Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin [[ MT(1) ]] and MT(2) receptors, which are primarily located in the suprachiasmatic nucleus, the body's \"master clock.\" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades.", "label": "AGONIST", "metadata": []}
{"text": "Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin MT(1) and [[ MT(2) ]] receptors, which are primarily located in the suprachiasmatic nucleus, the body's \"master clock.\" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades.", "label": "AGONIST", "metadata": []}
{"text": "<< Am80 >> slightly inhibited the growth of both myeloma cells and HUVECs, and remarkably inhibited the growth of HUVECs stimulated by [[ VEGF ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Am80 >> inhibited VEGF-induced phosphorylation of [[ VEGF receptor ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Am80 >> inhibited [[ VEGF ]]-induced phosphorylation of VEGF receptor.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, << VEGF >>-induced formation of tube-like structures in vitro and neovascularization in mouse corneas were significantly inhibited by [[ Am80 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effect of dihydropyridine << Ca2+-channel >> blockers [[ felodipine ]] and nicardipine on CaMPDE.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effect of dihydropyridine << Ca2+-channel >> blockers felodipine and [[ nicardipine ]] on CaMPDE.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effect of << dihydropyridine >> [[ Ca2+-channel ]] blockers felodipine and nicardipine on CaMPDE.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (<< PDE 1B1 >>) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by [[ felodipine ]] and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (<< PDE 1A2 >>) CaMPDE isozymes are inhibited by [[ felodipine ]] and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) << CaMPDE >> isozymes are inhibited by [[ felodipine ]] and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (<< PDE 1B1 >>) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by felodipine and [[ nicardipine ]] by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (<< PDE 1A2 >>) CaMPDE isozymes are inhibited by felodipine and [[ nicardipine ]] by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) << CaMPDE >> isozymes are inhibited by felodipine and [[ nicardipine ]] by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and nicardipine have similar affinities for 60-kDa << CaMPDE >> isozymes but bring about different levels of enzyme inhibition, suggesting the possibility of designing specific drugs that can protect the enzyme from inhibition by [[ dihydropyridine ]] Ca2+-channel blockers.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and nicardipine have similar affinities for 60-kDa CaMPDE isozymes but bring about different levels of enzyme inhibition, suggesting the possibility of designing specific drugs that can protect the enzyme from inhibition by << dihydropyridine >> [[ Ca2+-channel ]] blockers.", "label": "INHIBITOR", "metadata": []}
{"text": "Several inhibitors of << Lp-PLA(2) >> have been described, including [[ darapladib ]], which is currently in phase 3 clinical development for the treatment of atherosclerosis.", "label": "INHIBITOR", "metadata": []}
{"text": "We show that both << darapladib >> and a novel class of structurally distinct carbamate inhibitors inactivate [[ Lp-PLA(2) ]] in mouse tissues and human cell lines with high selectivity.", "label": "INHIBITOR", "metadata": []}
{"text": "We show that both darapladib and a novel class of structurally distinct << carbamate >> inhibitors inactivate [[ Lp-PLA(2) ]] in mouse tissues and human cell lines with high selectivity.", "label": "INHIBITOR", "metadata": []}
{"text": "Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol].", "label": "AGONIST", "metadata": []}
{"text": "Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist formoterol [[[ eformoterol ]]].", "label": "AGONIST", "metadata": []}
{"text": "Nitric oxide products of << VP-16 >> displayed significantly diminished [[ topoisomerase II ]]-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Consistent with these locations, << N-ethylmaleimide >>, an inhibitor of [[ ACS4 ]], inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum.", "label": "INHIBITOR", "metadata": []}
{"text": "Consistent with these locations, << N-ethylmaleimide >>, an inhibitor of ACS4, inhibited [[ ACS ]] activity 47% in MAM and 28% in endoplasmic reticulum.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Troglitazone >>, a second [[ ACS4 ]] inhibitor, inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Troglitazone >>, a second ACS4 inhibitor, inhibited [[ ACS ]] activity <10% in microsomes and mitochondria and 45% in MAM.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Triacsin C >>, a competitive inhibitor of both [[ ACS1 ]] and ACS4, inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Triacsin C >>, a competitive inhibitor of both ACS1 and [[ ACS4 ]], inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Triacsin C >>, a competitive inhibitor of both ACS1 and ACS4, inhibited [[ ACS ]] activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria.", "label": "INHIBITOR", "metadata": []}
{"text": "Re-feeding normal chow or a high << sucrose >> diet for 24 h after a 48-h fast increased both [[ ACS1 ]] and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition studies.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Re-feeding normal chow or a high << sucrose >> diet for 24 h after a 48-h fast increased both ACS1 and [[ ACS4 ]] protein expression 1.5-2.0-fold, consistent with inhibition studies.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results suggest that << ACS1 >> and ACS4 may be linked to [[ triacylglycerol ]] synthesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These results suggest that ACS1 and << ACS4 >> may be linked to [[ triacylglycerol ]] synthesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The << tyrosine kinase >> inhibitor [[ ZD1839 ]] (\"Iressa\") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The tyrosine kinase inhibitor << ZD1839 >> (\"Iressa\") inhibits [[ HER2 ]]-driven signaling and suppresses the growth of HER2-overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The tyrosine kinase inhibitor ZD1839 (\"<< Iressa >>\") inhibits HER2-driven signaling and suppresses the growth of [[ HER2 ]]-overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The << tyrosine kinase >> inhibitor ZD1839 (\"[[ Iressa ]]\") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The tyrosine kinase inhibitor ZD1839 (\"<< Iressa >>\") inhibits [[ HER2 ]]-driven signaling and suppresses the growth of HER2-overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The << tyrosine kinase >>[[ tyrosine ]] kinase inhibitor ZD1839 (\"Iressa\") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< ZD1839 >> (\"Iressa\"), a quinazoline [[ tyrosine kinase ]] inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "<< ZD1839 >> (\"Iressa\"), a quinazoline tyrosine kinase inhibitor selective for the [[ EGFR ]], has shown good activity in preclinical studies and in the early phase of clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "ZD1839 (\"<< Iressa >>\"), a quinazoline [[ tyrosine kinase ]] inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "ZD1839 (\"<< Iressa >>\"), a quinazoline tyrosine kinase inhibitor selective for the [[ EGFR ]], has shown good activity in preclinical studies and in the early phase of clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "ZD1839 (\"Iressa\"), a << quinazoline tyrosine >>[[ tyrosine kinase ]] inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials.", "label": "SUBSTRATE", "metadata": []}
{"text": "Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR, HER2, and HER3, accompanied by the loss of association of HER3 with << phosphatidylinositol 3-kinase >>[[ phosphatidylinositol ]] 3-kinase, and down-regulation of Akt activity.", "label": "SUBSTRATE", "metadata": []}
{"text": "These studies suggest that HER2-overexpressing tumors are particularly susceptible to the inhibition of HER family << tyrosine kinase >>[[ tyrosine ]] kinase signaling and suggest novel strategies to treat these particularly aggressive tumors.", "label": "SUBSTRATE", "metadata": []}
{"text": "[Pharmacological effects of a << mu-opioid receptor >> antagonist [[ naltrexone ]] on alcohol dependence].", "label": "ANTAGONIST", "metadata": []}
{"text": "In many countries, a << mu-opioid receptor >> antagonist [[ naltrexone ]] has been used in the treatment of alcohol dependence.", "label": "ANTAGONIST", "metadata": []}
{"text": "RESULTS: In drug discrimination studies, << lisuride >> fully mimicked the [[ 5-HT(1A) ]] agonist LY 293284, only partially substituted for LSD and DOI, and failed to substitute for (+)-amphetamine.", "label": "AGONIST", "metadata": []}
{"text": "RESULTS: In drug discrimination studies, lisuride fully mimicked the << 5-HT(1A) >> agonist [[ LY 293284 ]], only partially substituted for LSD and DOI, and failed to substitute for (+)-amphetamine.", "label": "AGONIST", "metadata": []}
{"text": "Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD.", "label": "ANTAGONIST", "metadata": []}
{"text": "Lisuride dose dependently decreased body temperature in rats with a potency similar to that of the selective << 5-HT(1A) >> agonist [[ LY 293284 ]].", "label": "AGONIST", "metadata": []}
{"text": "<< Bupropion >>, an efficacious antidepressant and smoking cessation agent, inhibits dopamine and norepinephrine transporters ([[ DAT ]] and NET, respectively).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Bupropion >>, an efficacious antidepressant and smoking cessation agent, inhibits dopamine and norepinephrine transporters (DAT and [[ NET ]], respectively).", "label": "INHIBITOR", "metadata": []}
{"text": "To eliminate the interaction of << bupropion >> with [[ DAT ]] or NET, nomifensine or desipramine, respectively, was included in the superfusion buffer.", "label": "INHIBITOR", "metadata": []}
{"text": "To eliminate the interaction of << bupropion >> with DAT or [[ NET ]], nomifensine or desipramine, respectively, was included in the superfusion buffer.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus, << bupropion >> acts as an antagonist at alpha3beta2* and alpha3beta4* nAChRs in rat striatum and hippocampus, respectively, across the same concentration range that inhibits [[ DAT ]] and NET function.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus, << bupropion >> acts as an antagonist at alpha3beta2* and alpha3beta4* nAChRs in rat striatum and hippocampus, respectively, across the same concentration range that inhibits DAT and [[ NET ]] function.", "label": "INHIBITOR", "metadata": []}
{"text": "The combination of << nAChR >> and transporter inhibition produced by [[ bupropion ]] may contribute to its clinical efficacy as a smoking cessation agent.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway.", "label": "ACTIVATOR", "metadata": []}
{"text": "Nitrogen-containing << bisphosphonates >> induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of [[ Ras ]] signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Nitrogen-containing << bisphosphonates >> induce apoptosis of hematopoietic tumor cells via inhibition of [[ Ras ]] signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nitrogen >>-containing bisphosphonates (N-BPs) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Nitrogen-containing << bisphosphonates >> (N-BPs) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Nitrogen-containing bisphosphonates (<< N >>-BPs) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Nitrogen-containing bisphosphonates (N-<< BPs >>) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of Ras prenylation and enhanced [[ Bim ]] expression.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of Ras prenylation and enhanced [[ Bim ]] expression.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, << N >>-BPs decreased the levels of [[ phosphorylated extracellular signal-regulated kinase ]] (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase ([[ ERK ]]) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, N-<< BPs >> decreased the levels of [[ phosphorylated extracellular signal-regulated kinase ]] (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase ([[ ERK ]]) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of [[ Ras ]] prenylation and enhanced Bim expression.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of [[ Ras ]] prenylation and enhanced Bim expression.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "ACTIVATOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and [[ caspase-3 ]], and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "ACTIVATOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "ACTIVATOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and [[ caspase-3 ]], and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "ACTIVATOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing [[ Bim ]] expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing [[ Bim ]] expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the [[ Ras ]]/MEK/ERK and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/[[ MEK ]]/ERK and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/[[ ERK ]] and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and [[ Ras ]]/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/[[ mTOR ]] pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the [[ Ras ]]/MEK/ERK and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/[[ MEK ]]/ERK and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/[[ ERK ]] and Ras/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and [[ Ras ]]/mTOR pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/[[ mTOR ]] pathways.", "label": "INHIBITOR", "metadata": []}
{"text": "The reduction of << P2X3 >> expression levels was reversed by the proteasomal inhibitor [[ MG-132 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the << chenodeoxycholic acid >> (CDCA)-induced expression of [[ Cdx2 ]] and MUC2 in normal rat gastric epithelial cells (RGM-1 cells).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the << chenodeoxycholic acid >> (CDCA)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (<< CDCA >>)-induced expression of [[ Cdx2 ]] and MUC2 in normal rat gastric epithelial cells (RGM-1 cells).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (<< CDCA >>)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "RGM-1 cells were treated with << CDCA >> or GW4064, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist.", "label": "AGONIST", "metadata": []}
{"text": "RGM-1 cells were treated with CDCA or << GW4064 >>, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist.", "label": "AGONIST", "metadata": []}
{"text": "RGM-1 cells were treated with CDCA or GW4064, an FXR agonist, in the presence or absence of << guggulsterone >>, an [[ FXR ]] antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< CDCA >> induced dose-dependent expression of [[ Cdx2 ]] and MUC2 at both the mRNA and protein levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The maximum stimulation of << Cdx2 >> and MUC2 mRNA induced by [[ CDCA ]] was observed at 3 h and by 6 h, respectively.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The maximum stimulation of Cdx2 and << MUC2 >> mRNA induced by [[ CDCA ]] was observed at 3 h and by 6 h, respectively.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The effects of CDCA and GW4064 on expression of << Cdx2 >> and MUC2 were abolished by [[ guggulsterone ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The effects of CDCA and GW4064 on expression of Cdx2 and << MUC2 >> were abolished by [[ guggulsterone ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Mazindol >> analogues as potential inhibitors of the [[ cocaine binding site ]] at the dopamine transporter.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mazindol >> analogues as potential inhibitors of the cocaine binding site at the [[ dopamine transporter ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Mazindol analogues as potential inhibitors of the cocaine binding site at the << dopamine transporter >>[[ dopamine ]] transporter.", "label": "SUBSTRATE", "metadata": []}
{"text": "Several active analogues were also evaluated for their ability to block uptake of DA, << 5-HT >>, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-[[ hSERT ]], and HEK-hNET cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and << NE >> and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-[[ hNET ]] cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "Several active analogues were also evaluated for their ability to block uptake of << DA >>, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-[[ hDAT ]], HEK-hSERT, and HEK-hNET cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Glyphosate >> affects aromatic amino acid biosynthesis by inhibiting [[ 5-enolpyruvylshikimate-3-phosphate synthase ]] (EPSPS).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Glyphosate >> affects aromatic amino acid biosynthesis by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase ([[ EPSPS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Glufosinate >> inhibits [[ glutamine synthetase ]] and blocks biosynthesis of glutamine.", "label": "INHIBITOR", "metadata": []}
{"text": "Glufosinate inhibits << glutamine synthetase >> and blocks biosynthesis of [[ glutamine ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Mechanisms of Glucose Lowering of << Dipeptidyl Peptidase-4 >> Inhibitor [[ Sitagliptin ]] When Used Alone or With Metformin in Type 2 Diabetes: A double-tracer study.", "label": "INHIBITOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "ACTIVATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "ACTIVATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h.", "label": "ACTIVATOR", "metadata": []}
{"text": "Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, << V(5+) >> significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, << V(5+) >> significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, << V(5+) >> significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.", "label": "UPREGULATOR", "metadata": []}
{"text": "Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h.", "label": "UPREGULATOR", "metadata": []}
{"text": "In vitro, V(5+) decreased the << TCDD >>-mediated induction of [[ Cyp1a1 ]] mRNA, protein, and catalytic activity levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In vitro, << V(5+) >> decreased the TCDD-mediated induction of [[ Cyp1a1 ]] mRNA, protein, and catalytic activity levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, V(5+) significantly inhibited the << TCDD >>-induced [[ AhR ]]-dependent luciferase activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, << V(5+) >> significantly inhibited the TCDD-induced [[ AhR ]]-dependent luciferase activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< V(5+) >> also increased [[ serum hemoglobin ]] (Hb) levels in animals treated for 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< V(5+) >> also increased serum hemoglobin ([[ Hb ]]) levels in animals treated for 24 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon treatment of isolated hepatocytes with Hb alone or in the presence of << TCDD >>, there was an increase in the [[ AhR ]]-dependent luciferase activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< GCS >> therapy results in reduced mRNA expression of [[ interleukin-4 ]] (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< GCS >> therapy results in reduced mRNA expression of interleukin-4 ([[ IL-4 ]]) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< GCS >> therapy results in reduced mRNA expression of interleukin-4 (IL-4) and [[ IL-5 ]] in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In vitro studies with blood-derived T cells, however, show inhibition of all three << cytokines >> by [[ GCS ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Dexamethasone (<< DEX >>) inhibited the anti-CD3-induced production of [[ IL-4 ]], IL-5 and IFN-gamma in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DEX >>) inhibited the anti-CD3-induced production of IL-4, [[ IL-5 ]] and IFN-gamma in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DEX >>) inhibited the anti-CD3-induced production of IL-4, IL-5 and [[ IFN-gamma ]] in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of [[ IL-4 ]], IL-5 and IFN-gamma in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of IL-4, [[ IL-5 ]] and IFN-gamma in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and [[ IFN-gamma ]] in all 20 clones tested.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DEX >>) inhibited the anti-[[ CD3 ]]-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dexamethasone >> (DEX) inhibited the anti-[[ CD3 ]]-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested.", "label": "INHIBITOR", "metadata": []}
{"text": "<< DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005).", "label": "UPREGULATOR", "metadata": []}
{"text": "<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005).", "label": "UPREGULATOR", "metadata": []}
{"text": "Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited IL-2 production partially and enhanced [[ IL-2R alpha ]] expression and proliferation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers << DEX >> blocked [[ IL-2 ]] production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers << DEX >> blocked IL-2 production and decreased [[ IL-2R alpha ]] expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited [[ IL-2 ]] production partially and enhanced IL-2R alpha expression and proliferation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In conclusion, the production of << IL-4 >> and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In conclusion, the production of IL-4 and << IL-5 >> by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by << DEX >> than that of [[ IFN-gamma ]], which may account for the therapeutic effects of glucocorticosteroids in patients with asthma.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pregnane X Receptor Mediates Dyslipidemia Induced by the << HIV Protease >> Inhibitor [[ Amprenavir ]] in Mice.", "label": "INHIBITOR", "metadata": []}
{"text": "In the present study, we identified << amprenavir >>, a widely used HIV PI, as a potent [[ PXR ]]-selective agonist.", "label": "AGONIST", "metadata": []}
{"text": "<< Amprenavir >> efficiently activated [[ PXR ]] and induced PXR target gene expression in vitro and in vivo.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Amprenavir >> efficiently activated PXR and induced [[ PXR ]] target gene expression in vitro and in vivo.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Amprenavir >>-mediated [[ PXR ]] activation stimulated the expression of several key intestinal genes involved in lipid homeostasis.", "label": "ACTIVATOR", "metadata": []}
{"text": "Anti-diabetic Activity of Swertiamarin is due to an Active Metabolite, << Gentianine >>, that Upregulates [[ PPAR-γ ]] Gene Expression in 3T3-L1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Swertiamarin >> treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of [[ adiponectin ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On the other hand, treatment with << gentianine >> significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of [[ PPAR-γ ]], GLUT-4 and adiponectin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On the other hand, treatment with << gentianine >> significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, [[ GLUT-4 ]] and adiponectin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On the other hand, treatment with << gentianine >> significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and [[ adiponectin ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Jaspamide >> also inhibited other channels including [[ Cav1.2 ]], Cav3.2, and HCN2; however, the Kv11.1 (hERG) channel was minimally affected.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Jaspamide >> also inhibited other channels including Cav1.2, [[ Cav3.2 ]], and HCN2; however, the Kv11.1 (hERG) channel was minimally affected.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Jaspamide >> also inhibited other channels including Cav1.2, Cav3.2, and [[ HCN2 ]]; however, the Kv11.1 (hERG) channel was minimally affected.", "label": "INHIBITOR", "metadata": []}
{"text": "Treatment with << carvedilol >> reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and [[ NGF-beta ]] to the baseline values.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Treatment with << carvedilol >> reversed both protein and mRNA of [[ HIF-1alpha ]], VEGF, BNP, and NGF-beta to the baseline values.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Treatment with << carvedilol >> reversed both protein and mRNA of HIF-1alpha, [[ VEGF ]], BNP, and NGF-beta to the baseline values.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Treatment with << carvedilol >> reversed both protein and mRNA of HIF-1alpha, VEGF, [[ BNP ]], and NGF-beta to the baseline values.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Increased immunohistochemical labeling of << HIF-1alpha >>, VEGF, and BNP in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Increased immunohistochemical labeling of HIF-1alpha, << VEGF >>, and BNP in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Increased immunohistochemical labeling of HIF-1alpha, VEGF, and << BNP >> in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Treatment with << carvedilol >> is associated with a reversal of abnormal regulation of [[ HIF-1alpha ]] and VEGF in the failing ventricular myocardium.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Treatment with << carvedilol >> is associated with a reversal of abnormal regulation of HIF-1alpha and [[ VEGF ]] in the failing ventricular myocardium.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These effects were fully counteracted by dietary << phenolics >> which inhibited ROS overproduction and GSH consumption, rendered the reactive transcription of glutathione-associated enzymes unnecessary and blocked the intracellular signals leading to the overexpression and rearrangement of [[ p66Shc ]] signalling molecule.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The enzyme requires PLP and divalent cations such as Ca(2+), Mg(2+), or Mn(2+), but not ATP, whereas mammalian << serine racemase >> activity is increased by [[ ATP ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to << AMP >> by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to << adenosine >> by [[ ecto-5'-nucleotidase ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of << cAMP >> to AMP by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase.", "label": "SUBSTRATE", "metadata": []}
{"text": "In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of << AMP >> to adenosine by [[ ecto-5'-nucleotidase ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "A broad-spectrum << phosphodiesterase >> (PDE) inhibitor ([[ 1,3-isobutyl-1-methylxanthine ]], 300 microM, n=6) and an ecto-phosphodiesterase inhibitor (1,3-dipropyl-8-p-sulfophenylxanthine, 1 mM, n=6) significantly attenuated cAMP-induced AMP secretion by 60 and 74%, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "A broad-spectrum phosphodiesterase (<< PDE >>) inhibitor ([[ 1,3-isobutyl-1-methylxanthine ]], 300 microM, n=6) and an ecto-phosphodiesterase inhibitor (1,3-dipropyl-8-p-sulfophenylxanthine, 1 mM, n=6) significantly attenuated cAMP-induced AMP secretion by 60 and 74%, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], << PDE3 >> ([[ milrinone ]], 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of << PDE1 >> ([[ 8-methoxymethyl-3-isobutyl-1-methylxanthine ]], 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), << PDE2 >> [[[ erythro-9-(2-hydroxy-3-nonyl)adenine ]], 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), << PDE4 >> (Ro 20-1724 [[[ 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one ]]], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), << PDE5 >> and PDE6 ([[ zaprinast ]], 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and << PDE6 >> ([[ zaprinast ]], 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and << PDE7 >> [[[ BRL-50481 ]] (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and << PDE7 >> [BRL-50481 ([[ 5-nitro-2,N,N-trimethylbenzenesulfonamide ]]), 10 microM] did not alter renal ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Administration of a concentration (100 microM) of << dipyridamole >> that blocks [[ PDE8 ]] inhibited ecto-phosphodiesterase activity (by 44%).", "label": "INHIBITOR", "metadata": []}
{"text": "Administration of a concentration (100 microM) of << dipyridamole >> that blocks PDE8 inhibited ecto-[[ phosphodiesterase ]] activity (by 44%).", "label": "INHIBITOR", "metadata": []}
{"text": "However, a lower concentration of << dipyridamole >> (3 microM) that blocks [[ PDE9 ]], PDE10, and PDE11, but not PDE8, did not inhibit ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "However, a lower concentration of << dipyridamole >> (3 microM) that blocks PDE9, [[ PDE10 ]], and PDE11, but not PDE8, did not inhibit ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "However, a lower concentration of << dipyridamole >> (3 microM) that blocks PDE9, PDE10, and [[ PDE11 ]], but not PDE8, did not inhibit ecto-phosphodiesterase activity.", "label": "INHIBITOR", "metadata": []}
{"text": "These data support the conclusion that renal ecto-<< phosphodiesterase >> activity is not mediated by PDE1, PDE2, PDE3, PDE4, PDE5, PDE6, PDE7, PDE9, PDE10, or PDE11 and is inhibited by high concentrations of [[ dipyridamole ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Ambrisentan >> is an [[ endothelin type A (ET(A))-selective receptor ]] antagonist that is metabolized primarily by glucuronidation but also undergoes oxidative metabolism by CYP3A4.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Ambrisentan >> is an endothelin type A (ET(A))-selective receptor antagonist that is metabolized primarily by glucuronidation but also undergoes oxidative metabolism by [[ CYP3A4 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The potential for << ketoconazole >>, the archetypal strong inhibitor of [[ CYP3A4 ]], to alter the pharmacokinetic profile of ambrisentan and its oxidative metabolite, 4-hydroxymethyl ambrisentan, was assessed in an open-label, nonrandomized, 2-period, single-sequence study in 16 healthy men.", "label": "INHIBITOR", "metadata": []}
{"text": "In summary, << ketoconazole >> had no clinically significant effect on the pharmacokinetics or safety profile of ambrisentan; therefore, no changes in ambrisentan dose should be necessary when the drug is administered concomitantly with known [[ CYP3A4 ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Although << glutathione S-transferase omega 1 >> (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze [[ DMAs(V) ]] reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain.", "label": "SUBSTRATE", "metadata": []}
{"text": "Although glutathione S-transferase omega 1 (GSTO1) and << arsenic methyltransferase >> have been shown or thought to catalyze [[ DMAs(V) ]] reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain.", "label": "SUBSTRATE", "metadata": []}
{"text": "Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs(V) and the accumulation of RBC-bound DMAs, whereas the indirect << methyltransferase >> inhibitor periodate-oxidized [[ adenosine ]] was without effect.", "label": "INHIBITOR", "metadata": []}
{"text": "Although << thioredoxin reductase >> (TRR) inhibitors ([[ aurothioglucose ]] and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction.", "label": "INHIBITOR", "metadata": []}
{"text": "Although thioredoxin reductase (<< TRR >>) inhibitors ([[ aurothioglucose ]] and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction.", "label": "INHIBITOR", "metadata": []}
{"text": "Although << thioredoxin reductase >> (TRR) inhibitors (aurothioglucose and [[ Sb(III) ]]) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction.", "label": "INHIBITOR", "metadata": []}
{"text": "Although thioredoxin reductase (<< TRR >>) inhibitors (aurothioglucose and [[ Sb(III) ]]) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction.", "label": "INHIBITOR", "metadata": []}
{"text": "The << kinase >> activity of EGFR was little inhibited by [[ TT-B ]] in a cell-free system.", "label": "INHIBITOR", "metadata": []}
{"text": "The kinase activity of << EGFR >> was little inhibited by [[ TT-B ]] in a cell-free system.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and [[ tyrosine kinases ]] VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases [[ VEGFR ]]/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/[[ PDGFR ]] in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets [[ RAF ]]/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/[[ MEK ]]/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and [[ tyrosine kinases ]] VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases [[ VEGFR ]]/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/[[ PDGFR ]] in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets [[ RAF ]]/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/[[ MEK ]]/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and [[ tyrosine kinases ]] VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases [[ VEGFR ]]/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/[[ PDGFR ]] in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets [[ RAF ]]/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/[[ MEK ]]/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "label": "INHIBITOR", "metadata": []}
{"text": "A novel class of << biaryl urea >> that inhibits [[ C-RAF ]] kinase was discovered using a combination of medicinal and combinatorial chemistry approaches.", "label": "INHIBITOR", "metadata": []}
{"text": "A novel class of << biaryl urea >> that inhibits C-RAF [[ kinase ]] was discovered using a combination of medicinal and combinatorial chemistry approaches.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> inhibited the [[ kinase ]] activity of both C-RAF and B-RAF (wild type and V600E mutant).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> inhibited the kinase activity of both [[ C-RAF ]] and B-RAF (wild type and V600E mutant).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> inhibited the kinase activity of both C-RAF and [[ B-RAF ]] (wild type and V600E mutant).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sorafenib >> inhibited the kinase activity of both C-RAF and B-RAF (wild type and [[ V600E ]] mutant).", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the [[ vascular endothelial growth factor receptor ]] family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family ([[ VEGFR-2 ]] and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and [[ VEGFR-3 ]]) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and [[ platelet-derived growth factor receptor ]] family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family ([[ PDGFR-beta ]] and Kit), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and [[ Kit ]]), which play key roles in tumor progression and angiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of [[ Raf ]] and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and [[ Kit ]] signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of [[ VEGFR ]] and PDGFR signaling).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and [[ PDGFR ]] signaling).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Rapamycin >> inhibits [[ proteinase ]] and selected peptidase activities of the catalytic core proteasome at low micromolar concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rapamycin >> inhibits proteinase and selected [[ peptidase ]] activities of the catalytic core proteasome at low micromolar concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rapamycin >> inhibits proteinase and selected peptidase activities of the catalytic core [[ proteasome ]] at low micromolar concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the << singlet oxygen >> (1O2) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (<< 1O2 >>) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "For determination of << plasmin >> activity, 10 microL thereof was incubated with 150 microL 1.5 M [[ arginine ]], pH 8.7, and 100 microL 20 mM CT preoxidized (15 minutes 37 degrees C) pooled normal citrate buffered EDTA-plasma for 30 minutes (37 degrees C).", "label": "SUBSTRATE", "metadata": []}
{"text": "For determination of [<< PA >>+Pli]-activity, [[ arginine ]] was added after this incubation.", "label": "SUBSTRATE", "metadata": []}
{"text": "For determination of [PA+<< Pli >>]-activity, [[ arginine ]] was added after this incubation.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< KCNK1 >>, a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after [[ phenobarbital ]] treatment.", "label": "ACTIVATOR", "metadata": []}
{"text": "KCNK1, a member of the family of two-pore << K(+) ion channels >>, is specifically induced in the livers of male mice after [[ phenobarbital ]] treatment.", "label": "ACTIVATOR", "metadata": []}
{"text": "Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor.", "label": "ACTIVATOR", "metadata": []}
{"text": "Here, we have determined the molecular mechanism of this male-specific activation of the << Kcnk1 >> gene and characterized KCNK1 as a [[ phenobarbital ]]-inducible antihyperplasia factor.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Upon activation by << phenobarbital >>, [[ nuclear receptor ]] CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter.", "label": "ACTIVATOR", "metadata": []}
{"text": "Upon activation by << phenobarbital >>, nuclear receptor [[ CAR ]] binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results indicate that << phenobarbital >> treatment induces [[ KCNK1 ]] to elicit a male-specific and growth-suppressing signal.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Methylphenidate >>, an inhibitor of [[ dopamine and norepinephrine transporters ]] (DAT and NET, respectively), is a standard treatment for ADHD.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Methylphenidate >>, an inhibitor of dopamine and norepinephrine transporters ([[ DAT ]] and NET, respectively), is a standard treatment for ADHD.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Methylphenidate >>, an inhibitor of dopamine and norepinephrine transporters (DAT and [[ NET ]], respectively), is a standard treatment for ADHD.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Methylphenidate >> increased [[ DAT ]] Vmax in SHR mPFC and decreased DAT Vmax in WKY OFC.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Methylphenidate >> increased DAT Vmax in SHR mPFC and decreased [[ DAT ]] Vmax in WKY OFC.", "label": "INHIBITOR", "metadata": []}
{"text": "Also, << methylphenidate >> decreased [[ DAT ]] Km in WIS OFC.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration.", "label": "UPREGULATOR", "metadata": []}
{"text": "OBJECTIVE: To evaluate the extent of human cyclooxygenase-1 (COX-1) inhibition by << meloxicam >>, which has been reported to preferentially inhibit [[ cyclooxygenase-2 ]] (COX-2).", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: To evaluate the extent of human cyclooxygenase-1 (COX-1) inhibition by << meloxicam >>, which has been reported to preferentially inhibit cyclooxygenase-2 ([[ COX-2 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: To evaluate the extent of << human cyclooxygenase-1 >> (COX-1) inhibition by [[ meloxicam ]], which has been reported to preferentially inhibit cyclooxygenase-2 (COX-2).", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: To evaluate the extent of human cyclooxygenase-1 (<< COX-1 >>) inhibition by [[ meloxicam ]], which has been reported to preferentially inhibit cyclooxygenase-2 (COX-2).", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of << meloxicam >> were compared with those of diclofenac, a nonselective [[ COX ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of meloxicam were compared with those of << diclofenac >>, a nonselective [[ COX ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS: << COX-1 >> inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg [[ meloxicam ]] and 75 mg diclofenac and at steady state (15 mg meloxicam daily and 150 mg diclofenac daily).", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS: << COX-1 >> inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg [[ diclofenac ]] and at steady state (15 mg meloxicam daily and 150 mg diclofenac daily).", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS: << COX-1 >> inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg [[ meloxicam ]] daily and 150 mg diclofenac daily).", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS: << COX-1 >> inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg meloxicam daily and 150 mg [[ diclofenac ]] daily).", "label": "INHIBITOR", "metadata": []}
{"text": "Thus our data suggest that the << COX-2 >> preference of [[ meloxicam ]] observed in vitro may not result in clinical advantages when the higher dose of 15 mg is needed.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of [[ VEGF ]] and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and [[ MMP-9 ]] through Akt pathway in MDA-MB-231 breast cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and MMP-9 through [[ Akt ]] pathway in MDA-MB-231 breast cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Gelatin zymography showed that << DMBT >> inhibited secretion and activity of [[ MMP-9 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Western blotting demonstrated that << DMBT >> effectively suppressed the expression of [[ VEGF ]], p-VEGFR-2, p-EGFR, and p-Akt.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, [[ p-VEGFR-2 ]], p-EGFR, and p-Akt.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, p-VEGFR-2, [[ p-EGFR ]], and p-Akt.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and [[ p-Akt ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand [[ MMP-9 ]], resulting from the inhibition of Akt pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand MMP-9, resulting from the inhibition of [[ Akt ]] pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Expression of L-type pyruvate kinase (<< L-PK >>) is upregulated in the liver by dietary [[ carbohydrate ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Expression of << L-type pyruvate kinase >> (L-PK) is upregulated in the liver by dietary [[ carbohydrate ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Felbamate >> block of recombinant [[ N-methyl-D-aspartate receptors ]]: selectivity for the NR2B subunit.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felbamate >> block of recombinant N-methyl-D-aspartate receptors: selectivity for the [[ NR2B ]] subunit.", "label": "INHIBITOR", "metadata": []}
{"text": "The anticonvulsant << felbamate >> blocks [[ N-methyl-D-asparate (NMDA) receptors ]] but fails to exhibit the neurobehavioral toxicity characteristic of other NMDA receptor antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "The anticonvulsant << felbamate >> blocks N-methyl-D-asparate (NMDA) receptors but fails to exhibit the neurobehavioral toxicity characteristic of other [[ NMDA receptor ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of << felbamate >> block of recombinant [[ NMDA receptors ]] composed of the NR1a subunit and various NR2 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of << felbamate >> block of recombinant NMDA receptors composed of the [[ NR1a ]] subunit and various NR2 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of << felbamate >> block of recombinant NMDA receptors composed of the NR1a subunit and various [[ NR2 ]] subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felbamate >> produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the [[ rat NR1a ]] subunit, and either the NR2A, NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felbamate >> produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the [[ NR2A ]], NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felbamate >> produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, [[ NR2B ]] or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felbamate >> produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, NR2B or [[ NR2C ]] subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV).", "label": "INHIBITOR", "metadata": []}
{"text": "The higher affinity of << felbamate >> block of [[ NMDA receptors ]] containing the NR2B subunit could be accounted for by more rapid association and slower dissociation from these sites.", "label": "INHIBITOR", "metadata": []}
{"text": "The higher affinity of << felbamate >> block of NMDA receptors containing the [[ NR2B ]] subunit could be accounted for by more rapid association and slower dissociation from these sites.", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << felbamate >> exhibits modest selectivity for [[ NMDA receptors ]] composed of NR1a/NR2B subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << felbamate >> exhibits modest selectivity for NMDA receptors composed of [[ NR1a ]]/NR2B subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << felbamate >> exhibits modest selectivity for NMDA receptors composed of NR1a/[[ NR2B ]] subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "This selectivity could, in part, account for the more favorable clinical profile of << felbamate >> in comparison with [[ NMDA receptor ]] antagonists that do not show subunit selectivity.", "label": "ANTAGONIST", "metadata": []}
{"text": "In four (10 %) patients the peak << ACTH >>-stimulated [[ cortisol ]] values were lower than 18 μg/dL.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< ACTH >>-stimulated peak [[ cortisol ]], delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< ACTH >>-stimulated peak cortisol, [[ delta cortisol ]], and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< ACTH >>-stimulated peak cortisol, delta cortisol, and [[ delta DHEA ]]-S levels are decreased during hyperthyroidism, probably due to increased turnover.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Previously, we showed that the human kappa-opioid receptor (<< hkor >>) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< U50, 488H >> caused a significant down-regulation of the [[ hkor ]], although etorphine did not.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Coexpression of GRK2 or GRK2 and arrestin-2 permitted << etorphine >> to induce down-regulation of the [[ hkor ]], although expression of arrestin-2 or dynamin I alone did not.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Expression of the dominant negative mutants << rab5A >>-N133I or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Expression of the dominant negative mutants rab5A-N133I or << rab7 >>-N125I blunted [[ U50,488H ]]-induced down-regulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Expression of the dominant negative mutants rab5A-N133I or rab7-<< N125I >> blunted [[ U50,488H ]]-induced down-regulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Pretreatment with lysosomal enzyme inhibitors [(2S, 3S)trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester or chloroquine] or proteasome inhibitors (<< proteasome >> inhibitor I, [[ MG-132 ]], or lactacystin) decreased the extent of U50,488H-induced down-regulation.", "label": "INHIBITOR", "metadata": []}
{"text": "Pretreatment with lysosomal enzyme inhibitors [(2S, 3S)trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester or chloroquine] or proteasome inhibitors (<< proteasome >> inhibitor I, MG-132, or [[ lactacystin ]]) decreased the extent of U50,488H-induced down-regulation.", "label": "INHIBITOR", "metadata": []}
{"text": "These results indicate that << U50,488H >>-induced down-regulation of the [[ hkor ]] involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In Alexander cells, only when they were transfected with FXR+RXR, << GW4064 >> caused up-regulation of [[ SHP ]] and OSTβ, and a down-regulation of CYP27A1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In Alexander cells, only when they were transfected with FXR+RXR, << GW4064 >> caused up-regulation of SHP and [[ OSTβ ]], and a down-regulation of CYP27A1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In Alexander cells, only when they were transfected with FXR+RXR, << GW4064 >> caused up-regulation of SHP and OSTβ, and a down-regulation of [[ CYP27A1 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, GCs have a synergistic effect on << GW4064 >>-induced [[ FXR ]] activation, whereas chenodeoxycholate and GW4064 have an additive effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "Kinetic parameters for << PAM >> inactivation by [[ 4-oxo-5-acetamido-6-phenyl-hex-2-enoic acid and 4-oxo-5-acetamido-6-(2-thienyl)-hex-2-enoic acid ]] were obtained by using both the conventional dilution assay method and the more complex progress curve method.", "label": "INHIBITOR", "metadata": []}
{"text": "Stereochemical studies established that << PAM >> inactivation by [[ 4-oxo-5-acetamido-6-(2-thienyl)-hex-2-enoic acid ]] is stereospecific with respect to the moiety at the P(2) position, which is consistent with previous results with substrates and reversible inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast, << 2, 4-dioxo-5-acetamido-6-phenylhexanoic acid >>, which is a competitive inhibitor with respect to ascorbate, exhibits a low degree of stereospecificity in binding to the ascorbate sites of both [[ PAM ]] and dopamine-beta-hydroxylase.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast, << 2, 4-dioxo-5-acetamido-6-phenylhexanoic acid >>, which is a competitive inhibitor with respect to ascorbate, exhibits a low degree of stereospecificity in binding to the ascorbate sites of both PAM and [[ dopamine-beta-hydroxylase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of << [(3)H]estradiol glucuronide >> (E217βG) (a prototypical [[ MRP ]] substrate) into MRP-enriched inside-out membrane vesicles.", "label": "SUBSTRATE", "metadata": []}
{"text": "Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3)H]estradiol glucuronide (<< E217βG >>) (a prototypical [[ MRP ]] substrate) into MRP-enriched inside-out membrane vesicles.", "label": "SUBSTRATE", "metadata": []}
{"text": "Sixteen of 34 << CGPs >> inhibited [[ MRP1 ]]-mediated E217βG uptake by >50% (IC50's 0.7-7.6 μM).", "label": "INHIBITOR", "metadata": []}
{"text": "Sixteen of 34 CGPs inhibited << MRP1 >>-mediated [[ E217βG ]] uptake by >50% (IC50's 0.7-7.6 μM).", "label": "SUBSTRATE", "metadata": []}
{"text": "When tested in the intact cells, only 4 of 16 << CGPs >> (at 10 μM) inhibited [[ MRP1 ]]-mediated calcein efflux by >50% (III-1, V-3, -4, -6) while a fifth (I-5) inhibited efflux by just 23%.", "label": "INHIBITOR", "metadata": []}
{"text": "When tested in the intact cells, only 4 of 16 CGPs (at 10 μM) inhibited << MRP1 >>-mediated [[ calcein ]] efflux by >50% (III-1, V-3, -4, -6) while a fifth (I-5) inhibited efflux by just 23%.", "label": "SUBSTRATE", "metadata": []}
{"text": "These five << CGPs >> also inhibited [(3)H]E217βG uptake by [[ MRP4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "These five CGPs also inhibited << [(3)H]E217βG >> uptake by [[ MRP4 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Gemfibrozil >>, a lipid-lowering drug, inhibits the induction of [[ nitric-oxide synthase ]] in human astrocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Gemfibrozil, a lipid-lowering drug, inhibits the induction of << nitric-oxide synthase >>[[ nitric-oxide ]] synthase in human astrocytes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Gemfibrozil >>, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of [[ inducible nitric-oxide synthase ]] (iNOS) in human U373MG astroglial cells and primary astrocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Gemfibrozil >>, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Gemfibrozil >>, a lipid-lowering drug, inhibited [[ cytokine ]]-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of [[ inducible nitric-oxide synthase ]] (iNOS) in human U373MG astroglial cells and primary astrocytes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of << inducible nitric-oxide synthase >>[[ nitric-oxide ]] synthase (iNOS) in human U373MG astroglial cells and primary astrocytes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible << nitric-oxide >> synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Similar to << gemfibrozil >>, clofibrate, another fibrate drug, also inhibited the expression of [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Similar to gemfibrozil, << clofibrate >>, another fibrate drug, also inhibited the expression of [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Similar to gemfibrozil, clofibrate, another << fibrate >> drug, also inhibited the expression of [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of human iNOS promoter-driven luciferase activity by << gemfibrozil >> in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << human iNOS promoter >>-driven luciferase activity by [[ gemfibrozil ]] in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of iNOS.", "label": "INHIBITOR", "metadata": []}
{"text": "Since << gemfibrozil >> is known to activate [[ peroxisome proliferator-activated receptor-alpha ]] (PPAR-alpha), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS.", "label": "ACTIVATOR", "metadata": []}
{"text": "Since << gemfibrozil >> is known to activate peroxisome proliferator-activated receptor-alpha ([[ PPAR-alpha ]]), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS.", "label": "ACTIVATOR", "metadata": []}
{"text": "Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we investigated the role of << PPAR-alpha >> in [[ gemfibrozil ]]-mediated inhibition of iNOS.", "label": "ACTIVATOR", "metadata": []}
{"text": "Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we investigated the role of PPAR-alpha in << gemfibrozil >>-mediated inhibition of [[ iNOS ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Gemfibrozil >> induced [[ peroxisome proliferator-responsive element ]] (PPRE)-dependent luciferase activity, which was inhibited by the expression of DeltahPPAR-alpha, the dominant-negative mutant of human PPAR-alpha.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Gemfibrozil >> induced peroxisome proliferator-responsive element ([[ PPRE ]])-dependent luciferase activity, which was inhibited by the expression of DeltahPPAR-alpha, the dominant-negative mutant of human PPAR-alpha.", "label": "ACTIVATOR", "metadata": []}
{"text": "However, DeltahPPAR-alpha was unable to abrogate << gemfibrozil >>-mediated inhibition of [[ iNOS ]] suggesting that gemfibrozil inhibits iNOS independent of PPAR-alpha.", "label": "INHIBITOR", "metadata": []}
{"text": "However, DeltahPPAR-alpha was unable to abrogate gemfibrozil-mediated inhibition of iNOS suggesting that << gemfibrozil >> inhibits [[ iNOS ]] independent of PPAR-alpha.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, << gemfibrozil >> strongly inhibited the activation of [[ NF-kappaB ]], AP-1, and C/EBPbeta but not that of GAS in cytokine-stimulated astroglial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, << gemfibrozil >> strongly inhibited the activation of NF-kappaB, [[ AP-1 ]], and C/EBPbeta but not that of GAS in cytokine-stimulated astroglial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, << gemfibrozil >> strongly inhibited the activation of NF-kappaB, AP-1, and [[ C/EBPbeta ]] but not that of GAS in cytokine-stimulated astroglial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << gemfibrozil >> inhibits the induction of [[ iNOS ]] probably by inhibiting the activation of NF-kappaB, AP-1, and C/EBPbeta and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << gemfibrozil >> inhibits the induction of iNOS probably by inhibiting the activation of [[ NF-kappaB ]], AP-1, and C/EBPbeta and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << gemfibrozil >> inhibits the induction of iNOS probably by inhibiting the activation of NF-kappaB, [[ AP-1 ]], and C/EBPbeta and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << gemfibrozil >> inhibits the induction of iNOS probably by inhibiting the activation of NF-kappaB, AP-1, and [[ C/EBPbeta ]] and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting << alpha2 adrenergic receptor >> (AR) agonist ([[ dexmedetomidine ]]).", "label": "AGONIST", "metadata": []}
{"text": "OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]).", "label": "AGONIST", "metadata": []}
{"text": "The inhibitory effect of << sodium nitroprusside >> on [[ HIF-1 ]] activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "We demonstrate that among the three nitrates, only << SNP >> inhibits [[ HIF-1 ]] activation in response to hypoxia.", "label": "INHIBITOR", "metadata": []}
{"text": "<< SNP >> inhibits the accumulation of HIF-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of [[ HIF-1alpha ]] via a mechanism that is not dependent on either NO or soluble guanylate cyclase.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< SNP >> inhibits the accumulation of [[ HIF-1alpha ]], the regulatory subunit of HIF-1, and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase.", "label": "INHIBITOR", "metadata": []}
{"text": "<< SNP >> inhibits the accumulation of HIF-1alpha, the regulatory subunit of [[ HIF-1 ]], and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Indomethacin >> activates [[ carbonic anhydrase ]] and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> activates carbonic anhydrase and antagonizes the effect of the specific [[ carbonic anhydrase ]] inhibitor acetazolamide, by a direct mechanism of action.", "label": "ACTIVATOR", "metadata": []}
{"text": "Indomethacin activates << carbonic anhydrase >> and antagonizes the effect of the specific carbonic anhydrase inhibitor [[ acetazolamide ]], by a direct mechanism of action.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific << carbonic anhydrase >> inhibitor [[ acetazolamide ]], by a direct mechanism of action.", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte [[ CA I ]] and CA II activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte CA I and [[ CA II ]] activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Acetazolamide >>, a specific inhibitor of [[ CA ]], reduces the activity of CA I and CA II from red cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetazolamide >>, a specific inhibitor of CA, reduces the activity of [[ CA I ]] and CA II from red cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetazolamide >>, a specific inhibitor of CA, reduces the activity of CA I and [[ CA II ]] from red cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Indomethacin >> completely antagonizes [[ CA ]] activity, i.e. abolishes the inhibitory effect of acetazolamide on CA.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> completely antagonizes CA activity, i.e. abolishes the inhibitory effect of acetazolamide on [[ CA ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Indomethacin completely antagonizes << CA >> activity, i.e. abolishes the inhibitory effect of [[ acetazolamide ]] on CA.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin completely antagonizes CA activity, i.e. abolishes the inhibitory effect of << acetazolamide >> on [[ CA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase (COX) inhibitor, is also an activator of [[ CA ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "CONCLUSIONS: Our results show that << indomethacin >>, a known [[ cyclooxygenase ]] (COX) inhibitor, is also an activator of CA.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase ([[ COX ]]) inhibitor, is also an activator of CA.", "label": "INHIBITOR", "metadata": []}
{"text": "Our data also prove that << indomethacin >> is not only an activator of [[ CA ]] but also antagonizes the effect of acetazolamide, a specific inhibitor of this enzyme.", "label": "ACTIVATOR", "metadata": []}
{"text": "Our data also prove that indomethacin is not only an activator of << CA >> but also antagonizes the effect of [[ acetazolamide ]], a specific inhibitor of this enzyme.", "label": "INHIBITOR", "metadata": []}
{"text": "In view of the role of CA in acid-base balance as well as the fact that an increase or decrease in its activity is accompanied by an increase or decrease in intra- and extracellular pH, our results suggest that: firstly, << CA >> activation induced by [[ indomethacin ]] might cause changes in COX activity; secondly, PGs are synthetized as a consequence of the changes in COX activity, a hypothesis that requires further study.", "label": "ACTIVATOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of [[ pyrano[2,3-b]quinolines ]] (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of [[ pyrano[2,3-b]quinolines ]] (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of [[ pyrano[2,3-b]quinolines ]] (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of [[ pyrano[2,3-b]quinolines ]] (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [[ [1,8]naphthyridines ]] (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [[ [1,8]naphthyridines ]] (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [[ [1,8]naphthyridines ]] (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [[ [1,8]naphthyridines ]] (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), [[ 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines ]] (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), [[ 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines ]] (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), [[ 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines ]] (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), [[ 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines ]] (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), [[ 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline ]] (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), [[ 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline ]] (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), [[ 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline ]] (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), [[ 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline ]] (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine ]] (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine ]] (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The << acetylcholinesterase >> (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine ]] (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine ]] (16) are described.", "label": "INHIBITOR", "metadata": []}
{"text": "These compounds are competitive and, in a few cases, non-competitive inhibitors for << AChE >>, the most potent being compound (14), though three-fold less active than [[ tacrine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The << BuChE >> inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than [[ tacrine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Juglone >>, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of [[ AR ]] expression in human prostate cancer LNCaP cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of [[ androgen receptor ]] (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor ([[ AR ]]) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and [[ prostate-specific antigen ]] (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen ([[ PSA ]]) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of [[ AR ]] and PSA genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and [[ PSA ]] genes with and/or without dihydrotestosterone (DHT).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Take together, our results demonstrated that << juglone >> might induce the apoptosis in LNCaP cell via down-regulation of [[ AR ]] expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Astemizole >>, a potent [[ histamine H1-receptor ]] antagonist: effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels.", "label": "ANTAGONIST", "metadata": []}
{"text": "The efficacy of << astemizole >>, a new, long acting, oral [[ histamine H1-receptor ]] antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Tacrine >>, the first of the [[ cholinesterase ]] inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "Other << cholinesterase >> inhibitors, including [[ rivastigmine ]], with superior properties in terms of specificity of action and low risk of adverse effects, have now been introduced.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-(N,N-dimethyl)-amiloride >> (50 microM; DMA), a concentration that selectively inhibits the [[ NHE ]] isoforms NHE1 and NHE2, but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-(N,N-dimethyl)-amiloride >> (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms [[ NHE1 ]] and NHE2, but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-(N,N-dimethyl)-amiloride >> (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and [[ NHE2 ]], but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-(N,N-dimethyl)-amiloride >> (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not [[ NHE3 ]], did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the [[ NHE ]] isoforms NHE1 and NHE2, but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the NHE isoforms [[ NHE1 ]] and NHE2, but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the NHE isoforms NHE1 and [[ NHE2 ]], but not NHE3, did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not [[ NHE3 ]], did not affect DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "Nevertheless, 3 mM << DMA >>, a higher concentration that inhibits [[ NHE1 ]], NHE2, and NHE3, significantly increased DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "Nevertheless, 3 mM << DMA >>, a higher concentration that inhibits NHE1, [[ NHE2 ]], and NHE3, significantly increased DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "Nevertheless, 3 mM << DMA >>, a higher concentration that inhibits NHE1, NHE2, and [[ NHE3 ]], significantly increased DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, << S1611 >> and S3226, both specific inhibitors of [[ NHE3 ]] only, or perfusion with Na+-free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, S1611 and << S3226 >>, both specific inhibitors of [[ NHE3 ]] only, or perfusion with Na+-free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH.", "label": "INHIBITOR", "metadata": []}
{"text": "Nevertheless, coperfusion with 0.1 and 0.3 mM << 5-nitro-2-(3-phenylpropylamino) benzoic acid >>, which inhibits the [[ cystic fibrosis transmembrane conductor regulator ]] (CFTR), dose dependently inhibited S3226-induced DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "Nevertheless, coperfusion with 0.1 and 0.3 mM << 5-nitro-2-(3-phenylpropylamino) benzoic acid >>, which inhibits the cystic fibrosis transmembrane conductor regulator ([[ CFTR ]]), dose dependently inhibited S3226-induced DBS.", "label": "INHIBITOR", "metadata": []}
{"text": "In conclusion, only specific apical NHE3 inhibition increased DBS, whereas prostaglandin synthesis, Na+-HCO3- cotransporter activation, or intracellular << HCO3 >>- formation by [[ carbonic anhydrase ]] was not involved.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Mechanisms limiting distribution of the << threonine-protein kinase B-RaF >>(V600E) inhibitor [[ dabrafenib ]] to the brain: implications for the treatment of melanoma brain metastases.", "label": "INHIBITOR", "metadata": []}
{"text": "Mechanisms limiting distribution of the threonine-protein kinase B-RaF(<< V600E >>) inhibitor [[ dabrafenib ]] to the brain: implications for the treatment of melanoma brain metastases.", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that << dabrafenib >> is an avid substrate for both [[ P-gp ]] and BCRP.", "label": "SUBSTRATE", "metadata": []}
{"text": "In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that << dabrafenib >> is an avid substrate for both P-gp and [[ BCRP ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Further, compared with << vemurafenib >>, another [[ BRAF ]](V600E) inhibitor, dabrafenib showed greater brain penetration with a similar dose.", "label": "INHIBITOR", "metadata": []}
{"text": "Further, compared with << vemurafenib >>, another BRAF([[ V600E ]]) inhibitor, dabrafenib showed greater brain penetration with a similar dose.", "label": "INHIBITOR", "metadata": []}
{"text": "Since the original discovery of << azoles >> analogs as [[ PXR ]] antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Since the original discovery of << azoles >> analogs as PXR antagonists, we have preliminarily defined an important [[ PXR ]] antagonist pharmacophore and developed less-toxic PXR antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Since the original discovery of << azoles >> analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic [[ PXR ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Activation of endogenous << somatostatin receptor subtype 2 >> (sst2) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activation of endogenous somatostatin receptor subtype 2 (<< sst2 >>) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected << rat D2 dopamine receptors >> (rD2(long)) by [[ quinpirole ]] had no effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected rat D2 dopamine receptors (<< rD2 >>(long)) by [[ quinpirole ]] had no effect.", "label": "ACTIVATOR", "metadata": []}
{"text": "In contrast, in the same system, << N >>-type currents, formed from transiently transfected alpha(1B)/alpha(2)delta-1/beta(3), showed strong [[ G-protein ]]-mediated inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Levels of << Cx43 >> protein were also decreased in a dose- and time-dependent manner following [[ antofine ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Co-treatment of astrocytes with antofine and the intracellular Ca(2+) chelator << BAPTA-AM >> prevented downregulation of [[ Cx43 ]] and inhibition of GJIC.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Co-treatment of astrocytes with << antofine >> and the intracellular Ca(2+) chelator BAPTA-AM prevented downregulation of [[ Cx43 ]] and inhibition of GJIC.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, co-treatment with << antofine >> and a specific PKCβ inhibitor prevented endocytosis of gap junctions, downregulation of [[ Cx43 ]], and inhibition of GJIC.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, these findings indicate that << antofine >> induces Cx43 gap junction disassembly by the [[ PKCβ ]] signaling pathway.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Torasemide >> inhibits [[ angiotensin II ]]-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats.", "label": "INHIBITOR", "metadata": []}
{"text": "Isometric contraction induced by a submaximal concentration of << Ang II >> (10(-7) mol/L) was reduced in a dose-dependent way by [[ torasemide ]] (IC(50)=0.5+/-0.04 micromol/L).", "label": "INHIBITOR", "metadata": []}
{"text": "The stimulatory effect of [Ca(2+)](i) induced by a submaximal concentration of << Ang II >> (10(-7) mol/L) was blocked by [[ torasemide ]] (IC(50)=0.5+/-0.3 nmol/L).", "label": "INHIBITOR", "metadata": []}
{"text": "Our findings suggest that << torasemide >> blocks the vasoconstrictor action of [[ Ang II ]] in vitro.", "label": "INHIBITOR", "metadata": []}
{"text": "This action can be related to the ability of << torasemide >> to block the increase of [Ca(2+)](i) induced by [[ Ang II ]] in VSMCs.", "label": "INHIBITOR", "metadata": []}
{"text": "Among the isolated compounds, << trans-dihydromorin >> (8), oxyresveratrol (9), and steppogenin (12) were found to exhibit significant [[ tyrosinase ]] inhibition activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Among the isolated compounds, trans-dihydromorin (8), << oxyresveratrol >> (9), and steppogenin (12) were found to exhibit significant [[ tyrosinase ]] inhibition activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Among the isolated compounds, trans-dihydromorin (8), oxyresveratrol (9), and << steppogenin >> (12) were found to exhibit significant [[ tyrosinase ]] inhibition activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Prostaglandin E1, E2, << STA2 >> (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of << thromboxane A2 >>), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was [[ sulprostone ]]>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was sulprostone>[[ PGE2 ]], PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was sulprostone>PGE2, [[ PGE1 ]]>STA2>>17-phenyl-trinor-PGE2.", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was sulprostone>PGE2, PGE1>[[ STA2 ]]>>17-phenyl-trinor-PGE2.", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was sulprostone>PGE2, PGE1>STA2>>[[ 17-phenyl-trinor-PGE2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an [[ EP1 ]]-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "AGONIST", "metadata": []}
{"text": "Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an [[ EP3 ]]-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.", "label": "AGONIST", "metadata": []}
{"text": "SC-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that << PGE1 >>- and PGE2-induced inhibition of the [[ HVA Ca2+ channels ]] is possibly mediated by the EP3 receptor.", "label": "INHIBITOR", "metadata": []}
{"text": "SC-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that PGE1- and << PGE2 >>-induced inhibition of the [[ HVA Ca2+ channels ]] is possibly mediated by the EP3 receptor.", "label": "INHIBITOR", "metadata": []}
{"text": "<< SC-51089 >> (10(-5) M), a selective [[ EP1-receptor ]] antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that PGE1- and PGE2-induced inhibition of the HVA Ca2+ channels is possibly mediated by the EP3 receptor.", "label": "ANTAGONIST", "metadata": []}
{"text": "The inhibitory effect of PGE1 or sulprostone was prevented by pretreatment with pertussis toxin [islet activating protein (IAP)] or phorbol-12-myristate-13-acetate (PMA), and the << protein kinase C >> (PKC) inhibitor [[ chelerythrine ]] blocked the action of PMA.", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibitory effect of PGE1 or sulprostone was prevented by pretreatment with pertussis toxin [islet activating protein (IAP)] or phorbol-12-myristate-13-acetate (PMA), and the protein kinase C (<< PKC >>) inhibitor [[ chelerythrine ]] blocked the action of PMA.", "label": "INHIBITOR", "metadata": []}
{"text": "It was concluded that << PGE1 >> selectively reduces both N- and R-type Ca2+ currents by activating a [[ G-protein ]] probably through the EP3 receptor in paratracheal ganglion cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Inhibition of << MCP-1 >> and MIP-2 transcription and translation by [[ mimosine ]] in muscle tissue infected with the parasite Trichinella spiralis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of MCP-1 and << MIP-2 >> transcription and translation by [[ mimosine ]] in muscle tissue infected with the parasite Trichinella spiralis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << MCP-1 >> transcription and translation was completely inhibited by [[ mimosine ]], while MIP-2 transcription and translation was partially inhibited at 30 and 40 days; yet it was totally inhibited after 10 and 20 days in encysted diaphragm tissue infected by T. spiralis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that MCP-1 transcription and translation was completely inhibited by << mimosine >>, while [[ MIP-2 ]] transcription and translation was partially inhibited at 30 and 40 days; yet it was totally inhibited after 10 and 20 days in encysted diaphragm tissue infected by T. spiralis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "This is described in a case study of the expedited review and approval of << peramivir >>, a novel [[ neuraminidase ]] inhibitor, in Japan in the context of the emergence of new strain of influenza in 2009.", "label": "INHIBITOR", "metadata": []}
{"text": "The influence of sex, ethnicity, and << CYP2B6 >> genotype on [[ bupropion ]] metabolism as an index of hepatic CYP2B6 activity in humans.", "label": "SUBSTRATE", "metadata": []}
{"text": "To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using << bupropion >> (Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC) as a [[ CYP2B6 ]] probe substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (<< Wellbutrin SR >> GlaxoSmithKline, Research Triangle Park, NC) as a [[ CYP2B6 ]] probe substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "These results suggest that << CYP2B6 >> genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of [[ bupropion ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of << CYP2B6 >> activity in women, when measured by the metabolism of [[ bupropion ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The << bupropion >> metabolic ratio appears to detect known differences in [[ CYP2B6 ]] activity associated with genetic polymorphism, across different ethnic groups.", "label": "SUBSTRATE", "metadata": []}
{"text": "The identification of the << succinate receptor >> SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists.", "label": "AGONIST", "metadata": []}
{"text": "The identification of the succinate receptor << SUCNR1 >> in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists.", "label": "AGONIST", "metadata": []}
{"text": "<< β-ionone >> was also shown to induce the expression of cleaved-[[ caspase-3 ]] and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< β-ionone >> was also shown to induce the expression of cleaved-caspase-3 and inhibit [[ bcl-2 ]] expression in SGC-7901 cells in a dose-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The significantly decreased levels of << p-PI3K >> and p-AKT expression were observed in SGC-7901 cells after [[ β-ionone ]] treatments in a time- and dose-dependent manner (P < 0.01).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The significantly decreased levels of p-PI3K and << p-AKT >> expression were observed in SGC-7901 cells after [[ β-ionone ]] treatments in a time- and dose-dependent manner (P < 0.01).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "However, AII receptor blockers differ from ACE inhibitors with respect to side effects, and induce less cough, a side effect which may be related to bradykinin or other mediators such as substance P. Within the class of << AII >> blockers, [[ eprosartan ]] differs from other currently available agents in terms of chemical structure, as it is a non-biphenyl, non-tetrazole, non-peptide antagonist with a dual pharmacological mode of action.", "label": "INHIBITOR", "metadata": []}
{"text": "In clinical trials, eprosartan has been demonstrated to be at least as effective in reducing blood pressure as the << ACE >> inhibitor [[ enalapril ]], and has significantly lower side effects.", "label": "INHIBITOR", "metadata": []}
{"text": "Reductive detoxification of << arylhydroxylamine >> carcinogens by human NADH cytochrome b5 reductase and [[ cytochrome b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Reductive detoxification of << arylhydroxylamine >> carcinogens by [[ human NADH cytochrome b5 reductase ]] and cytochrome b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by [[ NADH cytochrome b5 reductase ]] (b5R) and cytochrome b5 (cyt b5).", "label": "SUBSTRATE", "metadata": []}
{"text": "On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase ([[ b5R ]]) and cytochrome b5 (cyt b5).", "label": "SUBSTRATE", "metadata": []}
{"text": "On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and [[ cytochrome b5 ]] (cyt b5).", "label": "SUBSTRATE", "metadata": []}
{"text": "On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and cytochrome b5 ([[ cyt b5 ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic << hydroxylamines >> of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic << hydroxylamines >> of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the << aromatic amine >> 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the << aromatic amine >> 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (<< 4-ABP >>; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (<< 4-ABP >>; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the << heterocyclic amine >> 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the << heterocyclic amine >> 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine << 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine >> (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine << 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine >> (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5.", "label": "SUBSTRATE", "metadata": []}
{"text": "We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited [[ N-hydroxy-4-aminobiphenyl ]] (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).", "label": "SUBSTRATE", "metadata": []}
{"text": "Polyclonal antisera to either b5R or << cyt b5 >> significantly inhibited [[ N-hydroxy-4-aminobiphenyl ]] (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).", "label": "SUBSTRATE", "metadata": []}
{"text": "Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).", "label": "SUBSTRATE", "metadata": []}
{"text": "Polyclonal antisera to either b5R or << cyt b5 >> significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).", "label": "SUBSTRATE", "metadata": []}
{"text": "Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Pranlukast >> is a new, orally active, selective inhibitor of [[ CysLt1 ]] leukotriene receptor.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pranlukast >> is a new, orally active, selective inhibitor of CysLt1 [[ leukotriene receptor ]].", "label": "INHIBITOR", "metadata": []}
{"text": "We used mutagenesis of these residues, combined with an investigation of << hERG >> block by close analogs of [[ clofilium ]] and ibutilide, to assess how specific alterations in drug structure affected potency and binding interactions.", "label": "INHIBITOR", "metadata": []}
{"text": "We used mutagenesis of these residues, combined with an investigation of << hERG >> block by close analogs of clofilium and [[ ibutilide ]], to assess how specific alterations in drug structure affected potency and binding interactions.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Parathion >> is a [[ cholinesterase ]] inhibitor that induces the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses.", "label": "INHIBITOR", "metadata": []}
{"text": "There was also an increase in << c-kit >>, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, << Trio >>, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, << Rho-A >>, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, << Rac-3 >>, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, << Notch-4 >>, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, << Dvl-2 >>, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, << Ezrin >>, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, << beta catenin >> and mutant p53 protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant << p53 >> protein expression in the [[ parathion ]]-treated cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase >> (EC 3.1.4.45; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome.", "label": "PRODUCT-OF", "metadata": []}
{"text": "N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (<< EC 3.1.4.45 >>; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome.", "label": "PRODUCT-OF", "metadata": []}
{"text": "N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (EC 3.1.4.45; << phosphodiester alpha-GlcNAcase >>) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The purified << phosphodiester alpha-GlcNAcase >> has a specific activity of 498 micromol of [[ [3H]GlcNAc-alpha-phosphomannose-alpha-methyl ]] cleaved per h per mg of protein using 0.5 mM [3H]GlcNAc-alpha-phosphomannose-alpha-methyl as substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "The purified << phosphodiester alpha-GlcNAcase >> has a specific activity of 498 micromol of [3H]GlcNAc-alpha-phosphomannose-alpha-methyl cleaved per h per mg of protein using 0.5 mM [[ [3H]GlcNAc-alpha-phosphomannose-alpha-methyl ]] as substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), [[ lactic dehydrogenase ]] (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase ([[ LDH ]]), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), [[ superoxide dismutase ]] (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase ([[ SOD ]]), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and [[ catalase ]] (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase ([[ CAT ]])) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The vascular protective effects of << kinsenoside >> were speculated to be attributed to oxidative stress inhibition and the reduction of [[ nuclear factor kappa B ]] (NF-κB) mRNA expression levels in high glucose conditions.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The vascular protective effects of << kinsenoside >> were speculated to be attributed to oxidative stress inhibition and the reduction of nuclear factor kappa B ([[ NF-κB ]]) mRNA expression levels in high glucose conditions.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Tolbutamide >> and gliclazide block the K(ATP) channel K(ir)6.2/Sur1, causing membrane depolarization and stimulating [[ insulin ]] secretion in pancreatic beta cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Tolbutamide >> and gliclazide block the [[ K(ATP) channel ]] K(ir)6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Tolbutamide >> and gliclazide block the K(ATP) channel [[ K(ir)6.2 ]]/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Tolbutamide >> and gliclazide block the K(ATP) channel K(ir)6.2/[[ Sur1 ]], causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Insulin >> secretion stimulated by both 200 μM [[ tolbutamide ]] and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Insulin >> secretion stimulated by both 200 μM tolbutamide and 20 μM [[ gliclazide ]], concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Insulin >> secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by [[ 8-pCPT-2'-O-Me-cAMP-AM ]] at concentrations ≥2 μM in INS-1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Insulin >> secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by [[ thapsigargin ]] (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Insulin >> secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker [[ nicardipine ]] (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Insulin secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the << L-type Ca(2+) channel >> blocker [[ nicardipine ]] (2 μM) and was potentiated by 8-pCPT-2'-O-Me-cAMP-AM at concentrations ≥2 μM in INS-1 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Both << tolbutamide >> and gliclazide stimulated [[ phospholipase C ]] activity; however, only gliclazide did so independently of its activity at K(ATP) channels, and this activity was partially inhibited by pertussis toxin.", "label": "ACTIVATOR", "metadata": []}
{"text": "Both tolbutamide and << gliclazide >> stimulated [[ phospholipase C ]] activity; however, only gliclazide did so independently of its activity at K(ATP) channels, and this activity was partially inhibited by pertussis toxin.", "label": "ACTIVATOR", "metadata": []}
{"text": "Both tolbutamide and gliclazide stimulated phospholipase C activity; however, only << gliclazide >> did so independently of its activity at [[ K(ATP) channels ]], and this activity was partially inhibited by pertussis toxin.", "label": "ACTIVATOR", "metadata": []}
{"text": "8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor [[ bisindolylmaleimide I ]] (1 μM).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< 8-pCPT-2'-O-Me-cAMP-AM >> potentiation of [[ insulin ]] secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by [[ tolbutamide ]] was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by [[ 2-APB ]] (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "8-pCPT-2'-O-Me-cAMP-AM potentiation of insulin secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the << PKC >> inhibitor [[ bisindolylmaleimide I ]] (1 μM).", "label": "INHIBITOR", "metadata": []}
{"text": "Our data demonstrate that the actions of both tolbutamide and gliclazide are strongly potentiated by 8-pCPT-2'-O-Me-cAMP-AM, that << gliclazide >> can stimulate [[ phospholipase C ]] activity via a partially pertussis toxin-sensitive mechanism, and that 8-pCPT-2'-O-Me-cAMP-AM potentiation of tolbutamide action may involve activation of a 2-APB-sensitive Ca(2+) influx.", "label": "ACTIVATOR", "metadata": []}
{"text": "Phosphorylation of << AMPK >> at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to [[ 2-deoxyglucose ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Phosphorylation of ER-stress marker << eIF2α >> was also increased but only at 30 min of [[ 2-deoxyglucose ]] exposure.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to [[ TSC2 ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 2-Deoxyglucose >> increased phosphorylation of [[ tuberous sclerosis complex 2 ]] (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 ([[ TSC2 ]]) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on [[ AMPK ]] consensus sites but did not change the amount of TSC1 bound to TSC2.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Conivaptan >>: a dual [[ vasopressin receptor v1a/v2 ]] antagonist [corrected].", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Conivaptan >> is a nonpeptide dual [[ V1a/V2 AVP receptor ]] antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which histamine is considered to be of pathogenic importance and conversely to help elucidate the role of [[ histamine ]] in disease, through an evaluation of their influence on disease expression.", "label": "AGONIST", "metadata": []}
{"text": "<< H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which [[ histamine ]] is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression.", "label": "AGONIST", "metadata": []}
{"text": "While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.", "label": "AGONIST", "metadata": []}
{"text": "While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.", "label": "AGONIST", "metadata": []}
{"text": "The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition.", "label": "AGONIST", "metadata": []}
{"text": "The recent development of H1-receptor antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of << H1-receptor >> blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition.", "label": "AGONIST", "metadata": []}
{"text": "<< Cholesterol esterase >> (CE) induced surface erosion of poly(ethylene carbonate) ([[ PEC ]]) and drug release from PEC under mild physiological environment was investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cholesterol esterase (<< CE >>) induced surface erosion of poly(ethylene carbonate) ([[ PEC ]]) and drug release from PEC under mild physiological environment was investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Cholesterol esterase >> (CE) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cholesterol esterase (<< CE >>) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Intravenous << arginine >> significantly increased the acute [[ glucagon ]] response (129 +/- 12 vs 36 +/- 6 ng/l in controls; p < 0.01), notably without affecting plasma glucose.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Isolated islets displayed improved << glucose >>-stimulated [[ insulin ]] secretion after GRA treatment (0.061 +/- 0.007 vs 0.030 +/- 0.004 pmol islet(-1) h(-1) at 16.7 mmol/l glucose; p < 0.001), without affecting islet glucose oxidation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2].", "label": "PRODUCT-OF", "metadata": []}
{"text": "PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2].", "label": "PRODUCT-OF", "metadata": []}
{"text": "PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [[[ PI(4,5)P2 ]]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [[[ PI(4,5)P2 ]]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [[[ PI(4,5)P2 ]]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [[[ PI(4)P ]]] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [[[ PI(4)P ]]] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [[[ PI(4)P ]]] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].", "label": "SUBSTRATE", "metadata": []}
{"text": "Accordingly, loss of << pip5k1β >> function in FRDA cells was accompanied by decreased [[ PI(4,5)P2 ]] levels and was shown instrumental for destabilization of the actin network and delayed cell spreading.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The expression of << regucalcin >> is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by [[ streptozotocin ]] administration in vivo.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< AMPK >> activators [[ metformin ]] and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< AMPK >> activators metformin and [[ AICAR ]] partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> treatment led to an increase in lipid peroxidation, [[ glutathione peroxidase ]] and glucose-6-phosphate dehydrogenase activities and to a decrease in catalase activity and glutathione levels in gastric mucosa.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> treatment led to an increase in lipid peroxidation, glutathione peroxidase and [[ glucose-6-phosphate dehydrogenase ]] activities and to a decrease in catalase activity and glutathione levels in gastric mucosa.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Indomethacin >> treatment led to an increase in lipid peroxidation, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities and to a decrease in [[ catalase ]] activity and glutathione levels in gastric mucosa.", "label": "INHIBITOR", "metadata": []}
{"text": "Reversible inhibition of << human carboxylesterases >> by [[ acyl glucuronides ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting [[ alcohols ]], amines, and thiols, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce [[ carboxylic acids ]] and resulting alcohols, amines, and thiols, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, [[ amines ]], and thiols, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and [[ thiols ]], respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze [[ esters ]], amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, [[ amides ]], and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Carboxylesterases >> hydrolyze esters, amides, and [[ thioesters ]] to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Uridine 5'-diphosphate- glucuronosyltransferases are colocalized with << carboxylesterases >> and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to acyl glucuronides, but it is currently unknown if [[ acyl glucuronides ]], being esters, also interact with carboxylesterases.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize [[ carboxylic acids ]] to acyl glucuronides, but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uridine 5'-diphosphate- glucuronosyltransferases are colocalized with << carboxylesterases >> and have the potential to further metabolize [[ carboxylic acids ]] to acyl glucuronides, but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.", "label": "SUBSTRATE", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of [[ human carboxylesterases 1 ]] (hCES1) and 2 (hCES2).", "label": "INHIBITOR", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2).", "label": "INHIBITOR", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 (hCES1) and 2 ([[ hCES2 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of [[ human carboxylesterases 1 ]] (hCES1) and 2 (hCES2).", "label": "SUBSTRATE", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2).", "label": "SUBSTRATE", "metadata": []}
{"text": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 (hCES1) and 2 ([[ hCES2 ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Methods: The stability of six << acyl glucuronides >> in the presence of [[ hCES1 ]], hCES2, and buffer alone (100 mM potassium phosphate, pH 7.4, 37°C) were investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Methods: The stability of six << acyl glucuronides >> in the presence of hCES1, [[ hCES2 ]], and buffer alone (100 mM potassium phosphate, pH 7.4, 37°C) were investigated.", "label": "SUBSTRATE", "metadata": []}
{"text": "Diclofenac-β-d-glucuronide, << clopidogrel-β-d-glucuronide >>, ibuprofen-β-d-glucuronide, (R)-naproxen-β-d-glucuronide, and (S)-naproxen-β-d-glucuronide selectively inhibited [[ hCES1 ]], with Ki values of 4.32 ± 0.47, 24.8 ± 4.2, 355 ± 38, 468 ± 21, 707 ± 64 µM, respectively, but did not significantly inhibit hCES2.", "label": "INHIBITOR", "metadata": []}
{"text": "Diclofenac-β-d-glucuronide, clopidogrel-β-d-glucuronide, << ibuprofen-β-d-glucuronide >>, (R)-naproxen-β-d-glucuronide, and (S)-naproxen-β-d-glucuronide selectively inhibited [[ hCES1 ]], with Ki values of 4.32 ± 0.47, 24.8 ± 4.2, 355 ± 38, 468 ± 21, 707 ± 64 µM, respectively, but did not significantly inhibit hCES2.", "label": "INHIBITOR", "metadata": []}
{"text": "Diclofenac-β-d-glucuronide, clopidogrel-β-d-glucuronide, ibuprofen-β-d-glucuronide, << (R)-naproxen-β-d-glucuronide >>, and (S)-naproxen-β-d-glucuronide selectively inhibited [[ hCES1 ]], with Ki values of 4.32 ± 0.47, 24.8 ± 4.2, 355 ± 38, 468 ± 21, 707 ± 64 µM, respectively, but did not significantly inhibit hCES2.", "label": "INHIBITOR", "metadata": []}
{"text": "Diclofenac-β-d-glucuronide, clopidogrel-β-d-glucuronide, ibuprofen-β-d-glucuronide, (R)-naproxen-β-d-glucuronide, and << (S)-naproxen-β-d-glucuronide >> selectively inhibited [[ hCES1 ]], with Ki values of 4.32 ± 0.47, 24.8 ± 4.2, 355 ± 38, 468 ± 21, 707 ± 64 µM, respectively, but did not significantly inhibit hCES2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Diclofenac-β-d-glucuronide >>, clopidogrel-β-d-glucuronide, ibuprofen-β-d-glucuronide, (R)-naproxen-β-d-glucuronide, and (S)-naproxen-β-d-glucuronide selectively inhibited [[ hCES1 ]], with Ki values of 4.32 ± 0.47, 24.8 ± 4.2, 355 ± 38, 468 ± 21, 707 ± 64 µM, respectively, but did not significantly inhibit hCES2.", "label": "INHIBITOR", "metadata": []}
{"text": "Conclusion: Drug-drug interaction studies may be warranted for drugs that metabolize to << acyl glucuronides >> due to the potential inhibition of [[ hCESs ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << DOX >>-treated WT and p65(-/-) MEFs differed in their expression of various apoptosis-associated molecules, when the former demonstrated a decrease in the percentage of [[ p65 ]]-positive and a more prominent decrease in the percentage of p53-positive cells, while a decreased percentage of IκBα-positive and a more prominent decrease in the percentage of bcl-2-positive cells was detected among the latter.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "RESULTS: << DZN >> induced histophatological damages and elevated the level of cardiac marker [[ CK-MB ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of << caspase 3 >> and release of cytochrome c to the cytosol induced by [[ DZN ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of << cytochrome c >> to the cytosol induced by [[ DZN ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of [[ cytochrome c ]] to the cytosol induced by DZN.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/<< Bcl2 >> ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and [[ CK-MB ]], increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of [[ Bax ]]/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/[[ Bcl2 ]] ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and [[ CK-MB ]], increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of [[ Bax ]]/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/[[ Bcl2 ]] ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Effect of << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity on contractile receptor function in airway smooth muscle.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the present study, we investigated the effect of << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions.", "label": "ACTIVATOR", "metadata": []}
{"text": "After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist [[ 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium ]] (McN-A-343) and histamine.", "label": "AGONIST", "metadata": []}
{"text": "After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]].", "label": "AGONIST", "metadata": []}
{"text": "After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full << muscarinic receptor >> agonist [[ methacholine ]], the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine.", "label": "AGONIST", "metadata": []}
{"text": "In conclusion, << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol.", "label": "ACTIVATOR", "metadata": []}
{"text": "In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].", "label": "AGONIST-INHIBITOR", "metadata": []}
{"text": "<< Beta-glucogallin >> reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of [[ aldose reductase ]] in murine macrophages and ocular tissues.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Aldose reductase >> (AR) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Aldose reductase >> (AR) catalyzes the reduction of toxic lipid [[ aldehydes ]] to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS).", "label": "SUBSTRATE", "metadata": []}
{"text": "Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid [[ aldehydes ]] to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Beta-glucogallin >> (BGG), a recently described [[ AR ]] inhibitor, was purified from extracts of the Indian gooseberry (Emblica officinalis).", "label": "INHIBITOR", "metadata": []}
{"text": "Beta-glucogallin (<< BGG >>), a recently described [[ AR ]] inhibitor, was purified from extracts of the Indian gooseberry (Emblica officinalis).", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we found that << BGG >> showed low cytotoxicity in Raw264.7 murine macrophages and effectively inhibited [[ AR ]] activity as measured by a decrease in sorbitol accumulation.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, << BGG >>-mediated inhibition of AR prevented LPS-induced activation of [[ JNK ]] and p38 and lowered ROS levels, which could inhibit LPS-induced apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << BGG >>-mediated inhibition of AR prevented LPS-induced activation of JNK and [[ p38 ]] and lowered ROS levels, which could inhibit LPS-induced apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << BGG >>-mediated inhibition of [[ AR ]] prevented LPS-induced activation of JNK and p38 and lowered ROS levels, which could inhibit LPS-induced apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Exogenous << C2-ceramide >> activates [[ c-fos serum response element ]] via Rac-dependent signalling pathway.", "label": "ACTIVATOR", "metadata": []}
{"text": "Treatment of Rat-2 fibroblast cells with << C2-ceramide >> caused the stimulation of [[ c-fos SRE ]]-dependent reporter gene activity in a dose- and time-dependent manner by transient transfection analysis.", "label": "ACTIVATOR", "metadata": []}
{"text": "Next, we examined the role of Rho family GTPases in the << ceramide >>-induced signalling to [[ SRE ]] activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "By reporter gene analysis following transient transfections with various plasmids expressing a dominant negative mutant form of Cdc42, Rac1 or RhoA, << C2-ceramide >>-induced [[ SRE ]] activation was shown to be selectively repressed by pEXV-RacN17 encoding a dominant negative mutant of Rac1, suggesting that Rac activity is essential for the signalling cascade of ceramide to the nucleus.", "label": "ACTIVATOR", "metadata": []}
{"text": "In a further study to analyse the downstream mediator of Rac in the ceramide-signalling pathway, we observed that either pretreatment with mepacrine, a potent and specific inhibitor of phospholipase A2, or co-transfection with antisense cytosolic phospholipase A2 (cPLA2) oligonucleotide repressed the << C2-ceramide >>-induced [[ SRE ]] activation selectively, implying a critical role of cPLA2 in C2-ceramide-induced signalling to nucleus.", "label": "ACTIVATOR", "metadata": []}
{"text": "Consistent with these results, the translocation of cPLA2 protein as well as the release of << arachidonic acid >>, a principal product of [[ phospholipase A2 ]], was rapidly induced by the addition of C2-ceramide in a Rac-dependent manner.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Together, our findings suggest the critical role of 'Rac and subsequent activation of << phospholipase A2 >>' in [[ ceramide ]]-signalling to nucleus.", "label": "ACTIVATOR", "metadata": []}
{"text": "Effect of << ramelteon >> (TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice.", "label": "AGONIST", "metadata": []}
{"text": "Effect of ramelteon (<< TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice.", "label": "AGONIST", "metadata": []}
{"text": "Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (<< ramelteon >>, TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice.", "label": "AGONIST", "metadata": []}
{"text": "Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice.", "label": "AGONIST", "metadata": []}
{"text": "Effect of << (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide >> (ramelteon, TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice.", "label": "AGONIST", "metadata": []}
{"text": "Synthesis and cancer stem cell-based activity of substituted << 5-morpholino-7H-thieno[3,2-b]pyran-7-ones >> designed as next generation [[ PI3K ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Our previous work, built on the early pioneering multikinase inhibitor << LY294002 >>, resulted in the only [[ PI3K ]] vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "Our previous work, built on the early pioneering multikinase inhibitor << LY294002 >>, resulted in the only PI3K vascular-targeted [[ PI3K ]] inhibitor prodrug, SF1126, which has now completed Phase I clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only << PI3K >> vascular-targeted PI3K inhibitor prodrug, [[ SF1126 ]], which has now completed Phase I clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted << PI3K >> inhibitor prodrug, [[ SF1126 ]], which has now completed Phase I clinical trials.", "label": "INHIBITOR", "metadata": []}
{"text": "This work resulted in the discovery of the << 5-morpholino-7H-thieno[3,2-b]pyran-7-one >> system as the foundation of a new compound class of potential [[ PI3K ]] inhibitors having improved potency toward PI3K.", "label": "INHIBITOR", "metadata": []}
{"text": "This work resulted in the discovery of the << 5-morpholino-7H-thieno[3,2-b]pyran-7-one >> system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward [[ PI3K ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< CP-690550 >>, a [[ JAK3 ]] inhibitor is currently in phase II clinical trials.FK778, is a synthetic malononitrilamide that targets the critical enzyme of the de novo pyrimidine synthesis, dihydroorotic acid dehydrogenase, and receptor-associated tyrosine kinases has completed phase II trials.", "label": "INHIBITOR", "metadata": []}
{"text": "Firstly, the V(max) of << GAD >> was increased when ApoCaM was present whereas the affinity for the substrate, [[ glutamate ]], was not affected.", "label": "SUBSTRATE", "metadata": []}
{"text": "Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase ([[ CBS ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase ([[ CBS ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS).", "label": "PRODUCT-OF", "metadata": []}
{"text": "Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS).", "label": "SUBSTRATE", "metadata": []}
{"text": "Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS).", "label": "SUBSTRATE", "metadata": []}
{"text": "Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase ([[ CBS ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS).", "label": "SUBSTRATE", "metadata": []}
{"text": "In this study, we investigated the presence of H(2)S and the expression of << H(2)S >> synthesizing enzymes, [[ CSE ]] and CBS, in isolated mouse pancreatic acini.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In this study, we investigated the presence of H(2)S and the expression of << H(2)S >> synthesizing enzymes, CSE and [[ CBS ]], in isolated mouse pancreatic acini.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Caerulein >> increased the levels of H(2)S and [[ CSE ]] mRNA expression while CBS mRNA expression was decreased.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Caerulein >> increased the levels of H(2)S and CSE mRNA expression while [[ CBS ]] mRNA expression was decreased.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, cells pre-treated with << DL-propargylglycine >> (PAG, 3 mM), a [[ CSE ]] inhibitor, reduced the formation of H(2)S in caerulein treated cells, suggesting that CSE may be the main enzyme involved in H(2)S formation in mouse acinar cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, cells pre-treated with DL-propargylglycine (<< PAG >>, 3 mM), a [[ CSE ]] inhibitor, reduced the formation of H(2)S in caerulein treated cells, suggesting that CSE may be the main enzyme involved in H(2)S formation in mouse acinar cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, cells pre-treated with DL-propargylglycine (PAG, 3 mM), a CSE inhibitor, reduced the formation of H(2)S in caerulein treated cells, suggesting that << CSE >> may be the main enzyme involved in [[ H(2)S ]] formation in mouse acinar cells.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Furthermore, << substance P >> (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (<< SP >>) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (SP) concentration in the acini and expression of << SP >> gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (SP) concentration in the acini and expression of SP gene (<< preprotachykinin-A >>, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, << PPT-A >>) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and << neurokinin-1 receptor >> (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (<< NK-1R >>), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed [[ SP ]] concentration, PPT-A expression and NK1-R expression in the acini.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed SP concentration, [[ PPT-A ]] expression and NK1-R expression in the acini.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed SP concentration, PPT-A expression and [[ NK1-R ]] expression in the acini.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, << sodium hydrosulphide >> (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in [[ SP ]] concentration and expression of PPT-A and NK1-R in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, << sodium hydrosulphide >> (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of [[ PPT-A ]] and NK1-R in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, << sodium hydrosulphide >> (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of PPT-A and [[ NK1-R ]] in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in [[ SP ]] concentration and expression of PPT-A and NK1-R in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of [[ PPT-A ]] and NK1-R in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of PPT-A and [[ NK1-R ]] in acinar cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by [[ SP ]]-NK-1R related pathway in mouse pancreatic acinar cells.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by SP-[[ NK-1R ]] related pathway in mouse pancreatic acinar cells.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of AchE activity, [[ CRP ]], NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of AchE activity, CRP, [[ NF-κB ]], and MCP-1 accompanied with a significant depletion in the Ach level.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of AchE activity, CRP, NF-κB, and [[ MCP-1 ]] accompanied with a significant depletion in the Ach level.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of [[ AchE ]] activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level.", "label": "UPREGULATOR", "metadata": []}
{"text": "6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST).", "label": "PRODUCT-OF", "metadata": []}
{"text": "6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase ([[ GST ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< 6-DHSG >> was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< 6-DHSG >> was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase ([[ GST ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "The concentration response to << levcromakalim >> (LEVC), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "The concentration response to levcromakalim (<< LEVC >>), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Sulfhydration of << sulfonylurea receptor 2B >> (SUR2B) was induced by [[ NaHS ]] and colonic inflammation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Sulfhydration of sulfonylurea receptor 2B (<< SUR2B >>) was induced by [[ NaHS ]] and colonic inflammation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., << sotalol >> or ibutilide in patients with a mutation in the [[ IKr ]]-coding gene KCNH2 (HERG).", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., << sotalol >> or ibutilide in patients with a mutation in the IKr-coding gene [[ KCNH2 ]] (HERG).", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., << sotalol >> or ibutilide in patients with a mutation in the IKr-coding gene KCNH2 ([[ HERG ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or << ibutilide >> in patients with a mutation in the [[ IKr ]]-coding gene KCNH2 (HERG).", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or << ibutilide >> in patients with a mutation in the IKr-coding gene [[ KCNH2 ]] (HERG).", "label": "INHIBITOR", "metadata": []}
{"text": "Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or << ibutilide >> in patients with a mutation in the IKr-coding gene KCNH2 ([[ HERG ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Although inhibition of << LH >> release can be achieved by [[ estrogen ]] and progestins, an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH.", "label": "INHIBITOR", "metadata": []}
{"text": "Although inhibition of << LH >> release can be achieved by estrogen and [[ progestins ]], an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH.", "label": "INHIBITOR", "metadata": []}
{"text": "Mechanisms of << cefadroxil >> uptake in the choroid plexus: studies in wild-type and [[ PEPT2 ]] knockout mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "The choroid plexus uptake of << [(3)H]cefadroxil >> was studied in [[ peptide transporter 2 ]] (PEPT2) wild-type and null mice as a function of temperature, transport inhibitors, pH, and saturability.", "label": "SUBSTRATE", "metadata": []}
{"text": "The choroid plexus uptake of << [(3)H]cefadroxil >> was studied in peptide transporter 2 ([[ PEPT2 ]]) wild-type and null mice as a function of temperature, transport inhibitors, pH, and saturability.", "label": "SUBSTRATE", "metadata": []}
{"text": "At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM << cefadroxil >> was reduced by 83% in [[ PEPT2 ]](-/-) mice as compared with PEPT2(+/+) mice (p < 0.001).", "label": "SUBSTRATE", "metadata": []}
{"text": "At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM << cefadroxil >> was reduced by 83% in PEPT2(-/-) mice as compared with [[ PEPT2 ]](+/+) mice (p < 0.001).", "label": "SUBSTRATE", "metadata": []}
{"text": "Glycylsarcosine coadministration could inhibit the uptake of << cefadroxil >> in [[ PEPT2 ]](+/+) mice (p < 0.01) but not PEPT2(-/-) mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "Glycylsarcosine coadministration could inhibit the uptake of << cefadroxil >> in PEPT2(+/+) mice (p < 0.01) but not [[ PEPT2 ]](-/-) mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "Although a proton-stimulated uptake of << cefadroxil >> was demonstrated in [[ PEPT2 ]](+/+) mice (pH 6.5 versus pH 7.4; p < 0.01), no pH dependence was observed in PEPT2(-/-) mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "Although a proton-stimulated uptake of << cefadroxil >> was demonstrated in PEPT2(+/+) mice (pH 6.5 versus pH 7.4; p < 0.01), no pH dependence was observed in [[ PEPT2 ]](-/-) mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "These findings demonstrate that << PEPT2 >> is the primary transporter responsible for [[ cefadroxil ]] uptake in the choroid plexus.", "label": "SUBSTRATE", "metadata": []}
{"text": "The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis.", "label": "AGONIST", "metadata": []}
{"text": "The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w.", "label": "AGONIST", "metadata": []}
{"text": "The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist IB-MECA [[ (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide ]] at a dose of 0.75 mg/kg b.w.", "label": "AGONIST", "metadata": []}
{"text": "In the << IB-MECA >> group, [[ α-amylase ]] activity was decreased with statistically high significance compared to group I.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP.", "label": "AGONIST", "metadata": []}
{"text": "<< Pyrrolopyrazines >> as Selective [[ Spleen Tyrosine Kinase ]] Inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "We describe the discovery of several << pyrrolopyrazines >> as potent and selective [[ Syk ]] inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Ozone >> plus PM(2.5) exposure, however, induced [[ CRP ]], IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, [[ CK ]], LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, CK, [[ LDH ]] and MDA increase, SOD and HRV decrease significantly in a dose-response way.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, [[ SOD ]] and HRV decrease significantly in a dose-response way.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Flavopiridol >>, a [[ cyclin-dependent kinase ]] inhibitor, arrests cell division and causes apoptosis in non-small lung cancer cells [283660].", "label": "INHIBITOR", "metadata": []}
{"text": "In ex vivo experiments with tumor cells from refractory chronic lymphoblastic leukemia, dose-dependent << CDK2 >> inhibition associated with apoptotic changes was seen at concentrations greater than 100 nM of [[ flavopiridol ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Flavopiridol >> inhibits [[ CDK ]] with an IC50 value of 0.4 mM [285707].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Carbonic anhydrase >> inhibitors: [[ aromatic and heterocyclic sulfonamides ]] incorporating adamantyl moieties with strong anticonvulsant activity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Carbonic anhydrase >> inhibitors: aromatic and heterocyclic sulfonamides incorporating [[ adamantyl ]] moieties with strong anticonvulsant activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two << human CA >> isozymes involved in important physiological processes, CA I, and CA II, of the same order of magnitude as the clinically used drugs acetazolamide and [[ methazolamide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, << CA I >>, and CA II, of the same order of magnitude as the clinically used drugs acetazolamide and [[ methazolamide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, CA I, and << CA II >>, of the same order of magnitude as the clinically used drugs acetazolamide and [[ methazolamide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two << human CA >> isozymes involved in important physiological processes, CA I, and CA II, of the same order of magnitude as the clinically used drugs [[ acetazolamide ]] and methazolamide.", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, << CA I >>, and CA II, of the same order of magnitude as the clinically used drugs [[ acetazolamide ]] and methazolamide.", "label": "INHIBITOR", "metadata": []}
{"text": "Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, CA I, and << CA II >>, of the same order of magnitude as the clinically used drugs [[ acetazolamide ]] and methazolamide.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of glutamate to gamma-aminobutyric acid ([[ GABA ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to gamma-aminobutyric acid ([[ GABA ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of glutamate to gamma-aminobutyric acid ([[ GABA ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA).", "label": "SUBSTRATE", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA).", "label": "SUBSTRATE", "metadata": []}
{"text": "BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA).", "label": "SUBSTRATE", "metadata": []}
{"text": "FCEO significantly inhibited << nitric oxide >> (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of [[ inducible nitric oxide synthase ]] (iNOS) and cyclooxygenase (COX)-2, respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "FCEO significantly inhibited << nitric oxide >> (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase ([[ iNOS ]]) and cyclooxygenase (COX)-2, respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "FCEO significantly inhibited nitric oxide (<< NO >>) and prostaglandin E2 (PGE2) by suppressing the protein expression of [[ inducible nitric oxide synthase ]] (iNOS) and cyclooxygenase (COX)-2, respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "FCEO significantly inhibited nitric oxide (<< NO >>) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase ([[ iNOS ]]) and cyclooxygenase (COX)-2, respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "FCEO significantly inhibited nitric oxide (NO) and << prostaglandin E2 >> (PGE2) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and [[ cyclooxygenase (COX)-2 ]], respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "FCEO significantly inhibited nitric oxide (NO) and prostaglandin E2 (<< PGE2 >>) by suppressing the protein expression of inducible nitric oxide synthase (iNOS) and [[ cyclooxygenase (COX)-2 ]], respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Amrinone >> and milrinone, selective PDE3 inhibitors, suppressed [[ TNF ]] secretion to a lesser extent.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Amrinone and << milrinone >>, selective PDE3 inhibitors, suppressed [[ TNF ]] secretion to a lesser extent.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Amrinone >> and milrinone, selective [[ PDE3 ]] inhibitors, suppressed TNF secretion to a lesser extent.", "label": "INHIBITOR", "metadata": []}
{"text": "Amrinone and << milrinone >>, selective [[ PDE3 ]] inhibitors, suppressed TNF secretion to a lesser extent.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of << theophylline >> (unspecific [[ PDE ]] inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the PDE5 inhibitors zaprinast and E 4021 were weak.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of theophylline (unspecific PDE inhibitor), << vinpocetine >> ([[ PDE1 ]] inhibitor), EHNA (PDE2 inhibitor) and the PDE5 inhibitors zaprinast and E 4021 were weak.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of theophylline (unspecific PDE inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the << PDE5 >> inhibitors [[ zaprinast ]] and E 4021 were weak.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of theophylline (unspecific PDE inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the << PDE5 >> inhibitors zaprinast and [[ E 4021 ]] were weak.", "label": "INHIBITOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids << beclomethasone >>, dexamethasone and fluticasone inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids beclomethasone, << dexamethasone >> and fluticasone inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids beclomethasone, dexamethasone and << fluticasone >> inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids << beclomethasone >>, dexamethasone and fluticasone inhibited the LPS induced TNF release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced [[ TNF ]] release, with the exception of dexamethasone, was much less pronounced.", "label": "INHIBITOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids beclomethasone, << dexamethasone >> and fluticasone inhibited the LPS induced TNF release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced [[ TNF ]] release, with the exception of dexamethasone, was much less pronounced.", "label": "INHIBITOR", "metadata": []}
{"text": "In human blood, the tested glucocorticoids beclomethasone, dexamethasone and << fluticasone >> inhibited the LPS induced TNF release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced [[ TNF ]] release, with the exception of dexamethasone, was much less pronounced.", "label": "INHIBITOR", "metadata": []}
{"text": "The selective PDE 4 inhibitors, and to a certain extent the PDE3 inhibitors amrinone and << milrinone >>, reduced the [[ GM-CSF ]] release in a concentration dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The selective PDE 4 inhibitors, and to a certain extent the PDE3 inhibitors << amrinone >> and milrinone, reduced the [[ GM-CSF ]] release in a concentration dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The selective << PDE 4 >> inhibitors, and to a certain extent the PDE3 inhibitors amrinone and [[ milrinone ]], reduced the GM-CSF release in a concentration dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "The selective PDE 4 inhibitors, and to a certain extent the << PDE3 >> inhibitors amrinone and [[ milrinone ]], reduced the GM-CSF release in a concentration dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "The selective << PDE 4 >> inhibitors, and to a certain extent the PDE3 inhibitors [[ amrinone ]] and milrinone, reduced the GM-CSF release in a concentration dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "The selective PDE 4 inhibitors, and to a certain extent the << PDE3 >> inhibitors [[ amrinone ]] and milrinone, reduced the GM-CSF release in a concentration dependent manner.", "label": "INHIBITOR", "metadata": []}
{"text": "Activating << glucocorticoid receptor >>-ERK signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activating glucocorticoid receptor-<< ERK >> signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activating glucocorticoid receptor-ERK signaling pathway contributes to << ginsenoside Rg1 >> protection against [[ β-amyloid peptide ]]-induced human endothelial cells apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rg1 >> attenuated the Aβ25-35-associated mitochondrial apoptotic events, accompanied by inhibiting [[ HIF-1α ]] expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Rg1 >> attenuated the [[ Aβ25-35 ]]-associated mitochondrial apoptotic events, accompanied by inhibiting HIF-1α expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination.", "label": "INHIBITOR", "metadata": []}
{"text": "These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or << p-ERK >> inhibitor [[ U0126 ]] rather than estrogen receptor α antagonist ICI 82,780.", "label": "INHIBITOR", "metadata": []}
{"text": "These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than << estrogen receptor α >> antagonist [[ ICI 82,780 ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "These protective effects were abolished by << glucocorticoid receptor >> (GR) antagonist [[ RU486 ]] or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780.", "label": "ANTAGONIST", "metadata": []}
{"text": "These protective effects were abolished by glucocorticoid receptor (<< GR >>) antagonist [[ RU486 ]] or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780.", "label": "ANTAGONIST", "metadata": []}
{"text": "Taken together, our results suggested that << Rg1 >> protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent [[ ERK ]] phosphorylation pathways: (1) down-regulating HIF-1α initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades.", "label": "ACTIVATOR", "metadata": []}
{"text": "Taken together, our results suggested that << Rg1 >> protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating [[ HIF-1α ]] initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, our results suggested that << Rg1 >> protected against [[ Aβ25-35 ]]-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating HIF-1α initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades.", "label": "INHIBITOR", "metadata": []}
{"text": "These data provided a novel insight to the mechanisms of << Rg1 >>protective effects on [[ Aβ25-35 ]]-induced endothelial cells apoptosis, suggesting that GR-ERK signaling pathway might play an important role in it.", "label": "INHIBITOR", "metadata": []}
{"text": "Effectiveness of << endopeptidase >> inhibition ([[ candoxatril ]]) in congestive heart failure.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Candoxatril >> is a novel, orally active inhibitor of [[ neutral endopeptidase ]] EC 3.4.24.11, the enzyme that degrades atrial natriuretic peptide (ANP).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Candoxatril >> is a novel, orally active inhibitor of neutral endopeptidase [[ EC 3.4.24.11 ]], the enzyme that degrades atrial natriuretic peptide (ANP).", "label": "INHIBITOR", "metadata": []}
{"text": "On study day 1, << candoxatril >> acutely increased plasma [[ ANP ]] levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On study day 10, the acute effects of << candoxatril >> were similar to those on day 1 (i.e., [[ ANP ]] was further increased, aldosterone was suppressed, and right and left ventricular filling pressures were decreased).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "The << alpha(1)-adrenoceptor >> antagonist, [[ tamsulosin ]], is selective for alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "The alpha(1)-adrenoceptor antagonist, << tamsulosin >>, is selective for [[ alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), [[ tumor necrosis factor alpha ]] (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha ([[ TNF-α ]]), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), [[ nuclear factor kappa B ]] (NF-κB) genes expression in cisplatin injected rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B ([[ NF-κB ]]) genes expression in cisplatin injected rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), << tumor necrosis factor alpha >> (TNF-α), nuclear factor kappa B (NF-κB) genes expression in [[ cisplatin ]] injected rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (<< TNF-α >>), nuclear factor kappa B (NF-κB) genes expression in [[ cisplatin ]] injected rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), << nuclear factor kappa B >> (NF-κB) genes expression in [[ cisplatin ]] injected rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (<< NF-κB >>) genes expression in [[ cisplatin ]] injected rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate [[ cyclic GMP-dependent protein kinase ]] (PKG); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease beta-catenin protein expression at times and doses consistent with apoptosis.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase ([[ PKG ]]); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease beta-catenin protein expression at times and doses consistent with apoptosis.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease [[ beta-catenin ]] protein expression at times and doses consistent with apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate [[ c-jun NH2-terminal kinase ]] (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease beta-catenin protein expression at times and doses consistent with apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate c-jun NH2-terminal kinase ([[ JNK ]]); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease beta-catenin protein expression at times and doses consistent with apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Cotreatment with << U0126 >> and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, [[ JNK ]], and beta-catenin.", "label": "ACTIVATOR", "metadata": []}
{"text": "Cotreatment with U0126 and << YC-1 >> synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, [[ JNK ]], and beta-catenin.", "label": "ACTIVATOR", "metadata": []}
{"text": "Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of << sulindac >> treatment on ERK1/2, [[ JNK ]], and beta-catenin.", "label": "ACTIVATOR", "metadata": []}
{"text": "Cotreatment with << U0126 >> and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and [[ beta-catenin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Cotreatment with U0126 and << YC-1 >> synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and [[ beta-catenin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of << sulindac >> treatment on ERK1/2, JNK, and [[ beta-catenin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some 2-carbonyl derivatives of [[ diphenidol ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some [[ 2-carbonyl ]] derivatives of diphenidol.", "label": "ANTAGONIST", "metadata": []}
{"text": "A series of 2-carbonyl analogues of the muscarinic antagonist << diphenidol >> bearing 1-substituents of different lipophilic, electronic, and steric properties was synthesized and their affinity for the [[ M2 and M3 muscarinic receptor ]] subtypes was evaluated by functional tests.", "label": "ANTAGONIST", "metadata": []}
{"text": "This work showed that appropriate structural modification of << diphenidol >> can lead to [[ M2 ]]-selective muscarinic antagonists of possible interest in the field of Alzheimer's disease.", "label": "ANTAGONIST", "metadata": []}
{"text": "Activation of an apoptotic signal transduction pathway involved in the upregulation of << calpain >> and apoptosis-inducing factor in [[ aldosterone ]]-induced primary cultured cardiomyocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and << apoptosis-inducing factor >> in [[ aldosterone ]]-induced primary cultured cardiomyocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In this study, aldosterone (<< ALD >>)-induced apoptosis of cardiomyocyte was evaluated based on the previous studies, and the roles of [[ calpain ]] signaling were clarified.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In this study, << aldosterone >> (ALD)-induced apoptosis of cardiomyocyte was evaluated based on the previous studies, and the roles of [[ calpain ]] signaling were clarified.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< ALD >> increased calpain expression and [[ caspase-3 ]] activity and promoted Bid cleavage.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< ALD >> increased [[ calpain ]] expression and caspase-3 activity and promoted Bid cleavage.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The upregulation of calpain, tBid and << caspase-3 >> activity were further inhibited by treatment with EGTA in the presence of [[ ALD ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "The upregulation of << calpain >>, tBid and caspase-3 activity were further inhibited by treatment with EGTA in the presence of [[ ALD ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The upregulation of calpain, << tBid >> and caspase-3 activity were further inhibited by treatment with EGTA in the presence of [[ ALD ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The upregulation of << calpain >>, tBid and caspase-3 activity were further inhibited by treatment with [[ EGTA ]] in the presence of ALD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The upregulation of calpain, << tBid >> and caspase-3 activity were further inhibited by treatment with [[ EGTA ]] in the presence of ALD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The upregulation of calpain, tBid and << caspase-3 >> activity were further inhibited by treatment with [[ EGTA ]] in the presence of ALD.", "label": "INHIBITOR", "metadata": []}
{"text": "Additionally, << AIF >> levels in the cytosol decreased due to [[ EGTA ]] but not due to calpeptin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the << ALD >>-induced increase of [[ calpain ]] and AIF levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the << ALD >>-induced increase of calpain and [[ AIF ]] levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, treatment with << spironoclactone >> not only attenuated the pro-apoptotic effect of ALD but reversed the ALD-induced increase of [[ calpain ]] and AIF levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, treatment with << spironoclactone >> not only attenuated the pro-apoptotic effect of ALD but reversed the ALD-induced increase of calpain and [[ AIF ]] levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Loperamide >> is a peripheral opiate agonist able to inhibit [[ ACTH ]] secretion.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In all patients << loperamide >> induced a significant fall in plasma [[ ACTH ]] levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of << CRH >>-induced ACTH secretion was significantly lower after [[ loperamide ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of CRH-induced << ACTH >> secretion was significantly lower after [[ loperamide ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< CCl(4) >> intoxication caused hepatic necrosis and increased serum [[ ALT ]] activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating [[ nuclear factor-kappaB ]] (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB ([[ NF-κB ]]), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of [[ tumor necrosis factor-alpha ]] (TNF-α) and cyclooxygenase-2 (COX-2).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha ([[ TNF-α ]]) and cyclooxygenase-2 (COX-2).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and [[ cyclooxygenase-2 ]] (COX-2).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 ([[ COX-2 ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "Furthermore, RA significantly inhibited the << CCl(4) >>-induced apoptosis, which was evident from decreased cleavage of [[ caspase-3 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pre-clinical pharmacology of << zolmitriptan >> (Zomig; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine.", "label": "AGONIST", "metadata": []}
{"text": "Pre-clinical pharmacology of zolmitriptan (<< Zomig >>; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine.", "label": "AGONIST", "metadata": []}
{"text": "Pre-clinical pharmacology of zolmitriptan (Zomig; formerly << 311C90 >>), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine.", "label": "AGONIST", "metadata": []}
{"text": "Zolmitriptan (Zomig; formerly << 311C90 >>) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura.", "label": "AGONIST", "metadata": []}
{"text": "<< Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura.", "label": "AGONIST", "metadata": []}
{"text": "Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura.", "label": "AGONIST", "metadata": []}
{"text": "These actions are consistent with a pre-junctional inhibition of neuropeptide release from perivascular afferents of the trigeminal nerve, as confirmed by independent studies showing that << zolmitriptan >> blocks elevations of [[ calcitonin-gene-related peptide ]] in jugular venous blood during electrical stimulation of the trigeminal ganglion.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities.", "label": "UPREGULATOR", "metadata": []}
{"text": "They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with << rhArg >>, to [[ citrulline ]], which is converted back to arginine via ASS.", "label": "PRODUCT-OF", "metadata": []}
{"text": "They all expressed ASS, but not << ornithine transcarbamylase >> (OTC), the enzyme that converts [[ ornithine ]], the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS.", "label": "SUBSTRATE", "metadata": []}
{"text": "They all expressed ASS, but not ornithine transcarbamylase (<< OTC >>), the enzyme that converts [[ ornithine ]], the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS.", "label": "SUBSTRATE", "metadata": []}
{"text": "They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of << arginine >> with [[ rhArg ]], to citrulline, which is converted back to arginine via ASS.", "label": "SUBSTRATE", "metadata": []}
{"text": "They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with rhArg, to citrulline, which is converted back to << arginine >> via [[ ASS ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to << rhArg >>-mediated [[ arginine ]] depletion.", "label": "SUBSTRATE", "metadata": []}
{"text": "Therefore, pretreatment tumor gene expression profiling of ASS and OTC could aid in predicting tumor response to << arginine >> depletion with [[ arginine-depleting enzymes ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective << 5-HT1F >> receptor agonist ([[ LY 344864 ]]) on c-fos protein expression in the trigeminal nucleus caudalis.", "label": "AGONIST", "metadata": []}
{"text": "<< c-fos >> expression was induced in urethane-anaesthetized rats by intracisternal [[ capsaicin ]] administration.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Sumatriptan and LY 344864 decreased the number of << capsaicin >>-induced [[ c-fos ]]-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Sumatriptan >> and LY 344864 decreased the number of capsaicin-induced [[ c-fos ]]-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Sumatriptan and << LY 344864 >> decreased the number of capsaicin-induced [[ c-fos ]]-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist << SDZ 21-009 >>, which displays high affinity for [[ rat 5-HT1B ]] receptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists << SC-51089 >> (EP1 specific) and AH 6809 ([[ EP1 ]] and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).", "label": "AGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> ([[ EP1 ]] and EP2 specific).", "label": "ANTAGONIST", "metadata": []}
{"text": "The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> (EP1 and [[ EP2 ]] specific).", "label": "ANTAGONIST", "metadata": []}
{"text": "In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the << PGE1 >> mediated stimulation of [[ Na,K-ATPase beta ]] subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of SC-51089.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE1 mediated stimulation of << Na,K-ATPase beta >> subunit gene transcription includes the stimulatory effect of [[ 17-phenyl trinor PGE2 ]], as well as the inhibitory effects of SC-51089.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE1 mediated stimulation of << Na,K-ATPase beta >> subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of [[ SC-51089 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the << PKC >> inhibitor Go 6976, [[ thapsigargin ]], as well as the calmodulin antagonists W7 and W13.", "label": "INHIBITOR", "metadata": []}
{"text": "Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the << PKC >> inhibitor [[ Go 6976 ]], thapsigargin, as well as the calmodulin antagonists W7 and W13.", "label": "INHIBITOR", "metadata": []}
{"text": "Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the << calmodulin >> antagonists [[ W7 ]] and W13.", "label": "ANTAGONIST", "metadata": []}
{"text": "Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the << calmodulin >> antagonists W7 and [[ W13 ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Spiro heterocycles as potential inhibitors of << SIRT1 >>: Pd/C-mediated synthesis of novel [[ N-indolylmethyl spiroindoline-3,2'-quinazolines ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Novel << N-indolylmethyl substituted spiroindoline-3,2'-quinazolines >> were designed as potential inhibitiors of [[ SIRT1 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of << inducible nitric-oxide synthase >> by [[ 15-deoxy-Delta12,14-prostaglandin J2 ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Cyclopentenone prostaglandins >> suppress activation of microglia: down-regulation of [[ inducible nitric-oxide synthase ]] by 15-deoxy-Delta12,14-prostaglandin J2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Cyclopentenone prostaglandins >> were potent inhibitors of [[ iNOS ]] induction and were more effective than their precursors, prostaglandins E2 and D2.", "label": "INHIBITOR", "metadata": []}
{"text": "Cyclopentenone prostaglandins were potent inhibitors of << iNOS >> induction and were more effective than their precursors, [[ prostaglandins E2 and D2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In activated microglia, << 15d-PGJ2 >> suppressed iNOS promoter activity, [[ iNOS ]] mRNA, and protein levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In activated microglia, << 15d-PGJ2 >> suppressed [[ iNOS promoter ]] activity, iNOS mRNA, and protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 15d-PGJ2 >> did not block nuclear translocation or DNA-binding activity of the transcription factor NFkappaB, but it did inhibit the activity of an [[ NFkappaB ]] reporter construct, suggesting that the mechanism of suppression of microglial iNOS by 15d-PGJ2 may involve interference with NFkappaB transcriptional activity in the nucleus.", "label": "INHIBITOR", "metadata": []}
{"text": "15d-PGJ2 did not block nuclear translocation or DNA-binding activity of the transcription factor NFkappaB, but it did inhibit the activity of an NFkappaB reporter construct, suggesting that the mechanism of suppression of microglial << iNOS >> by [[ 15d-PGJ2 ]] may involve interference with NFkappaB transcriptional activity in the nucleus.", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro studies, however, revealed that << EO >> inhibits [[ fibrin ]] clot formation because of the Ca2+-chelating ability of its constituent ethanolamine, although oleate or benzyl alcohol exhibited procoagulant activity in FPA formation in vitro.", "label": "INHIBITOR", "metadata": []}
{"text": "The activation may be accelerated by an acute inflammatory process provoked by << oleate >>, which is supported by such clinical manifestations as mild fever, retrosternal pain leukocytosis and an increase in plasma [[ fibrinogen ]] level which was observed in all during the period.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "OBJECTIVE: Celecoxib and << rofecoxib >> are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the [[ cyclo-oxygenase-2 ]] (COX-2) isoenzyme at therapeutic concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: Celecoxib and << rofecoxib >> are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 ([[ COX-2 ]]) isoenzyme at therapeutic concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: << Celecoxib >> and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the [[ cyclo-oxygenase-2 ]] (COX-2) isoenzyme at therapeutic concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: << Celecoxib >> and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 ([[ COX-2 ]]) isoenzyme at therapeutic concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "This study was conducted in order to understand the association between acute renal failure and the two << COX-2 >> inhibitors [[ celecoxib ]] and rofecoxib.", "label": "INHIBITOR", "metadata": []}
{"text": "This study was conducted in order to understand the association between acute renal failure and the two << COX-2 >> inhibitors celecoxib and [[ rofecoxib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< (+)-Tamsulosin >>, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "(+)-Tamsulosin, << (-)-tamsulosin >>, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "(+)-Tamsulosin, (-)-tamsulosin, << SL 89,0591 >>, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, << Rec 15/2739 >>, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, << SNAP 1069 >> and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "The potency of the antipsychotic drug, << risperidone >>, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and [[ alpha 1B-adrenoceptor ]]-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potency of the antipsychotic drug, << risperidone >>, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of [[ alpha 1-adrenoceptor ]] subtype-discriminating antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potency of the antipsychotic drug, << risperidone >>, to antagonize [[ alpha 1A-adrenoceptor ]]-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "In this article, the action of << dasatinib >> (BMS-354825) is contrasted with that of imatinib, a [[ kinase ]] inhibitor that is currently being used to treat chronic myelogenous leukemia and other disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "In this article, the action of dasatinib (<< BMS-354825 >>) is contrasted with that of imatinib, a [[ kinase ]] inhibitor that is currently being used to treat chronic myelogenous leukemia and other disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "In this article, the action of dasatinib (BMS-354825) is contrasted with that of << imatinib >>, a [[ kinase ]] inhibitor that is currently being used to treat chronic myelogenous leukemia and other disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "The work of Chen and colleagues shows that << dasatinib >> is a particularly potent inhibitor of [[ PDGFR ]] and that the compound also targets Src kinase.", "label": "INHIBITOR", "metadata": []}
{"text": "The work of Chen and colleagues shows that << dasatinib >> is a particularly potent inhibitor of PDGFR and that the compound also targets [[ Src kinase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "From these data, it is inferred that both the << SERT >> and NET contribute to the active clearance of exogenously applied [[ 5-HT ]] in the dentate gyrus.", "label": "SUBSTRATE", "metadata": []}
{"text": "From these data, it is inferred that both the SERT and << NET >> contribute to the active clearance of exogenously applied [[ 5-HT ]] in the dentate gyrus.", "label": "SUBSTRATE", "metadata": []}
{"text": "In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region.", "label": "ANTAGONIST", "metadata": []}
{"text": "These and other data have generated a working hypothesis that activation of the terminal serotonin autoreceptor enhances the kinetics of << 5-HT >> uptake through an effect on the [[ serotonin transporter ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "These and other data have generated a working hypothesis that activation of the terminal << serotonin autoreceptor >> enhances the kinetics of [[ 5-HT ]] uptake through an effect on the serotonin transporter.", "label": "SUBSTRATE", "metadata": []}
{"text": "The anti-amnesic effect of minaprine on the cycloheximide-induced memory impairment was also antagonized by a serotonin (5-HT) releaser, p-chloroamphetamine, and by a 5-HT precursor, 5-hydroxytryptophan, whereas a << 5-HT1A >>-selective agonist, [[ 8-hydroxy-2-(di-n-propylamino)tetralin ]], was inactive.", "label": "AGONIST", "metadata": []}
{"text": "The memory-improving effect of minaprine on cycloheximide-induced amnesia was potentiated by a selective << 5-HT2 >> antagonist, [[ ritanserin ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Even though the activities of << MAT >> and GNMT were elevated, the concentration of liver S-adenosylmethionine was decreased (24%, p<0.001) and [[ S-adenosylhomocysteine ]] increased (113%, p<0.001) in the dwarf mice.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Even though the activities of MAT and << GNMT >> were elevated, the concentration of liver S-adenosylmethionine was decreased (24%, p<0.001) and [[ S-adenosylhomocysteine ]] increased (113%, p<0.001) in the dwarf mice.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Even though the activities of << MAT >> and GNMT were elevated, the concentration of liver [[ S-adenosylmethionine ]] was decreased (24%, p<0.001) and S-adenosylhomocysteine increased (113%, p<0.001) in the dwarf mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "Even though the activities of MAT and << GNMT >> were elevated, the concentration of liver [[ S-adenosylmethionine ]] was decreased (24%, p<0.001) and S-adenosylhomocysteine increased (113%, p<0.001) in the dwarf mice.", "label": "SUBSTRATE", "metadata": []}
{"text": "Activation of << alpha 2B-adrenoceptors >> mediates the cardiovascular effects of [[ etomidate ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]].", "label": "AGONIST", "metadata": []}
{"text": "METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, << dexmedetomidine >>, were determined in mice deficient in [[ alpha2-receptor ]] subtypes.", "label": "AGONIST", "metadata": []}
{"text": "Inhibition of binding of the << alpha2-receptor >> antagonist [[ [3H]RX821002 ]] to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro.", "label": "ANTAGONIST", "metadata": []}
{"text": "Inhibition of binding of the alpha2-receptor antagonist << [3H]RX821002 >> to recombinant [[ alpha2-receptors ]] by etomidate was tested in human embryonic kidney (HEK293) cells in vitro.", "label": "ANTAGONIST", "metadata": []}
{"text": "In membranes from HEK293 cells transfected with << alpha2-receptors >>, etomidate inhibited binding of the alpha2-antagonist, [[ [3H]RX821002 ]], with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm).", "label": "ANTAGONIST", "metadata": []}
{"text": "In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, << [3H]RX821002 >>, with higher potency from alpha2B- and alpha2C-receptors than from [[ alpha2A-receptors ]] (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm).", "label": "ANTAGONIST", "metadata": []}
{"text": "In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the [[ extracellular signal-related kinases ]] ERK1/2.", "label": "ACTIVATOR", "metadata": []}
{"text": "In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the extracellular signal-related kinases [[ ERK1/2 ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "CONCLUSIONS: These results indicate that << etomidate >> acts as an agonist at [[ alpha2-adrenoceptors ]], which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure.", "label": "AGONIST", "metadata": []}
{"text": "Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to << SiO(2) >> NPs, the messenger RNA level of apoptotic genes ([[ caspase-3 ]] and caspase-9) were upregulated in a dose-dependent manner.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to << SiO(2) >> NPs, the messenger RNA level of apoptotic genes (caspase-3 and [[ caspase-9 ]]) were upregulated in a dose-dependent manner.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, activities of << caspase-3 >> and caspase-9 enzymes were also significantly higher in both kinds of cells exposed to [[ SiO(2) ]] NPs.", "label": "ACTIVATOR", "metadata": []}
{"text": "Moreover, activities of caspase-3 and << caspase-9 >> enzymes were also significantly higher in both kinds of cells exposed to [[ SiO(2) ]] NPs.", "label": "ACTIVATOR", "metadata": []}
{"text": "The << CYP2B6*6 >> Allele Significantly Alters the N-demethylation of [[ Ketamine ]] Enantiomers In Vitro.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Ketamine >> is primarily metabolized to norketamine by hepatic [[ cytochrome P450 (CYP) 2B6 ]] and CYP3A4-mediated N-demethylation.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Ketamine >> is primarily metabolized to norketamine by hepatic cytochrome P450 (CYP) 2B6 and [[ CYP3A4 ]]-mediated N-demethylation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << CYP2B6*6 >> allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in [[ ketamine ]] metabolism.", "label": "SUBSTRATE", "metadata": []}
{"text": "We examined the N-demethylation of individual << ketamine >> enantiomers using human liver microsomes (HLMs) genotyped for the [[ CYP2B6*6 ]] allele, insect cell expressed recombinant CYP2B6 and CYP3A4 enzymes and COS-1 cell expressed recombinant CYP2B6.1 and CYP2B6.6 protein variant.", "label": "SUBSTRATE", "metadata": []}
{"text": "The intrinsic clearance for both << ketamine >> enantiomers by the high affinity enzyme in HLMs with [[ CYP2B6*1 ]]/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< ThioTEPA >> ([[ CYP2B6 ]] inhibitor, 25 μM) and the monoclonal antibody against CYP2B6 but not troleandomycin (CYP3A4 inhibitor, 25 μM) or the monoclonal antibody against CYP3A4 inhibited ketamine N-demethylation at clinically relevant concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "ThioTEPA (CYP2B6 inhibitor, 25 μM) and the monoclonal antibody against CYP2B6 but not << troleandomycin >> ([[ CYP3A4 ]] inhibitor, 25 μM) or the monoclonal antibody against CYP3A4 inhibited ketamine N-demethylation at clinically relevant concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "These results indicate a major role of << CYP2B6 >> in [[ ketamine ]] N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity.", "label": "SUBSTRATE", "metadata": []}
{"text": "These results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the << CYP2B6*6 >> allele on enzyme-[[ ketamine ]] binding and catalytic activity.", "label": "SUBSTRATE", "metadata": []}
{"text": "PURPOSE: Testosterone-to-estradiol ratio levels in infertile men improve during treatment with the << aromatase >> inhibitor, [[ testolactone ]], and resulting changes in semen parameters.", "label": "INHIBITOR", "metadata": []}
{"text": "We evaluated the effect of << anastrozole >>, a more selective [[ aromatase ]] inhibitor, on the hormonal and semen profiles of infertile men with abnormal baseline testosterone-to-estradiol ratios.", "label": "INHIBITOR", "metadata": []}
{"text": "The results show that CYP2E1 inhibits << CYP2B4 >>-mediated metabolism of [[ benzphetamine ]] (BNZ) with a K(i) of 0.04 µM.", "label": "SUBSTRATE", "metadata": []}
{"text": "The results show that CYP2E1 inhibits << CYP2B4 >>-mediated metabolism of benzphetamine ([[ BNZ ]]) with a K(i) of 0.04 µM.", "label": "SUBSTRATE", "metadata": []}
{"text": "However, CYP2B4 is not an inhibitor of << CYP2E1 >>-mediated [[ p-nitrophenol ]] hydroxylation.", "label": "SUBSTRATE", "metadata": []}
{"text": "To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of << phenylalkylphosphonamidate >> derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against [[ PSMA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of << glutamic acid >> were synthesized and evaluated for their inhibitory potencies against [[ PSMA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In PFC, << DEX >> caused activation of [[ AKT ]], augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria.", "label": "ACTIVATOR", "metadata": []}
{"text": "In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival [[ Bcl-2 ]] protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced [[ Bcl-2 ]]/Bax protein ratio, as well Bcl-2 translocation to mitochondria.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/[[ Bax ]] protein ratio, as well Bcl-2 translocation to mitochondria.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Results of RT-PCR analysis showed decrease of << p53 >> mRNA level and no significant difference in Bcl-2 and Bax mRNA expressions in [[ DEX ]]-treated rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Antitumor activity of << sorafenib >> in [[ FLT3 ]]-driven leukemic cells.", "label": "INHIBITOR", "metadata": []}
{"text": "We show that << sorafenib >> (BAY 43-9006, Nexavar) potently inhibits [[ FLT3 ]] enzymatic and signaling activities.", "label": "INHIBITOR", "metadata": []}
{"text": "We show that sorafenib (<< BAY 43-9006 >>, Nexavar) potently inhibits [[ FLT3 ]] enzymatic and signaling activities.", "label": "INHIBITOR", "metadata": []}
{"text": "We show that sorafenib (BAY 43-9006, << Nexavar >>) potently inhibits [[ FLT3 ]] enzymatic and signaling activities.", "label": "INHIBITOR", "metadata": []}
{"text": "In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, << sorafenib >> blocked basal and ligand dependent [[ FLT3 ]]-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and Stat5 phosphorylation.", "label": "INHIBITOR", "metadata": []}
{"text": "In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, << sorafenib >> blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as [[ extracellular signal-regulated kinase1/2 ]] and Stat5 phosphorylation.", "label": "INHIBITOR", "metadata": []}
{"text": "In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, << sorafenib >> blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and [[ Stat5 ]] phosphorylation.", "label": "INHIBITOR", "metadata": []}
{"text": "In leukemia cell lines MV4-11 and EOL-1, << sorafenib >> treatment resulted in decreased cell proliferation and inhibition of [[ FLT3 ]] signaling.", "label": "INHIBITOR", "metadata": []}
{"text": "The growth of the << FLT3 >>-independent RS4-11 cell line was only weakly inhibited by [[ sorafenib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The demonstration that << sorafenib >> exhibits potent target inhibition and efficacy in [[ FLT3 ]]-driven models suggests that this compound may have a therapeutic benefit for patients with FLT3-driven leukemias.", "label": "INHIBITOR", "metadata": []}
{"text": "The demonstration that << sorafenib >> exhibits potent target inhibition and efficacy in FLT3-driven models suggests that this compound may have a therapeutic benefit for patients with [[ FLT3 ]]-driven leukemias.", "label": "INHIBITOR", "metadata": []}
{"text": "<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of [[ Bax ]]/Bcl-2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/[[ Bcl-2 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< DBDCT >> up-regulated the expression of [[ Bax ]], down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/Bcl-2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of [[ Bcl-2 ]], and significantly increased the ratio of Bax/Bcl-2.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< DBDCT >> also caused the phosphorylation of [[ JNK ]] and p38(MAPK).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< DBDCT >> also caused the phosphorylation of JNK and [[ p38 ]](MAPK).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< DBDCT >> also caused the phosphorylation of JNK and p38([[ MAPK ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "Structure-based design of << aliskiren >>, a novel orally effective [[ renin ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "This led to the discovery of << aliskiren >>, a highly potent and selective inhibitor of [[ human renin ]] in vitro, and in vivo; once-daily oral doses of aliskiren inhibit renin and lower blood pressure in sodium-depleted marmosets and hypertensive human patients.", "label": "INHIBITOR", "metadata": []}
{"text": "This led to the discovery of aliskiren, a highly potent and selective inhibitor of human renin in vitro, and in vivo; once-daily oral doses of << aliskiren >> inhibit [[ renin ]] and lower blood pressure in sodium-depleted marmosets and hypertensive human patients.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Aliskiren >> represents the first in a novel class of [[ renin ]] inhibitors with the potential for treatment of hypertension and related cardiovascular diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Everolimus >> (RAD001, Afinitor((R)) Novartis) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Everolimus >> (RAD001, Afinitor((R)) Novartis) is the first oral inhibitor of mTOR ([[ mammalian target of rapamycin ]]) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "Everolimus (<< RAD001 >>, Afinitor((R)) Novartis) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "Everolimus (<< RAD001 >>, Afinitor((R)) Novartis) is the first oral inhibitor of mTOR ([[ mammalian target of rapamycin ]]) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "Everolimus (RAD001, << Afinitor((R)) Novartis >>) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "Everolimus (RAD001, << Afinitor((R)) Novartis >>) is the first oral inhibitor of mTOR ([[ mammalian target of rapamycin ]]) to reach the oncology clinic.", "label": "INHIBITOR", "metadata": []}
{"text": "A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the << VEGFR >> tyrosine kinase inhibitors sunitinib and/or [[ sorafenib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR << tyrosine kinase >> inhibitors sunitinib and/or [[ sorafenib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the << VEGFR >> tyrosine kinase inhibitors [[ sunitinib ]] and/or sorafenib.", "label": "INHIBITOR", "metadata": []}
{"text": "A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR << tyrosine kinase >> inhibitors [[ sunitinib ]] and/or sorafenib.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and structure-activity relationship of << pyripyropene A >> derivatives as potent and selective [[ acyl-CoA:cholesterol acyltransferase 2 ]] (ACAT2) inhibitors: Part 2.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and structure-activity relationship of << pyripyropene A >> derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 ([[ ACAT2 ]]) inhibitors: Part 2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Adrenaline >> inhibits [[ insulin ]] secretion via pertussis toxin-sensitive mechanisms.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Somatostatin >> which also inhibits [[ insulin ]] secretion was less efficient (inhibition by 20%).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In contrast to << adrenaline >> and somatostatin, galanin, another inhibitor of [[ insulin ]] secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In contrast to adrenaline and << somatostatin >>, galanin, another inhibitor of [[ insulin ]] secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These G-proteins are likely to be involved in the adrenaline-induced inhibition of dihydropyridine-sensitive Ca2+ currents and in other signal transduction pathways contributing to the << adrenaline >>-induced inhibition of [[ insulin ]] secretion.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/[[ GluN2B ]] N-Methyl-D-aspartate Receptor Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as GluN1/[[ GluN2B ]] N-Methyl-D-aspartate Receptor Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Ifenprodil >>, known as the [[ GluNR2B ]] antagonist of reference, was chosen as the template for the elaboration of probes.", "label": "ANTAGONIST", "metadata": []}
{"text": "Molecular determinants for the selective inhibition of << cyclooxygenase-2 >> by [[ lumiracoxib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Lumiracoxib is the first example of a marketed << COX-2 >> inhibitor of the [[ arylacetic acid ]] class, and it is reported to be the most selective COXIB in vivo.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Lumiracoxib >> is the first example of a marketed [[ COX-2 ]] inhibitor of the arylacetic acid class, and it is reported to be the most selective COXIB in vivo.", "label": "INHIBITOR", "metadata": []}
{"text": "Using standard assays, << lumiracoxib >> was found to be a poor inhibitor of purified [[ ovine COX-1 ]] and a relatively weak inhibitor of purified human COX-2.", "label": "INHIBITOR", "metadata": []}
{"text": "Using standard assays, << lumiracoxib >> was found to be a poor inhibitor of purified ovine COX-1 and a relatively weak inhibitor of purified [[ human COX-2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Kinetic studies with << lumiracoxib >> demonstrated that it was a time-dependent and slowly reversible inhibitor of [[ human COX-2 ]] that exhibited at least two binding steps during inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition studies demonstrated that the << methyl >> group on the phenylacetic acid ring is required for [[ COX-2 ]] selectivity.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition studies demonstrated that the methyl group on the << phenylacetic acid >> ring is required for [[ COX-2 ]] selectivity.", "label": "INHIBITOR", "metadata": []}
{"text": "The chemical identity and position of the substituents on the lower << aniline >> ring were important in determining the potency and extent of [[ COX ]] inhibition as well as COX-2 selectivity.", "label": "INHIBITOR", "metadata": []}
{"text": "Mutation of Ser-530 to Ala or Val-349 to Ala or Leu abolished the potent inhibition observed with wild-type << human COX-2 >> and key [[ lumiracoxib ]] analogs.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a << Val-349 to Ile >> mutant was inhibited with equal potency to human COX-2 with [[ 2,6-dichloro ]]-, 2,6-dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a Val-349 to Ile mutant was inhibited with equal potency to << human COX-2 >> with [[ 2,6-dichloro ]]-, 2,6-dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a << Val-349 to Ile >> mutant was inhibited with equal potency to human COX-2 with 2,6-dichloro-, [[ 2,6-dimethyl ]]-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a Val-349 to Ile mutant was inhibited with equal potency to << human COX-2 >> with 2,6-dichloro-, [[ 2,6-dimethyl ]]-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a << Val-349 to Ile >> mutant was inhibited with equal potency to human COX-2 with 2,6-dichloro-, 2,6-dimethyl-, or [[ 2-chloro-6-methyl ]]-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a Val-349 to Ile mutant was inhibited with equal potency to << human COX-2 >> with 2,6-dichloro-, 2,6-dimethyl-, or [[ 2-chloro-6-methyl ]]-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a << Val-349 to Ile >> mutant was inhibited with equal potency to human COX-2 with 2,6-dichloro-, 2,6-dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of [[ lumiracoxib ]], actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, a Val-349 to Ile mutant was inhibited with equal potency to << human COX-2 >> with 2,6-dichloro-, 2,6-dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of [[ lumiracoxib ]], actually showed an increase in potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together with a recent crystal structure of a lumiracoxib-COX-2 complex, the kinetic analyses presented herein of the inhibition of mutant << COX-2s >> by [[ lumiracoxib ]] allows the definition of the molecular basis of COX-2 inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on << VMAT2 >> activity by measuring adenosine triphosphate-dependent [[ [(3)H]dopamine ]] uptake into synaptic vesicles prepared from rat striatum.", "label": "SUBSTRATE", "metadata": []}
{"text": "Moreover, kinetic analysis revealed that inhibition by << reserpine >>, a typical [[ VMAT2 ]] inhibitor, was uncompetitive, decreasing maximum velocity and affinity for dopamine.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, kinetic analysis revealed that inhibition by reserpine, a typical << VMAT2 >> inhibitor, was uncompetitive, decreasing maximum velocity and affinity for [[ dopamine ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "These results suggest that fluoxetine inhibited the activity of << VMAT2 >> by a mechanism different from that of [[ reserpine ]] and did not directly interact with the active site of VMAT2.", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << fluoxetine >> inhibited the activity of VMAT2 by a mechanism different from that of reserpine and did not directly interact with the active site of [[ VMAT2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "These results suggest that << fluoxetine >> inhibited the activity of [[ VMAT2 ]] by a mechanism different from that of reserpine and did not directly interact with the active site of VMAT2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Betaxolol >>, a [[ beta(1)-adrenoceptor ]] antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other beta-adrenoceptor antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Betaxolol >>, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other [[ beta-adrenoceptor ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Betaxolol >>, a [[ beta(1)-adrenoceptor ]] antagonist used for the treatment of glaucoma, is known to be neuroprotective in paradigms of ischaemia/excitotoxicity.", "label": "ANTAGONIST", "metadata": []}
{"text": "In this study, we examined whether << betaxolol >> and other [[ beta-adrenoceptor ]] antagonists interact directly with neurotoxin binding to sites 1 and 2 of the voltage-sensitive sodium channel (Na(+) channel) in rat cerebrocortical synaptosomes.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of [[ propranolol ]]>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>[[ betaxolol ]] approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately [[ levobetaxolol ]]>levobunolol approximately carteolol>/=timolol>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>[[ levobunolol ]] approximately carteolol>/=timolol>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately [[ carteolol ]]>/=timolol>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=[[ timolol ]]>atenolol.", "label": "ANTAGONIST", "metadata": []}
{"text": "Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>[[ atenolol ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Leukotriene D4 >> induces cognitive impairment through enhancement of [[ CysLT₁ R ]]-mediated amyloid-β generation in mice.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Leukotriene D4 >> induces cognitive impairment through enhancement of CysLT₁ R-mediated [[ amyloid-β ]] generation in mice.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of [[ Aβ1-40 ]] and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and [[ Aβ1-42 ]] in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of [[ amyloid precursor protein ]] (APP).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein ([[ APP ]]).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< LTD4 >> also induced expression of [[ cysteinyl leukotriene receptor 1 ]] (CysLT(1)R) and NF-κB p65 in the hippocampus and cortex.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 ([[ CysLT(1)R ]]) and NF-κB p65 in the hippocampus and cortex.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 (CysLT(1)R) and [[ NF-κB ]] p65 in the hippocampus and cortex.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 (CysLT(1)R) and NF-κB [[ p65 ]] in the hippocampus and cortex.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Pretreatment with << pranlukast >> (1.5 ng/mouse, intracerebroventricularly), a [[ CysLT(1)R ]] antagonist, blocked LTD4-induced amyloidogenesis, memory deficits.", "label": "ANTAGONIST", "metadata": []}
{"text": "Moreover, << LTD4 >>-induced increases in [[ CysLT(1)R ]] and NF-κB p65 in the brain were also attenuated by pranlukast.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, << LTD4 >>-induced increases in CysLT(1)R and [[ NF-κB ]] p65 in the brain were also attenuated by pranlukast.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, << LTD4 >>-induced increases in CysLT(1)R and NF-κB [[ p65 ]] in the brain were also attenuated by pranlukast.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, LTD4-induced increases in << CysLT(1)R >> and NF-κB p65 in the brain were also attenuated by [[ pranlukast ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, LTD4-induced increases in CysLT(1)R and << NF-κB >> p65 in the brain were also attenuated by [[ pranlukast ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, LTD4-induced increases in CysLT(1)R and NF-κB << p65 >> in the brain were also attenuated by [[ pranlukast ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results suggest that << LTD4 >> increases Aβ peptide burden via activation of [[ CysLT(1)R ]], which further affects APP levels and activity of β- and γ-secretases via the NF-κB pathway.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results suggest that << LTD4 >> increases [[ Aβ peptide ]] burden via activation of CysLT(1)R, which further affects APP levels and activity of β- and γ-secretases via the NF-κB pathway.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Statins >> increase [[ p21 ]] through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Statins >> increase p21 through inhibition of [[ histone deacetylase ]] activity and release of promoter-associated HDAC1/2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Statins >> are [[ 3-hydroxy-3-methylglutaryl-CoA reductase ]] inhibitors broadly used for the control of hypercholesterolemia.", "label": "INHIBITOR", "metadata": []}
{"text": "In the subsequent enzymatic assay, it was shown that << lovastatin >> inhibited [[ HDAC2 ]] activity competitively with a K(i) value of 31.6 micromol/L.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular [[ tyrosine kinase ]] BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase [[ BCR ]]-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-[[ ABL ]] and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the [[ platelet derived growth factor (PDGF) receptor ]], is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the [[ macrophage colony stimulating factor (M-CSF) receptor ]], c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, [[ c-FMS ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Recent studies have reported that << imatinib mesylate >>, a [[ kinase ]] inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Given that << M-CSF >> signalling through c-FMS plays an important role in osteoclast biology, we speculated that blocking such a pathway with [[ imatinib ]] may modulate osteoclast activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Given that M-CSF signalling through << c-FMS >> plays an important role in osteoclast biology, we speculated that blocking such a pathway with [[ imatinib ]] may modulate osteoclast activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Imatinib was also found to inhibit M-CSF-induced osteoclast survival as well as M-CSF-induced osteoclast bone resorbing activity, but was without effect on interleukin 1alpha (IL-1alpha) and receptor activator of nuclear factor kappa B ligand (RANKL)-induced inhibition of osteoclasts apoptosis, further supporting the hypothesis that << imatinib >> may affect mature osteoclasts through the inhibition of [[ c-FMS ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Imatinib >> was also found to inhibit [[ M-CSF ]]-induced osteoclast survival as well as M-CSF-induced osteoclast bone resorbing activity, but was without effect on interleukin 1alpha (IL-1alpha) and receptor activator of nuclear factor kappa B ligand (RANKL)-induced inhibition of osteoclasts apoptosis, further supporting the hypothesis that imatinib may affect mature osteoclasts through the inhibition of c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Imatinib >> was also found to inhibit M-CSF-induced osteoclast survival as well as [[ M-CSF ]]-induced osteoclast bone resorbing activity, but was without effect on interleukin 1alpha (IL-1alpha) and receptor activator of nuclear factor kappa B ligand (RANKL)-induced inhibition of osteoclasts apoptosis, further supporting the hypothesis that imatinib may affect mature osteoclasts through the inhibition of c-FMS.", "label": "INHIBITOR", "metadata": []}
{"text": "Structural basis for << LFA-1 >> inhibition upon [[ lovastatin ]] binding to the CD11a I-domain.", "label": "INHIBITOR", "metadata": []}
{"text": "We report here that << lovastatin >>, a drug clinically used for lowering cholesterol levels, inhibits the interaction of [[ human LFA-1 ]] with its counter-receptor intercellular adhesion molecule-1.", "label": "INHIBITOR", "metadata": []}
{"text": "We report here that << lovastatin >>, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor [[ intercellular adhesion molecule-1 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Particularly, the effects of << doxycycline >> used as a non selective [[ MMP ]] inhibitor in experimental and clinical studies will be discussed.", "label": "INHIBITOR", "metadata": []}
{"text": "Time-dependent changes in hepatic and intestinal induction of << cytochrome P450 3A >> after administration of [[ dexamethasone ]] to rats.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using << dexamethasone 21-phosphate >> (DEX-P) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (<< DEX-P >>) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (<< MDZ >>) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using << dexamethasone 21-phosphate >> (DEX-P) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (<< DEX-P >>) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and [[ midazolam ]] (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate (DEX-P) and [[ midazolam ]] (MDZ) as an inducer and a substrate to CYP3A, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam ([[ MDZ ]]) as an inducer and a substrate to CYP3A, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (<< MDZ >>) as an inducer and a substrate to [[ CYP3A ]], respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "3. << CYP3A >> induction in the liver increased depending on the dose of [[ DEX-P ]], whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of DEX-P.", "label": "ACTIVATOR", "metadata": []}
{"text": "3. << CYP3A >> induction in the liver increased depending on the dose of DEX-P, whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of [[ DEX-P ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "4. Administration of a single dose of << DEX-P >> showed a temporal increase in [[ CYP3A ]] activity in both tissues and the induction ratios reached maximum values at 12 h after DEX-P administration.", "label": "ACTIVATOR", "metadata": []}
{"text": "4. Administration of a single dose of DEX-P showed a temporal increase in << CYP3A >> activity in both tissues and the induction ratios reached maximum values at 12 h after [[ DEX-P ]] administration.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< LDH >> is responsible for pyruvate conversion to [[ lactate ]] through glycolysis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< LDH >> is responsible for [[ pyruvate ]] conversion to lactate through glycolysis.", "label": "SUBSTRATE", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of << dasatinib >> (BMS-354825): a potent oral multi-targeted [[ kinase ]] inhibitor against SRC and BCR-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of << dasatinib >> (BMS-354825): a potent oral multi-targeted kinase inhibitor against [[ SRC ]] and BCR-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of << dasatinib >> (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of << dasatinib >> (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-[[ ABL ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted [[ kinase ]] inhibitor against SRC and BCR-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted kinase inhibitor against [[ SRC ]] and BCR-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL.", "label": "INHIBITOR", "metadata": []}
{"text": "Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted kinase inhibitor against SRC and BCR-[[ ABL ]].", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: << Dasatinib >> (BMS-354825), a potent oral multi-targeted [[ kinase ]] inhibitor against SRC and BCR-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: << Dasatinib >> (BMS-354825), a potent oral multi-targeted kinase inhibitor against [[ SRC ]] and BCR-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: << Dasatinib >> (BMS-354825), a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: << Dasatinib >> (BMS-354825), a potent oral multi-targeted kinase inhibitor against SRC and BCR-[[ ABL ]], has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: Dasatinib (<< BMS-354825 >>), a potent oral multi-targeted [[ kinase ]] inhibitor against SRC and BCR-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: Dasatinib (<< BMS-354825 >>), a potent oral multi-targeted kinase inhibitor against [[ SRC ]] and BCR-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: Dasatinib (<< BMS-354825 >>), a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: Dasatinib (<< BMS-354825 >>), a potent oral multi-targeted kinase inhibitor against SRC and BCR-[[ ABL ]], has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance.", "label": "INHIBITOR", "metadata": []}
{"text": "The results of this study suggest that << noradrenaline >> predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an [[ alphalD-adrenoceptor ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "An increase in the << ADP >>/ATP ratio opens [[ K(ATP) channels ]], leading to membrane hyperpolarization.", "label": "ACTIVATOR", "metadata": []}
{"text": "An increase in the ADP/<< ATP >> ratio opens [[ K(ATP) channels ]], leading to membrane hyperpolarization.", "label": "ACTIVATOR", "metadata": []}
{"text": "Comparison of the effect of << rofecoxib >> (a [[ cyclooxygenase 2 ]] inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVE: This randomized, double-blind study tested the hypothesis that << rofecoxib >>, a drug that specifically inhibits [[ cyclooxygenase 2 ]], would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design).", "label": "INHIBITOR", "metadata": []}
{"text": "<< [-]-Huperzine A >> ([-]-Hup A), is a naturally occurring potent reversible [[ AChE ]] inhibitor that penetrates the blood-brain barrier.", "label": "INHIBITOR", "metadata": []}
{"text": "[-]-Huperzine A (<< [-]-Hup A >>), is a naturally occurring potent reversible [[ AChE ]] inhibitor that penetrates the blood-brain barrier.", "label": "INHIBITOR", "metadata": []}
{"text": "The synthetic stereoisomer, << [+]-Hup A >>, is less toxic due to poor [[ AChE ]] inhibition and is suitable for both pre-/post-exposure treatments of nerve agent toxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of [[ Ras homologous protein A ]], the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of [[ apoptosis signal-regulating kinase 1 ]], c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, [[ c-jun-N-terminal kinase ]], p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, [[ p38 ]], inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, [[ inhibitor of kappaBα ]] (IκBα) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα ([[ IκBα ]]) kinase, and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) [[ kinase ]], and inositol requiring enzyme 1α.", "label": "ACTIVATOR", "metadata": []}
{"text": "Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and [[ inositol requiring enzyme 1α ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor [[ NF-κB ]], HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, [[ HSF1 ]], AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, [[ AP-1 ]], and ATF-2, together with the expression of HSP70 and Bax proteins.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and [[ ATF-2 ]], together with the expression of HSP70 and Bax proteins.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of [[ HSP70 ]] and Bax proteins.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both << cAMP >> and cGMP ([[ PDE10A ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Cloning and characterization of a novel << human phosphodiesterase >> that hydrolyzes both [[ cAMP ]] and cGMP (PDE10A).", "label": "SUBSTRATE", "metadata": []}
{"text": "Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and << cGMP >> ([[ PDE10A ]]).", "label": "SUBSTRATE", "metadata": []}
{"text": "Cloning and characterization of a novel << human phosphodiesterase >> that hydrolyzes both cAMP and [[ cGMP ]] (PDE10A).", "label": "SUBSTRATE", "metadata": []}
{"text": "Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed [[ cAMP ]] and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP.", "label": "SUBSTRATE", "metadata": []}
{"text": "Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and [[ cGMP ]] with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP.", "label": "SUBSTRATE", "metadata": []}
{"text": "Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with [[ cGMP ]] was almost twice that with cAMP.", "label": "SUBSTRATE", "metadata": []}
{"text": "Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with [[ cAMP ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Of the << PDE >> inhibitors tested, [[ dipyridamole ]] was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and cGMP hydrolysis, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "Of the << PDE >> inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of [[ cAMP ]] and cGMP hydrolysis, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "Of the << PDE >> inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and [[ cGMP ]] hydrolysis, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << cytosine >> analog 5-aza-2'-deoxycytidine (decitabine) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The cytosine analog << 5-aza-2'-deoxycytidine >> (decitabine) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The cytosine analog 5-aza-2'-deoxycytidine (<< decitabine >>) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "We examined if subcutaneous << decitabine >> could increase [[ HbF ]] levels and improve SSD pathophysiology without cytotoxicity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Weekly subcutaneous << decitabine >> produces cumulative increases in [[ HbF ]] and total hemoglobin through a noncytotoxic mechanism of action.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Weekly subcutaneous << decitabine >> produces cumulative increases in HbF and total [[ hemoglobin ]] through a noncytotoxic mechanism of action.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Nox4 >> oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "Nox4 << oxidase >> activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Nox4 >> oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Nox4 << oxidase >> activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 [[ quinone ]] derivatives (AA-861, tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines.", "label": "ACTIVATOR", "metadata": []}
{"text": "In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives ([[ AA-861 ]], tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines.", "label": "ACTIVATOR", "metadata": []}
{"text": "In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, [[ tBuBHQ ]], tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines.", "label": "ACTIVATOR", "metadata": []}
{"text": "In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, tBuBHQ, [[ tBuBQ ]], and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines.", "label": "ACTIVATOR", "metadata": []}
{"text": "In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, tBuBHQ, tBuBQ, and [[ duroquinone ]]) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines.", "label": "ACTIVATOR", "metadata": []}
{"text": "Such model of << Nox4 >> activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which [[ quinones ]] and Nox4 are implicated.", "label": "ACTIVATOR", "metadata": []}
{"text": "Although the inhibition of << cyclooxygenases >> by [[ aspirin ]], which leads to its anti-inflammatory/analgesic properties, has been well studied, the mechanisms involved in its chemopreventive effects as well as some of its adverse effects are as yet ill-defined.", "label": "INHIBITOR", "metadata": []}
{"text": "In a recent study using protein-specific anti-acetyl lysine antibodies and immunological methods, we demonstrated the ability of << aspirin >> to acetylate the [[ tumor suppressor protein p53 ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Second, << ICRF-187 >>, a [[ Top2 ]] catalytic inhibitor known to deplete Top2β, specifically sensitized MEFs to CPT.", "label": "INHIBITOR", "metadata": []}
{"text": "Second, << ICRF-187 >>, a Top2 catalytic inhibitor known to deplete [[ Top2β ]], specifically sensitized MEFs to CPT.", "label": "INHIBITOR", "metadata": []}
{"text": "To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon << CPT >> exposure, the [[ RNA polymerase II large subunit ]] (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas RNAP LS remained depleted without recovery in Top2β-deficient cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon << CPT >> exposure, the RNA polymerase II large subunit ([[ RNAP LS ]]) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas RNAP LS remained depleted without recovery in Top2β-deficient cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon << CPT >> exposure, the RNA polymerase II large subunit (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas [[ RNAP LS ]] remained depleted without recovery in Top2β-deficient cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and [[ p53 ]] accumulation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to [[ RNAP LS ]] depletion and p53 accumulation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Effects of << felodipine >> (a dihydropyridine [[ calcium channel ]] blocker) and analogues on calmodulin-dependent enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "Effects of felodipine (a << dihydropyridine >> [[ calcium channel ]] blocker) and analogues on calmodulin-dependent enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "We have examined the effects on the activities of three calmodulin-dependent enzymes (cAMP phosphodiesterase, caldesmon kinase and myosin light chain kinase) of the dihydropyridine << Ca2+ channel >> blocker [[ felodipine ]] and three analogues (p-chloro, oxidized and t-butyl) exhibiting different pharmacological potencies.", "label": "INHIBITOR", "metadata": []}
{"text": "The << cAMP phosphodiesterase >> was inhibited completely by [[ felodipine ]] and the p-chloro analogue with IC50 values of 3.7 and 1.5 microM respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "The << cAMP phosphodiesterase >> was inhibited completely by felodipine and the [[ p-chloro ]] analogue with IC50 values of 3.7 and 1.5 microM respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felodipine >> and the p-chloro analogue inhibited the basal (Ca2+/calmodulin-independent) activity of [[ cAMP phosphodiesterase ]] as well as the calmodulin-stimulated activity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felodipine >> and the p-chloro analogue inhibited the basal (Ca2+/calmodulin-independent) activity of cAMP phosphodiesterase as well as the [[ calmodulin ]]-stimulated activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and the << p-chloro >> analogue inhibited the basal (Ca2+/calmodulin-independent) activity of [[ cAMP phosphodiesterase ]] as well as the calmodulin-stimulated activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and the << p-chloro >> analogue inhibited the basal (Ca2+/calmodulin-independent) activity of cAMP phosphodiesterase as well as the [[ calmodulin ]]-stimulated activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Calmodulin was relatively ineffective in preventing inhibition of << cAMP phosphodiesterase >> by [[ felodipine ]] and the p-chloro analogue.", "label": "INHIBITOR", "metadata": []}
{"text": "Calmodulin was relatively ineffective in preventing inhibition of << cAMP phosphodiesterase >> by felodipine and the [[ p-chloro ]] analogue.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felodipine >> and the p-chloro analogue inhibited Ca2+/calmodulin-dependent [[ caldesmon kinase ]] with similar potencies (IC50 = 17.4 microM), whereas the oxidized and t-butyl analogues caused no inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and the << p-chloro >> analogue inhibited Ca2+/calmodulin-dependent [[ caldesmon kinase ]] with similar potencies (IC50 = 17.4 microM), whereas the oxidized and t-butyl analogues caused no inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, << felodipine >> and the p-chloro analogue inhibited [[ myosin light chain kinase ]] activity whether the isolated 20 kD light chain (IC50 = 12.6 microM) or intact myosin (IC50 = 11.0 microM) was used as substrate.", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, felodipine and the << p-chloro >> analogue inhibited [[ myosin light chain kinase ]] activity whether the isolated 20 kD light chain (IC50 = 12.6 microM) or intact myosin (IC50 = 11.0 microM) was used as substrate.", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and the << p-chloro >> analogue inhibited the actin-activated [[ Mg2+-ATPase ]] activity of smooth muscle myosin (IC50 = 25.1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Felodipine and the << p-chloro >> analogue inhibited the actin-activated Mg2+-ATPase activity of smooth muscle [[ myosin ]] (IC50 = 25.1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felodipine >> and the p-chloro analogue inhibited the actin-activated [[ Mg2+-ATPase ]] activity of smooth muscle myosin (IC50 = 25.1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Felodipine >> and the p-chloro analogue inhibited the actin-activated Mg2+-ATPase activity of smooth muscle [[ myosin ]] (IC50 = 25.1 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, << felodipine >> and the p-chloro analogue blocked [[ myosin ]] filament assembly induced by low concentrations of calmodulin, whereas the oxidized and t-butyl analogues did not.", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, felodipine and the << p-chloro >> analogue blocked [[ myosin ]] filament assembly induced by low concentrations of calmodulin, whereas the oxidized and t-butyl analogues did not.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated << myosin >> Mg2+-ATPase and myosin filament assembly by [[ felodipine ]] and the p-chloro analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated myosin << Mg2+-ATPase >> and myosin filament assembly by [[ felodipine ]] and the p-chloro analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated myosin Mg2+-ATPase and << myosin >> filament assembly by [[ felodipine ]] and the p-chloro analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated << myosin >> Mg2+-ATPase and myosin filament assembly by felodipine and the [[ p-chloro ]] analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated myosin << Mg2+-ATPase >> and myosin filament assembly by felodipine and the [[ p-chloro ]] analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "Again, inhibition of the actin-activated myosin Mg2+-ATPase and << myosin >> filament assembly by felodipine and the [[ p-chloro ]] analogue could be reversed by raising the calmodulin concentration.", "label": "INHIBITOR", "metadata": []}
{"text": "These observations suggest that some of the pharmacological actions of << felodipine >> on smooth muscle may involve inhibition of [[ calmodulin-dependent enzymes ]] which are functionally involved in the regulation of smooth muscle contraction.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Aldosterone >>-induced [[ ENaC ]] and basal Na(+)/K(+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Aldosterone >>-induced ENaC and basal [[ Na(+)/K(+)-ATPase ]] trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Aldosterone >> also induces the rapid phosphorylation of [[ Protein Kinase D1 ]] (PKD1).", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Aldosterone >> also induces the rapid phosphorylation of Protein Kinase D1 ([[ PKD1 ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "This effect has been attributed to the antagonist effects of << pindolol >> at the [[ 5-HT(1A) ]] receptor.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the present study, we compared the pharmacology of << (+/-)pindolol >>, WAY-100635 (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the present study, we compared the pharmacology of (+/-)pindolol, << WAY-100635 >> (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and << isamoltane >> (a [[ 5-HT(1B) ]] antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat.", "label": "ANTAGONIST", "metadata": []}
{"text": "In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that << (+/-)pindolol >> produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic [[ 5-HT(1A) ]] receptor.", "label": "ANTAGONIST", "metadata": []}
{"text": "In the local presence into the LC of the << α2-adrenoceptor >> antagonist [[ RS79948 ]] (1 μM), systemic citalopram increased NA in the LC (Emax = 157 ± 25 %) and PFC (Emax = 175 ± 24 %).", "label": "ANTAGONIST", "metadata": []}
{"text": "Local LC citalopram effect was abolished by LC presence of the << 5-HT3 >> receptor antagonist [[ MDL72222 ]] (1 μM) but not the 5-HT1/2 receptor antagonist methiothepin (1 μM).", "label": "ANTAGONIST", "metadata": []}
{"text": "Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM).", "label": "ANTAGONIST", "metadata": []}
{"text": "alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach.", "label": "AGONIST", "metadata": []}
{"text": "Noradrenaline and << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively.", "label": "AGONIST", "metadata": []}
{"text": "<< Noradrenaline >> and phenylephrine ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively.", "label": "AGONIST", "metadata": []}
{"text": "Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "AGONIST", "metadata": []}
{"text": "Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective << alpha(1A)-adrenoceptor >> antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "AGONIST", "metadata": []}
{"text": "Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective << alpha(1D)-adrenoceptor >> antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "AGONIST", "metadata": []}
{"text": "<< Prazosin >> (nonselective [[ alpha(1)-adrenoceptor ]] antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "Prazosin (nonselective alpha(1)-adrenoceptor antagonist), << silodosin >> (selective [[ alpha(1A)-adrenoceptor ]] antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and << BMY-7378 >> (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective [[ alpha(1D)-adrenoceptor ]] antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (<< 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride >>) (selective [[ alpha(1D)-adrenoceptor ]] antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).", "label": "ANTAGONIST", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including << barbiturates >>, ethanol, and neurosteroids, can also inhibit [[ L-type voltage-gated calcium channels ]] (L-VGCCs), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including << barbiturates >>, ethanol, and neurosteroids, can also inhibit L-type voltage-gated calcium channels ([[ L-VGCCs ]]), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including barbiturates, << ethanol >>, and neurosteroids, can also inhibit [[ L-type voltage-gated calcium channels ]] (L-VGCCs), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including barbiturates, << ethanol >>, and neurosteroids, can also inhibit L-type voltage-gated calcium channels ([[ L-VGCCs ]]), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including barbiturates, ethanol, and << neurosteroids >>, can also inhibit [[ L-type voltage-gated calcium channels ]] (L-VGCCs), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "BDZs and other positive GABA(A)R modulators, including barbiturates, ethanol, and << neurosteroids >>, can also inhibit L-type voltage-gated calcium channels ([[ L-VGCCs ]]), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< BDZs >> and other positive GABA(A)R modulators, including barbiturates, ethanol, and neurosteroids, can also inhibit [[ L-type voltage-gated calcium channels ]] (L-VGCCs), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< BDZs >> and other positive GABA(A)R modulators, including barbiturates, ethanol, and neurosteroids, can also inhibit L-type voltage-gated calcium channels ([[ L-VGCCs ]]), which could contribute to reduced neuronal excitability.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Ca(v)1.3 >> channels were less sensitive to [[ pentobarbital ]] inhibition than Ca(v)1.2 channels, similar to dihydropyridine (DHP) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "Ca(v)1.3 channels were less sensitive to << pentobarbital >> inhibition than [[ Ca(v)1.2 ]] channels, similar to dihydropyridine (DHP) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Ca(v)1.3 >> channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to [[ dihydropyridine ]] (DHP) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than << Ca(v)1.2 >> channels, similar to [[ dihydropyridine ]] (DHP) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Ca(v)1.3 >> channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine ([[ DHP ]]) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than << Ca(v)1.2 >> channels, similar to dihydropyridine ([[ DHP ]]) L-VGCC antagonists.", "label": "INHIBITOR", "metadata": []}
{"text": "Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to << dihydropyridine >> (DHP) [[ L-VGCC ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine (<< DHP >>) [[ L-VGCC ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "All GABA(A)R modulators induced a negative shift in the steady-state inactivation curve of Ca(v)1.3 channels, but only << BDZs >> and pentobarbital induced a negative shift in [[ Ca(v)1.2 ]] channel inactivation.", "label": "INHIBITOR", "metadata": []}
{"text": "All GABA(A)R modulators induced a negative shift in the steady-state inactivation curve of Ca(v)1.3 channels, but only BDZs and << pentobarbital >> induced a negative shift in [[ Ca(v)1.2 ]] channel inactivation.", "label": "INHIBITOR", "metadata": []}
{"text": "Despite the structural similarity between benzothiazepines and BDZs, mutation of an amino acid important for diltiazem potency (<< I1150A >>) did not affect [[ diazepam ]] potency.", "label": "INHIBITOR", "metadata": []}
{"text": "Although << L-VGCC >> inhibition by [[ BDZs ]] occurred at concentrations that are possibly too high to be clinically relevant and is not likely to play a role in the up-regulation of L-VGCCs during long-term treatment, pentobarbital and ethanol inhibited L-VGCCs at clinically relevant concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "Although L-VGCC inhibition by BDZs occurred at concentrations that are possibly too high to be clinically relevant and is not likely to play a role in the up-regulation of L-VGCCs during long-term treatment, << pentobarbital >> and ethanol inhibited [[ L-VGCCs ]] at clinically relevant concentrations.", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent [[ heme oxygenase-1 ]] induction.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via [[ NF-κB ]] suppression and Nrf-2-dependent heme oxygenase-1 induction.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we found that << 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of [[ inducible NO synthase ]] (iNOS) in BV2 microglia.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In this study, we found that << 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase ([[ iNOS ]]) in BV2 microglia.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (<< 5HHMF >>) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of [[ inducible NO synthase ]] (iNOS) in BV2 microglia.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (<< 5HHMF >>) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase ([[ iNOS ]]) in BV2 microglia.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of [[ nuclear factor-κB ]] (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB ([[ NF-κB ]]) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely [[ p65 ]] and p50, which are important molecules involved in the regulation of iNOS expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and [[ p50 ]], which are important molecules involved in the regulation of iNOS expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << 5HHMF >> blocked LPS-induced phosphorylation of [[ IκB ]], resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pyrrolidine dithiocarbamate >> (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced [[ iNOS ]] expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pyrrolidine dithiocarbamate (<< PDTC >>), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced [[ iNOS ]] expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that << 5HHMF >> downregulated [[ iNOS ]] expression by suppressing NF-κB activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pyrrolidine dithiocarbamate >> (PDTC), a specific [[ NF-κB ]] inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Pyrrolidine dithiocarbamate (<< PDTC >>), a specific [[ NF-κB ]] inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that << 5HHMF >> downregulated iNOS expression by suppressing [[ NF-κB ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus, we found that << 5HHMF >> enhances heme oxygenase-1 (HO-1) expression via [[ nuclear factor-erythroid 2-related factor 2 ]] (Nrf2) activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, we found that << 5HHMF >> enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 ([[ Nrf2 ]]) activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, we found that << 5HHMF >> enhances [[ heme oxygenase-1 ]] (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Thus, we found that << 5HHMF >> enhances heme oxygenase-1 ([[ HO-1 ]]) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, << cobalt protoporphyrin >> (CoPP), a specific [[ HO-1 ]] inducer, predominantly suppressed LPS-induced NO production.", "label": "ACTIVATOR", "metadata": []}
{"text": "In addition, cobalt protoporphyrin (<< CoPP >>), a specific [[ HO-1 ]] inducer, predominantly suppressed LPS-induced NO production.", "label": "ACTIVATOR", "metadata": []}
{"text": "In contrast, << zinc protoporphyrin >> (ZnPP), a specific [[ HO-1 ]] inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast, zinc protoporphyrin (<< ZnPP >>), a specific [[ HO-1 ]] inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production.", "label": "INHIBITOR", "metadata": []}
{"text": "Further, << 5HHMF >> increased specific DNA-binding activity of [[ Nrf2 ]], and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of [[ HO-1 ]] activity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity.", "label": "UPREGULATOR", "metadata": []}
{"text": "Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity.", "label": "UPREGULATOR", "metadata": []}
{"text": "Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity.", "label": "UPREGULATOR", "metadata": []}
{"text": "Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed << 5HHMF >>-induced NO inhibition, which was followed by suppression of [[ HO-1 ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and antitumor activity of << 1,3,4-oxadiazole >> possessing 1,4-benzodioxan moiety as a novel class of potent [[ methionine aminopeptidase type II ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and antitumor activity of 1,3,4-oxadiazole possessing << 1,4-benzodioxan >> moiety as a novel class of potent [[ methionine aminopeptidase type II ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of << 2,4,6-trisubstituted 1,3,5-triazines >> as [[ CB2 ]] agonists.", "label": "AGONIST", "metadata": []}
{"text": "One of the << CB2 >> agonists, [[ N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine ]] (19, -logEC(50)=7.5, E(max)=255%) was selected for further development.", "label": "AGONIST", "metadata": []}
{"text": "As far as we are aware, the compound's << 1,3,5-triazine >> scaffold represents a new core structure for [[ CB2 ]] agonists.", "label": "AGONIST", "metadata": []}
{"text": "The discovery of an inducible << oxidase >> whose apparent substrate preference is [[ spermine ]] indicates that polyamine catabolism is more complex than that originally proposed.", "label": "SUBSTRATE", "metadata": []}
{"text": "Purified << PAOh1 >>/SMO oxidizes both [[ spermine ]] (K(m)=1.6 microM) and N(1)-acetylspermine (K(m)=51 microM), but does not oxidize spermidine.", "label": "SUBSTRATE", "metadata": []}
{"text": "Purified PAOh1/<< SMO >> oxidizes both [[ spermine ]] (K(m)=1.6 microM) and N(1)-acetylspermine (K(m)=51 microM), but does not oxidize spermidine.", "label": "SUBSTRATE", "metadata": []}
{"text": "Purified << PAOh1 >>/SMO oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine.", "label": "SUBSTRATE", "metadata": []}
{"text": "Purified PAOh1/<< SMO >> oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine.", "label": "SUBSTRATE", "metadata": []}
{"text": "The purified human enzyme also does not oxidize eight representative antitumor polyamine analogues; however, specific oligamine analogues were found to be potent inhibitors of the oxidation of << spermine >> by [[ PAOh1 ]]/SMO.", "label": "SUBSTRATE", "metadata": []}
{"text": "The purified human enzyme also does not oxidize eight representative antitumor polyamine analogues; however, specific oligamine analogues were found to be potent inhibitors of the oxidation of << spermine >> by PAOh1/[[ SMO ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The i.c.v. administration of very low doses of << okadaic acid >> (0.001-1 pg/mouse) and cantharidin (0.001-1 ng/mouse), which inhibit [[ PP2A ]], produced a dose-dependent antagonism of the antinociception induced by morphine (s.c.).", "label": "INHIBITOR", "metadata": []}
{"text": "The i.c.v. administration of very low doses of okadaic acid (0.001-1 pg/mouse) and << cantharidin >> (0.001-1 ng/mouse), which inhibit [[ PP2A ]], produced a dose-dependent antagonism of the antinociception induced by morphine (s.c.).", "label": "INHIBITOR", "metadata": []}
{"text": "On the other hand, high doses of << okadaic acid >> (10 ng/mouse, i.c.v.) and cantharidin (1 microg/mouse, i.c.v.), which also block [[ PP1 ]], and calyculin-A (0.1 fg/mouse-1 ng/mouse, i.c.v.), which inhibits equally both PP1 and PP2A, did not modify the morphine-induced antinociception.", "label": "INHIBITOR", "metadata": []}
{"text": "On the other hand, high doses of okadaic acid (10 ng/mouse, i.c.v.) and << cantharidin >> (1 microg/mouse, i.c.v.), which also block [[ PP1 ]], and calyculin-A (0.1 fg/mouse-1 ng/mouse, i.c.v.), which inhibits equally both PP1 and PP2A, did not modify the morphine-induced antinociception.", "label": "INHIBITOR", "metadata": []}
{"text": "On the other hand, high doses of okadaic acid (10 ng/mouse, i.c.v.) and cantharidin (1 microg/mouse, i.c.v.), which also block PP1, and << calyculin-A >> (0.1 fg/mouse-1 ng/mouse, i.c.v.), which inhibits equally both [[ PP1 ]] and PP2A, did not modify the morphine-induced antinociception.", "label": "INHIBITOR", "metadata": []}
{"text": "On the other hand, high doses of okadaic acid (10 ng/mouse, i.c.v.) and cantharidin (1 microg/mouse, i.c.v.), which also block PP1, and << calyculin-A >> (0.1 fg/mouse-1 ng/mouse, i.c.v.), which inhibits equally both PP1 and [[ PP2A ]], did not modify the morphine-induced antinociception.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << mammalian isoforms I-XIV >> with a series of natural product [[ polyphenols ]] and phenolic acids.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << mammalian isoforms I-XIV >> with a series of natural product polyphenols and [[ phenolic acids ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, << p-coumaric acid >>, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, << p-coumaric acid >>, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, << p-coumaric acid >>, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, << p-coumaric acid >>, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, << caffeic acid >>, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, << caffeic acid >>, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, << caffeic acid >>, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, << caffeic acid >>, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, << ferulic acid >>, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, << ferulic acid >>, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, << ferulic acid >>, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, << ferulic acid >>, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phenolic acids >> and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phenolic acids >> and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phenolic acids >> and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phenolic acids >> and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, << quercetin >>, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, << quercetin >>, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, << quercetin >>, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, << quercetin >>, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Phenols >> like the ones investigated here possess a [[ CA ]] inhibition mechanism distinct of that of the sulfonamides/sulfamates used clinically or the coumarins.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenols like the ones investigated here possess a << CA >> inhibition mechanism distinct of that of the [[ sulfonamides ]]/sulfamates used clinically or the coumarins.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenols like the ones investigated here possess a << CA >> inhibition mechanism distinct of that of the sulfonamides/[[ sulfamates ]] used clinically or the coumarins.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenols like the ones investigated here possess a << CA >> inhibition mechanism distinct of that of the sulfonamides/sulfamates used clinically or the [[ coumarins ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield [[ pyruvate ]] or 2-oxobutyrate.", "label": "PRODUCT-OF", "metadata": []}
{"text": "L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield [[ pyruvate ]] or 2-oxobutyrate.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of [[ L-serine ]] and L-threonine to yield pyruvate or 2-oxobutyrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of [[ L-serine ]] and L-threonine to yield pyruvate or 2-oxobutyrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and [[ L-threonine ]] to yield pyruvate or 2-oxobutyrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and [[ L-threonine ]] to yield pyruvate or 2-oxobutyrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "Synthesis and evaluation of << carbamoylmethylene >> linked prodrugs of BMS-582949, a clinical [[ p38α ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and evaluation of carbamoylmethylene linked prodrugs of << BMS-582949 >>, a clinical [[ p38α ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << carbamoylmethylene >> linked prodrugs of 1 (BMS-582949), a clinical [[ p38α ]] inhibitor, were synthesized and evaluated.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of carbamoylmethylene linked prodrugs of 1 (<< BMS-582949 >>), a clinical [[ p38α ]] inhibitor, were synthesized and evaluated.", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: << Ethanol >> given to rats in drinking water decreased the level of [[ p-CREB ]] protein in the nucleus accumbens (-75 %) at the time of exposure to ethanol.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The decrement of << p-CREB >> protein in the nucleus accumbens remained at 24 h (-35 %) and 72 h (-28 %) of [[ ethanol ]] withdrawal, which recovered toward control level after 7 d of ethanol withdrawal.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The decrement of << p-CREB >> protein in the nucleus accumbens remained at 24 h (-35 %) and 72 h (-28 %) of ethanol withdrawal, which recovered toward control level after 7 d of [[ ethanol ]] withdrawal.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "However, when naloxone was administered concurrently with << ethanol >> treatment, it antagonized the down-regulation of [[ p-CREB ]] protein in the nucleus accumbens (142 %) of rats exposed to ethanol.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "However, when naloxone was administered concurrently with ethanol treatment, it antagonized the down-regulation of << p-CREB >> protein in the nucleus accumbens (142 %) of rats exposed to [[ ethanol ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence.", "label": "UPREGULATOR", "metadata": []}
{"text": "CONCLUSION: A long-term intake of << ethanol >> solution down-regulates the phosphorylation of [[ CREB ]] in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kind of the molecular mechanisms associated with ethanol dependence.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Adenosine and N(6)-cyclopentyl-adenosine (<< CPA >>, [[ A1R ]] agonist) constricted MVs but not MAs.", "label": "AGONIST", "metadata": []}
{"text": "<< Adenosine >> and N(6)-cyclopentyl-adenosine (CPA, [[ A1R ]] agonist) constricted MVs but not MAs.", "label": "AGONIST", "metadata": []}
{"text": "Adenosine and << N(6)-cyclopentyl-adenosine >> (CPA, [[ A1R ]] agonist) constricted MVs but not MAs.", "label": "AGONIST", "metadata": []}
{"text": "The << A2A adenosine receptor >> agonist CGS21680 ([[ C23H29N7O6.HCl.xH2O ]]) (0.001-0.1 μM) did not alter NE oxidation currents.", "label": "AGONIST", "metadata": []}
{"text": "The << A2A adenosine receptor >> agonist [[ CGS21680 ]] (C23H29N7O6.HCl.xH2O) (0.001-0.1 μM) did not alter NE oxidation currents.", "label": "AGONIST", "metadata": []}
{"text": "<< Pasireotide >> (Signifor(®)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of [[ corticotropin ]] from the pituitary adenoma in patients with Cushing's disease.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pasireotide (<< Signifor >>(®)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of [[ corticotropin ]] from the pituitary adenoma in patients with Cushing's disease.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Also, << SB365 >> showed anti-angiogenic activity by decreasing the expression of [[ HIF-1α ]] and VEGF.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Also, << SB365 >> showed anti-angiogenic activity by decreasing the expression of HIF-1α and [[ VEGF ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "When further examined for its anticancer mechanism, << SB365 >> effectively suppressed the [[ AKT ]]/mTOR pathway both in vitro and in vivo.", "label": "INHIBITOR", "metadata": []}
{"text": "When further examined for its anticancer mechanism, << SB365 >> effectively suppressed the AKT/[[ mTOR ]] pathway both in vitro and in vivo.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, our study demonstrated that << SB365 >> inhibits the [[ AKT ]]/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, our study demonstrated that << SB365 >> inhibits the AKT/[[ mTOR ]] pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in << SGLT1 >> activity induced by [[ gentamicin C ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Megalin, a family of << endocytic receptors >> related to the low-density lipoprotein (LDL) receptor, is a major pathway for proximal tubular [[ aminoglycoside ]] accumulation.", "label": "SUBSTRATE", "metadata": []}
{"text": "Megalin, a family of endocytic receptors related to the << low-density lipoprotein (LDL) receptor >>, is a major pathway for proximal tubular [[ aminoglycoside ]] accumulation.", "label": "SUBSTRATE", "metadata": []}
{"text": "We previously reported that << aminoglycoside >> antibiotics reduce [[ SGLT1 ]]-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In this study, using a model of << gentamicin C >> (GMC)-induced reduction in [[ SGLT1 ]] activity, we examined whether ligands for megalin protect LLC-PK1 cells from the GMC-induced reduction in SGLT1 activity.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, using a model of gentamicin C (<< GMC >>)-induced reduction in [[ SGLT1 ]] activity, we examined whether ligands for megalin protect LLC-PK1 cells from the GMC-induced reduction in SGLT1 activity.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, using a model of gentamicin C (GMC)-induced reduction in SGLT1 activity, we examined whether ligands for megalin protect LLC-PK1 cells from the << GMC >>-induced reduction in [[ SGLT1 ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the << SGLT1 >>-dependent [[ methyl alpha-D-glucopyranoside ]] (AMG) uptake and levels of SGLT1 expression were determined.", "label": "SUBSTRATE", "metadata": []}
{"text": "Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the << SGLT1 >>-dependent methyl alpha-D-glucopyranoside ([[ AMG ]]) uptake and levels of SGLT1 expression were determined.", "label": "SUBSTRATE", "metadata": []}
{"text": "Actions of << nizatidine >>, a selective [[ histamine H2-receptor ]] antagonist, on gastric acid secretion in dogs, rats and frogs.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Nizatidine >> (LY139037), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion.", "label": "ANTAGONIST", "metadata": []}
{"text": "Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion.", "label": "ANTAGONIST", "metadata": []}
{"text": "3D-QSAR-assisted drug design: identification of a potent << quinazoline >>-based [[ Aurora kinase ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Three different 3D-QSAR models were built and validated by using a set of 66 << pyrazole >> (Model I) and furanopyrimidine (Model II) compounds with IC(50) values toward [[ Aurora kinase A ]] ranging from 33 nM to 10.5 μM.", "label": "INHIBITOR", "metadata": []}
{"text": "Three different 3D-QSAR models were built and validated by using a set of 66 pyrazole (Model I) and << furanopyrimidine >> (Model II) compounds with IC(50) values toward [[ Aurora kinase A ]] ranging from 33 nM to 10.5 μM.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on these suggestions, the rational redesign of << furanopyrimidine >> 24 (clog P=7.41; [[ Aurora A ]] IC(50) =43 nM; HCT-116 IC(50) =400 nM) led to the identification of quinazoline 67 (clog P=5.28; Aurora A IC(50) =25 nM; HCT-116 IC(50) =23 nM).", "label": "INHIBITOR", "metadata": []}
{"text": "Based on these suggestions, the rational redesign of furanopyrimidine 24 (clog P=7.41; Aurora A IC(50) =43 nM; HCT-116 IC(50) =400 nM) led to the identification of << quinazoline >> 67 (clog P=5.28; [[ Aurora A ]] IC(50) =25 nM; HCT-116 IC(50) =23 nM).", "label": "INHIBITOR", "metadata": []}
{"text": "Chelation of calcium ions by BAPTA-AM or blockade of << ERK1/2 >> activation by [[ UO126 ]] also prevented the NMDA effects.", "label": "INHIBITOR", "metadata": []}
{"text": "Thus prolonged activation of NMDA receptors in hippocampal neurons reduced << GABAR δ subunit >> expression through [[ Ca2+ ]] entry and at least in part by ERK1/2 activation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Amitriptyline >> is a [[ TrkA ]] and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.", "label": "AGONIST", "metadata": []}
{"text": "<< Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.", "label": "AGONIST", "metadata": []}
{"text": "<< Amitriptyline >>, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes [[ TrkA ]] autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity.", "label": "AGONIST", "metadata": []}
{"text": "Thus, << amitriptyline >> acts as a [[ TrkA ]] and TrkB agonist and possesses marked neurotrophic activity.", "label": "AGONIST", "metadata": []}
{"text": "Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/<< ErbB2 >> kinase inhibitor [[ GW572016 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< GW572016 >>, a reversible small molecule inhibitor of [[ EGFR ]] and ErbB2 tyrosine kinases, inhibits baseline p95ErbB2 phosphorylation in BT474 cells and tumor xenografts.", "label": "INHIBITOR", "metadata": []}
{"text": "<< GW572016 >>, a reversible small molecule inhibitor of EGFR and [[ ErbB2 ]] tyrosine kinases, inhibits baseline p95ErbB2 phosphorylation in BT474 cells and tumor xenografts.", "label": "INHIBITOR", "metadata": []}
{"text": "<< GW572016 >>, a reversible small molecule inhibitor of EGFR and ErbB2 [[ tyrosine kinases ]], inhibits baseline p95ErbB2 phosphorylation in BT474 cells and tumor xenografts.", "label": "INHIBITOR", "metadata": []}
{"text": "<< GW572016 >>, a reversible small molecule inhibitor of EGFR and ErbB2 tyrosine kinases, inhibits baseline [[ p95ErbB2 ]] phosphorylation in BT474 cells and tumor xenografts.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-[[ Erk1/2 ]], phospho-AKT, and cyclin D steady-state protein levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-Erk1/2, phospho-[[ AKT ]], and cyclin D steady-state protein levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and [[ cyclin D ]] steady-state protein levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << p95ErbB2 >>, p185ErbB2, and EGFR phosphorylation by [[ GW572016 ]] resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and cyclin D steady-state protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of p95ErbB2, << p185ErbB2 >>, and EGFR phosphorylation by [[ GW572016 ]] resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and cyclin D steady-state protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of p95ErbB2, p185ErbB2, and << EGFR >> phosphorylation by [[ GW572016 ]] resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and cyclin D steady-state protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Increased phosphorylation of << p95ErbB2 >> and AKT in response to HRG was abrogated to varying degrees by [[ GW572016 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Increased phosphorylation of p95ErbB2 and << AKT >> in response to HRG was abrogated to varying degrees by [[ GW572016 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac sulfide >> inhibited [[ 14-3-3epsilon proteins ]] in HT-29 and DLD-1 cells in a time- and concentration-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Indomethacin >> and SC-236, a selective [[ cyclooxygenase-2 ]] (COX-2) inhibitor, exerted a similar effect as sulindac.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Indomethacin >> and SC-236, a selective cyclooxygenase-2 ([[ COX-2 ]]) inhibitor, exerted a similar effect as sulindac.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin and << SC-236 >>, a selective [[ cyclooxygenase-2 ]] (COX-2) inhibitor, exerted a similar effect as sulindac.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin and << SC-236 >>, a selective cyclooxygenase-2 ([[ COX-2 ]]) inhibitor, exerted a similar effect as sulindac.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac sulfide >> inhibited [[ PPARdelta ]] protein expression and PPARdelta transcriptional activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Sulindac sulfide >> inhibited PPARdelta protein expression and [[ PPARdelta ]] transcriptional activity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of [[ dCK ]] in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 (hENT1) in all cell lines.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the [[ human nucleoside equilibrative transporter 1 ]] (hENT1) in all cell lines.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 ([[ hENT1 ]]) in all cell lines.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of [[ phosphorylated Akt ]], enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 (hENT1) in all cell lines.", "label": "INHIBITOR", "metadata": []}
{"text": "These data demonstrated that 1) gemcitabine and pemetrexed synergistically interact against NSCLC cells through the suppression of Akt phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) << pemetrexed >> enhances [[ dCK ]] and hENT1 expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These data demonstrated that 1) gemcitabine and pemetrexed synergistically interact against NSCLC cells through the suppression of Akt phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) << pemetrexed >> enhances dCK and [[ hENT1 ]] expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These data demonstrated that 1) << gemcitabine >> and pemetrexed synergistically interact against NSCLC cells through the suppression of [[ Akt ]] phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) pemetrexed enhances dCK and hENT1 expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations.", "label": "INHIBITOR", "metadata": []}
{"text": "These data demonstrated that 1) gemcitabine and << pemetrexed >> synergistically interact against NSCLC cells through the suppression of [[ Akt ]] phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) pemetrexed enhances dCK and hENT1 expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Kynurenic acid >> (KA) is an endogenous [[ glutamate receptor ]] antagonist at the level of the different ionotropic glutamate receptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Kynurenic acid >> (KA) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "Kynurenic acid (<< KA >>) is an endogenous [[ glutamate receptor ]] antagonist at the level of the different ionotropic glutamate receptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "Kynurenic acid (<< KA >>) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "One of the enzymes responsible for the production of << KA >>, [[ kynurenine aminotransferase I ]] (KATI), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15).", "label": "PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of << KA >>, kynurenine aminotransferase I ([[ KATI ]]), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15).", "label": "PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]).", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "Combined treatment of << Mn >> and DA further augments cell toxicity, ROS production and [[ JNK ]] phosphorylation in LRRK2 deficient cells compared to controls.", "label": "ACTIVATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in [[ MSG ]]-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in << MSG >>-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice ([[ MSG ]], 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (<< MSG >>, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.).", "label": "UPREGULATOR", "metadata": []}
{"text": "Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.).", "label": "UPREGULATOR", "metadata": []}
{"text": "Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.).", "label": "UPREGULATOR", "metadata": []}
{"text": "The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of << PDE5 >> that breaks down [[ cGMP ]], the key pathway for the production of erectile function in humans.", "label": "SUBSTRATE", "metadata": []}
{"text": "Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of << sildenafil >> (Viagra, Pfizer) - the first approved selective [[ PDE ]] inhibitor for the treatment of ED.", "label": "INHIBITOR", "metadata": []}
{"text": "Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (<< Viagra >>, Pfizer) - the first approved selective [[ PDE ]] inhibitor for the treatment of ED.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sildenafil >> is inhibitory of [[ PDE5 ]] at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sildenafil >> is inhibitory of PDE5 at a rate tenfold higher than for the next [[ PDE ]] (PDE6), which produces visual changes through the retinal rods.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sildenafil >> is inhibitory of PDE5 at a rate tenfold higher than for the next PDE ([[ PDE6 ]]), which produces visual changes through the retinal rods.", "label": "INHIBITOR", "metadata": []}
{"text": "With the use of << sildenafil >>, it has been clearly, clinically demonstrated that the selective inhibition of [[ PDE5 ]] is an appropriate, effective, safe method for the treatment of ED of all aetiologies and severities.", "label": "INHIBITOR", "metadata": []}
{"text": "<< cAspAT >> activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the [[ thiazolidinedione ]] (TZD) rosiglitazone.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< cAspAT >> activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione ([[ TZD ]]) rosiglitazone.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< cAspAT >> activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione (TZD) [[ rosiglitazone ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "<< RORalpha >> ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "RORalpha ectopic expression activated the << cAspAT >> gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Finally, the amounts of << RORalpha >> and cAspAT mRNAs were similarly increased by [[ TZD ]] treatment of human adipose tissue explants, confirming coordinated regulation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Finally, the amounts of RORalpha and << cAspAT >> mRNAs were similarly increased by [[ TZD ]] treatment of human adipose tissue explants, confirming coordinated regulation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Our data identify << cAspAT >> as a new member of glyceroneogenesis, transcriptionally regulated by [[ TZD ]] via the control of RORalpha expression by PPARgamma in adipocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< ABT-199 >>, a potent and selective [[ BCL-2 ]] inhibitor, achieves antitumor activity while sparing platelets.", "label": "INHIBITOR", "metadata": []}
{"text": "The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both [[ BCL-2 ]] and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers.", "label": "INHIBITOR", "metadata": []}
{"text": "The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both BCL-2 and [[ BCL-2-like 1 ]] (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers.", "label": "INHIBITOR", "metadata": []}
{"text": "The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both BCL-2 and BCL-2-like 1 ([[ BCL-X(L) ]]), which has shown clinical efficacy in some BCL-2-dependent hematological cancers.", "label": "INHIBITOR", "metadata": []}
{"text": "Here we report the re-engineering of << navitoclax >> to create a highly potent, orally bioavailable and [[ BCL-2 ]]-selective inhibitor, ABT-199.", "label": "INHIBITOR", "metadata": []}
{"text": "Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and << BCL-2 >>-selective inhibitor, [[ ABT-199 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Suppression of TβR1 by the pharmacological inhibitor (<< SB431542 >>) markedly reduced [[ VEGF ]] release by HFL-1 in response to CSE and this effect was confirmed by TβR1 siRNA.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Suppression of << TβR1 >> by the pharmacological inhibitor ([[ SB431542 ]]) markedly reduced VEGF release by HFL-1 in response to CSE and this effect was confirmed by TβR1 siRNA.", "label": "INHIBITOR", "metadata": []}
{"text": "<< NCFP >> binds to the CPPHA site on mGlu5 and potentiates [[ mGlu5 ]]-mediated responses in both recombinant and native systems.", "label": "ACTIVATOR", "metadata": []}
{"text": "Combination treatment with the selective << 5-HT1A >> antagonist [[ WAY100635 ]] produced a dose-dependent augmentation of venlafaxine-induced (3-30 mg/kg s.c) extracellular 5-HT concentrations, but had no further effect on NA above that produced by venlafaxine alone.", "label": "ANTAGONIST", "metadata": []}
{"text": "The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA.", "label": "ANTAGONIST", "metadata": []}
{"text": "The selective GluR5 kainate receptor agonist ATPA induces spontaneous epileptiform bursting that is sensitive to the << GluR5 >> kainate receptor antagonist [[ LY293558 ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "The selective GluR5 kainate receptor agonist ATPA induces spontaneous epileptiform bursting that is sensitive to the GluR5 << kainate receptor >> antagonist [[ LY293558 ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "However, << topiramate >> at low concentrations causes slow inhibition of [[ GluR5 ]] kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of GluR5 kainate receptor responses.", "label": "INHIBITOR", "metadata": []}
{"text": "However, << topiramate >> at low concentrations causes slow inhibition of GluR5 [[ kainate receptor ]]-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of GluR5 kainate receptor responses.", "label": "INHIBITOR", "metadata": []}
{"text": "However, << topiramate >> at low concentrations causes slow inhibition of GluR5 kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of [[ GluR5 ]] kainate receptor responses.", "label": "INHIBITOR", "metadata": []}
{"text": "However, << topiramate >> at low concentrations causes slow inhibition of GluR5 kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of GluR5 [[ kainate receptor ]] responses.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Multidrug resistance-associated proteins >> are involved in the transport of the [[ glutathione ]] conjugates of the ultimate carcinogen of benzo[a]pyrene in human Caco-2 cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "The ultimate carcinogenic Phase I BP metabolite anti-BP-7,8-dihydrodiol-9,10-epoxide (BPDE) can be detoxified by << glutathione >> conjugate formation catalyzed by [[ glutathione S-transferases ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Inhibition studies revealed that the << multidrug resistance-associated proteins >> (ABCCs) are involved in the transport of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Inhibition studies revealed that the multidrug resistance-associated proteins (<< ABCCs >>) are involved in the transport of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Stable << ABCC1 >>, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Stable ABCC1, << ABCC2 >> and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Stable ABCC1, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that << ABCC1 >> mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Stable ABCC1, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and << ABCC2 >> the apical excretion of [[ BPDE glutathione ]] conjugates.", "label": "SUBSTRATE", "metadata": []}
{"text": "Pretreatment of human breast carcinoma MCF-7 cells for 24 h with the groundnut extract and soybean << isoflavone >> increased gene expression of [[ heme oxygenase-1 ]] (HO-1), a major antioxidative stress enzyme.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Pretreatment of human breast carcinoma MCF-7 cells for 24 h with the groundnut extract and soybean << isoflavone >> increased gene expression of heme oxygenase-1 ([[ HO-1 ]]), a major antioxidative stress enzyme.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Comparison of << cyclooxygenase >> inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and [[ bromfenac sodium ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Comparison of << cyclooxygenase >> inhibitory activity and ocular anti-inflammatory effects of [[ ketorolac tromethamine ]] and bromfenac sodium.", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring [[ prostaglandin E(2) ]] (PGE(2)) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid.", "label": "PRODUCT-OF", "metadata": []}
{"text": "METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring prostaglandin E(2) ([[ PGE(2) ]]) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid.", "label": "PRODUCT-OF", "metadata": []}
{"text": "RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against [[ COX-2 ]] (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "RESULTS: Ketorolac was six times more active against << COX-1 >> (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "RESULTS: Ketorolac was six times more active against COX-1 (IC(50) = 0.02 microM) than << COX-2 >> (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Tumor-growth-promoting << cyclooxygenase-2 >> [[ prostaglandin E2 ]] pathway provides medulloblastoma therapeutic targets.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PGE(2) >> is synthesized from arachidonic acid by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases ([[ PGES ]]) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "PRODUCT-OF", "metadata": []}
{"text": "PGE(2) is synthesized from << arachidonic acid >> by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and prostaglandin E synthases ([[ PGES ]]) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< EP(1) >> and EP(3) receptor antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "EP(1) and << EP(3) receptor >> antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< EP(1) >> and EP(3) receptor antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "EP(1) and << EP(3) receptor >> antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists [[ ONO-AE3-208 ]] and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "label": "ANTAGONIST", "metadata": []}
{"text": "Inhibitors of << PDE4 >> ([[ rolipram ]]; 0.1-10 microM) and PDE3 (cilostazol; 0.1-10 microM) delayed spontaneous eosinophil apoptosis maximally by 25% and 15%, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibitors of PDE4 (rolipram; 0.1-10 microM) and << PDE3 >> ([[ cilostazol ]]; 0.1-10 microM) delayed spontaneous eosinophil apoptosis maximally by 25% and 15%, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibitor of << cGMP-specific PDE5 >> ([[ zaprinast ]]; 0.1-10 microM) did not affect eosinophil apoptosis and only slightly increased spontaneous neutrophil apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< GW9662 >>, a PPARgamma antagonist, prevented (P < 0.01) the lutein-induced [[ iNOS ]] mRNA downregulation in HD11 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< GW9662 >>, a [[ PPARgamma ]] antagonist, prevented (P < 0.01) the lutein-induced iNOS mRNA downregulation in HD11 cells.", "label": "ANTAGONIST", "metadata": []}
{"text": "Stereospecific inhibition of << monoamine uptake transporters >> by [[ meta-hydroxyephedrine ]] isomers.", "label": "INHIBITOR", "metadata": []}
{"text": "To extend structure-activity analyses of binding sites within << monoamine transporters >> and to determine which stereoisomer displayed the best selectivity for PET imaging applications, we tested the [[ HED ]] compounds for their abilities to inhibit [(3)H]neurotransmitter uptake into platelets, transfected cells, and chromaffin vesicles.", "label": "INHIBITOR", "metadata": []}
{"text": "We hypothesized that the << HED >> compounds would be most potent at the [[ norepinephrine transporter ]] (NET) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers.", "label": "INHIBITOR", "metadata": []}
{"text": "We hypothesized that the << HED >> compounds would be most potent at the norepinephrine transporter ([[ NET ]]) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers.", "label": "INHIBITOR", "metadata": []}
{"text": "<< TCDD >> inhibition of canonical [[ wnt ]] signaling disrupts prostatic bud formation in mouse urogenital sinus.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of [[ Lgr5 ]], a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a [[ RSPO receptor ]] that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins ([[ Rspo2 ]] and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and [[ Rspo3 ]]) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of [[ Lef1 ]], Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, [[ Tcf1 ]], and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and [[ Wif1 ]], established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In support of the hypothesis that << TCDD >> decreases canonical [[ Wnt ]] signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators ([[ Rspo2 ]] and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors ([[ Dkk1 ]] and Dkk2) of the pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and [[ Dkk2 ]]) of the pathway.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Thus, the << TCDD >>-induced reduction in canonical [[ Wnt ]] signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of << TCDD >> on canonical [[ Wnt ]] signaling and prostatic bud formation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "We discovered that each RSPO alone or in combination partially rescues << TCDD >> inhibition of both canonical [[ Wnt ]] signaling and prostatic bud formation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes [[ arachidonic acids ]] to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes [[ arachidonic acids ]] to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system.", "label": "SUBSTRATE", "metadata": []}
{"text": "However, whether increasing << EETs >> production by [[ CYP2J2 ]] overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and << EETs >> markedly suppressed Ang II-induced inflammatory [[ cytokine ]] expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and << EETs >> markedly suppressed [[ Ang II ]]-induced inflammatory cytokine expression.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, overexpressed CYP2J2 and << EETs >> inhibited [[ Ang II ]]-induced macrophage migration in a VSMC-macrophage coculture system.", "label": "INHIBITOR", "metadata": []}
{"text": "A decrease in << ADA >> activity was observed when the slices were exposed to [[ organoselenium ]] at the concentrations of 1, 10 and 30 µM.", "label": "INHIBITOR", "metadata": []}
{"text": "Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with << aflatoxin B(1) >> decreased the frequencies of SCE and the malondialdehyde level and increased amount of [[ superoxide dismutase ]], glutathione and glutathione peroxidase which were decreased by aflatoxin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with aflatoxin B(1) decreased the frequencies of SCE and the malondialdehyde level and increased amount of superoxide dismutase, glutathione and << glutathione peroxidase >> which were decreased by [[ aflatoxin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Phenobarbital >> (PB), a typical [[ CAR ]] activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and vascular endothelial growth factor-a.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including [[ erythropoietin ]], heme oxygenase-1 and vascular endothelial growth factor-a.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, [[ heme oxygenase-1 ]] and vascular endothelial growth factor-a.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and [[ vascular endothelial growth factor-a ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Cobalt chloride >>, a typical [[ HIF ]] activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including [[ cyp2b9 ]] and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and [[ cyp2b10 ]], an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes << S-adenosylmethionine >>, [[ MAT1A ]], is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND & AIMS: Of the 2 genes (<< MAT1A >>, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND & AIMS: Of the 2 genes (MAT1A, << MAT2A >>) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding << methionine adenosyltransferase >>, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The beta subunit has been cloned and shown to lower the K(m) of << methionine adenosyltransferase II alpha2 >> (the MAT2A product) for methionine and to render the enzyme more susceptible to [[ S-adenosylmethionine ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the << MAT2A >> product) for methionine and to render the enzyme more susceptible to [[ S-adenosylmethionine ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "The beta subunit has been cloned and shown to lower the K(m) of << methionine adenosyltransferase II alpha2 >> (the MAT2A product) for [[ methionine ]] and to render the enzyme more susceptible to S-adenosylmethionine inhibition.", "label": "SUBSTRATE", "metadata": []}
{"text": "The beta subunit has been cloned and shown to lower the K(m) of methionine adenosyltransferase II alpha2 (the << MAT2A >> product) for [[ methionine ]] and to render the enzyme more susceptible to S-adenosylmethionine inhibition.", "label": "SUBSTRATE", "metadata": []}
{"text": "Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific << CB1 >> antagonist [[ SR 141716A ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "The channel activators << avermectin >> and moxidectin usually retain their inhibitory potency in the [[ Rdl ]] subunit mutants.", "label": "INHIBITOR", "metadata": []}
{"text": "The channel activators avermectin and << moxidectin >> usually retain their inhibitory potency in the [[ Rdl ]] subunit mutants.", "label": "INHIBITOR", "metadata": []}
{"text": "At 10(-6)M in transcription assays, none of these compounds showed progestin agonist activity, whereas << mifepristone >> and its monodemethylated metabolite manifested slight [[ glucocorticoid ]] agonist activity.", "label": "AGONIST", "metadata": []}
{"text": "5-Fluorouracil (<< 5-FU >>), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (<< 5-FU >>), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-Fluorouracil >> (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "<< 5-Fluorouracil >> (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), << 5-fluoro-2'-deoxyuridine >> (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), << 5-fluoro-2'-deoxyuridine >> (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (<< FdUrd >>) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (<< FdUrd >>) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and << 5-trifluorothymidine >> (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and << 5-trifluorothymidine >> (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (<< F3(d)Thd >>) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS).", "label": "INHIBITOR", "metadata": []}
{"text": "5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (<< F3(d)Thd >>) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "When DLD-1/FdUrd cells expressing increased TS mRNA were treated with FdUrd and F3(d)Thd for only 4 h, the resistance ratios of DLD-1/FdUrd cells to parental DLD-1 cells were markedly different for FdUrd and F3(d)Thd, suggesting that the cytotoxicity with short-time exposure to << F3(d)Thd >> is due to a mechanism other than [[ TS ]] inhibition, although the cytotoxicity of F3(d)Thd in the short-time is low compared to that of long-time exposure.", "label": "INHIBITOR", "metadata": []}
{"text": "In conclusion, << F3(d)Thd >>, an antimetabolite that inhibits [[ TS ]] activity, may be effective against 5-FU and/or FdUrd-resistance in colorectal cancer cells caused by amplification of TS and/or deletion of orotate phosphoribosyltransferase.", "label": "INHIBITOR", "metadata": []}
{"text": "The failure of the myometrium to respond to << ritodrine >> (desensitization) was associated with significant reductions in agonist-induced cyclic adenosine monophosphate production and [[ beta 2-adrenergic receptor ]] concentration in myometrial tissue collected from these animals compared with the saline solution-treated controls.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Antiarrhythmic effects of << (-)-epicatechin-3-gallate >>, a novel [[ sodium channel ]] agonist in cultured neonatal rat ventricular myocytes.", "label": "AGONIST", "metadata": []}
{"text": "<< Choline dehydrogenase >> (CHDH) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in [[ choline ]] oxidation.", "label": "SUBSTRATE", "metadata": []}
{"text": "Choline dehydrogenase (<< CHDH >>) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in [[ choline ]] oxidation.", "label": "SUBSTRATE", "metadata": []}
{"text": "Choline dehydrogenase (CHDH) and << betaine-homocysteine methyltransferase >> (BHMT) are 2 enzymes involved in [[ choline ]] oxidation.", "label": "SUBSTRATE", "metadata": []}
{"text": "Choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (<< BHMT >>) are 2 enzymes involved in [[ choline ]] oxidation.", "label": "SUBSTRATE", "metadata": []}
{"text": "Liver << BHMT >> activity was 1.3-fold higher in rats fed the Met deficient diet containing [[ choline ]], which was reflected in corresponding increases in mRNA content and immunodetectable protein.", "label": "ACTIVATOR", "metadata": []}
{"text": "Liver << BHMT >> activity was 1.3-fold higher in rats fed the Met deficient diet containing [[ choline ]], which was reflected in corresponding increases in mRNA content and immunodetectable protein.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Independent of dietary << choline >>, supplemental Met increased hepatic [[ BHMT ]] activity approximately 30%.", "label": "ACTIVATOR", "metadata": []}
{"text": "Independent of dietary choline, supplemental << Met >> increased hepatic [[ BHMT ]] activity approximately 30%.", "label": "ACTIVATOR", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban ([[ PLB ]]), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), [[ phospho-PLB ]], and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and [[ calsequestrin 2 ]] are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins [[ sarcoendoplasmic reticulum ATPase 2a ]] (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a ([[ SERCA2a ]]), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), [[ sodium calcium exchanger-1 ]], phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, [[ phospholamban ]] (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< DNA methyltransferase 3a >> expression was increased in all [[ BPA ]] males and BPA 0.5 females and reduced in BPA 200 females.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< DNA methyltransferase 3a >> expression was increased in all BPA males and [[ BPA ]] 0.5 females and reduced in BPA 200 females.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< DNA methyltransferase 3a >> expression was increased in all BPA males and BPA 0.5 females and reduced in [[ BPA ]] 200 females.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The results showed that << wogonoside >> promotes the expression of [[ LC3-II ]] and Beclin-1.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The results showed that << wogonoside >> promotes the expression of LC3-II and [[ Beclin-1 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Wogonoside >> also suppressed the activation of mammalian target of rapamycin (mTOR) and [[ p70-S6 kinase ]] (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Wogonoside >> also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase ([[ p70S6K) ]] by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Wogonoside >> also suppressed the activation of [[ mammalian target of rapamycin ]] (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Wogonoside >> also suppressed the activation of mammalian target of rapamycin ([[ mTOR ]]) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "The << mitochondrial respiratory chain complex IV >> (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water.", "label": "SUBSTRATE", "metadata": []}
{"text": "The mitochondrial respiratory chain complex IV (<< cytochrome c oxidase >>) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Pelargonidin >> activates the [[ AhR ]] and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< AhR >>-dependent reporter gene expression in transfected HepG2 cells was increased by [[ pelargonidin ]] in a concentration-dependent manner at 24h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM << 2,3,7,8-tetrachlorodibenzodioxin >> (TCDD), the most potent activator of [[ AhR ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (<< TCDD >>), the most potent activator of [[ AhR ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Similarly, << pelargonidin >> induced the expression of [[ CYP1A1 ]] mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM [[ 2,3,7,8-tetrachlorodibenzodioxin ]] (TCDD), the most potent activator of AhR.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< CYP1A1 >> and CYP1A2 mRNAs were also increased by [[ pelargonidin ]] in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and << CYP1A2 >> mRNAs were also increased by [[ pelargonidin ]] in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme.", "label": "UPREGULATOR", "metadata": []}
{"text": "Enzyme kinetic analyses using human liver microsomes revealed inhibition of << CYP1A1 >> activity by [[ delphinidin ]] (IC50 78 μM) and pelargonidin (IC50 33 μM).", "label": "INHIBITOR", "metadata": []}
{"text": "Enzyme kinetic analyses using human liver microsomes revealed inhibition of << CYP1A1 >> activity by delphinidin (IC50 78 μM) and [[ pelargonidin ]] (IC50 33 μM).", "label": "INHIBITOR", "metadata": []}
{"text": "Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, << pelargonidin >> can bind to and activate the [[ AhR ]] and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and << pelargonidin >> and delphinidin inhibit the [[ CYP1A1 ]] catalytic activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and pelargonidin and << delphinidin >> inhibit the [[ CYP1A1 ]] catalytic activity.", "label": "INHIBITOR", "metadata": []}
{"text": "In HEK-293 cells stably transfected with this receptor, << serotonin >> elicits a potent stimulation of [[ adenylyl cyclase ]] activity, which is blocked by antipsychotic and antidepressant drugs.", "label": "ACTIVATOR", "metadata": []}
{"text": "A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma << glucose >> improved with [[ insulin ]] detemir without an increased incidence of hypoglycaemia.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the [[ PUFA ]] biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI).", "label": "PRODUCT-OF", "metadata": []}
{"text": "OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the PUFA biosynthetic pathway and consequently modifies the effect of [[ alpha-linolenic acid ]] (ALA) on myocardial infarction (MI).", "label": "SUBSTRATE", "metadata": []}
{"text": "OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the PUFA biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid ([[ ALA ]]) on myocardial infarction (MI).", "label": "SUBSTRATE", "metadata": []}
{"text": "We evaluated the effects of << angiotensin II >> and an angiotensin-converting enzyme inhibitor ([[ cilazapril ]]) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats.", "label": "INHIBITOR", "metadata": []}
{"text": "We evaluated the effects of angiotensin II and an << angiotensin-converting enzyme >> inhibitor ([[ cilazapril ]]) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats.", "label": "INHIBITOR", "metadata": []}
{"text": "We topically applied the nitric oxide synthase (<< NOS >>) inhibitor, [[ NG-nitro-L-arginine ]], on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet.", "label": "INHIBITOR", "metadata": []}
{"text": "We topically applied the << nitric oxide synthase >> (NOS) inhibitor, [[ NG-nitro-L-arginine ]], on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Cadmium >> activates [[ NADPH oxidase ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in [[ p53 ]] activation and the pro-apoptotic protein Bax.", "label": "ACTIVATOR", "metadata": []}
{"text": "However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein [[ Bax ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The inhibitory effect of << ginseng saponins >> on the stress-induced plasma [[ interleukin-6 ]] level in mice.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Ginseng total << saponins >>, ginsenosides Rb2, Rg1 and Rd administered intraperitoneally attenuated the immobilization stress-induced increase in plasma [[ IL-6 ]] level.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Ginseng total saponins, << ginsenosides Rb2, Rg1 and Rd >> administered intraperitoneally attenuated the immobilization stress-induced increase in plasma [[ IL-6 ]] level.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Ginsenosides Rb2, Rd and Rg1 significantly decreased << norepinephrine >> and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage cell line (RAW 264.7).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Ginsenosides Rb2, Rd and Rg1 significantly decreased norepinephrine and/or << epinephrine >>-induced increase of [[ IL-6 ]] level in macrophage cell line (RAW 264.7).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Ginsenosides Rb2, Rd and Rg1 >> significantly decreased norepinephrine and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage cell line (RAW 264.7).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or << epinephrine >>-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking << norepinephrine >>- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Thus, it can be suggested that the inhibitory action of << ginseng saponins >> against the immobilization stress-induced increase of plasma [[ IL-6 ]] level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or epinephrine-induced increase of IL-6 level in macrophage rather than in the brain.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Thus, it can be suggested that the inhibitory action of << ginseng saponins >> against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the [[ incretin hormones ]] glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones [[ glucagon-like peptide-1 ]] and glucose-dependent insulinotropic polypeptide.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and [[ glucose-dependent insulinotropic polypeptide ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting [[ DPP-4 ]] inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "label": "INHIBITOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "label": "INHIBITOR", "metadata": []}
{"text": "Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 ([[ DPP-4 ]]) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.", "label": "INHIBITOR", "metadata": []}
{"text": "Improvements from baseline in mean << glycosylated haemoglobin >> (HbA(1c)) were significantly greater with [[ sitagliptin ]] monotherapy than with placebo in patients with type 2 diabetes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Improvements from baseline in mean glycosylated haemoglobin (<< HbA(1c) >>) were significantly greater with [[ sitagliptin ]] monotherapy than with placebo in patients with type 2 diabetes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, << sitagliptin >> improved [[ HbA(1c) ]] to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to metformin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to [[ metformin ]] or pioglitazone and was noninferior to glipizide when added to metformin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or [[ pioglitazone ]] and was noninferior to glipizide when added to metformin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to [[ metformin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, pretreatment with << Z-Val-Ala-Asp-fluoromethylketone >> (Z-VAD-fmk), a broad spectrum of [[ caspase ]] inhibitor, could not rescue apoptotic cells from ClpP toxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, pretreatment with Z-Val-Ala-Asp-fluoromethylketone (<< Z-VAD-fmk >>), a broad spectrum of [[ caspase ]] inhibitor, could not rescue apoptotic cells from ClpP toxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Orlistat >> is a new inhibitor of [[ pancreatic lipase ]] enzyme.", "label": "INHIBITOR", "metadata": []}
{"text": "In the long term, << orlistat >> has been shown to be more effective than placebo in reducing body weight and serum total and [[ low-density lipoprotein ]] cholesterol levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Genistin >> decreased [[ myosin light chain kinase ]] (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Genistin >> decreased myosin light chain kinase ([[ MLCK ]]) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Genistin >> decreased myosin light chain kinase (MLCK) protein contents and [[ MLCK ]] mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of << MLCK >> contents and inhibition of MLCK activity are involved in the [[ genistin ]]-induced inhibitory effects.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Genistin >> decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-[[ ATPase ]] activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects.", "label": "INHIBITOR", "metadata": []}
{"text": "Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of << MLCK >> activity are involved in the [[ genistin ]]-induced inhibitory effects.", "label": "INHIBITOR", "metadata": []}
{"text": "It was found that expression of << Sim2 >> protein in cortical neurons was increased in [[ streptozotocin ]]-induced diabetes mellitus rat model.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, << curcumin >> alleviated [[ Sim2 ]] expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, << curcumin >> alleviated Sim2 expression, and reversely raised [[ Drebrin ]] expression in neurons treated with hyperglycaemia.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Polymorphisms in dopamine transporter (<< SLC6A3 >>) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Polymorphisms in << dopamine transporter >> (SLC6A3) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the G protein-coupled receptor agonist acetylcholine (ACh) and by << cyclopiazonic acid >> (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial [[ SERCA ]] pump.", "label": "INHIBITOR", "metadata": []}
{"text": "Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the G protein-coupled receptor agonist acetylcholine (ACh) and by cyclopiazonic acid (<< CPA >>), which promotes store-operated Ca(2+) entry by inhibiting the endothelial [[ SERCA ]] pump.", "label": "INHIBITOR", "metadata": []}
{"text": "Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist [[ acetylcholine ]] (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump.", "label": "AGONIST", "metadata": []}
{"text": "Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist acetylcholine ([[ ACh ]]) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump.", "label": "AGONIST", "metadata": []}
{"text": "Potentiation was prevented by catalase, the catalase/superoxide dismutase mimetic manganese porphyrin and the << NADPH oxidase >> inhibitor [[ apocynin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the << superoxide >> anion generated by [[ NADPH oxidase ]] can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as [[ l-phenylalanine ammonia-lyase ]] (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase ([[ PAL ]]) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and [[ chalcone synthase ]] (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase ([[ CHS ]]), and an antioxidant enzyme such as ascorbate peroxidase (APX).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as [[ ascorbate peroxidase ]] (APX).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase ([[ APX ]]).", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Acetaminophen >> (paracetamol) is a selective [[ cyclooxygenase-2 ]] inhibitor in man.", "label": "INHIBITOR", "metadata": []}
{"text": "Acetaminophen (<< paracetamol >>) is a selective [[ cyclooxygenase-2 ]] inhibitor in man.", "label": "INHIBITOR", "metadata": []}
{"text": "The fact that << acetaminophen >> acts functionally as a selective [[ COX-2 ]] inhibitor led us to investigate the hypothesis of whether it works via preferential COX-2 blockade.", "label": "INHIBITOR", "metadata": []}
{"text": "Ex vivo << COX >> inhibition and pharmacokinetics of [[ acetaminophen ]] were assessed in 5 volunteers receiving single 1000 mg doses orally.", "label": "INHIBITOR", "metadata": []}
{"text": "Coagulation-induced << thromboxane B(2) >> and lipopolysaccharide-induced prostaglandin E(2) were measured ex vivo and in vitro in human whole blood as indices of [[ COX-1 ]] and COX-2 activity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Coagulation-induced thromboxane B(2) and lipopolysaccharide-induced << prostaglandin E(2) >> were measured ex vivo and in vitro in human whole blood as indices of COX-1 and [[ COX-2 ]] activity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "In vitro, << acetaminophen >> elicited a 4.4-fold selectivity toward [[ COX-2 ]] inhibition (IC(50)=113.7 micromol/L for COX-1; IC(50)=25.8 micromol/L for COX-2).", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro, << acetaminophen >> elicited a 4.4-fold selectivity toward COX-2 inhibition (IC(50)=113.7 micromol/L for [[ COX-1 ]]; IC(50)=25.8 micromol/L for COX-2).", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro, << acetaminophen >> elicited a 4.4-fold selectivity toward COX-2 inhibition (IC(50)=113.7 micromol/L for COX-1; IC(50)=25.8 micromol/L for [[ COX-2 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acetaminophen >> plasma concentrations remained above the in vitro IC(50) for [[ COX-2 ]] for at least 5 h postadministration.", "label": "INHIBITOR", "metadata": []}
{"text": "Ex vivo IC(50) values (<< COX-1 >>: 105.2 micromol/L; COX-2: 26.3 micromol/L) of [[ acetaminophen ]] compared favorably with its in vitro IC(50) values.", "label": "INHIBITOR", "metadata": []}
{"text": "Ex vivo IC(50) values (COX-1: 105.2 micromol/L; << COX-2 >>: 26.3 micromol/L) of [[ acetaminophen ]] compared favorably with its in vitro IC(50) values.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast to previous concepts, << acetaminophen >> inhibited [[ COX-2 ]] by more than 80%, i.e., to a degree comparable to nonsteroidal antiinflammatory drugs (NSAIDs) and selective COX-2 inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "In view of its substantial << COX-2 >> inhibition, recently defined cardiovascular warnings for use of COX-2 inhibitors should also be considered for [[ acetaminophen ]].", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVES: The alkaloid << galantamine >> (GAL), which exhibits a combined [[ anticholinesterase ]] and direct parasympathomimetic mechanism of action, is employed in conjunction with therapeutic interventions in the stimulation of central cholinergic transfer in cognitive diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "OBJECTIVES: The alkaloid galantamine (<< GAL >>), which exhibits a combined [[ anticholinesterase ]] and direct parasympathomimetic mechanism of action, is employed in conjunction with therapeutic interventions in the stimulation of central cholinergic transfer in cognitive diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: Following administration of the highest of the << GAL >> doses used (2.5; 5; 10 mg/kg i.m.), [[ AChE ]] activity decreased mainly in the frontal cortex, hippocampus and hypophysis.", "label": "INHIBITOR", "metadata": []}
{"text": "In the interaction of << GAL >> and CAR, [[ AChE ]] inhibition was stronger but without any statistical significance.", "label": "INHIBITOR", "metadata": []}
{"text": "<< NaAsO(2) >> increased the mRNA levels of the [[ light and medium subunits of neurofilament ]] and decreased the mRNA levels of tau and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< NaAsO(2) >> increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of [[ tau ]] and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< NaAsO(2) >> increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and [[ tubulin ]] in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "A << naloxone-steroid hybrid azine >> with selective and long-acting opioid antagonism at [[ delta receptors ]] in vitro.", "label": "ANTAGONIST", "metadata": []}
{"text": "Inhibition of << dipeptidyl peptidase-IV >> (DPP-IV) by [[ atorvastatin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of dipeptidyl peptidase-IV (<< DPP-IV >>) by [[ atorvastatin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In this report, we show that the hypolipidemic agent << atorvastatin >> is a competitive inhibitor of [[ porcine DPP-IV ]] in vitro, with K(i)=57.8+/-2.3 microM.", "label": "INHIBITOR", "metadata": []}
{"text": "These results may have implications in the development of novel << DPP-IV >> inhibitors based on the use of [[ atorvastatin ]] as a lead compound for the treatment of type 2 diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Neoechinulin A >> suppresses [[ amyloid-β ]] oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, focus was given to evaluate the ability of << neoechinulin A >>, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric [[ amyloid-β 1-42 ]] (Aβ42).", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, focus was given to evaluate the ability of << neoechinulin A >>, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 ([[ Aβ42 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, focus was given to evaluate the ability of neoechinulin A, an << indole >> alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric [[ amyloid-β 1-42 ]] (Aβ42).", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, focus was given to evaluate the ability of neoechinulin A, an << indole >> alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 ([[ Aβ42 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Neoechinulin A >> treatment significantly inhibited the generation of reactive oxygen and nitrogen species in [[ Aβ42 ]]-activated BV-2 microglia cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator [[ tumour necrosis factor-α ]] (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α ([[ TNF-α ]]), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), [[ interleukin-1β ]] (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β ([[ IL-1β ]]), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), [[ interleukin-6 ]] (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 ([[ IL-6 ]]), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of [[ nuclear factor-κB ]] (NF-κB) p65 and p50 subunits.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB ([[ NF-κB ]]) p65 and p50 subunits.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) [[ p65 ]] and p50 subunits.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and [[ p50 ]] subunits.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of [[ mitogen-activated protein kinase ]] (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase ([[ MAPK ]]) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule [[ p38 ]], apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, [[ apoptosis signal-regulating kinase 1 ]] (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 ([[ ASK-1 ]]) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Epi >> increased the activity of the [[ human WNT6 promoter ]] through Cav1-dependent binding of β-catenin to the proximal WNT6 promoter.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Epi >> increased the activity of the human WNT6 promoter through Cav1-dependent binding of β-catenin to the proximal [[ WNT6 promoter ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Epi >> increased both [[ WNT6 ]]/Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Epi >> increased both WNT6/[[ Wnt6 ]] and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Epi >> increased both WNT6/Wnt6 and [[ Cav1 ]] expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results showed that << WNT6 >> and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to [[ anthracycline ]] drugs.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These results showed that WNT6 and << Cav1 >> are upregulated by chemotherapeutics and enhance the resistance of GC cells to [[ anthracycline ]] drugs.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that << TCDD >> up-regulated the expression and secretion of [[ tumor necrosis factor-alpha ]] (TNF-α) in a time-dependent manner in cultured HAPI microglial cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that << TCDD >> up-regulated the expression and secretion of tumor necrosis factor-alpha ([[ TNF-α ]]) in a time-dependent manner in cultured HAPI microglial cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< TCDD >> also caused a fast (within 30min as judged by the increase in its mRNA level) activation of [[ cytosolic phospholipase A2 ]] (cPLA2).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< TCDD >> also caused a fast (within 30min as judged by the increase in its mRNA level) activation of cytosolic phospholipase A2 ([[ cPLA2 ]]).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "This initial action was accompanied by up-regulation of << cyclooxygenase-2 >> (COX-2), an important inflammation marker within 1h after [[ TCDD ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "This initial action was accompanied by up-regulation of cyclooxygenase-2 (<< COX-2 >>), an important inflammation marker within 1h after [[ TCDD ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Further, << TCDD >> exposure could induce phosphorylation- and ubiquitination-dependent degradation of [[ IкBα ]], and the translocation of NF-κB p65 from the cytosol to the nucleus in this microglial cell line.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, the << NF-κB >> signaling pathway can be activated after [[ TCDD ]] treatment.", "label": "ACTIVATOR", "metadata": []}
{"text": "However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In concert with these results, we highlighted that the secretion of pro-inflammatory << cytokine >> and NF-κB activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "In concert with these results, we highlighted that the secretion of pro-inflammatory cytokine and << NF-κB >> activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "The ARB << eprosartan >> is a nonbiphenyl nontetrazole [[ angiotensin II type 1 receptor ]] (AT1) antagonist, which acts to decrease total peripheral resistance.", "label": "ANTAGONIST", "metadata": []}
{"text": "The ARB << eprosartan >> is a nonbiphenyl nontetrazole angiotensin II type 1 receptor ([[ AT1 ]]) antagonist, which acts to decrease total peripheral resistance.", "label": "ANTAGONIST", "metadata": []}
{"text": "The putative << alpha 1L-adrenoceptor >> antagonist [[ JTH-601 ]], but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA.", "label": "ANTAGONIST", "metadata": []}
{"text": "The putative alpha 1L-adrenoceptor antagonist JTH-601, but not the << alpha 1B-adrenoceptor >> antagonist [[ chloroethylclonidine ]] (10 microM) antagonized noradrenaline-induced contractions of SMA.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potency of the selective alpha 1D-adrenoceptor antagonist BMY 7378 against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective alpha 1A-adrenoceptor antagonist RS-17053 against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective << alpha 1A-adrenoceptor >> agonist [[ A-61603 ]] (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement.", "label": "AGONIST", "metadata": []}
{"text": "The potency of the selective << alpha 1D-adrenoceptor >> antagonist [[ BMY 7378 ]] against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective alpha 1A-adrenoceptor antagonist RS-17053 against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective alpha 1A-adrenoceptor agonist A-61603 (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potency of the selective alpha 1D-adrenoceptor antagonist BMY 7378 against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective << alpha 1A-adrenoceptor >> antagonist [[ RS-17053 ]] against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective alpha 1A-adrenoceptor agonist A-61603 (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement.", "label": "ANTAGONIST", "metadata": []}
{"text": "Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist [[ SCH 39166 ]] ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg).", "label": "ANTAGONIST", "metadata": []}
{"text": "Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg).", "label": "ANTAGONIST", "metadata": []}
{"text": "Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the << dopamine D2 receptor >> antagonist [[ raclopride ]] (both at 0.003-0.03 mg/kg).", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Carvedilol >> reduced the risk of death or heart failure in patients with above-median levels of [[ N-BNP ]] or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Carvedilol >> reduced the risk of death or heart failure in patients with above-median levels of N-BNP or [[ adrenomedullin ]], or both, to rates not significantly different from those observed in patients with levels below the median value.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Carvedilol >> reduced mortality and heart failure in patients with higher pre-treatment plasma [[ N-BNP ]] and adrenomedullin.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Carvedilol >> reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and [[ adrenomedullin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of phosphoinositide 3-kinase using << Ly294002 >> augmented a decrease in the [[ p21 ]] level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of << phosphoinositide 3-kinase >> using [[ Ly294002 ]] augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, the data provide evidence that the synergistic antiproliferative effect of << resveratrol >> and clofarabine is linked to the inhibition of [[ Akt ]] and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, the data provide evidence that the synergistic antiproliferative effect of << resveratrol >> and clofarabine is linked to the inhibition of Akt and [[ Sp1 ]] activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and << clofarabine >> is linked to the inhibition of [[ Akt ]] and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and << clofarabine >> is linked to the inhibition of Akt and [[ Sp1 ]] activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Phillyrin >> attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of [[ LKB1 ]]/AMP-activated protein kinase-dependent signalling.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Phillyrin >> attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/[[ AMP-activated protein kinase ]]-dependent signalling.", "label": "ACTIVATOR", "metadata": []}
{"text": "Phillyrin strongly inhibited high << glucose >>-induced [[ fatty acid synthase ]] (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Phillyrin strongly inhibited high << glucose >>-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Phillyrin >> strongly inhibited high glucose-induced [[ fatty acid synthase ]] (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Phillyrin >> strongly inhibited high glucose-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, use of the pharmacological << AMP-activated protein kinase >> (AMPK) inhibitor [[ compound C ]] revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, use of the pharmacological AMP-activated protein kinase (<< AMPK >>) inhibitor [[ compound C ]] revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor << compound C >> revealed that [[ AMPK ]] is essential for suppressing SREBP-1c expression in phillyrin-treated cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the << phillyrin >>-enhanced activation of [[ AMPK ]] in HepG2 hepatocytes.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through [[ LKB1 ]]/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/[[ AMPK ]] activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that << phillyrin >> is a novel [[ AMPK ]] activator with a role in the prevention and treatment of obesity.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of [[ SREBP-1c ]] and FAS through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and [[ FAS ]] through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Benzenesulfonamides >> incorporating cyanoacrylamide moieties strongly inhibit [[ Saccharomyces cerevisiae β-carbonic anhydrase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Benzenesulfonamides incorporating << cyanoacrylamide >> moieties strongly inhibit [[ Saccharomyces cerevisiae β-carbonic anhydrase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << benzenesulfonamides >> incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << benzenesulfonamides >> incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, [[ ScCA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << benzenesulfonamides >> incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the [[ β-carbonic anhydrase ]] (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << benzenesulfonamides >> incorporating cyanoacrylamide moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase ([[ CA ]], EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating << cyanoacrylamide >> moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating << cyanoacrylamide >> moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, [[ ScCA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating << cyanoacrylamide >> moieties (tyrphostine analogs) were assayed as inhibitors of the [[ β-carbonic anhydrase ]] (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating << cyanoacrylamide >> moieties (tyrphostine analogs) were assayed as inhibitors of the β-carbonic anhydrase ([[ CA ]], EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (<< tyrphostine >> analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (<< tyrphostine >> analogs) were assayed as inhibitors of the β-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, [[ ScCA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (<< tyrphostine >> analogs) were assayed as inhibitors of the [[ β-carbonic anhydrase ]] (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of benzenesulfonamides incorporating cyanoacrylamide moieties (<< tyrphostine >> analogs) were assayed as inhibitors of the β-carbonic anhydrase ([[ CA ]], EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Artemisinic acid >> inhibits melanogenesis through downregulation of C/EBP α-dependent expression of [[ HMG-CoA reductase ]] gene.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Artemisinic acid >> inhibits melanogenesis through downregulation of [[ C/EBP α ]]-dependent expression of HMG-CoA reductase gene.", "label": "INHIBITOR", "metadata": []}
{"text": "The mRNA levels of << microphthalmia-associated transcription factor >> (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mRNA levels of microphthalmia-associated transcription factor (<< MITF >>) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes << tyrosinase >>, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, << tyrosinase-related protein (TRP)-1 >>, and TRP-2 were reduced by [[ artemisinic acid ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and << TRP-2 >> were reduced by [[ artemisinic acid ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the mRNA levels of melanogenesis-related genes (<< c-KIT >>, stem cell factor (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, << stem cell factor >> (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (<< SCF >>), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and << macrophage migration inhibitory factor >> (MIF)) were down-regulated by [[ artemisinic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (<< MIF >>)) were down-regulated by [[ artemisinic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, cAMP production and << protein kinase A >> (PKA) activity were suppressed by [[ artemisinic acid ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, cAMP production and protein kinase A (<< PKA >>) activity were suppressed by [[ artemisinic acid ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that << artemisinic acid >> regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the [[ hydroxymethylglutaryl CoA (HMG CoA) reductase ]] gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) α gene.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that << artemisinic acid >> regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA (HMG CoA) reductase gene, which was mediated through reduced expression of the [[ CCAAT/enhancer-binding protein (C/EBP) α ]] gene.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, these findings indicate that the inhibition of melanogenesis by << artemisinic acid >> occurs through reduced expression of the [[ HMG CoA reductase ]] gene, which is mediated by C/EBP α inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, these findings indicate that the inhibition of melanogenesis by << artemisinic acid >> occurs through reduced expression of the HMG CoA reductase gene, which is mediated by [[ C/EBP α ]] inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "As determined by Western and Northern blot analyses, << 5 alpha-NET >> inhibited the P4-induced [[ UG ]] gene expression in a dose-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The estrogenic agent << 3 beta,5 alpha-NET >> and estradiol at a dose of 1.0 mg also inhibited the [[ UG ]] gene expression induced by P4.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The estrogenic agent 3 beta,5 alpha-NET and << estradiol >> at a dose of 1.0 mg also inhibited the [[ UG ]] gene expression induced by P4.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Both << 5 alpha-NET >> and 3 beta,5 alpha-NET blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The inhibition of UG synthesis and << PR >> down-regulation by [[ 5 alpha-NET ]] and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The inhibition of << UG >> synthesis and PR down-regulation by [[ 5 alpha-NET ]] and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of UG synthesis and << PR >> down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these [[ NET ]] metabolites possess antiprogestational properties.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The inhibition of UG synthesis and << PR >> down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these [[ NET ]] metabolites possess antiprogestational properties.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose << dioscin >>, as indicated by an up-regulated expression of [[ LC3-II ]] and beclin-1 proteins.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose << dioscin >>, as indicated by an up-regulated expression of LC3-II and [[ beclin-1 ]] proteins.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR.", "label": "UPREGULATOR", "metadata": []}
{"text": "Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR.", "label": "UPREGULATOR", "metadata": []}
{"text": "Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased [[ PI3K ]] expression and decreased phosphorylation of Akt and mTOR.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of [[ Akt ]] and mTOR.", "label": "INHIBITOR", "metadata": []}
{"text": "Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and [[ mTOR ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Our results showed that << 2-hydroxy-3-methylanthraquinone >> decreased phosphorylation-ERK1/2 (p-ERK1/2), and increased [[ p-p38MAPK ]], but did not affect expressions of p-JNK1/2 in U937 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Moreover, treatment of U937 cells with << 2-hydroxy-3-methylanthraquinone >> resulted in activation of [[ caspase-3 ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Furthermore, PD98059 (ERK1/2 inhibitor) significantly enhanced 2-hydroxy-3-methylanthraquinone-induced apoptosis in U937 cells, whereas caspase-3 inhibitor or << SB203580 >> ([[ p-p38MAPK ]] inhibitor), decreased apoptosis in U937 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, our study for the first time suggests that << 2-hydroxy-3-methylanthraquinone >> is able to enhance apoptosis of U937 cells, at least in part, through activation of [[ p-p38MAPK ]] and downregulation of p-ERK1/2.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line.", "label": "UPREGULATOR", "metadata": []}
{"text": "Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line.", "label": "UPREGULATOR", "metadata": []}
{"text": "A new series of << N2-substituted-5-(p-toluenesulfonylamino)phthalimide >> analogues as [[ α-glucosidase ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "Several members of a new family of non-sugar-type << α-glycosidase >> inhibitors, bearing a [[ 5-(p-toluenesulfonylamino)phthalimide ]] moiety and various substituent at the N2 position, were synthesized and their activities were investigated.", "label": "INHIBITOR", "metadata": []}
{"text": "Structure-activity relationship studies indicated that << 5-(p-toluenesulfonylamino)phthalimide >> moiety is a favorable scaffold to exert the [[ α-glucosidase ]] inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities.", "label": "INHIBITOR", "metadata": []}
{"text": "The lysosomal inhibitor << chloroquine >> significantly increased [[ RCAN1 ]] accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Here, we have now found that activation of << p38 >> MAPK by [[ anisomycin ]] potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Here, we have now found that activation of p38 << MAPK >> by [[ anisomycin ]] potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Here, we have now found that activation of p38 MAPK by << anisomycin >> potentiated induction of [[ CYP2B6 ]] mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "siRNA knockdown of p38 MAPK abrogated the ability of << anisomycin >> to synergistically induce [[ CYP2B6 ]] mRNA.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to << CYP2B6 >>, [[ anisomycin ]] co-treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to CYP2B6, << anisomycin >> co-treatment potentiated an increase in [[ CYP2A7 ]] and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition to CYP2B6, << anisomycin >> co-treatment potentiated an increase in CYP2A7 and [[ CYP2C9 ]] mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major [[ human cytochrome P450 ]] enzymes, inhibition of the biliary efflux transporters BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary [[ efflux transporters ]] BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters [[ BSEP ]] and MRP2 or mitochondrial toxicity to THLE or HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters BSEP and [[ MRP2 ]] or mitochondrial toxicity to THLE or HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Auranofin >>, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of [[ TLR4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Our results demonstrated that << auranofin >> suppressed TLR4-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of [[ COX-2 ]], a pro-inflammatory enzyme.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Our results demonstrated that << auranofin >> suppressed [[ TLR4 ]]-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme.", "label": "INHIBITOR", "metadata": []}
{"text": "Our results demonstrated that << auranofin >> suppressed TLR4-mediated activation of transcription factors, [[ NF-kappaB ]] and IRF3, and expression of COX-2, a pro-inflammatory enzyme.", "label": "INHIBITOR", "metadata": []}
{"text": "Our results demonstrated that << auranofin >> suppressed TLR4-mediated activation of transcription factors, NF-kappaB and [[ IRF3 ]], and expression of COX-2, a pro-inflammatory enzyme.", "label": "INHIBITOR", "metadata": []}
{"text": "This suppression was well correlated with the inhibitory effect of << auranofin >> on the homodimerization of [[ TLR4 ]] induced by an agonist.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << auranofin >> inhibited [[ NF-kappaB ]] activation induced by MyD88-dependent downstream signaling components of TLR4, MyD88, IKKbeta, and p65.", "label": "INHIBITOR", "metadata": []}
{"text": "<< IRF3 >> activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by [[ auranofin ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "IRF3 activation induced by MyD88-independent signaling components, << TRIF >> and TBK1, was also downregulated by [[ auranofin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "IRF3 activation induced by MyD88-independent signaling components, TRIF and << TBK1 >>, was also downregulated by [[ auranofin ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Our results first demonstrate that << auranofin >> suppresses the multiple steps in [[ TLR4 ]] signaling, especially the homodimerization of TLR4.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Our results first demonstrate that << auranofin >> suppresses the multiple steps in TLR4 signaling, especially the homodimerization of [[ TLR4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The results suggest that the suppression of << TLR4 >> activity by auranofin may be the molecular mechanism through which [[ auranofin ]] exerts anti-rheumatic activity.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The results suggest that the suppression of << TLR4 >> activity by [[ auranofin ]] may be the molecular mechanism through which auranofin exerts anti-rheumatic activity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Vandetanib >> (Caprelsa(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and [[ epidermal growth-factor receptors ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Vandetanib >> (Caprelsa(®), AstraZeneca) is a once-daily oral [[ tyrosine kinase ]] inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Vandetanib >> (Caprelsa(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by [[ growth-factor receptor tyrosine kinase ]] RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Vandetanib >> (Caprelsa(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase [[ RET ]] (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "Vandetanib (<< Caprelsa >>(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and [[ epidermal growth-factor receptors ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Vandetanib (<< Caprelsa >>(®), AstraZeneca) is a once-daily oral [[ tyrosine kinase ]] inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and epidermal growth-factor receptors.", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is << tranexamic acid >> (TXA), which, as a lysine mimetic, inhibits binding of [[ plasminogen ]] to fibrin.", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is << tranexamic acid >> (TXA), which, as a lysine mimetic, inhibits binding of plasminogen to [[ fibrin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is tranexamic acid (<< TXA >>), which, as a lysine mimetic, inhibits binding of [[ plasminogen ]] to fibrin.", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is tranexamic acid (<< TXA >>), which, as a lysine mimetic, inhibits binding of plasminogen to [[ fibrin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is tranexamic acid (TXA), which, as a << lysine >> mimetic, inhibits binding of [[ plasminogen ]] to fibrin.", "label": "INHIBITOR", "metadata": []}
{"text": "One exception is tranexamic acid (TXA), which, as a << lysine >> mimetic, inhibits binding of plasminogen to [[ fibrin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Coupling this computational technique with a high-quality low-throughput screen identified << 5-(4-piperidyl)-3-isoxazolol >> (4-PIOL) as a potent [[ plasminogen ]] binding inhibitor with the potential for the treatment of various bleeding disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "Coupling this computational technique with a high-quality low-throughput screen identified 5-(4-piperidyl)-3-isoxazolol (<< 4-PIOL >>) as a potent [[ plasminogen ]] binding inhibitor with the potential for the treatment of various bleeding disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "Epididymal tissue from wild-type mice responded in vitro to << noradrenaline >> and isoprenaline with increased glycerol release, reduced [[ IL-6 ]] release, and increased cAMP accumulation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Epididymal tissue from wild-type mice responded in vitro to noradrenaline and << isoprenaline >> with increased glycerol release, reduced [[ IL-6 ]] release, and increased cAMP accumulation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Phospholipase A2 >> inhibitors [[ p-bromophenacyl bromide ]] and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "ACTIVATOR", "metadata": []}
{"text": "Phospholipase A2 inhibitors << p-bromophenacyl bromide >> and arachidonyl trifluoromethyl ketone suppressed [[ interleukin-2 ]] (IL-2) expression in murine primary splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Phospholipase A2 inhibitors << p-bromophenacyl bromide >> and arachidonyl trifluoromethyl ketone suppressed interleukin-2 ([[ IL-2 ]]) expression in murine primary splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Phospholipase A2 inhibitors p-bromophenacyl bromide and << arachidonyl trifluoromethyl ketone >> suppressed [[ interleukin-2 ]] (IL-2) expression in murine primary splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Phospholipase A2 inhibitors p-bromophenacyl bromide and << arachidonyl trifluoromethyl ketone >> suppressed interleukin-2 ([[ IL-2 ]]) expression in murine primary splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Phospholipase A2 >> inhibitors p-bromophenacyl bromide and [[ arachidonyl trifluoromethyl ketone ]] suppressed interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Therefore, the objective of the present study was to investigate the effects of << PLA2 >> inhibitors [[ p-bromophenacyl bromide ]] (BPB) and arachidonyl trifluoromethyl ketone (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Therefore, the objective of the present study was to investigate the effects of << PLA2 >> inhibitors p-bromophenacyl bromide ([[ BPB ]]) and arachidonyl trifluoromethyl ketone (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Therefore, the objective of the present study was to investigate the effects of << PLA2 >> inhibitors p-bromophenacyl bromide (BPB) and [[ arachidonyl trifluoromethyl ketone ]] (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Therefore, the objective of the present study was to investigate the effects of << PLA2 >> inhibitors p-bromophenacyl bromide (BPB) and arachidonyl trifluoromethyl ketone ([[ AACOCF3 ]]) on interleukin-2 (IL-2) expression in murine primary splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner.", "label": "UPREGULATOR", "metadata": []}
{"text": "Pretreatment of the splenocytes with both << BPB >> and AACOCF3 suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pretreatment of the splenocytes with both BPB and << AACOCF3 >> suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition > 90% of << IL-2 >> secretion was observed at 1 microM [[ BPB ]] and 10 microM AACOCF3 compared to the respective vehicle control.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition > 90% of << IL-2 >> secretion was observed at 1 microM BPB and 10 microM [[ AACOCF3 ]] compared to the respective vehicle control.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Likewise, << IL-2 >> steady-state mRNA expression was inhibited by both PLA2 inhibitors in a concentration-dependent fashion with > 90% inhibition at 1 microM [[ BPB ]] and 20 microM AACOCF3.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Likewise, << IL-2 >> steady-state mRNA expression was inhibited by both PLA2 inhibitors in a concentration-dependent fashion with > 90% inhibition at 1 microM BPB and 20 microM [[ AACOCF3 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Likewise, IL-2 steady-state mRNA expression was inhibited by both << PLA2 >> inhibitors in a concentration-dependent fashion with > 90% inhibition at 1 microM [[ BPB ]] and 20 microM AACOCF3.", "label": "INHIBITOR", "metadata": []}
{"text": "Likewise, IL-2 steady-state mRNA expression was inhibited by both << PLA2 >> inhibitors in a concentration-dependent fashion with > 90% inhibition at 1 microM BPB and 20 microM [[ AACOCF3 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, these data demonstrated that PLA2 inhibitors << BPB >> and AACOCF3 are robust inhibitors of [[ IL-2 ]] expression at both the mRNA and protein levels in murine splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, these data demonstrated that PLA2 inhibitors BPB and << AACOCF3 >> are robust inhibitors of [[ IL-2 ]] expression at both the mRNA and protein levels in murine splenocytes.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Taken together, these data demonstrated that << PLA2 >> inhibitors [[ BPB ]] and AACOCF3 are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, these data demonstrated that << PLA2 >> inhibitors BPB and [[ AACOCF3 ]] are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes.", "label": "INHIBITOR", "metadata": []}
{"text": "The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are surgery and << imatinib >>, a selective [[ tyrosine kinase ]] inhibitor that allows achieving a stable or responding disease in about 80% of patients with unresectable/metastatic GIST.", "label": "INHIBITOR", "metadata": []}
{"text": "We have previously reported that << TZDs >> reduce estrogen synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC).", "label": "INHIBITOR", "metadata": []}
{"text": "We have previously reported that TZDs reduce << estrogen >> synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC).", "label": "PRODUCT-OF", "metadata": []}
{"text": "We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether << TZD >> inhibition of [[ aromatase ]] plays a role in their effects on bone metabolism.", "label": "INHIBITOR", "metadata": []}
{"text": "<< TZDs >> also inhibited [[ alkaline phosphatase ]] activity (58-75%, p<0.046) and osteocalcin production (52-75%, p<0.031).", "label": "INHIBITOR", "metadata": []}
{"text": "<< TZDs >> also inhibited alkaline phosphatase activity (58-75%, p<0.046) and [[ osteocalcin ]] production (52-75%, p<0.031).", "label": "INHIBITOR", "metadata": []}
{"text": "<< TZD >> effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on [[ aromatase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.", "label": "SUBSTRATE_PRODUCT-OF", "metadata": []}
{"text": "The << M564G >> mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated << CrAT >> showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type << CrAT >>, and lower activity toward its natural substrate, [[ acetyl-CoA ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "The << M564G >> mutated CrAT showed higher activity toward longer chain [[ acyl-CoAs ]]: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated << CrAT >> showed higher activity toward longer chain [[ acyl-CoAs ]]: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated CrAT showed higher activity toward longer chain << acyl-CoAs >>: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type [[ CrAT ]], and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << M564G >> mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward [[ myristoyl-CoA ]] was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated << CrAT >> showed higher activity toward longer chain acyl-CoAs: activity toward [[ myristoyl-CoA ]] was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward << myristoyl-CoA >> was 1250-fold higher than that of the wild-type [[ CrAT ]], and lower activity toward its natural substrate, acetyl-CoA.", "label": "SUBSTRATE", "metadata": []}
{"text": "Kinetic constants of the mutant << CrAT >> showed modification in favor of longer [[ acyl-CoAs ]] as substrates.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in << carnitine octanoyltransferase >> (COT) decreased activity toward its natural substrates, medium- and long-chain [[ acyl-CoAs ]], and increased activity toward short-chain acyl-CoAs.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in carnitine octanoyltransferase (<< COT >>) decreased activity toward its natural substrates, medium- and long-chain [[ acyl-CoAs ]], and increased activity toward short-chain acyl-CoAs.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in << carnitine octanoyltransferase >> (COT) decreased activity toward its natural substrates, medium- and long-chain acyl-CoAs, and increased activity toward short-chain [[ acyl-CoAs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in carnitine octanoyltransferase (<< COT >>) decreased activity toward its natural substrates, medium- and long-chain acyl-CoAs, and increased activity toward short-chain [[ acyl-CoAs ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "We conclude that Met564 blocks the entry of medium- and long-chain << acyl-CoAs >> to the catalytic site of [[ CrAT ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Catecholamines (<< adrenaline >>, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase ([[ phenylalanine hydroxylase ]], EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (<< adrenaline >>, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (<< adrenaline >>, noradrenaline and dopamine) are potent inhibitors of [[ phenylalanine 4-monooxygenase ]] (phenylalanine hydroxylase, EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, << noradrenaline >> and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase ([[ phenylalanine hydroxylase ]], EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, << noradrenaline >> and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, << noradrenaline >> and dopamine) are potent inhibitors of [[ phenylalanine 4-monooxygenase ]] (phenylalanine hydroxylase, EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, noradrenaline and << dopamine >>) are potent inhibitors of phenylalanine 4-monooxygenase ([[ phenylalanine hydroxylase ]], EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, noradrenaline and << dopamine >>) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Catecholamines (adrenaline, noradrenaline and << dopamine >>) are potent inhibitors of [[ phenylalanine 4-monooxygenase ]] (phenylalanine hydroxylase, EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Catecholamines >> (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase ([[ phenylalanine hydroxylase ]], EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Catecholamines >> (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Catecholamines >> (adrenaline, noradrenaline and dopamine) are potent inhibitors of [[ phenylalanine 4-monooxygenase ]] (phenylalanine hydroxylase, EC 1.14.16.1).", "label": "INHIBITOR", "metadata": []}
{"text": "Central and peripheral administration of << kisspeptin >> stimulates the hypothalamic-pituitary-gonadal (HPG) axis whilst pre-administration of a [[ gonadotrophin releasing hormone ]] (GnRH) antagonist abolishes this effect.", "label": "INHIBITOR", "metadata": []}
{"text": "Central and peripheral administration of << kisspeptin >> stimulates the hypothalamic-pituitary-gonadal (HPG) axis whilst pre-administration of a gonadotrophin releasing hormone ([[ GnRH ]]) antagonist abolishes this effect.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dexamethasone >> (DEX), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]].", "label": "AGONIST", "metadata": []}
{"text": "Dexamethasone (<< DEX >>), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]].", "label": "AGONIST", "metadata": []}
{"text": "Dexamethasone (DEX), << betamethasone >> (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]].", "label": "AGONIST", "metadata": []}
{"text": "Dexamethasone (DEX), betamethasone (<< BM >>), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]].", "label": "AGONIST", "metadata": []}
{"text": "The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity.", "label": "AGONIST", "metadata": []}
{"text": "Moreover, in rat hepatoma H4-II-E cells, the esterified-<< BM >> failed to induce tyrosine aminotransferase, which is regulated by [[ GR ]]-mediated transactivation activity.", "label": "AGONIST", "metadata": []}
{"text": "Consistent with the weak transactivation activity of esterified-<< BM >> mediated by [[ rat GR ]], there were few side effects, evaluated by thymus involution and body weight loss, in an antigen-induced asthmatic model in rats.", "label": "AGONIST", "metadata": []}
{"text": "Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and [[ all-trans retinoic acid ]] (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and all-trans retinoic acid ([[ atRA ]]) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Although the data collected on << IGFBP-rP3 >> in prostate are modest, its role as a growth stimulator and/or protooncogene is supported by its preferential expression in cancerous cells and its down-regulation by [[ atRA ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "On the basis of FIP1L1-PDGFRa fusion gene hypereosinophilic syndrome would be classified as a clonal disease and in the FIP1L1-PDGFRa positive cases the << tyrosine kinase >> inhibitor [[ imatinib mesylate ]] (Glivec) would be effective.", "label": "INHIBITOR", "metadata": []}
{"text": "Transport by << OATP1B1 >> and OATP1B3 enhances the cytotoxicity of epigallocatechin 3-O-gallate and several [[ quercetin ]] derivatives.", "label": "SUBSTRATE", "metadata": []}
{"text": "Transport by OATP1B1 and << OATP1B3 >> enhances the cytotoxicity of epigallocatechin 3-O-gallate and several [[ quercetin ]] derivatives.", "label": "SUBSTRATE", "metadata": []}
{"text": "Transport by << OATP1B1 >> and OATP1B3 enhances the cytotoxicity of [[ epigallocatechin 3-O-gallate ]] and several quercetin derivatives.", "label": "SUBSTRATE", "metadata": []}
{"text": "Transport by OATP1B1 and << OATP1B3 >> enhances the cytotoxicity of [[ epigallocatechin 3-O-gallate ]] and several quercetin derivatives.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates << estradiol 17β-glucuronide >>, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates << estradiol 17β-glucuronide >>, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, << estrone 3-sulfate >>, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, << estrone 3-sulfate >>, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and << dehydroepiandrosterone sulfate >> (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and << dehydroepiandrosterone sulfate >> (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and dehydroepiandrosterone sulfate (<< DHEAS >>) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3.", "label": "SUBSTRATE", "metadata": []}
{"text": "Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and dehydroepiandrosterone sulfate (<< DHEAS >>) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Compound 6 stimulated OATP1B3-mediated << estradiol 17β-glucuronide >> uptake by increasing the apparent affinity of [[ OATP1B3 ]] for its substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "Compound 6 stimulated << OATP1B3 >>-mediated [[ estradiol 17β-glucuronide ]] uptake by increasing the apparent affinity of OATP1B3 for its substrate.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cytotoxicity assays demonstrated that << epigallocatechin 3-O-gallate >> (EGCG) and most of compounds 1-6 killed preferentially [[ OATP ]]-expressing CHO cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cytotoxicity assays demonstrated that epigallocatechin 3-O-gallate (<< EGCG >>) and most of compounds 1-6 killed preferentially [[ OATP ]]-expressing CHO cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "EGCG, 1, and 3 were the most potent cytotoxic compounds, with << EGCG >> and 3 selectively killing [[ OATP1B3 ]]-expressing cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Reboxetine >>, a selective norepinephrine reuptake inhibitor, exhibits high affinity and selectivity for the [[ human norepinephrine transporter ]].", "label": "INHIBITOR", "metadata": []}
{"text": "We previously employed a chemical genomic strategy to identify a novel small molecule, << MAC13243 >>, as a likely inhibitor of the [[ bacterial lipoprotein ]] targeting chaperone, LolA.", "label": "INHIBITOR", "metadata": []}
{"text": "We previously employed a chemical genomic strategy to identify a novel small molecule, << MAC13243 >>, as a likely inhibitor of the bacterial lipoprotein targeting [[ chaperone ]], LolA.", "label": "INHIBITOR", "metadata": []}
{"text": "We previously employed a chemical genomic strategy to identify a novel small molecule, << MAC13243 >>, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, [[ LolA ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of [[ Oct4 ]] and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and [[ Nanog ]] proteins, while only BPA could downregulate the expression of E-cadherin protein.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only << BPA >> could downregulate the expression of [[ E-cadherin ]] protein.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "To this end, 158N murine oligodendrocytes were treated with << 7KC >> or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "To this end, 158N murine oligodendrocytes were treated with << 7KC >> or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and [[ caspase-3 ]] activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and [[ caspase-3 ]] activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains.", "label": "ACTIVATOR", "metadata": []}
{"text": "Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving GSK-3 and [[ caspase-3 ]] activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Sulindac sulfide >> inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and [[ Bad ]] in human colon cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac sulfide >> inhibits [[ epidermal growth factor ]]-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac >> and selective [[ cyclooxygenase (COX)-2 ]] inhibitors cause regression of colonic polyps in familial polyposis patients.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sulindac >> metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit [[ ERK1/2 ]] phosphorylation in human colon cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "EGF-stimulated phosphorylation of ERK and Bad is blocked by pretreatment with << U0126 >>, a selective [[ MAP kinase kinase (MKK)1/2 ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "<< EGF >>-stimulated phosphorylation of ERK and Bad is blocked by pretreatment with [[ U0126 ]], a selective MAP kinase kinase (MKK)1/2 inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "EGF-stimulated phosphorylation of << ERK >> and Bad is blocked by pretreatment with [[ U0126 ]], a selective MAP kinase kinase (MKK)1/2 inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "EGF-stimulated phosphorylation of ERK and << Bad >> is blocked by pretreatment with [[ U0126 ]], a selective MAP kinase kinase (MKK)1/2 inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, pretreatment with << sulindac sulfide >> blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total [[ Bad ]] but not ERK1/2 protein levels.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Similarly, pretreatment with << sulindac sulfide >> blocks the ability of [[ EGF ]] to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Similarly, pretreatment with << sulindac sulfide >> blocks the ability of EGF to induce ERK1/2 and [[ Bad ]] phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels.", "label": "INHIBITOR", "metadata": []}
{"text": "The ability of << sulindac >> to block [[ ERK1/2 ]] signaling by the EGF receptor may account for at least part of its potent growth-inhibitory effects against cancer cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The ability of << sulindac >> to block ERK1/2 signaling by the [[ EGF receptor ]] may account for at least part of its potent growth-inhibitory effects against cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "After inflammation was established mice were dosed with the << H4R >> antagonist, [[ JNJ 7777120 ]], or anti-IL-13 antibody for comparison.", "label": "ANTAGONIST", "metadata": []}
{"text": "Development and validation of a non-radioactive << DNA polymerase >> assay for studying cytomegalovirus resistance to [[ foscarnet ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of << polymerases >> containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of [[ foscarnet ]] eight to 14 times higher than those required to inhibit wild-type polymerases.", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (<< V715M >>, T700A and N495K) was inhibited by concentrations of [[ foscarnet ]] eight to 14 times higher than those required to inhibit wild-type polymerases.", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, << T700A >> and N495K) was inhibited by concentrations of [[ foscarnet ]] eight to 14 times higher than those required to inhibit wild-type polymerases.", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and << N495K >>) was inhibited by concentrations of [[ foscarnet ]] eight to 14 times higher than those required to inhibit wild-type polymerases.", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of << foscarnet >> eight to 14 times higher than those required to inhibit wild-type [[ polymerases ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Absorption and secretion of << fluoride >> increase at acid pH levels, possibly because of its non-ionized state at these pHs and/or because of participation of a F(-)/H(+) cotransporter or a [[ F(-)/OH(-) antiporter ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Absorption and secretion of << fluoride >> increase at acid pH levels, possibly because of its non-ionized state at these pHs and/or because of participation of a [[ F(-)/H(+) cotransporter ]] or a F(-)/OH(-) antiporter.", "label": "SUBSTRATE", "metadata": []}
{"text": "Structure activity relationship studies of << tricyclic bispyran sulfone >> [[ γ-secretase ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (<< SCH 900229 >>), a potent, [[ PS1 ]]-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (<< SCH 900229 >>), a potent, PS1-selective [[ γ-secretase ]] inhibitor and clinical candidate for the treatment of Alzheimer's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing [[ K18 ]] as well as an increase in the abundance of K18 mRNA.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of [[ K18 ]] mRNA.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a \"neuroadaptive response\".", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a \"neuroadaptive response\".", "label": "DOWNREGULATOR", "metadata": []}
{"text": "To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "However, only << MDMA >> reduced [[ SERT ]] density.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Curcumin >> improves TNBS-induced colitis in rats by inhibiting [[ IL-27 ]] expression via the TLR4/NF-κB signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Curcumin >> improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the [[ TLR4 ]]/NF-κB signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Curcumin >> improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the TLR4/[[ NF-κB ]] signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-κB signaling pathway and [[ IL-27 ]] expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the [[ TLR4 ]]/NF-κB signaling pathway and IL-27 expression.", "label": "INHIBITOR", "metadata": []}
{"text": "This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the TLR4/[[ NF-κB ]] signaling pathway and IL-27 expression.", "label": "INHIBITOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of [[ NF-κB ]] mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, [[ IL-27 ]] mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, [[ TLR4 ]] protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, [[ NF-κB ]] p65 protein, and IL-27 p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB [[ p65 ]] protein, and IL-27 p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and [[ IL-27 ]] p28 protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 [[ p28 ]] protein (p < 0.05).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, [[ myeloperoxidase ]] activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05).", "label": "INHIBITOR", "metadata": []}
{"text": "There was no significant difference in << TLR4 >>, NF-κB, and IL-27 mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "There was no significant difference in TLR4, << NF-κB >>, and IL-27 mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "There was no significant difference in << TLR4 >>, NF-κB, and IL-27 mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "There was no significant difference in TLR4, << NF-κB >>, and IL-27 mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The anti-inflammatory actions of << curcumin >> on colitis may involve inhibition of the TLR4/NF-κB signaling pathway and of [[ IL-27 ]] expression.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The anti-inflammatory actions of << curcumin >> on colitis may involve inhibition of the [[ TLR4 ]]/NF-κB signaling pathway and of IL-27 expression.", "label": "INHIBITOR", "metadata": []}
{"text": "The anti-inflammatory actions of << curcumin >> on colitis may involve inhibition of the TLR4/[[ NF-κB ]] signaling pathway and of IL-27 expression.", "label": "INHIBITOR", "metadata": []}
{"text": "A << KCC >> inhibitor-[[ [(dihydroindenyl)oxy] alkanoic acid ]] (DIOA)-blocked RVD more in HCEC than RCEC.", "label": "INHIBITOR", "metadata": []}
{"text": "A << KCC >> inhibitor-[(dihydroindenyl)oxy] alkanoic acid ([[ DIOA ]])-blocked RVD more in HCEC than RCEC.", "label": "INHIBITOR", "metadata": []}
{"text": "Under isotonic conditions, << N-ethylmaleimide >> (NEM) produced [[ KCC ]] activation and transient cell shrinkage.", "label": "ACTIVATOR", "metadata": []}
{"text": "Under isotonic conditions, N-ethylmaleimide (<< NEM >>) produced [[ KCC ]] activation and transient cell shrinkage.", "label": "ACTIVATOR", "metadata": []}
{"text": "Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide cholecystokinin ([[ CCK ]]) antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide [[ cholecystokinin ]] (CCK) antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "The most potent compound, << D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid >> (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini.", "label": "ANTAGONIST", "metadata": []}
{"text": "The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (<< lorglumide >>, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini.", "label": "ANTAGONIST", "metadata": []}
{"text": "The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, << CR 1409 >>), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini.", "label": "ANTAGONIST", "metadata": []}
{"text": "In vivo << lorglumide >> antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. [[ CCK-8 ]] or ceruletide (caerulein).", "label": "ANTAGONIST", "metadata": []}
{"text": "Synthesis and Structure-Activity Relationship Studies of Derivatives of the Dual << Aromatase >>-Sulfatase Inhibitor [[ 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and Structure-Activity Relationship Studies of Derivatives of the Dual Aromatase-<< Sulfatase >> Inhibitor [[ 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate ]].", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (<< F >>, Cl, Br) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (<< F >>, Cl, Br) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "<< 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate >> and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "<< 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate >> and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, << Cl >>, Br) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, << Cl >>, Br) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, << Br >>) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, << Br >>) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs).", "label": "INHIBITOR", "metadata": []}
{"text": "The most potent in vitro DASI discovered is an << imidazole >> derivative with IC50 values against [[ aromatase ]] and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5 nM, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "The most potent in vitro DASI discovered is an << imidazole >> derivative with IC50 values against aromatase and [[ steroid sulfatase ]] in a JEG-3 cell preparation of 0.2 and 2.5 nM, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "The parent << phenol >> of this compound inhibits [[ aromatase ]] with an IC50 value of 0.028 nM in the same assay.", "label": "INHIBITOR", "metadata": []}
{"text": "As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both << dimethyldiguanide >> (DC, 0.6gkg(-1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in down-regulation of blood glucose and [[ insulin ]] levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These findings demonstrate that cinnamon << polyphenols >> can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of [[ iNOS ]], NF-κB activation.", "label": "INHIBITOR", "metadata": []}
{"text": "These findings demonstrate that cinnamon << polyphenols >> can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of iNOS, [[ NF-κB ]] activation.", "label": "INHIBITOR", "metadata": []}
{"text": "These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans.", "label": "UPREGULATOR", "metadata": []}
{"text": "Effects of << ORF 17583 >>, other [[ histamine H2-receptor ]] antagonists and omeprazole on gastric acid secretory states in rats and dogs.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< ORF 17583 >>, a [[ histamine H2-receptor ]] antagonist, inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 4.9 mg/kg intraduodenal; 3.4 mg/kg p.o.; and 0.21 mg/kg i.p.) and in total gastric fistula or Heidenhain pouch dogs stimulated by betazole (ED50 = 0.12 mg/kg p.o. and 0.08 mg/kg i.v.), histamine, tetragastrin, bethanechol, 2-deoxy-D-glucose or a meal (ED50 values ranged from 0.11-0.26 mg/kg p.o.).", "label": "ANTAGONIST", "metadata": []}
{"text": "This study examined the inward transport of << l-[(14)C]alanine >>, an [[ ASCT2 ]] preferential substrate, in monolayers of immortalized renal proximal tubular epithelial (PTE) cells from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by << alanine >>, serine, and cysteine, which is consistent with amino acid transport through [[ ASCT2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, << serine >>, and cysteine, which is consistent with amino acid transport through [[ ASCT2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and << cysteine >>, which is consistent with amino acid transport through [[ ASCT2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In the presence of the system L inhibitor BCH, Na(+)-dependent << l-alanine >> uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and cysteine, which is consistent with amino acid transport through [[ ASCT2 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and cysteine, which is consistent with << amino acid >> transport through [[ ASCT2 ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells.", "label": "UPREGULATOR", "metadata": []}
{"text": "Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells.", "label": "UPREGULATOR", "metadata": []}
{"text": "Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through [[ ASCT2 ]] between WKY and SHR PTE cells correlated positively with differences in ASCT2 protein expression, this being more abundant in WKY PTE cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport.", "label": "UPREGULATOR", "metadata": []}
{"text": "In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport.", "label": "UPREGULATOR", "metadata": []}
{"text": "In conclusion, immortalized SHR and WKY PTE cells take up << l-alanine >> mainly through a high-affinity [[ Na(+)-dependent amino acid transporter ]], with functional features of ASCT2 transport.", "label": "SUBSTRATE", "metadata": []}
{"text": "In conclusion, immortalized SHR and WKY PTE cells take up << l-alanine >> mainly through a high-affinity Na(+)-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport.", "label": "SUBSTRATE", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide block [[ erg3 ]], a human brain K(+) channel.", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide block erg3, a [[ human brain K(+) channel ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> block [[ erg3 ]], a human brain K(+) channel.", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> block erg3, a [[ human brain K(+) channel ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the [[ cardiac K(+) channel ]] known as HERG (human ether-a-go-go-related gene; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as [[ HERG ]] (human ether-a-go-go-related gene; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG ([[ human ether-a-go-go-related gene ]]; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs << sertindole >> and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG (human ether-a-go-go-related gene; [[ erg1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> are known to prolong the QT interval on the electrocardiogram via a high affinity block of the [[ cardiac K(+) channel ]] known as HERG (human ether-a-go-go-related gene; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as [[ HERG ]] (human ether-a-go-go-related gene; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG ([[ human ether-a-go-go-related gene ]]; erg1).", "label": "INHIBITOR", "metadata": []}
{"text": "The antipsychotic drugs sertindole and << pimozide >> are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG (human ether-a-go-go-related gene; [[ erg1 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Block of << erg3 >> by [[ sertindole ]] also displayed a positive voltage-dependence.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pimozide >> blocked [[ erg3 ]] channel currents with an IC(50) of 103 nM and significant inhibition was noted at concentrations of 10 nM and higher.", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << erg3 >> can be blocked by certain antipsychotic drugs like [[ sertindole ]] and pimozide.", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << erg3 >> can be blocked by certain antipsychotic drugs like sertindole and [[ pimozide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "An amphiphile with branched << poly(ethylene glycol) >> architecture also activated the [[ lectin ]] pathway but only through L-ficolin recognition.", "label": "ACTIVATOR", "metadata": []}
{"text": "Conformational variations of both << phosphodiesterase-5 >> and inhibitors provide the structural basis for the physiological effects of vardenafil and [[ sildenafil ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Cucurbitacin I >> inhibits [[ rac1 ]] activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of janus tyrosine kinase 2 and p-rex1.", "label": "INHIBITOR", "metadata": []}
{"text": "Here we found that the anticancer agent << cucurbitacin I >>, a [[ Jak2 ]] inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Here we found that the anticancer agent << cucurbitacin I >>, a Jak2 inhibitor, reduced the activation of [[ Rac1 ]] and motility in response to the ErbB3 ligand heregulin in breast cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the [[ Rho ]] effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the Rho effector [[ Rho kinase ]] (ROCK) in breast cancer cells and induces the formation of stress fibers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the Rho effector Rho kinase ([[ ROCK ]]) in breast cancer cells and induces the formation of stress fibers.", "label": "ACTIVATOR", "metadata": []}
{"text": "Interestingly, disruption of the RhoA-ROCK pathway prevented the inhibitory effect of << cucurbitacin I >> on [[ Rac1 ]] activation by heregulin.", "label": "INHIBITOR", "metadata": []}
{"text": "Lastly, we found that << RhoA >> activation by [[ cucurbitacin I ]] is mediated by reactive oxygen species (ROS).", "label": "ACTIVATOR", "metadata": []}
{"text": "The ROS scavenger << N-acetyl l-cysteine >> and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on [[ Rac1 ]] activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "The ROS scavenger N-acetyl l-cysteine and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of << cucurbitacin I >> on [[ Rac1 ]] activation.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, they established that the inhibitory effect of << cucurbitacin I >> on [[ Rac1 ]] activity involves the alteration of the balance between Rho and Rac.", "label": "INHIBITOR", "metadata": []}
{"text": "Brain but not spinal << NR2B >> receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model.", "label": "ANTAGONIST", "metadata": []}
{"text": "Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an << NR2B >> subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model.", "label": "ANTAGONIST", "metadata": []}
{"text": "In order to examine the site of action of an << NR2B >> subtype-selective NMDA antagonist [[ CP-101,606 ]], we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration.", "label": "ANTAGONIST", "metadata": []}
{"text": "In order to examine the site of action of an NR2B subtype-selective << NMDA >> antagonist [[ CP-101,606 ]], we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration.", "label": "ANTAGONIST", "metadata": []}
{"text": "These findings suggest that the anti-allodynia effect of << CP-101,606 >> is ascribable to blockade of [[ NR2B ]] receptors at the brain, but not at the spinal cord.", "label": "INHIBITOR", "metadata": []}
{"text": "In contrast, intrathecal injection of a non-selective << NMDA >> antagonist, [[ memantine ]], significantly inhibited CCI-induced mechanical allodynia at a dose of 300 nmol, indicating the difference in the site of action between the non-selective NMDA antagonist and the NR2B-specific NMDA antagonist.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Rasagiline >> [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible [[ monoamine oxidase ]] (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rasagiline >> [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible monoamine oxidase ([[ MAO ]]) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Rasagiline [N-propargyl-1R(+)-aminoindan; << TVP1012 >>] is a potent irreversible [[ monoamine oxidase ]] (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Rasagiline [N-propargyl-1R(+)-aminoindan; << TVP1012 >>] is a potent irreversible monoamine oxidase ([[ MAO ]]) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Rasagiline [<< N-propargyl-1R(+)-aminoindan >>; TVP1012] is a potent irreversible [[ monoamine oxidase ]] (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Rasagiline [<< N-propargyl-1R(+)-aminoindan >>; TVP1012] is a potent irreversible monoamine oxidase ([[ MAO ]]) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "label": "INHIBITOR", "metadata": []}
{"text": "Reserpine-induced ptosis was reversed by << rasagiline >> at doses above 2 mg x kg(-1) i.p., which inhibit [[ MAO-A ]] as well as MAO-B, but not at MAO-B-selective doses.", "label": "INHIBITOR", "metadata": []}
{"text": "Reserpine-induced ptosis was reversed by << rasagiline >> at doses above 2 mg x kg(-1) i.p., which inhibit MAO-A as well as [[ MAO-B ]], but not at MAO-B-selective doses.", "label": "INHIBITOR", "metadata": []}
{"text": "However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both << MAO-A >> and MAO-B by [[ tranylcypromine ]] together with the monoamine precursors.", "label": "INHIBITOR", "metadata": []}
{"text": "However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and << MAO-B >> by [[ tranylcypromine ]] together with the monoamine precursors.", "label": "INHIBITOR", "metadata": []}
{"text": "However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both << MAO-A >> and MAO-B by tranylcypromine together with the [[ monoamine ]] precursors.", "label": "INHIBITOR", "metadata": []}
{"text": "However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and << MAO-B >> by tranylcypromine together with the [[ monoamine ]] precursors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rasagiline >> does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit [[ MAO-B ]] but not MAO-A.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rasagiline >> does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit MAO-B but not [[ MAO-A ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Omega class GSTs >> have dehydroascorbate reductase and thioltransferase activities and also catalyze the reduction of [[ monomethylarsonate ]], an intermediate in the pathway of arsenic biotransformation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces acetyl groups plus [[ aspartate ]] and has been proposed to occur in both soluble and membranous subfractions of white matter.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces acetyl groups plus [[ aspartate ]] and has been proposed to occur in both soluble and membranous subfractions of white matter.", "label": "PRODUCT-OF", "metadata": []}
{"text": "It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and [[ BRCA2 ]] mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Troglitazone inhibited the antigen-induced production of LTB(4), C(4) and E(4) and the potency of the inhibition was comparable to that of << zileuton >>, a specific inhibitor of [[ 5-lipoxygenase ]] (5-LOX) and a clinically used anti-asthmatic drug.", "label": "INHIBITOR", "metadata": []}
{"text": "Troglitazone inhibited the antigen-induced production of LTB(4), C(4) and E(4) and the potency of the inhibition was comparable to that of << zileuton >>, a specific inhibitor of 5-lipoxygenase ([[ 5-LOX ]]) and a clinically used anti-asthmatic drug.", "label": "INHIBITOR", "metadata": []}
{"text": "Troglitazone inhibited LTB(4) production by the supernatant fraction of RBL-2H3 cell lysate with similar potency to << zileuton >>, suggesting that troglitazone inhibits LT production by direct inhibition of [[ 5-LOX ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Troglitazone inhibited LTB(4) production by the supernatant fraction of RBL-2H3 cell lysate with similar potency to zileuton, suggesting that << troglitazone >> inhibits LT production by direct inhibition of [[ 5-LOX ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "These findings suggest that << troglitazone >> inhibits antigen-induced LT production in the IgE-sensitized RBL-2H3 cells and A23187-stimulated rat peritoneal neutrophils by direct inhibition of [[ 5-LOX ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "The positive correlation between << vitamin A >> and immunoglobulin A concentrations might be the result of the vitamin A inductive effect during [[ immunoglobulins A ]] synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "The positive correlation between vitamin A and immunoglobulin A concentrations might be the result of the << vitamin A >> inductive effect during [[ immunoglobulins A ]] synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "Experimental as well as clinical reports support the hypothesis that << calcium channel >> blockers such as [[ verapamil ]] may be an appropriate therapeutic approach in LQTS.", "label": "INHIBITOR", "metadata": []}
{"text": "METHODS AND RESULTS: In 8 Langendorff-perfused rabbit hearts, << veratridine >> (0.1 microM), an inhibitor of [[ sodium channel ]] inactivation, led to a marked increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p < 0.05) thereby mimicking LQT3.", "label": "INHIBITOR", "metadata": []}
{"text": "Specificity of << zebrafish retinol saturase >>: formation of [[ all-trans-13,14-dihydroretinol ]] and all-trans-7,8- dihydroretinol.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Specificity of << zebrafish retinol saturase >>: formation of all-trans-13,14-dihydroretinol and [[ all-trans-7,8- dihydroretinol ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Specifically, << all-trans-13,14-dihydroretinol >> is transiently oxidized to all-trans-13,14-dihydroretinoic acid before being oxidized further by [[ Cyp26 ]] enzymes.", "label": "SUBSTRATE", "metadata": []}
{"text": "Unlike mouse RetSat (mRetSat), << zRetSat A >> had an altered bond specificity saturating either the 13-14 or 7-8 double bonds of all-trans-retinol to produce either [[ all-trans-13,14-dihydroretinol ]] or all-trans-7,8-dihydroretinol, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Unlike mouse RetSat (mRetSat), << zRetSat A >> had an altered bond specificity saturating either the 13-14 or 7-8 double bonds of all-trans-retinol to produce either all-trans-13,14-dihydroretinol or [[ all-trans-7,8-dihydroretinol ]], respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Unlike mouse RetSat (mRetSat), << zRetSat A >> had an altered bond specificity saturating either the 13-14 or 7-8 double bonds of [[ all-trans-retinol ]] to produce either all-trans-13,14-dihydroretinol or all-trans-7,8-dihydroretinol, respectively.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< zRetSat A >> also saturated the 13-14 or 7-8 double bonds of [[ all-trans-3,4-didehydroretinol ]] (vitamin A2), a second endogenous form of vitamin A in zebrafish.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< zRetSat A >> also saturated the 13-14 or 7-8 double bonds of all-trans-3,4-didehydroretinol ([[ vitamin A2 ]]), a second endogenous form of vitamin A in zebrafish.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Rasagiline >> is a novel, potent, and irreversible [[ monoamine oxidase type B ]] (MAO-B) inhibitor which has been approved for treatment of PD.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rasagiline >> is a novel, potent, and irreversible monoamine oxidase type B ([[ MAO-B ]]) inhibitor which has been approved for treatment of PD.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Rasagiline >> inhibits [[ MAO-B ]] more potently than selegiline and has the advantage of once-daily dosing.", "label": "INHIBITOR", "metadata": []}
{"text": "Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that << lithium >> produces a large potentiation of the [[ GluR3 flop ]] splice variant and suggested that lithium might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).", "label": "ACTIVATOR", "metadata": []}
{"text": "Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).", "label": "UPREGULATOR", "metadata": []}
{"text": "We now show that mutation of the 769R/ G desensitization site (Lomeli, H.M.J., Melcher, T., Hoger, T., Geiger, J.R., Kuner, T., Monyer, H., Higuchi, M.B.A. and Seeburg, P.H, Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science, 9(266) (1994) 1709-1713) greatly attenuates the << lithium >>-induced potentiation of [[ GluR3 ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "Additionally, experiments with the non-desensitizing site-directed mutant GluR3(L507Y) (Stern-Bach, Y., Russo, S., Neuman, M. and Rosenmund, C., A point mutation in the glutamate binding site blocks desensitization of AMPA receptors. Neuron, 21 (1998) 907-918) further confirms that << lithium >> enhances [[ GluR3 ]] responses by reducing desensitization, since lithium's effects are reversed in this mutant.", "label": "ACTIVATOR", "metadata": []}
{"text": "Specifically, << aniracetam >>, which potentiates wild-type [[ AMPA receptors ]], is ineffective on the non-desensitizing GluR3(L507Y) mutant, but has synergistic effects with lithium on wild-type receptors.", "label": "ACTIVATOR", "metadata": []}
{"text": "Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing << GluR3 >>(L507Y) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors.", "label": "ACTIVATOR", "metadata": []}
{"text": "Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(<< L507Y >>) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors.", "label": "ACTIVATOR", "metadata": []}
{"text": "The << BH(4) >> treatment was associated with a 2-fold increase in [[ eNOS ]] activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats.", "label": "ACTIVATOR", "metadata": []}
{"text": "The << BH(4) >> treatment also partially improved the [[ insulin ]] sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "It has been claimed that << hCTR1 >>, the human high affinity copper transporter, is the major entry pathway for [[ cDDP ]] and related drugs via a mechanism that mimics copper.", "label": "SUBSTRATE", "metadata": []}
{"text": "It has been claimed that hCTR1, the << human high affinity copper transporter >>, is the major entry pathway for [[ cDDP ]] and related drugs via a mechanism that mimics copper.", "label": "SUBSTRATE", "metadata": []}
{"text": "We confirm the correlation between higher << hCTR1 >> levels and higher [[ Pt ]]-drug uptake in tumor cells sensitive to the drug.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the DRN, << brexpiprazole >> completely inhibited the firing of 5-HT neurons via [[ 5-HT1A ]] agonism and was more potent than aripiprazole (ED50 = 230 and 700 mug/kg, respectively).", "label": "AGONIST", "metadata": []}
{"text": "In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via << 5-HT1A >> agonism and was more potent than [[ aripiprazole ]] (ED50 = 230 and 700 mug/kg, respectively).", "label": "AGONIST", "metadata": []}
{"text": "In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential << 5-HT2A >> receptor agonist [[ DOI ]] (2,5-dimethoxy-4-iodoamphetamine) on norepinephrine neuronal firing (ED50 = 110 mug/kg), demonstrating 5-HT2A antagonistic action.", "label": "AGONIST", "metadata": []}
{"text": "In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential << 5-HT2A >> receptor agonist DOI ([[ 2,5-dimethoxy-4-iodoamphetamine ]]) on norepinephrine neuronal firing (ED50 = 110 mug/kg), demonstrating 5-HT2A antagonistic action.", "label": "AGONIST", "metadata": []}
{"text": "Brexpiprazole reversed the inhibitory effect of the DA agonist << apomorphine >> on VTA DA neurons (ED50 = 61 mug/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on [[ D2 receptors ]].", "label": "AGONIST", "metadata": []}
{"text": "Compared with aripiprazole, which significantly inhibited the firing activity of VTA DA neurons, << brexpiprazole >> displayed less efficacy at [[ D2 receptors ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "In the lateral geniculate nucleus, << brexpiprazole >> displayed [[ alpha1B-adrenoceptor ]] antagonistic action.", "label": "ANTAGONIST", "metadata": []}
{"text": "For << AII >> and ET1, MAP was also increased for the [[ fenofibrate ]] group but not in a dose-dependent fashion.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "For AII and << ET1 >>, MAP was also increased for the [[ fenofibrate ]] group but not in a dose-dependent fashion.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Nanobody-albumin nanoparticles (NANAPs) for the delivery of a << multikinase >> inhibitor [[ 17864 ]] to EGFR overexpressing tumor cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately 100nm were loaded with the << multikinase >> inhibitor [[ 17864 ]]-L(x)-a platinum-bound sunitinib analogue-which couples the drug to methionine residues of albumin and is released in a reductive environment.", "label": "INHIBITOR", "metadata": []}
{"text": "Endogenously produced asymmetrically methylated << arginine >> residues are competitive inhibitors of all three isoforms of [[ nitric oxide synthase ]] (NOS).", "label": "INHIBITOR", "metadata": []}
{"text": "Endogenously produced asymmetrically methylated << arginine >> residues are competitive inhibitors of all three isoforms of nitric oxide synthase ([[ NOS ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "The enzyme << dimethylarginine dimethylaminohydrolase >> (DDAH) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines.", "label": "SUBSTRATE", "metadata": []}
{"text": "The enzyme dimethylarginine dimethylaminohydrolase (<< DDAH >>) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines.", "label": "SUBSTRATE", "metadata": []}
{"text": "Previously we have proposed that regulation of asymmetric << methylarginine >> concentration by [[ DDAH ]] may provide a novel mechanism for the regulation of NOS activity in vivo.", "label": "SUBSTRATE", "metadata": []}
{"text": "Structure-based design of novel << dihydroisoquinoline >> [[ BACE-1 ]] inhibitors that do not engage the catalytic aspartates.", "label": "INHIBITOR", "metadata": []}
{"text": "The structure-activity relationship of a series of << dihydroisoquinoline >> [[ BACE-1 ]] inhibitors is described.", "label": "INHIBITOR", "metadata": []}
{"text": "Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating plasmin, has been demonstrated to induce [[ matrix metalloproteinase-9 ]] (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating [[ plasmin ]], has been demonstrated to induce matrix metalloproteinase-9 (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, tPA induced rapid << tyrosine >> phosphorylation on the beta subunit of LRP-1, which was followed by the activation of [[ Mek1 ]] and its downstream Erk-1 and -2.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, tPA induced rapid << tyrosine >> phosphorylation on the beta subunit of LRP-1, which was followed by the activation of Mek1 and its downstream [[ Erk-1 and -2 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The data show that << CP[c]Ph >> is less potent at inducing [[ CYP1A ]] gene expression in rainbow trout than benzo[a]pyrene (B[a]P), a well-known Ah-receptor agonist.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than [[ benzo[a]pyrene ]] (B[a]P), a well-known Ah-receptor agonist.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than benzo[a]pyrene ([[ B[a]P ]]), a well-known Ah-receptor agonist.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Interestingly, the << CP[c]Ph >> dependent up-regulation of [[ CYP1A ]] mRNA is positively correlated with the incidences of clastogenic changes in rainbow trout erythrocytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< CP[c]Ph >> has, comparably to B[a]P, a potential to repress expression of [[ tumor suppressor p53 ]], in the head kidney of rainbow trout.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "CP[c]Ph has, comparably to << B[a]P >>, a potential to repress expression of [[ tumor suppressor p53 ]], in the head kidney of rainbow trout.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Identification of << benzofuran >> central cores for the inhibition of [[ leukotriene A(4) hydrolase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to [[ LTB(4) ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Leukotriene A(4) hydrolase >> (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to [[ LTB(4) ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of [[ LTA(4) ]] to LTB(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Leukotriene A(4) hydrolase >> (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of [[ LTA(4) ]] to LTB(4).", "label": "SUBSTRATE", "metadata": []}
{"text": "This paper describes the identification and synthesis of substituted << benzofurans >> as [[ LTH(4)H ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Benzofuran >> 28 showed dose responsive target engagement and provides a useful tool to explore a [[ LTA(4)H ]] inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Minocycline >> treatment prevents the formation of activated [[ caspase-3 ]], a known effector of apoptosis, as well as the appearance of a calpain cleaved substrate, a marker of excitotoxic/necrotic cell death.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Neurochemical effects of the << monoamine oxidase >> inhibitor [[ phenelzine ]] on brain GABA and alanine: A comparison with vigabatrin.", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare << phenelzine >> (PLZ), an antidepressant drug with anxiolytic properties which inhibits [[ monoamine oxidase ]] (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare << phenelzine >> (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase ([[ MAO ]]) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with << vigabatrin >> (VIG), an anticonvulsant which elevates brain GABA by inhibition of [[ GABA transaminase ]] (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with << vigabatrin >> (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase ([[ GABA-T ]]), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (<< VIG >>), an anticonvulsant which elevates brain GABA by inhibition of [[ GABA transaminase ]] (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (<< VIG >>), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase ([[ GABA-T ]]), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (<< PLZ >>), an antidepressant drug with anxiolytic properties which inhibits [[ monoamine oxidase ]] (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "PURPOSE: To compare phenelzine (<< PLZ >>), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase ([[ MAO ]]) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: Both << PLZ >> and VIG inhibited [[ GABA-T ]] and elevated GABA levels.", "label": "INHIBITOR", "metadata": []}
{"text": "RESULTS: Both PLZ and << VIG >> inhibited [[ GABA-T ]] and elevated GABA levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Only << PLZ >> inhibited [[ MAO ]] and ALA-T and elevated ALA levels.", "label": "INHIBITOR", "metadata": []}
{"text": "Only << PLZ >> inhibited MAO and [[ ALA-T ]] and elevated ALA levels.", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of PLZ on both amino acids and their transaminases were blocked by pre-treatment with the << MAO >> inhibitor [[ tranylcypromine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The effects of PLZ on both amino acids and their << transaminases >> were blocked by pre-treatment with the MAO inhibitor [[ tranylcypromine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "This pretreament had no effect on the inhibition of << GABA-T >> or the elevation of brain GABA levels produced by [[ VIG ]].", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike << VIG >>, also inhibited [[ MAO ]] and ALA-T (and increased brain ALA levels).", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike << VIG >>, also inhibited MAO and [[ ALA-T ]] (and increased brain ALA levels).", "label": "INHIBITOR", "metadata": []}
{"text": "Pretreatment of rats with the << MAO >> inhibitor [[ tranylcypromine ]] prevented the increase in brain GABA and ALA levels with PLZ, but did not block the effect of VIG on GABA.", "label": "INHIBITOR", "metadata": []}
{"text": "Clinical pharmacology of << enalkiren >>, a novel, dipeptide [[ renin ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Clinical pharmacology of enalkiren, a novel, << dipeptide >> [[ renin ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Enalkiren >> (A-64662), a potent, dipeptide [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Enalkiren >> (A-64662), a potent, dipeptide renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "Enalkiren (<< A-64662 >>), a potent, dipeptide [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "Enalkiren (<< A-64662 >>), a potent, dipeptide renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "Enalkiren (A-64662), a potent, << dipeptide >> [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "Enalkiren (A-64662), a potent, << dipeptide >> renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Enalkiren >> has been shown to produce dose-related suppression of plasma [[ renin ]] activity (PRA) and angiotensin II when administered intravenously.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Enalkiren >> has been shown to produce dose-related suppression of plasma renin activity (PRA) and [[ angiotensin II ]] when administered intravenously.", "label": "INHIBITOR", "metadata": []}
{"text": "The results of clinical trials with << enalkiren >> are encouraging, and suggest that [[ renin ]] inhibitors may be safe, useful therapeutic agents in the management of hypertension.", "label": "INHIBITOR", "metadata": []}
{"text": "Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the [[ MDMA ]]-induced reduction in plasmalemmal DA transport.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal [[ DA ]] transport.", "label": "SUBSTRATE", "metadata": []}
{"text": "Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of [[ DA ]] prevented the MDMA-induced reduction in plasmalemmal DA transport.", "label": "SUBSTRATE", "metadata": []}
{"text": "In addition to affecting << DAT >> function, MDMA rapidly decreased vesicular [[ DA ]] transport as assessed in striatal vesicles prepared from treated rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of [[ CYP2D ]] and CYP3A, in rats.", "label": "INHIBITOR", "metadata": []}
{"text": "Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of CYP2D and [[ CYP3A ]], in rats.", "label": "INHIBITOR", "metadata": []}
{"text": "Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of [[ CYP2D ]] and CYP3A, in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of CYP2D and [[ CYP3A ]], in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of << baicalin >> on the metabolism of dextromethorphan (DXM), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.", "label": "INHIBITOR", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of << baicalin >> on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.", "label": "INHIBITOR", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (<< DXM >>), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (<< DXM >>), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.", "label": "SUBSTRATE", "metadata": []}
{"text": "Lineweaver-Burk plots demonstrated that << baicalin >> inhibited the activities of [[ CYP2D ]] and CYP3A in a non-competitive manner in rat liver microsomes (RLMs).", "label": "INHIBITOR", "metadata": []}
{"text": "Lineweaver-Burk plots demonstrated that << baicalin >> inhibited the activities of CYP2D and [[ CYP3A ]] in a non-competitive manner in rat liver microsomes (RLMs).", "label": "INHIBITOR", "metadata": []}
{"text": "The activity of << CYP3A >> in excised liver samples from rats following multiple [[ baicalin ]] treatment was significantly decreased compared to that of the control group (P<0.05), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, these data demonstrate that << baicalin >> inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, these data demonstrate that << baicalin >> inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and [[ CYP3A ]] activities.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities.", "label": "SUBSTRATE", "metadata": []}
{"text": "Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and [[ CYP3A ]] activities.", "label": "SUBSTRATE", "metadata": []}
{"text": "Identification of a novel << benzimidazole >> derivative as a highly potent [[ NPY Y5 receptor ]] antagonist with an anti-obesity profile.", "label": "ANTAGONIST", "metadata": []}
{"text": "We evaluated the clinical effectiveness of << esmolol >>, an ultra-short-acting [[ beta 1-adrenergic receptor ]] blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT).", "label": "INHIBITOR", "metadata": []}
{"text": "The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure.", "label": "AGONIST", "metadata": []}
{"text": "The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure.", "label": "AGONIST", "metadata": []}
{"text": "The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure.", "label": "AGONIST", "metadata": []}
{"text": "The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure.", "label": "AGONIST", "metadata": []}
{"text": "<< beta(1)-Adrenoceptor >> antagonism (10 mg kg(-1) [[ bisoprolol ]]) prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by beta(2)-AR antagonism (10 mg kg(-1) ICI 118 551).", "label": "ANTAGONIST", "metadata": []}
{"text": "The mouse << CYP2J >> subfamily includes members that have wide tissue distribution and are active in the metabolism of [[ arachidonic acid ]] (AA), linoleic acid (LA), and other lipids and xenobiotics.", "label": "SUBSTRATE", "metadata": []}
{"text": "The mouse << CYP2J >> subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), [[ linoleic acid ]] (LA), and other lipids and xenobiotics.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< CPT I >> (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.", "label": "PRODUCT-OF", "metadata": []}
{"text": "CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< CPT I >> (carnitine palmitoyltransferase I) catalyses the conversion of [[ palmitoyl-CoA ]] into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.", "label": "SUBSTRATE", "metadata": []}
{"text": "CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of [[ palmitoyl-CoA ]] into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols.", "label": "SUBSTRATE", "metadata": []}
{"text": "In addition, the new compound << perviridicin B >> (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound << perviridicin B >> (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known << rocaglate >> derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known << rocaglate >> derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known << sesquiterpene >>, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known << sesquiterpene >>, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, << 2-oxaisodauc-5-en-12-al >> (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, << 2-oxaisodauc-5-en-12-al >> (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.", "label": "INHIBITOR", "metadata": []}
{"text": "In further evaluation, the representative compound << N,N-diethyl-N-(2-(N-methyltetradecanamido)ethyl)prop-2-en-1-aminium bromide >> (3b) exhibited potent pro-apoptotic activity, through [[ RhoB ]] activation, in HeLa cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.", "label": "AGONIST-INHIBITOR", "metadata": []}
{"text": "Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.", "label": "AGONIST-INHIBITOR", "metadata": []}
{"text": "Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or [[ methiothepin ]] (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or [[ methiothepin ]] (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment with << tropisetron >> (1 microM), a [[ 5-HT3 ]] antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, << ketanserin >> (10 microM), a [[ 5-HT2 ]] antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.", "label": "ANTAGONIST", "metadata": []}
{"text": "Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, << thioperamide >> (10 microM), a [[ histamine H3 ]] antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Chlorpheniramine >> (10 microM), another [[ histamine H1 receptor ]] antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction.", "label": "ANTAGONIST", "metadata": []}
{"text": "These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional [[ 5-HT1-like receptor ]], located to sensory nerves.", "label": "ACTIVATOR", "metadata": []}
{"text": "These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.", "label": "AGONIST", "metadata": []}
{"text": "<< Vitamin C >> forestalls cigarette smoke induced [[ NF-κB ]] activation in alveolar epithelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced [[ NF-κB ]] activation that involves degradation of I-κBε and nuclear translocation of c-Rel/p50 in alveolar epithelial cells.", "label": "INHIBITOR", "metadata": []}
{"text": "We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Result showed that << vitamin C >> treatment resulted in markedly reduced [[ c-Rel ]] nuclear translocation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "All these results demonstrate that << vitamin C >> prevents CS(E)-induced [[ NF-κB ]] activation and thus it could be used for the prevention of CS-induced inflammatory diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as [[ monocyte chemotactic protein-1 ]] (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 ([[ MCP-1 ]]), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), [[ tumor necrosis factor-α ]] (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α ([[ TNF-α ]]), inducible NO synthase (iNOS), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), [[ inducible NO synthase ]] (iNOS), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase ([[ iNOS ]]), and receptor for AGE (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and [[ receptor for AGE ]] (RAGE).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE ([[ RAGE ]]).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Promoter and electromobility shift assays showed that transcriptional activation of << NF-κB >> was significantly reduced by [[ catalpol ]] treatment, while AP-1 was not.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of IκBα and the nuclear localization of [[ NF-κB ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of [[ IκBα ]] and the nuclear localization of NF-κB.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Catalpol >> also suppressed AGE-induced phosphorylation of [[ mitogen activated protein (MAP) kinases ]], degradation of IκBα and the nuclear localization of NF-κB.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by << catalpol >> treatment, through dual action of reducing ROS itself and inhibiting [[ NADPH oxidase ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Our findings indicate that << catalpol >> suppresses AGE-mediated inflammation by inhibiting ROS production and [[ NF-κB ]] activity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Etoposide >> (VP-16) is a [[ topoisomerase-II ]] (topo II) inhibitor chemotherapeutic agent.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Etoposide >> (VP-16) is a topoisomerase-II ([[ topo II ]]) inhibitor chemotherapeutic agent.", "label": "INHIBITOR", "metadata": []}
{"text": "Etoposide (<< VP-16 >>) is a [[ topoisomerase-II ]] (topo II) inhibitor chemotherapeutic agent.", "label": "INHIBITOR", "metadata": []}
{"text": "Etoposide (<< VP-16 >>) is a topoisomerase-II ([[ topo II ]]) inhibitor chemotherapeutic agent.", "label": "INHIBITOR", "metadata": []}
{"text": "<< MXF >> or VP-16 slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of [[ topo II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "MXF or << VP-16 >> slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of [[ topo II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of [[ MXF ]] and VP-16 compared to VP-16 alone.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of MXF and [[ VP-16 ]] compared to VP-16 alone.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of MXF and VP-16 compared to [[ VP-16 ]] alone.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In conclusion, the results suggest that the enhancement in the reduction of << topo II >> activity by the combined [[ MXF ]]/VP-16 treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs.", "label": "INHIBITOR", "metadata": []}
{"text": "In conclusion, the results suggest that the enhancement in the reduction of << topo II >> activity by the combined MXF/[[ VP-16 ]] treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs.", "label": "INHIBITOR", "metadata": []}
{"text": "<< TAS-102 >> currently undergoing clinical trials, has been demonstrated to have at least two mechanisms, inhibition of [[ TS ]] and incorporation into DNA.", "label": "INHIBITOR", "metadata": []}
{"text": "In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and << thymidilate synthase >> (TS) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of [[ TAS-102 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and thymidilate synthase (<< TS >>) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of [[ TAS-102 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors [[ saquinavir ]] and ritonavir have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes.", "label": "INHIBITOR", "metadata": []}
{"text": "Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors saquinavir and [[ ritonavir ]] have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes.", "label": "INHIBITOR", "metadata": []}
{"text": "Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.", "label": "AGONIST", "metadata": []}
{"text": "<< Labetalol >> (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "Labetalol (> or = 3 x 10(-8) M) and << dilevalol >> (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "The isoprenaline attenuation responses of the portal vein were inhibited by labetalol and dilevalol (both at > or = 10(-7) M) and the pA2 value for the << labetalol >> at [[ beta 2-adrenoceptors ]] was 7.59.", "label": "ANTAGONIST", "metadata": []}
{"text": "It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "It is concluded that labetalol and << dilevalol >> are [[ beta 1-adrenoceptor ]] selective antagonists.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< PR mRNA >> abundance in both myometruim and leiomyomata (center and marginal area) was significantly decreased in 4 patients continuing [[ mifepristone ]] treatment before the operation but not in the other 2 patients stopping RU486 1 month before operation.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "One of the mechanism of << mifepristone >> action on decreasing leiomyomata volume may be related to suppression on expression of [[ PR gene ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Experimental cystathioninuria was induced in rats by administration of the << cystathionine gamma-lyase >> inhibitor, [[ D,L-propargylglycine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals.", "label": "ANTAGONIST", "metadata": []}
{"text": "The non-selective << adenosine receptor >> antagonist ([[ caffeine ]]), and the selective adenosine A1 receptor antagonist (DPCPX), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice.", "label": "ANTAGONIST", "metadata": []}
{"text": "The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice.", "label": "ANTAGONIST", "metadata": []}
{"text": "Cross-inhibition of << SR-BI >>- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and [[ glyburide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Cross-inhibition of SR-BI- and << ABCA1 >>-mediated cholesterol transport by the small molecules BLT-4 and [[ glyburide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Cross-inhibition of << SR-BI >>- and ABCA1-mediated [[ cholesterol ]] transport by the small molecules BLT-4 and glyburide.", "label": "SUBSTRATE", "metadata": []}
{"text": "Cross-inhibition of SR-BI- and << ABCA1 >>-mediated [[ cholesterol ]] transport by the small molecules BLT-4 and glyburide.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< SR-BI >> is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of [[ cholesteryl esters ]] from lipid-rich HDL to cells and the efflux of unesterified cholesterol from cells to HDL.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< SR-BI >> is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterified [[ cholesterol ]] from cells to HDL.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< ABCA1 >> mediates the efflux of unesterified [[ cholesterol ]] and phospholipids from cells to lipid-poor apolipoprotein A-I (apoA-I).", "label": "SUBSTRATE", "metadata": []}
{"text": "The activities of << ABCA1 >> and other ATP binding cassette superfamily members are inhibited by the drug [[ glyburide ]], and SR-BI-mediated lipid transport is blocked by small molecule inhibitors called BLTs.", "label": "INHIBITOR", "metadata": []}
{"text": "The activities of ABCA1 and other << ATP binding cassette superfamily >> members are inhibited by the drug [[ glyburide ]], and SR-BI-mediated lipid transport is blocked by small molecule inhibitors called BLTs.", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one << BLT >>, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one << BLT >>, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one BLT, [<< 1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea >>] (BLT-4), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one BLT, [<< 1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea >>] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked << ABCA1 >>-mediated [[ cholesterol ]] efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).", "label": "SUBSTRATE", "metadata": []}
{"text": "Reciprocally, << glyburide >> blocked SR-BI-mediated selective lipid uptake and efflux at a potency similar to that for its inhibition of [[ ABCA1 ]] (IC(50) approximately 275-300 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "Reciprocally, << glyburide >> blocked [[ SR-BI ]]-mediated selective lipid uptake and efflux at a potency similar to that for its inhibition of ABCA1 (IC(50) approximately 275-300 microM).", "label": "INHIBITOR", "metadata": []}
{"text": "The reciprocal inhibition of << SR-BI >> and ABCA1 by BLT-4 and [[ glyburide ]] raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.", "label": "INHIBITOR", "metadata": []}
{"text": "The reciprocal inhibition of SR-BI and << ABCA1 >> by BLT-4 and [[ glyburide ]] raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.", "label": "INHIBITOR", "metadata": []}
{"text": "The treatment of mice with << Fe-NTA >> alone enhances [[ ornithine decarboxylase ]] activity to 4.6 folds, protein carbonyl formation increased up to 2.9 folds and DNA synthesis expressed in terms of [(3)H] thymidine incorporation increased to 3.2 folds, and antioxidants and antioxidant enzymes decreased to 1.8-2.5 folds, compared with the corresponding saline-treated controls.", "label": "ACTIVATOR", "metadata": []}
{"text": "<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including [[ polycyclic aromatic hydrocarbons ]] (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including [[ polycyclic aromatic hydrocarbons ]] (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites ([[ o-quinones ]]) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites ([[ o-quinones ]]) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.", "label": "SUBSTRATE", "metadata": []}
{"text": "Exposure to << PAHs >>, their metabolites, and ROS further increase [[ AKRs ]] isoform expression that may amplify oxidative damage.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Despite the importance of << AKRs >> in [[ PAHs ]] metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs).", "label": "SUBSTRATE", "metadata": []}
{"text": "The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of [[ nitrate reductase ]], glutamine synthetase, glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, glutamate synthase, and [[ glutamate dehydrogenase ]], promoting amino acid conversion and protein synthesis in soybean seedlings.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << monoamine oxidase >> by [[ phthalide ]] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, << isatin >> and phthalimide, are suitable scaffolds for the design of high potency [[ monoamine oxidase ]] (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, << isatin >> and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase ([[ MAO ]]) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, isatin and << phthalimide >>, are suitable scaffolds for the design of high potency [[ monoamine oxidase ]] (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, isatin and << phthalimide >>, are suitable scaffolds for the design of high potency monoamine oxidase ([[ MAO ]]) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the << MAO >> inhibitory properties of a series of [[ phthalide ]] [2-benzofuran-1(3H)-one] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the << MAO >> inhibitory properties of a series of phthalide [[[ 2-benzofuran-1(3H)-one ]]] analogues.", "label": "INHIBITOR", "metadata": []}
{"text": "In most instances, C6-substituted << phthalides >> exhibit [[ MAO-B ]] specific inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "The results also show that the binding modes of representative << phthalides >> are reversible and competitive at both [[ MAO ]] isoforms.", "label": "INHIBITOR", "metadata": []}
{"text": "Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific \"lid\" conformations of ECL2.", "label": "AGONIST-INHIBITOR", "metadata": []}
{"text": "Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, thymidine kinase-1 and [[ thymidylate synthase ]], in various types of cancer.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Thymidine kinase-1 >> (TK-1) and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Thymidine kinase-1 (<< TK-1) >> and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Thymidine kinase-1 (TK-1) and << thymidylate synthase >> (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Thymidine kinase-1 (TK-1) and thymidylate synthase (<< TS >>) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by TK-1 to its active monophosphated form, that in turn can inhibit [[ TS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS.", "label": "SUBSTRATE", "metadata": []}
{"text": "TAS-102 is a novel drug containing << trifluorothymidine >>, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS.", "label": "SUBSTRATE", "metadata": []}
{"text": "Gastrointestinal adenocarcinomas and squamous cell uterine carcinomas were often accompanied by high << TS >> expression, indicating activation of [[ pyrimidine ]] synthesis through both the salvage and de novo pathways.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The contractions to 5-HT were inhibited by << ketanserin >> and alosetron indicating involvement of [[ 5-HT(2A) ]] and 5-HT(3) receptors, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "The contractions to 5-HT were inhibited by ketanserin and << alosetron >> indicating involvement of 5-HT(2A) and [[ 5-HT(3) ]] receptors, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "Regarding << urease >> inhibition, [[ n-butanol ]] was the most potent fraction (IC50: 97 µg/mL).", "label": "INHIBITOR", "metadata": []}
{"text": "The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective << acetylcholinesterase >> reactivator, [[ 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate ]] (MMB-4).", "label": "ACTIVATOR", "metadata": []}
{"text": "The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective << acetylcholinesterase >> reactivator, 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate ([[ MMB-4 ]]).", "label": "ACTIVATOR", "metadata": []}
{"text": "Methylation-specific PCR and bisulfite sequencing identified methylation of this << CpG >> ((m)CpG) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in [[ DNA methyl transferase 3a ]] concentrations noted with advancing postnatal age (PN14 vs PN3).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Methylation-specific PCR and bisulfite sequencing identified methylation of this CpG (<< (m)CpG >>) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in [[ DNA methyl transferase 3a ]] concentrations noted with advancing postnatal age (PN14 vs PN3).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "5'-flanking region of glut3-luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that << (m)CpGs >> inhibit [[ glut3 ]] transcription.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting [[ Mecp2 ]] and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Separate 5-aza-2'-deoxycytidine pretreatment or in combination with << trichostatin A >> reduced (m)CpG and specific small interference RNAs targeting [[ Mecp2 ]] and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Separate 5-aza-2'-deoxycytidine pretreatment or in combination with << trichostatin A >> reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as [[ reboxetine ]], desipramine, and imipramine.", "label": "INHIBITOR", "metadata": []}
{"text": "A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as reboxetine, [[ desipramine ]], and imipramine.", "label": "INHIBITOR", "metadata": []}
{"text": "A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as reboxetine, desipramine, and [[ imipramine ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant << human UDP-glucuronosyltransferase 1A9 >>--potent inhibition by [[ niflumic acid ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In conclusion, of the seven NSAIDs investigated, << niflumic acid >> was the most potent inhibitor of recombinant [[ UGT1A9 ]] via 4-MUG in a competitive manner.", "label": "INHIBITOR", "metadata": []}
{"text": "Neither the superoxide radical scavenger, tiron, nor the inhibitor of the << dopamine (DA) transporter >>, [[ GBR 12909 ]], prevented the metabolites' toxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "Importantly, pre-treatment with buthionine sulfoximine (<< BSO >>), an inhibitor of [[ γ-GCS ]], prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "Importantly, pre-treatment with << buthionine sulfoximine >> (BSO), an inhibitor of [[ γ-GCS ]], prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< MNU >>-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high [[ MGMT ]] staining.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< MNU >>-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of [[ E-cadherin ]], and high MGMT staining.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters ([[ alanine aminotransferase ]], aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, [[ aspartate aminotransferase ]], alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, [[ alkaline phosphatase ]], total protein, albumin, bilirubin, cholesterol, urea and creatinine).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, [[ albumin ]], bilirubin, cholesterol, urea and creatinine).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an [[ N-methyl d-aspartate receptor ]] (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.", "label": "ANTAGONIST", "metadata": []}
{"text": "However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Doxorubicin >> is mainly excreted into the bile via [[ P-glycoprotein ]] (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein ([[ P-gp ]]) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein (P-gp) and [[ multidrug resistance-associated protein 2 ]] (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 ([[ Mrp2 ]]) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via [[ cytochrome P450 (CYP) 3A ]] subfamily.", "label": "SUBSTRATE", "metadata": []}
{"text": "The slower CL was due to the reduction of hepatic biliary excretion (67.0% decrease) and hepatic << CYP3A >> subfamily-mediated metabolism (21.9% decrease) of [[ doxorubicin ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "Activation of << AMP-activated Protein Kinase >> and Phosphorylation of Glycogen Synthase Kinase3 β Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Activation of AMP-activated Protein Kinase and Phosphorylation of << Glycogen Synthase Kinase3 β >> Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Interestingly, << ursolic acid >> increased the phosphorylation of [[ AMPK ]] and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Interestingly, << ursolic acid >> increased the phosphorylation of AMPK and [[ coenzyme A carboxylase ]] and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Interestingly, << ursolic acid >> increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of [[ GSK3β ]] at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas << ursolic acid >> attenuated the phosphorylation of [[ AKT ]] and mTOR in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas << ursolic acid >> attenuated the phosphorylation of AKT and [[ mTOR ]] in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of << PARP >> and caspase 3 induced by [[ ursolic acid ]] in HepG2 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of PARP and << caspase 3 >> induced by [[ ursolic acid ]] in HepG2 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Conversely, AMPK inhibitor << compound C >> or GSK3β inhibitor SB216763 blocked the cleavages of PARP and [[ caspase 3 ]] induced by ursolic acid in HepG2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Conversely, AMPK inhibitor compound C or GSK3β inhibitor << SB216763 >> blocked the cleavages of PARP and [[ caspase 3 ]] induced by ursolic acid in HepG2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Conversely, << AMPK >> inhibitor [[ compound C ]] or GSK3β inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Conversely, AMPK inhibitor compound C or << GSK3β >> inhibitor [[ SB216763 ]] blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor MG132 suppressed << AMPK >> activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by [[ ursolic acid ]] in HepG2 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, << GSK3β >> phosphorylation, cleaved PARP and deceased AEG-1 induced by [[ ursolic acid ]] in HepG2 cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor << MG132 >> suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased [[ AEG-1 ]] induced by ursolic acid in HepG2 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased << AEG-1 >> induced by [[ ursolic acid ]] in HepG2 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased << AEG-1 >> induced by [[ ursolic acid ]] in HepG2 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor << MG132 >> suppressed [[ AMPK ]] activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, proteosomal inhibitor << MG132 >> suppressed AMPK activation, [[ GSK3β ]] phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via [[ AMPK ]] activation and GSK3β phosphorylation as a potent chemopreventive agent.", "label": "ACTIVATOR", "metadata": []}
{"text": "Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via AMPK activation and [[ GSK3β ]] phosphorylation as a potent chemopreventive agent.", "label": "ACTIVATOR", "metadata": []}
{"text": "Using << paraoxon >> as a reference [[ acetylcholinesterase ]] (AChE) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Using << paraoxon >> as a reference acetylcholinesterase ([[ AChE ]]) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "We then showed that static exposure of embryos to << paraoxon >> (31.2-500 nM) from 5 to 96 hpf resulted in significant stage- and concentration-dependent [[ AChE ]] inhibition, albeit these effects were fully reversible within 48 h following transfer to clean water.", "label": "INHIBITOR", "metadata": []}
{"text": "Based on these studies, the frequency of spontaneous tail contractions at 26 hpf - a developmental stage with minimal << AChE >> expression and activity - was significantly higher following exposure to [[ paraoxon ]] concentrations as low as 31.2 nM.", "label": "ACTIVATOR", "metadata": []}
{"text": "Based on these studies, the frequency of spontaneous tail contractions at 26 hpf - a developmental stage with minimal << AChE >> expression and activity - was significantly higher following exposure to [[ paraoxon ]] concentrations as low as 31.2 nM.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "There is, however, much information on the direct (acute and chronic) effects of << alcohol >> on the binding properties of opioid receptors, as well as modulation of opioid peptide synthesis and secretion (e.g. a suggested increase in [[ beta-endorphin ]] release).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Conversely, opioid antagonists such as naloxone and << naltrexone >> (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions.", "label": "ACTIVATOR", "metadata": []}
{"text": "Conversely, opioid antagonists such as << naloxone >> and naltrexone (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Esmolol >>, a unique cardioselective [[ beta 1-adrenergic receptor ]] blocker with a half-life of 9 minutes, can enable some patients with relative contraindications to beta blockers to nevertheless benefit from early beta-blocking therapy.", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by << acetazolamide >>, ethoxzolamide, and cyanate, [[ CA V ]] is very similar to CA II.", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by << acetazolamide >>, ethoxzolamide, and cyanate, CA V is very similar to [[ CA II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, << ethoxzolamide >>, and cyanate, [[ CA V ]] is very similar to CA II.", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, << ethoxzolamide >>, and cyanate, CA V is very similar to [[ CA II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, ethoxzolamide, and << cyanate >>, [[ CA V ]] is very similar to CA II.", "label": "INHIBITOR", "metadata": []}
{"text": "In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, ethoxzolamide, and << cyanate >>, CA V is very similar to [[ CA II ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Adenylosuccinate synthetase >> (AdSS) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Adenylosuccinate synthetase (<< AdSS >>) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Adenylosuccinate synthetase (<< AdSS >>) catalyzes the [[ Mg2+ ]] dependent condensation of a molecule of IMP with aspartate to form adenylosuccinate, in a reaction driven by the hydrolysis of GTP to GDP.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Phosphate >>, a product of the reaction, was found to be a potent inhibitor of [[ MjAdSS ]] showing biphasic inhibition of enzyme activity.", "label": "INHIBITOR", "metadata": []}
{"text": "The anti-inflammatory drugs << sodium salicylate >> and aspirin inhibited the activation of [[ NF-kappa B ]], which further explains the mechanism of action of these drugs.", "label": "INHIBITOR", "metadata": []}
{"text": "The anti-inflammatory drugs sodium salicylate and << aspirin >> inhibited the activation of [[ NF-kappa B ]], which further explains the mechanism of action of these drugs.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sodium salicylate >> and aspirin also inhibited [[ NF-kappa B ]]-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sodium salicylate >> and aspirin also inhibited NF-kappa B-dependent transcription from the [[ Ig kappa ]] enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Sodium salicylate and << aspirin >> also inhibited [[ NF-kappa B ]]-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Sodium salicylate and << aspirin >> also inhibited NF-kappa B-dependent transcription from the [[ Ig kappa ]] enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic [[ morphine ]] and naloxone challenge in Cath.a cells and primary striatal cultures.", "label": "ACTIVATOR", "metadata": []}
{"text": "Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic [[ morphine ]] and naloxone challenge in Cath.a cells and primary striatal cultures.", "label": "ACTIVATOR", "metadata": []}
{"text": "Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures.", "label": "ACTIVATOR", "metadata": []}
{"text": "Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures.", "label": "ACTIVATOR", "metadata": []}
{"text": "The << Na(+)/Ca(2+) exchanger >> (NCX) is a bidirectional transporter that normally extrudes Ca(2+) from the cell (forward mode), but also brings [[ Ca(2+) ]] into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization.", "label": "SUBSTRATE", "metadata": []}
{"text": "The << Na(+)/Ca(2+) exchanger >> (NCX) is a bidirectional transporter that normally extrudes [[ Ca(2+) ]] from the cell (forward mode), but also brings Ca(2+) into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization.", "label": "SUBSTRATE", "metadata": []}
{"text": "The pharmacology of NCX inhibitors has been studied extensively since the development of << KB-R7943 >>, a prototype benzyloxyphenyl [[ NCX ]] inhibitor, in 1996.", "label": "INHIBITOR", "metadata": []}
{"text": "The pharmacology of NCX inhibitors has been studied extensively since the development of KB-R7943, a prototype << benzyloxyphenyl >> [[ NCX ]] inhibitor, in 1996.", "label": "INHIBITOR", "metadata": []}
{"text": "Intriguingly, the inhibitory potency of << benzyloxyphenyl >> [[ NCX ]] inhibitors is directly coupled to the rate of Na(+)(i)-dependent inactivation.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing << ion channel >> blockers, such as amiodarone, dronedarone, bepridil, aprindine, and [[ cibenzoline ]], have been found to have an NCX inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and << cibenzoline >>, have been found to have an [[ NCX ]] inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing << ion channel >> blockers, such as [[ amiodarone ]], dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing ion channel blockers, such as << amiodarone >>, dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing << ion channel >> blockers, such as amiodarone, [[ dronedarone ]], bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing ion channel blockers, such as amiodarone, << dronedarone >>, bepridil, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing << ion channel >> blockers, such as amiodarone, dronedarone, [[ bepridil ]], aprindine, and cibenzoline, have been found to have an NCX inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing ion channel blockers, such as amiodarone, dronedarone, << bepridil >>, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing << ion channel >> blockers, such as amiodarone, dronedarone, bepridil, [[ aprindine ]], and cibenzoline, have been found to have an NCX inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, << aprindine >>, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.", "label": "INHIBITOR", "metadata": []}
{"text": "Efficacy and safety of the << dipeptidyl peptidase-4 >> inhibitor, [[ sitagliptin ]], in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.", "label": "INHIBITOR", "metadata": []}
{"text": "AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin.", "label": "INHIBITOR", "metadata": []}
{"text": "AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral dipeptidyl peptidase-4 ([[ DPP-4 ]]) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin.", "label": "INHIBITOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of TLR-4, Myd88, [[ ICAM-1 ]], TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, [[ TNFα ]], IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, [[ IL-1β ]] and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, IL-1β and [[ IL-6 ]] at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> suppressed the expression of [[ TLR-4 ]], Myd88, ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased NF-κB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of [[ p38 ]] mitogen-activated protein kinase (p38 MAPK).", "label": "INHIBITOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 [[ mitogen-activated protein kinase ]] (p38 MAPK).", "label": "INHIBITOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase ([[ p38 ]] MAPK).", "label": "INHIBITOR", "metadata": []}
{"text": "<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 [[ MAPK ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and biological evaluation of << phosphorylated flavonoids >> as potent and selective inhibitors of [[ cholesterol esterase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic [[ cholesterol esterase ]] (CEase) and acetylcholinesterase (AChE).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase ([[ CEase ]]) and acetylcholinesterase (AChE).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and [[ acetylcholinesterase ]] (AChE).", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase ([[ AChE ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "The results showed that most of the synthesized compounds exhibited nanomolar potency against << CEase >>, much better than the parent [[ flavonoids ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for [[ CEase ]] over AChE, which only showed micromolar potency inhibition of AChE.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for CEase over [[ AChE ]], which only showed micromolar potency inhibition of AChE.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of [[ AChE ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The structure-activity relationships revealed that the free << hydroxyl >> group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of [[ CEase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The structure-activity relationships revealed that the free hydroxyl group at position 5 and << phosphate >> group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of [[ CEase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the << phosphorylated flavonoids >> are favorable to the inhibition of [[ CEase ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In healthy rats, << ATB-429 >> dose dependently (25, 50, or 100 mg/kg) attenuated CRD-induced hypersensitivity and significantly inhibited CRD-induced overexpression of spinal [[ c-FOS ]] mRNA, whereas mesalamine had no effect.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "ATB-429-induced antinociception was reversed by << glibenclamide >>, a [[ ATP-sensitive K(+) (K(ATP)) channel ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Colonic << cyclooxygenase-2 >> and interkeukin-1beta mRNA and spinal c-FOS mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Colonic cyclooxygenase-2 and << interkeukin-1beta >> mRNA and spinal c-FOS mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal << c-FOS >> mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Block of human NaV1.5 << sodium channels >> by novel [[ alpha-hydroxyphenylamide ]] analogues of phenytoin.", "label": "INHIBITOR", "metadata": []}
{"text": "Block of << human NaV1.5 >> sodium channels by novel [[ alpha-hydroxyphenylamide ]] analogues of phenytoin.", "label": "INHIBITOR", "metadata": []}
{"text": "Block of human NaV1.5 << sodium channels >> by novel alpha-hydroxyphenylamide analogues of [[ phenytoin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Block of << human NaV1.5 >> sodium channels by novel alpha-hydroxyphenylamide analogues of [[ phenytoin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin.", "label": "SUBSTRATE", "metadata": []}
{"text": "Block of << human NaV1.5 >> [[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Voltage-gated sodium (Na) channels >>[[ Na ]]) channels are a critical component of electrically excitable cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Voltage-gated sodium (Na) channels >>[[ sodium ]] (Na) channels are a critical component of electrically excitable cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Phenytoin >> (diphenylhydantoin, DPH) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenytoin (<< diphenylhydantoin >>, DPH) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenytoin (diphenylhydantoin, << DPH >>) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.", "label": "INHIBITOR", "metadata": []}
{"text": "Phenytoin (diphenylhydantoin, DPH) is an established << sodium channel >>[[ sodium ]] channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.", "label": "SUBSTRATE", "metadata": []}
{"text": "In this study, we have synthesized novel << alpha-hydroxyphenylamide >> analogues of diphenylhydantoin and examined their ability to inhibit [[ human Na(V)1.5 ]] sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we have synthesized novel << alpha-hydroxyphenylamide >> analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 [[ sodium channels ]] expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit [[ human Na(V)1.5 ]] sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit human Na(V)1.5 [[ sodium channels ]] expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit << human Na(V)1.5 >> [[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 << sodium channels >>[[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "In comparison to << diphenylhydantoin >>, the novel chloro-substituted alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.", "label": "INHIBITOR", "metadata": []}
{"text": "In comparison to diphenylhydantoin, the novel << chloro >>-substituted alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.", "label": "INHIBITOR", "metadata": []}
{"text": "In comparison to diphenylhydantoin, the novel chloro-substituted << alpha-hydroxyphenylamide >> compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.", "label": "INHIBITOR", "metadata": []}
{"text": "This information may be useful in the development of more potent << sodium channel >>[[ sodium ]] channel blockers.", "label": "SUBSTRATE", "metadata": []}
{"text": "Effects of a << serotonin 5-HT(4) receptor >> antagonist [[ SB-207266 ]] on gastrointestinal motor and sensory function in humans.", "label": "ANTAGONIST", "metadata": []}
{"text": "METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist (SB-207266) on the [[ cisapride ]] mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects.", "label": "AGONIST", "metadata": []}
{"text": "METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist ([[ SB-207266 ]]) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects.", "label": "ANTAGONIST", "metadata": []}
{"text": "METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of [[ polyamine ]] levels in human cells, as acetylation of spermidine and spermine triggers export or degradation.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of [[ spermidine ]] and spermine triggers export or degradation.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and [[ spermine ]] triggers export or degradation.", "label": "SUBSTRATE", "metadata": []}
{"text": "These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating << SSAT >> activity or stability as a part of [[ polyamine ]] homeostasis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]].", "label": "DOWNREGULATOR", "metadata": []}
{"text": "In a cell-based model, << bleomycin >> suppressed Nrf2 activation via [[ extracellular signal-related kinase ]] phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.", "label": "ACTIVATOR", "metadata": []}
{"text": "In a cell-based model, << bleomycin >> suppressed [[ Nrf2 ]] activation via extracellular signal-related kinase phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.", "label": "INHIBITOR", "metadata": []}
{"text": "To confirm this novel mechanism of bleomycin-induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin-treated fibroblasts using a putative << Nrf2 >> activator, [[ caffeic acid phenethyl ester ]], and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.", "label": "ACTIVATOR", "metadata": []}
{"text": "To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.", "label": "UPREGULATOR", "metadata": []}
{"text": "Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor << TAK-441 >> for the inhibition of [[ Gli1 ]] messenger RNA expression and antitumor efficacy in xenografted tumor model mice.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pharmacokinetic and pharmacodynamic modeling of << hedgehog >> inhibitor [[ TAK-441 ]] for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice.", "label": "INHIBITOR", "metadata": []}
{"text": "6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (<< TAK-441 >>) is a potent, selective [[ hedgehog ]] signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer.", "label": "INHIBITOR", "metadata": []}
{"text": "The IC50 values for << Gli1 >> mRNA inhibition in the tumor and skin by [[ TAK-441 ]] were estimated to be 0.0457 and 0.113 μg/ml, respectively.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In this report, we evaluated the growth-inhibitory effects of << sulindac sulfide >>, a [[ COX-1 ]] and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines.", "label": "INHIBITOR", "metadata": []}
{"text": "In this report, we evaluated the growth-inhibitory effects of << sulindac sulfide >>, a COX-1 and [[ COX-2 ]] inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines.", "label": "INHIBITOR", "metadata": []}
{"text": "In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and << nordihydroguaiaretic acid >> (NDGA), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines.", "label": "INHIBITOR", "metadata": []}
{"text": "In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (<< NDGA >>), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Phenothiazines >> inhibit [[ S100A4 ]] function by inducing protein oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the [[ S100A4 ]]/myosin-IIA interaction.", "label": "INHIBITOR", "metadata": []}
{"text": "Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the S100A4/[[ myosin-IIA ]] interaction.", "label": "INHIBITOR", "metadata": []}
{"text": "Using a unique biosensor-based assay, trifluoperazine (<< TFP >>) was identified as an inhibitor that disrupts the [[ S100A4 ]]/myosin-IIA interaction.", "label": "INHIBITOR", "metadata": []}
{"text": "Using a unique biosensor-based assay, trifluoperazine (<< TFP >>) was identified as an inhibitor that disrupts the S100A4/[[ myosin-IIA ]] interaction.", "label": "INHIBITOR", "metadata": []}
{"text": "Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at << TFP >> concentrations that promote [[ S100A4 ]] oligomerization.", "label": "ACTIVATOR", "metadata": []}
{"text": "Assays examining the ability of << TFP >> to block [[ S100A4 ]]-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Assays examining the ability of << TFP >> to block S100A4-mediated disassembly of [[ myosin-IIA ]] filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of << S100A4 >> function occurs only at [[ TFP ]] concentrations that promote S100A4 oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Together these studies support a unique mode of inhibition in which << phenothiazines >> disrupt the [[ S100A4 ]]/myosin-IIA interaction by sequestering S100A4 via small molecule-induced oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Together these studies support a unique mode of inhibition in which << phenothiazines >> disrupt the S100A4/[[ myosin-IIA ]] interaction by sequestering S100A4 via small molecule-induced oligomerization.", "label": "INHIBITOR", "metadata": []}
{"text": "Cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]] in man.", "label": "AGONIST", "metadata": []}
{"text": "The aim of the present study was to evaluate the cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]], and determine whether beta 3-receptors are involved in mediating chronotropic or inotropic responses in man.", "label": "AGONIST", "metadata": []}
{"text": "Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist [[ salbutamol ]] 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.", "label": "AGONIST", "metadata": []}
{"text": "Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.", "label": "AGONIST", "metadata": []}
{"text": "Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both << BRL >> and SAL produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20.", "label": "ACTIVATOR", "metadata": []}
{"text": "Both BRL and << SAL >> produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20.", "label": "ACTIVATOR", "metadata": []}
{"text": "Disruption of contact inhibition, which was induced by toxic AhR ligands << 2,3,7,8-tetrachlorodibenzo-p-dioxin >> (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (<< TCDD >>) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or << polycyclic aromatic hydrocarbons >> in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by << TCDD >>, siRNA-mediated [[ Cx43 ]] knock-down was not sufficient to stimulate proliferation in contact-inhibited cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Although both intracellular and membrane << Cx43 >> pools were markedly reduced in cells released from contact inhibition by [[ TCDD ]], siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Dexamethasone >> suppresses histamine synthesis by repressing both transcription and activity of [[ HDC ]] in allergic rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> suppresses histamine synthesis by repressing both transcription and activity of [[ HDC ]] in allergic rats.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: << Histamine >> synthesized by [[ histidine decarboxylase ]] (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND: << Histamine >> synthesized by histidine decarboxylase ([[ HDC ]]) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND: Histamine synthesized by << histidine decarboxylase >> (HDC) from [[ L-histidine ]] is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.", "label": "SUBSTRATE", "metadata": []}
{"text": "BACKGROUND: Histamine synthesized by histidine decarboxylase (<< HDC >>) from [[ L-histidine ]] is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.", "label": "SUBSTRATE", "metadata": []}
{"text": "However the regulatory mechanism of << histamine >> synthesis by [[ HDC ]] remains to be elucidated.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Histamine content, << HDC >> activity and HDC mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Histamine content, HDC activity and << HDC >> mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, << HDC >> activity and HDC mRNA induced by [[ TDI ]] in TDI-sensitized rats.", "label": "ACTIVATOR", "metadata": []}
{"text": "Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by [[ TDI ]] in TDI-sensitized rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats.", "label": "UPREGULATOR", "metadata": []}
{"text": "Pretreatment with << dexamethasone >> significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and [[ HDC ]] mRNA induced by TDI in TDI-sensitized rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Pretreatment with << dexamethasone >> significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, [[ HDC ]] activity and HDC mRNA induced by TDI in TDI-sensitized rats.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of HDC gene expression and [[ HDC ]] activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Repression of << HDC >> gene expression and HDC activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Repression of HDC gene expression and << HDC >> activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS A diet that partially replaces << carbohydrate >> with unsaturated fat may improve [[ insulin ]] sensitivity in a population at risk for cardiovascular disease.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with [[ CYP2B6 ]] polymorphisms in humans.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known [[ CYP2B6 ]] and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known CYP2B6 and [[ CYP3A ]] inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we assessed the effects of clopidogrel and << clarithromycin >>, known [[ CYP2B6 ]] and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.", "label": "INHIBITOR", "metadata": []}
{"text": "In this study, we assessed the effects of clopidogrel and << clarithromycin >>, known CYP2B6 and [[ CYP3A ]] inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.", "label": "INHIBITOR", "metadata": []}
{"text": "Increased << IL-5 >> activity in the serum was inhibited by both [[ pranlukast ]] and MCI-826 by over 90%.", "label": "INHIBITOR", "metadata": []}
{"text": "Increased << IL-5 >> activity in the serum was inhibited by both pranlukast and [[ MCI-826 ]] by over 90%.", "label": "INHIBITOR", "metadata": []}
{"text": "CONCLUSIONS: << CysLTs >> produced after antigen provocation sequentially induced IL-5 production from some immune component cells via [[ CysLT1 ]] receptor activation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Extracellular application of meclofenamate (EC(50) = 25 microM) and << diclofenac >> (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells.", "label": "ACTIVATOR", "metadata": []}
{"text": "The selective << norepinephrine (NE) transporter >> inhibitor [[ atomoxetine ]] (formerly called tomoxetine or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).", "label": "INHIBITOR", "metadata": []}
{"text": "The selective << norepinephrine (NE) transporter >> inhibitor atomoxetine (formerly called [[ tomoxetine ]] or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).", "label": "INHIBITOR", "metadata": []}
{"text": "The selective << norepinephrine (NE) transporter >> inhibitor atomoxetine (formerly called tomoxetine or [[ LY139603 ]]) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).", "label": "INHIBITOR", "metadata": []}
{"text": "Lung inflammation, << IL-4 >> production, and airway mast cell activity were also prevented under this early short-term treatment with [[ PGE2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Local << PGE2 >> administration prevented the increase of airway [[ IL-13 ]] and osteopontin and kept lung plasmacytoid dendritic cell counts close to baseline.", "label": "INHIBITOR", "metadata": []}
{"text": "Local << PGE2 >> administration prevented the increase of airway IL-13 and [[ osteopontin ]] and kept lung plasmacytoid dendritic cell counts close to baseline.", "label": "INHIBITOR", "metadata": []}
{"text": "Reactivators showed different activity in the reactivation of << rat brain AChE >> after [[ dichlorvos ]], paraoxon and tabun inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Reactivators showed different activity in the reactivation of << rat brain AChE >> after dichlorvos, [[ paraoxon ]] and tabun inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "Reactivators showed different activity in the reactivation of << rat brain AChE >> after dichlorvos, paraoxon and [[ tabun ]] inhibition.", "label": "INHIBITOR", "metadata": []}
{"text": "<< AChE >> was easier reactivated after [[ paraoxon ]] treatment.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, [[ TMB-4 ]] and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and [[ obidoxime ]] from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric [[ oximes ]], and BT-05 and BT-03 possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and [[ BT-05 ]] and BT-03 possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and [[ BT-03 ]] possessing asymmetric structure.", "label": "ACTIVATOR", "metadata": []}
{"text": "All compounds showed low activity toward inhibition of << AChE >> caused by [[ dichlorvos ]].", "label": "INHIBITOR", "metadata": []}
{"text": "State-dependent << mibefradil >> block of [[ Na+ channels ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mibefradil >> is a [[ T-type Ca2+ channel ]] antagonist with reported cross-reactivity with other classes of ion channels, including K+, Cl-, and Na+ channels.", "label": "ANTAGONIST", "metadata": []}
{"text": "Using whole-cell voltage clamp, we examined << mibefradil >> block of four [[ Na+ channel ]] isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).", "label": "INHIBITOR", "metadata": []}
{"text": "Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: [[ Nav1.5 ]] (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).", "label": "INHIBITOR", "metadata": []}
{"text": "Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), [[ Nav1.4 ]] (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).", "label": "INHIBITOR", "metadata": []}
{"text": "Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), [[ Nav1.2 ]] (brain), and Nav1.7 (peripheral nerve).", "label": "INHIBITOR", "metadata": []}
{"text": "Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and [[ Nav1.7 ]] (peripheral nerve).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mibefradil >> blocked [[ Nav1.5 ]] in a use/frequency-dependent manner, indicating preferential binding to states visited during depolarization.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mibefradil >> blocked currents of all [[ Na+ channel ]] isoforms with similar affinity and a dependence on holding potential, and drug off-rate was slowed at depolarized potentials (k(off) was 0.024/s at -130 mV and 0.007/s at -100 mV for Nav1.5).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mibefradil >> blocked currents of all Na+ channel isoforms with similar affinity and a dependence on holding potential, and drug off-rate was slowed at depolarized potentials (k(off) was 0.024/s at -130 mV and 0.007/s at -100 mV for [[ Nav1.5 ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, inhibiting the binding of the fast inactivation lid (<< Nav1.5 >> ICM + MTSET) did not alter [[ mibefradil ]] block, confirming that the drug does not preferentially interact with the fast-inactivated state.", "label": "INHIBITOR", "metadata": []}
{"text": "When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in [[ Nav1.5 ]] and greater block (88%) in an isoform (Nav1.4) that slow-inactivates more completely.", "label": "INHIBITOR", "metadata": []}
{"text": "When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in Nav1.5 and greater block (88%) in an isoform ([[ Nav1.4 ]]) that slow-inactivates more completely.", "label": "INHIBITOR", "metadata": []}
{"text": "Our results suggest that << mibefradil >> blocks [[ Na+ channels ]] in a state-dependent manner that does not depend on fast inactivation but probably involves interaction with one or more slow-inactivated state(s).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Docetaxel >> is a semisynthetic taxane that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Docetaxel is a semisynthetic << taxane >> that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Risperidone >> is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.", "label": "SUBSTRATE", "metadata": []}
{"text": "Both << risperidone >> and 9-hydroxyrisperidone are substrates of [[ P-glycoprotein ]] (P-gp), a transport protein involved in drug absorption, distribution, and elimination.", "label": "SUBSTRATE", "metadata": []}
{"text": "Both << risperidone >> and 9-hydroxyrisperidone are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination.", "label": "SUBSTRATE", "metadata": []}
{"text": "Both risperidone and << 9-hydroxyrisperidone >> are substrates of [[ P-glycoprotein ]] (P-gp), a transport protein involved in drug absorption, distribution, and elimination.", "label": "SUBSTRATE", "metadata": []}
{"text": "Both risperidone and << 9-hydroxyrisperidone >> are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination.", "label": "SUBSTRATE", "metadata": []}
{"text": "bis(Ethyl) oligoamine analogues of polyamines, such as SL-11144 and SL-11158, as well as arylamine analogues [BW-1, a bis(phenylbenzyl) 3-7-3 analogue] blocked uptake and interconversion of spermine at micromolar levels and, in the case of << BW-1 >>, acted as substrate for [[ PAO ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "<< SL-11158 >> inhibited [[ SSAT ]] activity with a mixed type of inhibition in which the analogue had a 70-fold higher affinity for the enzyme than the natural substrate, spermine.", "label": "INHIBITOR", "metadata": []}
{"text": "Synthesis and in vitro evaluation of << N-Aryl pyrido-quinazolines >> derivatives as potent [[ EGFR ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << pyrido-quinazolines >> have been synthesised, characterised and tested for their in vitro [[ EGFR ]] tyrosine kinase inhibitory activity.", "label": "INHIBITOR", "metadata": []}
{"text": "A series of << pyrido-quinazolines >> have been synthesised, characterised and tested for their in vitro EGFR [[ tyrosine kinase ]] inhibitory activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Exposure to << Cu >> NPs decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and [[ interleukin-8 ]] that mirrored our findings from subacute in vivo inhalation studies in mice.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Exposure to << Cu >> NPs decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated levels of [[ lactate dehydrogenase ]], intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting << TrxR >> with [[ auranofin ]] (AuF).", "label": "INHIBITOR", "metadata": []}
{"text": "The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting << TrxR >> with auranofin ([[ AuF ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "The TXM peptides were effective in inhibiting << AuF >>-induced [[ MAPK ]], JNK and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.", "label": "ACTIVATOR", "metadata": []}
{"text": "The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, [[ JNK ]] and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.", "label": "ACTIVATOR", "metadata": []}
{"text": "The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, JNK and [[ p38 ]](MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.", "label": "ACTIVATOR", "metadata": []}
{"text": "The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, JNK and p38([[ MAPK ]]) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.", "label": "ACTIVATOR", "metadata": []}
{"text": "Preferential block of late sodium current in the << LQT3 DeltaKPQ mutant >> by the class I(C) antiarrhythmic [[ flecainide ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the [[ long QT syndrome 3 (LQT3) sodium channel alpha ]] subunit mutation with three amino acids deleted (DeltaKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.", "label": "INHIBITOR", "metadata": []}
{"text": "Flecainide block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the << long QT syndrome 3 (LQT3) sodium channel alpha >>[[ sodium ]] channel alpha subunit mutation with three amino acids deleted (DeltaKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.", "label": "SUBSTRATE", "metadata": []}
{"text": "Compared with WT, << DeltaKPQ >> I(Na) was more sensitive to [[ flecainide ]], and flecainide preferentially inhibited late I(Na) (mean current between 20 and 23.5 ms after depolarization) compared with peak I(Na).", "label": "INHIBITOR", "metadata": []}
{"text": "Compared with WT, << DeltaKPQ >> I(Na) was more sensitive to flecainide, and [[ flecainide ]] preferentially inhibited late I(Na) (mean current between 20 and 23.5 ms after depolarization) compared with peak I(Na).", "label": "INHIBITOR", "metadata": []}
{"text": "We conclude that << DeltaKPQ >> interacts differently with [[ flecainide ]] than with WT, leading to increased block and slowed recovery, especially for late I(Na).", "label": "INHIBITOR", "metadata": []}
{"text": "Both << 5'-AMN >> and 5'-MABN had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum.", "label": "ANTAGONIST", "metadata": []}
{"text": "Both 5'-AMN and << 5'-MABN >> had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum.", "label": "ANTAGONIST", "metadata": []}
{"text": "Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of << dihydropteridinone >> based [[ Plk-2 ]] inhibitors.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Sphingosine-1-phosphate >> promotes the nuclear translocation of β-catenin and thereby induces [[ osteoprotegerin ]] gene expression in osteoblast-like cell lines.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< S1P >> activated [[ phosphatidylinositol 3-kinase ]] (PI3K)/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< S1P >> activated phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< S1P >> activated phosphatidylinositol 3-kinase (PI3K)/[[ Akt ]] signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< S1P >> activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of [[ glycogen synthase kinase-3β ]] and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.", "label": "INHIBITOR", "metadata": []}
{"text": "<< S1P >> increased the amount of [[ osteoprotegerin ]] at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These findings suggest that << S1P >> activates the [[ PI3K ]]/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "These findings suggest that << S1P >> activates the PI3K/[[ Akt ]] signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.", "label": "ACTIVATOR", "metadata": []}
{"text": "These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of [[ β-catenin ]] in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of [[ osteoptotegerin ]] and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including [[ alkaline phosphatase ]], probably relating to the inhibition of osteoclast formation and the mineralization, respectively.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Plerixafor >>, a [[ CXCR4 ]] antagonist for the mobilization of hematopoietic stem cells.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Plerixafor >> (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine [[ stromal cell-derived factor-1 ]] (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Plerixafor >> (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 ([[ SDF-1 ]]) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Plerixafor >> (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor [[ CXCR4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Plerixafor >> (AMD3100, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the [[ chemokine ]] stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (<< AMD3100 >>, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine [[ stromal cell-derived factor-1 ]] (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (<< AMD3100 >>, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 ([[ SDF-1 ]]) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (<< AMD3100 >>, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor [[ CXCR4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (<< AMD3100 >>, Genzyme Corporation) is a bicyclam molecule that antagonizes the binding of the [[ chemokine ]] stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (AMD3100, Genzyme Corporation) is a << bicyclam >> molecule that antagonizes the binding of the chemokine [[ stromal cell-derived factor-1 ]] (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (AMD3100, Genzyme Corporation) is a << bicyclam >> molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 ([[ SDF-1 ]]) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (AMD3100, Genzyme Corporation) is a << bicyclam >> molecule that antagonizes the binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its cognate receptor [[ CXCR4 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Plerixafor (AMD3100, Genzyme Corporation) is a << bicyclam >> molecule that antagonizes the binding of the [[ chemokine ]] stromal cell-derived factor-1 (SDF-1) to its cognate receptor CXCR4.", "label": "INHIBITOR", "metadata": []}
{"text": "This stimulation was attenuated by the << Pak >> inhibitor [[ 2,2'-dihydroxy-1,1'-dinaphthyldisulfide ]] (IPA3) or dominant-negative Pak1.", "label": "INHIBITOR", "metadata": []}
{"text": "This stimulation was attenuated by the << Pak >> inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide ([[ IPA3 ]]) or dominant-negative Pak1.", "label": "INHIBITOR", "metadata": []}
{"text": "Chronic insulin (24 h) activates NHE3 through the classic << phosphatidylinositol 3-kinase >>-serum- and glucocorticoid-dependent kinase 1 (PI3K-SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect can be blocked by the PI3K inhibitor [[ wortmannin ]] or a dominant-negative SGK1.", "label": "INHIBITOR", "metadata": []}
{"text": "Chronic insulin (24 h) activates NHE3 through the classic phosphatidylinositol 3-kinase-serum- and glucocorticoid-dependent kinase 1 (<< PI3K >>-SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect can be blocked by the PI3K inhibitor [[ wortmannin ]] or a dominant-negative SGK1.", "label": "INHIBITOR", "metadata": []}
{"text": "Chronic insulin (24 h) activates NHE3 through the classic phosphatidylinositol 3-kinase-serum- and glucocorticoid-dependent kinase 1 (PI3K-SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect can be blocked by the << PI3K >> inhibitor [[ wortmannin ]] or a dominant-negative SGK1.", "label": "INHIBITOR", "metadata": []}
{"text": "Results showed that neonatal << quinpirole >> treatment induced [[ D2 ]] priming that was eliminated by olanzapine treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Results showed that neonatal quinpirole treatment induced << D2 >> priming that was eliminated by [[ olanzapine ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal << NGF >>, BDNF and ChAT that was eliminated by [[ olanzapine ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal NGF, << BDNF >> and ChAT that was eliminated by [[ olanzapine ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal NGF, BDNF and << ChAT >> that was eliminated by [[ olanzapine ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal [[ NGF ]], BDNF and ChAT that was eliminated by olanzapine treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, [[ BDNF ]] and ChAT that was eliminated by olanzapine treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, BDNF and [[ ChAT ]] that was eliminated by olanzapine treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Neonatal << quinpirole >> treatment produced a significant decrease in [[ BDNF ]] and ChAT in the frontal cortex that was unaffected by olanzapine treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Neonatal << quinpirole >> treatment produced a significant decrease in BDNF and [[ ChAT ]] in the frontal cortex that was unaffected by olanzapine treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results show that << olanzapine >> eliminates [[ D2 receptor ]] priming and cognitive impairment and also alleviates decreases in neurotrophins and acetylcholinergic markers produced by D2 priming in the hippocampus.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Suppression of Src/ERK and << GSK-3 >>/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Suppression of Src/ERK and GSK-3/<< β-catenin >> signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53.", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]].", "label": "UPREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of [[ cyclin D1 ]], cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, [[ cyclin E ]], cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, [[ cyclin A ]], cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 ([[ CDK2 ]]), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in f[[ ocal adhesion kinase ]] (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase ([[ FAK ]])/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/[[ c-Src ]]/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/[[ extracellular signal-regulated kinase ]] (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase ([[ ERK ]]) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and [[ phosphoinositide 3-kinase ]] (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase ([[ PI3K ]])/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/[[ Akt ]]/ glycogen synthase kinase 3β (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ [[ glycogen synthase kinase 3β ]] (GSK-3β) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β ([[ GSK-3β ]]) signaling pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of [[ β-catenin ]], one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of [[ PI3K ]]/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/[[ Akt ]]/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/[[ GSK-3β ]] signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of [[ β-catenin ]]-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including [[ BMP4 ]], ID2, survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, [[ ID2 ]], survivin, cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, [[ survivin ]], cyclin D1, MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, [[ cyclin D1 ]], MMP7, and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, [[ MMP7 ]], and c-Myc.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and [[ c-Myc ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Overall, higher alcohol production was reduced by << ammonium >> supplementation, and this can be correlated with a general downregulation of genes encoding [[ decarboxylases ]] and dehydrogenases of the Ehrlich pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Overall, higher alcohol production was reduced by << ammonium >> supplementation, and this can be correlated with a general downregulation of genes encoding decarboxylases and [[ dehydrogenases ]] of the Ehrlich pathway.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as << cyclooxygenase-2 >> inhibiting [[ nitric oxide ]] donors.", "label": "INHIBITOR", "metadata": []}
{"text": "Novel analgesic/anti-inflammatory agents: << 1,5-diarylpyrrole nitrooxyalkyl ethers >> and related compounds as [[ cyclooxygenase-2 ]] inhibiting nitric oxide donors.", "label": "INHIBITOR", "metadata": []}
{"text": "New classes of << pyrrole >>-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported.", "label": "INHIBITOR", "metadata": []}
{"text": "New classes of pyrrole-derived << nitrooxyalkyl >> inverse esters, carbonates, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported.", "label": "INHIBITOR", "metadata": []}
{"text": "New classes of pyrrole-derived nitrooxyalkyl inverse << esters >>, carbonates, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported.", "label": "INHIBITOR", "metadata": []}
{"text": "New classes of pyrrole-derived nitrooxyalkyl inverse esters, << carbonates >>, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported.", "label": "INHIBITOR", "metadata": []}
{"text": "New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and << ethers >> (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Nitrooxy >> derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective [[ COX-2 ]] inhibitors in in vitro experimental models.", "label": "INHIBITOR", "metadata": []}
{"text": "The clinical profile of the << angiotensin II receptor >> blocker [[ eprosartan ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In clinical trials << eprosartan >> has proven to be at least as effective as the [[ ACE ]] inhibitor enalapril in reducing BP, but with a significantly lower incidence of side effects.", "label": "INHIBITOR", "metadata": []}
{"text": "A significant decrease of << aspartate aminotransferase >>, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after [[ CCl4 ]] and PC administration alone.", "label": "INHIBITOR", "metadata": []}
{"text": "A significant decrease of aspartate aminotransferase, << alanine aminotransferase >>, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after [[ CCl4 ]] and PC administration alone.", "label": "INHIBITOR", "metadata": []}
{"text": "A significant decrease of aspartate aminotransferase, alanine aminotransferase, << lactate dehydrogenase >> (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after [[ CCl4 ]] and PC administration alone.", "label": "INHIBITOR", "metadata": []}
{"text": "A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (<< LDH >>) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after [[ CCl4 ]] and PC administration alone.", "label": "INHIBITOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of [[ ethylmorphine-N-demethylase ]] and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and [[ aniline 4-hydroxylase ]] activity and cytochrome P450, compared to the CCl4 only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and [[ cytochrome P450 ]], compared to the CCl4 only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of << ethylmorphine-N-demethylase >> and aniline 4-hydroxylase activity and cytochrome P450, compared to the [[ CCl4 ]] only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and << aniline 4-hydroxylase >> activity and cytochrome P450, compared to the [[ CCl4 ]] only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and << cytochrome P450 >>, compared to the [[ CCl4 ]] only group.", "label": "ACTIVATOR", "metadata": []}
{"text": "In vitro inhibition of << diacylglycerol acyltransferase >> by [[ prenylflavonoids ]] from Sophora flavescens.", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, << kuraridin >> ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, << kuraridin >> ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), << kurarinol >> ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), << kurarinol >> ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), << kushenol H >> ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), << kushenol H >> ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and << kushenol K >> ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and << kushenol K >> ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, << kurarinone >> ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, << kurarinone >> ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a << chalcone >> of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four prenylflavonoids, kurarinone ( 1), a << chalcone >> of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Four << prenylflavonoids >>, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT).", "label": "INHIBITOR", "metadata": []}
{"text": "Four << prenylflavonoids >>, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "The << flavonoids >> inhibited [[ DGAT ]] activity in a dose-dependent manner with IC50 values of 10.9 microM ( 1), 9.8 microM ( 2), 8.6 microM ( 3), 142.0 microM ( 4) and 250 microM ( 5).", "label": "INHIBITOR", "metadata": []}
{"text": "These data suggest that the << lavandulyl >> side chain and the position of the hydroxy group are important for high [[ DGAT ]] inhibitory activity.", "label": "INHIBITOR", "metadata": []}
{"text": "These data suggest that the lavandulyl side chain and the position of the << hydroxy >> group are important for high [[ DGAT ]] inhibitory activity.", "label": "INHIBITOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of [[ E-selectin ]], VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, [[ VEGF ]], and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of [[ E-selectin ]], VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of E-selectin, [[ VEGF ]], and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and [[ iNOS ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DXM) decreased the expression of [[ CXCL-8 ]], VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DXM) decreased the expression of CXCL-8, [[ VEGF ]], and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Dexamethasone >> (DXM) decreased the expression of CXCL-8, VEGF, and [[ iNOS ]] induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DXM >>) decreased the expression of [[ CXCL-8 ]], VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DXM >>) decreased the expression of CXCL-8, [[ VEGF ]], and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (<< DXM >>) decreased the expression of CXCL-8, VEGF, and [[ iNOS ]] induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of [[ iNOS ]], decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INHIBITOR", "metadata": []}
{"text": "Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of [[ iNOS ]], decreased the expression of E-selectin, VEGF, and iNOS.", "label": "INHIBITOR", "metadata": []}
{"text": "<< DXM >> and 1400W attenuated the mRNA expression of [[ E-selectin ]] and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< DXM >> and 1400W attenuated the mRNA expression of E-selectin and [[ iNOS ]] induced by the costimulation of reIL-4, reTNF-alpha, and LPS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "DXM and << 1400W >> attenuated the mRNA expression of [[ E-selectin ]] and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "DXM and << 1400W >> attenuated the mRNA expression of E-selectin and [[ iNOS ]] induced by the costimulation of reIL-4, reTNF-alpha, and LPS.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The beneficial role of << 17beta-estradiol >> on blood pressure, cardiac hypertrophy, vascular [[ osteopontin ]] expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The beneficial role of 17beta-estradiol on blood pressure, cardiac hypertrophy, vascular << osteopontin >> expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of [[ medroxyprogesterone acetate ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of [[ GluN1 ]]/GluN2B receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Pharmacological doses of the << mTOR >> inhibitor [[ rapamycin ]] reduce albuminura in diabetes.", "label": "INHIBITOR", "metadata": []}
{"text": "High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates tuberin and activates [[ mTOR ]].", "label": "ACTIVATOR", "metadata": []}
{"text": "High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "High << glucose >> (HG) induces apoptosis of podocytes, inhibits [[ AMPK ]] activation, inactivates tuberin and activates mTOR.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced [[ Nox4 ]] and Nox1, NADPH oxidase activity and podocyte apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced Nox4 and [[ Nox1 ]], NADPH oxidase activity and podocyte apoptosis.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Inhibition of << mTOR >> by low dose [[ rapamycin ]] decreases HG-induced Nox4 and Nox1, NADPH oxidase activity and podocyte apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced Nox4 and Nox1, [[ NADPH oxidase ]] activity and podocyte apoptosis.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << mTOR >> by small dose of [[ rapamycin ]] reduces podocyte apoptosis, attenuates glomerular injury and albuminuria.", "label": "INHIBITOR", "metadata": []}
{"text": "Systemic administration of << beta2-adrenoceptor >> agonists, [[ formoterol ]] and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses.", "label": "AGONIST", "metadata": []}
{"text": "Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses.", "label": "AGONIST", "metadata": []}
{"text": "Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity.", "label": "AGONIST", "metadata": []}
{"text": "Two beta(2)-agonists, formoterol and << salmeterol >>, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity.", "label": "AGONIST", "metadata": []}
{"text": "A dose of 25 microg kg(-1) day(-1) of << formoterol >> elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar [[ beta-adrenoceptor ]] downregulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "A dose of 25 microg kg(-1) day(-1) of formoterol elicited greater EDL and soleus hypertrophy than << salmeterol >>, but resulted in similar [[ beta-adrenoceptor ]] downregulation.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "Clinical utility of << acarbose >>, an [[ alpha-glucosidase ]] inhibitor in cardiometabolic disorders.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Acarbose >>, an [[ alpha-glucosidase ]] inhibitor, delays the absorption of carbohydrate from the small intestine, thereby reducing postprandial hyperglycemia.", "label": "INHIBITOR", "metadata": []}
{"text": "The values of mean corpuscular hemoglobin concentration and mean corpuscular << hemoglobin >> increased in the [[ STX ]] group.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The values of mean corpuscular << hemoglobin >> concentration and mean corpuscular hemoglobin increased in the [[ STX ]] group.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "First, we showed that intracerebroventricular administration of << glucose >> in rats increases [[ DBI ]] expression in hypothalamic glial-like tanycytes.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On phosphorylation of << Ser40 >> by [[ protein kinase A ]], the affinity for H4biopterin increased ([S]0.5 = 11 +/- 2 microM) and the negative cooperativity was amplified (h = 0.27 +/- 0.03).", "label": "SUBSTRATE", "metadata": []}
{"text": "Disposition of a specific << cyclooxygenase-2 >> inhibitor, [[ valdecoxib ]], in human.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Valdecoxib >> is a potent and specific inhibitor of [[ cyclooxygenase-2 ]], which is used for the treatment of rheumatoid arthritis, osteoarthritis, and the dysmenorrhea pain.", "label": "INHIBITOR", "metadata": []}
{"text": "In mechanistic studies, << Silibinin >> decreased the protein level of [[ p34cdc2 ]], which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In addition, << Silibinin >> caused an increase in [[ p53 ]] and p21 protein level as well as mRNA levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, << Silibinin >> caused an increase in p53 and [[ p21 ]] protein level as well as mRNA levels.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "4-Hydroxynonenal (<< 4-HNE >>) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "4-Hydroxynonenal (<< 4-HNE >>) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< 4-Hydroxynonenal >> (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< 4-Hydroxynonenal >> (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "4-Hydroxynonenal (4-HNE) is a mutagenic << alpha,beta-unsaturated aldehyde >> produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "4-Hydroxynonenal (4-HNE) is a mutagenic << alpha,beta-unsaturated aldehyde >> produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms.", "label": "SUBSTRATE", "metadata": []}
{"text": "The alpha class << human GSTA4-4 >> enzyme (hGSTA4-4) has a particularly high catalytic efficiency toward [[ 4-HNE ]] conjugation.", "label": "SUBSTRATE", "metadata": []}
{"text": "The alpha class human GSTA4-4 enzyme (<< hGSTA4-4 >>) has a particularly high catalytic efficiency toward [[ 4-HNE ]] conjugation.", "label": "SUBSTRATE", "metadata": []}
{"text": "HepG2 cells transfected with an hGSTA4 vector construct exhibited high steady-state hGSTA4 mRNA, high << GST-4 >>[[ 4-HNE ]] catalytic activities, but lower basal glutathione (GSH) concentrations relative to insert-free vector (control) cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "Specifically, << hGSTA4 >> cells had significantly higher GSH concentrations when exposed to 5-15 microM [[ 4-HNE ]], but not at 20 microM 4-HNE, suggesting extensive GSH utilization at high concentrations of 4-HNE.", "label": "SUBSTRATE", "metadata": []}
{"text": "Specifically, << hGSTA4 >> cells had significantly higher GSH concentrations when exposed to 5-15 microM 4-HNE, but not at 20 microM [[ 4-HNE ]], suggesting extensive GSH utilization at high concentrations of 4-HNE.", "label": "SUBSTRATE", "metadata": []}
{"text": "In summary, our data indicates that over-expression of hGSTA4 at levels conferring high << GST >>-[[ 4-HNE ]] conjugating activity confers a partial growth advantage to HepG2 cells and protects against 4-HNE oxidative injury.", "label": "SUBSTRATE", "metadata": []}
{"text": "However, the loss of proliferative capacity of << hGSTA4 >> cells challenged with levels of [[ 4-HNE ]] associated with severe oxidative stress indicates a role of other aldehyde metabolizing enzymes, and/or GSH-electrophile transporter proteins, in providing full cellular protection against 4-HNE toxicity.", "label": "SUBSTRATE", "metadata": []}
{"text": "OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha (PPARalpha) and [[ PPARgamma ]] agonist, as a body-weight lowering, hypolipidemic and euglycemic agent.", "label": "AGONIST", "metadata": []}
{"text": "OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent.", "label": "AGONIST", "metadata": []}
{"text": "OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha ([[ PPARalpha ]]) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent.", "label": "AGONIST", "metadata": []}
{"text": "RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively.", "label": "UPREGULATOR", "metadata": []}
{"text": "db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively.", "label": "UPREGULATOR", "metadata": []}
{"text": "db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in [[ phosphoenolpyruvate carboxykinase ]] and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and carnitine acetyltransferase, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and [[ glucose 6-phosphatase ]] activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and carnitine acetyltransferase, respectively.", "label": "INHIBITOR", "metadata": []}
{"text": "The enzyme << cyclo-oxygenase >> catalyses the oxygenation of arachidonic acid, leading to the formation of [[ prostaglandins ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "The enzyme << cyclo-oxygenase >> catalyses the oxygenation of [[ arachidonic acid ]], leading to the formation of prostaglandins.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< hCOX-1 >> had a specific activity of 18.8 mumol of O2/mg with a Km of 13.8 microM for [[ arachidonate ]] and Vmax. of 1500 nmol of O2/nmol of enzyme, whereas hCOX-2 had a specific activity of 12.2 mumol of O2/mg with a Km of 8.7 microM for arachidonate and a Vmax. of 1090 nmol of O2/nmol of enzyme.", "label": "SUBSTRATE", "metadata": []}
{"text": "hCOX-1 had a specific activity of 18.8 mumol of O2/mg with a Km of 13.8 microM for arachidonate and Vmax. of 1500 nmol of O2/nmol of enzyme, whereas << hCOX-2 >> had a specific activity of 12.2 mumol of O2/mg with a Km of 8.7 microM for [[ arachidonate ]] and a Vmax. of 1090 nmol of O2/nmol of enzyme.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Indomethacin >> inhibited both [[ hCOX-1 ]] and hCOX-2, whereas NS-398 and Dup-697 selectively inhibited hCOX-2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Indomethacin >> inhibited both hCOX-1 and [[ hCOX-2 ]], whereas NS-398 and Dup-697 selectively inhibited hCOX-2.", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin inhibited both hCOX-1 and hCOX-2, whereas << NS-398 >> and Dup-697 selectively inhibited [[ hCOX-2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Indomethacin inhibited both hCOX-1 and hCOX-2, whereas NS-398 and << Dup-697 >> selectively inhibited [[ hCOX-2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Both << NS-398 >> and Dup-697 exhibited time-dependent inactivation of [[ hCOX-2 ]], as did indomethacin on both enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "Both NS-398 and << Dup-697 >> exhibited time-dependent inactivation of [[ hCOX-2 ]], as did indomethacin on both enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "Both NS-398 and Dup-697 exhibited time-dependent inactivation of << hCOX-2 >>, as did [[ indomethacin ]] on both enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "The competitive inhibitor of << hCOX-1 >>, [[ mefenamic acid ]], also displayed competitive inhibition of hCOX-2.", "label": "INHIBITOR", "metadata": []}
{"text": "The competitive inhibitor of hCOX-1, << mefenamic acid >>, also displayed competitive inhibition of [[ hCOX-2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< Doxycycline >> was shown to decrease cerebral [[ MMP-9 ]] activities and angiogenesis induced by vascular endothelial growth factor (VEGF).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Doxycycline >> was shown to decrease cerebral MMP-9 activities and angiogenesis induced by [[ vascular endothelial growth factor ]] (VEGF).", "label": "INHIBITOR", "metadata": []}
{"text": "<< Doxycycline >> was shown to decrease cerebral MMP-9 activities and angiogenesis induced by vascular endothelial growth factor ([[ VEGF ]]).", "label": "INHIBITOR", "metadata": []}
{"text": "Our results have shown that << MMP-9 >> messenger ribonucleic acid (mRNA) expression was inhibited by [[ doxycycline ]] starting at 10 mg/kg/day (P<0.02).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Minocycline >> showed more potent inhibition on [[ MMP-9 ]] mRNA expression, starting at 1 (P<0.005) and further at more than 30 (P<0.001) mg/kg/day.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "At the enzymatic activity level, << doxycycline >> started to suppress [[ MMP-9 ]] activity at 5 mg/kg/day (P<0.001), while minocycline had an effect at a lower dose, 1 mg/kg/day (P<0.02).", "label": "INHIBITOR", "metadata": []}
{"text": "We also assessed the potential relevant signaling pathway in vitro to elucidate the mechanisms underlying the << MMP-9 >> inhibition by [[ tetracyclines ]].", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro, << minocycline >>, but not doxycycline, inhibits [[ MMP-9 ]], at least in part, via the extracellular signaling-related kinase 1/2 (ERK1/2)-mediated pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "In vitro, minocycline, but not << doxycycline >>, inhibits [[ MMP-9 ]], at least in part, via the extracellular signaling-related kinase 1/2 (ERK1/2)-mediated pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "This study provided the evidence that the << tetracyclines >> inhibit stimulated cerebral [[ MMP-9 ]] at multiple levels and are effective at very low doses, offering great potential for therapeutic use.", "label": "INHIBITOR", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the << glycine decarboxylase complex >> (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (<< GDC >>, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, << EC 2.1.1.10 >>) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and << serine hydroxymethyltransferase >> (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (<< SHMT >>, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the << glycine decarboxylase complex >> (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (<< GDC >>, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, << EC 2.1.1.10 >>) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and << serine hydroxymethyltransferase >> (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (<< SHMT >>, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with glycine ([[ Gly ]]) as one-carbon (1-C) source.", "label": "SUBSTRATE", "metadata": []}
{"text": "An alternative THF-dependent pathway involves the << C1-THF synthase >>/SHMT activities with [[ formate ]] as 1-C source.", "label": "SUBSTRATE", "metadata": []}
{"text": "An alternative THF-dependent pathway involves the C1-THF synthase/<< SHMT >> activities with [[ formate ]] as 1-C source.", "label": "SUBSTRATE", "metadata": []}
{"text": "Firstly, transgenic plants overexpressing << formate dehydrogenase >> (FDH, EC 1.2.1.2) were used to continue our previous studies on the function of FDH in [[ formate ]] metabolism.", "label": "SUBSTRATE", "metadata": []}
{"text": "Firstly, transgenic plants overexpressing formate dehydrogenase (<< FDH >>, EC 1.2.1.2) were used to continue our previous studies on the function of FDH in [[ formate ]] metabolism.", "label": "SUBSTRATE", "metadata": []}
{"text": "Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, << EC 1.2.1.2 >>) were used to continue our previous studies on the function of FDH in [[ formate ]] metabolism.", "label": "SUBSTRATE", "metadata": []}
{"text": "Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, EC 1.2.1.2) were used to continue our previous studies on the function of << FDH >> in [[ formate ]] metabolism.", "label": "SUBSTRATE", "metadata": []}
{"text": "We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of formate to << CO(2) >> by the [[ FDH ]] reaction is the primary and preferred fate of the organic acid in Arabidopsis.", "label": "PRODUCT-OF", "metadata": []}
{"text": "We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of << formate >> to CO(2) by the [[ FDH ]] reaction is the primary and preferred fate of the organic acid in Arabidopsis.", "label": "SUBSTRATE", "metadata": []}
{"text": "The ratio between the GDC/<< SHMT >> and C1-THF synthase/SHMT pathways of [[ Ser ]] synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The ratio between the GDC/SHMT and C1-THF synthase/<< SHMT >> pathways of [[ Ser ]] synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The ratio between the << GDC >>/SHMT and C1-THF synthase/SHMT pathways of Ser synthesis from [[ [alpha-(13)C]Gly ]] and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1.", "label": "SUBSTRATE", "metadata": []}
{"text": "The ratio between the GDC/SHMT and << C1-THF synthase >>/SHMT pathways of Ser synthesis from [alpha-(13)C]Gly and [[ [(13)C]formate ]], respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1.", "label": "SUBSTRATE", "metadata": []}
{"text": "On the other hand, the accumulation of << Ser >> through the C1-THF synthase/[[ SHMT ]] pathway in glyD plants was 2.5-fold greater than that in WT plants.", "label": "PRODUCT-OF", "metadata": []}
{"text": "BACKGROUND: << Rivastigmine >> is a carbamate drug designed to inhibit both [[ acetylcholinesterase ]] and butyrylcholinesterase by reversibly covalently bonding to these enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: << Rivastigmine >> is a carbamate drug designed to inhibit both acetylcholinesterase and [[ butyrylcholinesterase ]] by reversibly covalently bonding to these enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Rivastigmine is a << carbamate >> drug designed to inhibit both [[ acetylcholinesterase ]] and butyrylcholinesterase by reversibly covalently bonding to these enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "BACKGROUND: Rivastigmine is a << carbamate >> drug designed to inhibit both acetylcholinesterase and [[ butyrylcholinesterase ]] by reversibly covalently bonding to these enzymes.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Topotecan >> is a [[ topoisomerase I ]] inhibitor which is currently evaluated as an adjuvant agent for malignant glioma.", "label": "INHIBITOR", "metadata": []}
{"text": "High << p53 >> protein levels, but not genetic or functional p53 status, were associated with increased [[ topotecan ]]-induced DNA/topoisomerase I complex formation.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Amiloride >> is a specific inhibitor of [[ uPA ]] but does not inhibit tPA.", "label": "INHIBITOR", "metadata": []}
{"text": "The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the << endothelin ET(B) receptor >> antagonist [[ RES 701-1 ]], by indomethacin, or by glibenclamide.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the << thromboxane A2 receptor >> antagonists [[ GR32191 ]] and ridogrel.", "label": "ANTAGONIST", "metadata": []}
{"text": "The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the << thromboxane A2 receptor >> antagonists GR32191 and [[ ridogrel ]].", "label": "ANTAGONIST", "metadata": []}
{"text": "A novel class of << quinoxalines >> has been discovered as antagonists of the [[ IgG ]]:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.", "label": "ANTAGONIST", "metadata": []}
{"text": "A novel class of << quinoxalines >> has been discovered as antagonists of the IgG:[[ FcRn ]] protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Agmatine >>, locally synthesized, is an endogenous agonist at [[ imidazoline receptors ]], a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.", "label": "AGONIST", "metadata": []}
{"text": "(S)-3-(Aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole (<< GSK2251052 >>) is a novel boron-containing antibiotic that inhibits [[ bacterial leucyl tRNA synthetase ]], and that has been in development for the treatment of serious Gram-negative infections.", "label": "INHIBITOR", "metadata": []}
{"text": "<< (S)-3-(Aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole >> (GSK2251052) is a novel boron-containing antibiotic that inhibits [[ bacterial leucyl tRNA synthetase ]], and that has been in development for the treatment of serious Gram-negative infections.", "label": "INHIBITOR", "metadata": []}
{"text": "A combination of in vitro metabolism experiments and a pharmacokinetic study in monkeys with the inhibitor << 4-methylpyrazole >> provided strong evidence that [[ alcohol dehydrogenase ]], potentially in association with aldehyde dehydrogenase, is the primary enzyme involved in the formation of the M3 metabolite.", "label": "INHIBITOR", "metadata": []}
{"text": "In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of << serotonin >>, possibly by facilitating the interaction of serotonin with transport-ready conformations of [[ SERT ]] when concentrations of serotonin were low and rate limiting.", "label": "SUBSTRATE", "metadata": []}
{"text": "In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of << serotonin >> with transport-ready conformations of [[ SERT ]] when concentrations of serotonin were low and rate limiting.", "label": "SUBSTRATE", "metadata": []}
{"text": "In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of << SERT >> when concentrations of [[ serotonin ]] were low and rate limiting.", "label": "SUBSTRATE", "metadata": []}
{"text": "They display sensitivity to << TK >> inhibitors, including [[ gefitinib ]] and erlotinib.", "label": "INHIBITOR", "metadata": []}
{"text": "They display sensitivity to << TK >> inhibitors, including gefitinib and [[ erlotinib ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Among the [Fe-S] cluster biosynthetic proteins are included a pyridoxal phosphate-dependent enzyme (<< NifS >>) that is involved in the activation of sulphur from [[ l-cysteine ]], and a molecular scaffold protein (NifU) upon which [Fe-S] cluster precursors are formed.", "label": "SUBSTRATE", "metadata": []}
{"text": "In addition, the number and area of << glutathione S-transferase placental form >> (GST-P) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, the number and area of glutathione S-transferase placental form (<< GST-P >>) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and << proliferating cell nuclear antigen >> (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and proliferating cell nuclear antigen (<< PCNA >>) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as [[ aspartate transaminase ]], alanine transaminase in serum whereas co-administration of CNF suppressed their increases.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as aspartate transaminase, [[ alanine transaminase ]] in serum whereas co-administration of CNF suppressed their increases.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as [[ nuclear factor (NF)-κB ]], tumor necrosis factor (TNF)-α and interleukin (IL)-1β in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently.", "label": "ACTIVATOR", "metadata": []}
{"text": "Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as nuclear factor (NF)-κB, [[ tumor necrosis factor (TNF)-α ]] and interleukin (IL)-1β in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently.", "label": "ACTIVATOR", "metadata": []}
{"text": "Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and [[ interleukin (IL)-1β ]] in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently.", "label": "ACTIVATOR", "metadata": []}
{"text": "Dietary << EPA >>/DHA treatment restored endogenous biosynthesis of n-3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving [[ insulin ]] sensitivity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Dietary EPA/<< DHA >> treatment restored endogenous biosynthesis of n-3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving [[ insulin ]] sensitivity.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased [[ adiponectin ]] expression and improved glucose tolerance parallel to insulin sensitivity in obese mice.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to [[ insulin ]] sensitivity in obese mice.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory [[ cytokines ]], increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, we validated the inhibition of << GSK-3β >>/NF-κB signaling following [[ cinobufagin ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, we validated the inhibition of GSK-3β/<< NF-κB >> signaling following [[ cinobufagin ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of << cinobufagin >>, while the phosphorylation of [[ GSK-3β ]] was simultaneously increased.", "label": "ACTIVATOR", "metadata": []}
{"text": "Western blots showed a decrease in nuclear << p65 >> protein expression after exposure to different concentrations of [[ cinobufagin ]], while the phosphorylation of GSK-3β was simultaneously increased.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Transduction with constitutively active forms of GSK-3β could protect against the downregulation of p65 and upregulation of cleaved-<< PARP >> that are induced by [[ cinobufagin ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Transduction with constitutively active forms of GSK-3β could protect against the downregulation of << p65 >> and upregulation of cleaved-PARP that are induced by [[ cinobufagin ]] treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "However, combined treatment with << cinobufagin >> and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-[[ PARP ]] in U2OS cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "However, combined treatment with cinobufagin and << SB216367 >> resulted in a significant reduction in p65 and an increase in cleaved-[[ PARP ]] in U2OS cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "However, combined treatment with << cinobufagin >> and SB216367 resulted in a significant reduction in [[ p65 ]] and an increase in cleaved-PARP in U2OS cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "However, combined treatment with cinobufagin and << SB216367 >> resulted in a significant reduction in [[ p65 ]] and an increase in cleaved-PARP in U2OS cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< [6]-gingerol >>: a novel [[ AT₁ ]] antagonist for the treatment of cardiovascular disease.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< [6]-Gingerol >> derived from Zingiber officinale Roscoe (ginger) was identified as a novel [[ angiotensin II type 1 receptor ]] antagonist, with an IC50 value of 8.173 µM.", "label": "ANTAGONIST", "metadata": []}
{"text": "The major ingredient of ginger, << [6]-gingerol >>, could inhibit [[ angiotensin II type 1 receptor ]] activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system.", "label": "INHIBITOR", "metadata": []}
{"text": "In patients who do not reach the LDL-C target, combination therapy with additional << LDL >>-C lowering drugs (e.g. [[ ezetimibe ]], bile acid sequestrants or fibrates) should be considered.", "label": "INHIBITOR", "metadata": []}
{"text": "In patients who do not reach the LDL-C target, combination therapy with additional << LDL >>-C lowering drugs (e.g. ezetimibe, [[ bile acid ]] sequestrants or fibrates) should be considered.", "label": "INHIBITOR", "metadata": []}
{"text": "In patients who do not reach the LDL-C target, combination therapy with additional << LDL >>-C lowering drugs (e.g. ezetimibe, bile acid sequestrants or [[ fibrates ]]) should be considered.", "label": "INHIBITOR", "metadata": []}
{"text": "N(5)-Substituted H(4)biopterin derivatives were not oxidized to products serving as substrates for dihydropteridine reductase and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: << N(5)-methyl >>- and N(5)-hydroxymethyl H(4)biopterin inhibited [[ phenylalanine hydroxylase ]], whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect.", "label": "INHIBITOR", "metadata": []}
{"text": "N(5)-Substituted H(4)biopterin derivatives were not oxidized to products serving as substrates for dihydropteridine reductase and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and << N(5)-hydroxymethyl H(4)biopterin >> inhibited [[ phenylalanine hydroxylase ]], whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect.", "label": "INHIBITOR", "metadata": []}
{"text": "<< N(5)-Substituted H(4)biopterin >> derivatives were not oxidized to products serving as substrates for [[ dihydropteridine reductase ]] and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and N(5)-hydroxymethyl H(4)biopterin inhibited phenylalanine hydroxylase, whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect.", "label": "SUBSTRATE", "metadata": []}
{"text": "Our data demonstrate differences in the mechanism of stimulation of << phenylalanine hydroxylase >> and nitric oxide synthase by [[ H(4)biopterin ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Transfection of the brain cDNA into COS-1 cells resulted in transporter activity that was blocked by the << VMAT >> inhibitor [[ reserpine ]] and a proton ionophore, but not by tetrabenazine, which has a high affinity for VMAT-2.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Mitochondrial arginase II >> modulates [[ nitric-oxide ]] synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells.", "label": "PRODUCT-OF", "metadata": []}
{"text": "<< Mitochondrial arginase II >> modulates nitric-oxide synthesis through nonfreely exchangeable [[ L-arginine ]] pools in human endothelial cells.", "label": "SUBSTRATE", "metadata": []}
{"text": "Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic [[ arginase I ]] and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic [[ arginase I ]] and mitochondrial arginase II.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II.", "label": "SUBSTRATE", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II.", "label": "SUBSTRATE", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic [[ arginase I ]] and mitochondrial arginase II.", "label": "SUBSTRATE", "metadata": []}
{"text": "Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]].", "label": "SUBSTRATE", "metadata": []}
{"text": "To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor [[ N(omega)-hydroxy-nor-L-arginine ]] (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).", "label": "INHIBITOR", "metadata": []}
{"text": "To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor N(omega)-hydroxy-nor-L-arginine ([[ Nor-NOHA ]]) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).", "label": "INHIBITOR", "metadata": []}
{"text": "To determine whether << arginases >> modulate the endothelial [[ NO ]] synthesis, we investigated the effects of the competitive arginase inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).", "label": "PRODUCT-OF", "metadata": []}
{"text": "In unstimulated cells, << Nor-NOHA >> dose-dependently reduced the [[ arginase ]] activity with maximal inhibition at 20 microM.", "label": "INHIBITOR", "metadata": []}
{"text": "When HUVECs were stimulated by thrombin without extracellular L-arginine, << Nor-NOHA >> dose-dependently increased the [[ NOS ]] activity and the NO release with maximal effects at 20 microM.", "label": "ACTIVATOR", "metadata": []}
{"text": "Extracellular << L-arginine >> also dose-dependently increased NO release and [[ arginase ]] activity.", "label": "ACTIVATOR", "metadata": []}
{"text": "However, despite activation of L-arginine uptake, the inhibition of << arginase >> activity by [[ Nor-NOHA ]] was still significant.", "label": "INHIBITOR", "metadata": []}
{"text": "These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane.", "label": "PRODUCT-OF", "metadata": []}
{"text": "However, pretreatment with agents that block late I(Na), like lidocaine, mexiletine, and << RSD1235 >>, a novel mixed [[ ion channel ]] blocker for the rapid pharmacologic conversion of atrial fibrillation, significantly attenuates the prolonging effects of Class III agents or those induced by ATX-II, a specific toxin that delays Na channel inactivation and amplifies late I(Na) greatly, mimicking LQT3.", "label": "INHIBITOR", "metadata": []}
{"text": "The << Na channel >> block caused by [[ lidocaine ]] and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.", "label": "INHIBITOR", "metadata": []}
{"text": "The << Na channel >> block caused by lidocaine and [[ RSD1235 ]] can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "INHIBITOR", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "INHIBITOR", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "INHIBITOR", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "INHIBITOR", "metadata": []}
{"text": "Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity.", "label": "UPREGULATOR", "metadata": []}
{"text": "Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [[[ diethylglyoxal bis-(guanylhydrazone) ]]; DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); [[ DEGBG ]]] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.", "label": "INHIBITOR", "metadata": []}
{"text": "Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that << polyamines >> might be involved in the [[ caspase ]] activating signal cascade.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.", "label": "DOWNREGULATOR", "metadata": []}
{"text": "On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start of<< carvedilol >> therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Two mechanisms of action have been identified for << A77 1726 >>: inhibition of [[ dihydroorotate dehydrogenase ]] (DHODH) and inhibition of tyrosine kinases.", "label": "INHIBITOR", "metadata": []}
{"text": "Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase ([[ DHODH ]]) and inhibition of tyrosine kinases.", "label": "INHIBITOR", "metadata": []}
{"text": "Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase (DHODH) and inhibition of [[ tyrosine kinases ]].", "label": "INHIBITOR", "metadata": []}
{"text": "<< DHODH >> inhibition occurs at lower concentrations of [[ A77 1726 ]] than that of tyrosine kinases and is currently considered the major mode of action.", "label": "INHIBITOR", "metadata": []}
{"text": "DHODH inhibition occurs at lower concentrations of << A77 1726 >> than that of [[ tyrosine kinases ]] and is currently considered the major mode of action.", "label": "INHIBITOR", "metadata": []}
{"text": "<< L-proline >> accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding [[ gamma-glutamyl kinase ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.", "label": "SUBSTRATE", "metadata": []}
{"text": "Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.", "label": "SUBSTRATE", "metadata": []}
{"text": "When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These results suggest that the altered << gamma-glutamyl kinase >> results in stabilization of the complex or has an indirect effect on gamma-glutamyl phosphate reductase activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.", "label": "PRODUCT-OF", "metadata": []}
{"text": "These results suggest that the altered gamma-glutamyl kinase results in stabilization of the complex or has an indirect effect on << gamma-glutamyl phosphate reductase >> activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.", "label": "PRODUCT-OF", "metadata": []}
{"text": "Structural optimization of << 2,5-thiophene amides >> as highly potent and selective [[ 17β-hydroxysteroid dehydrogenase type 2 ]] inhibitors for the treatment of osteoporosis.", "label": "INHIBITOR", "metadata": []}
{"text": "We report here the optimization of << human 17β-HSD2 >> inhibitors in the [[ 2,5-thiophene amide ]] class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group.", "label": "INHIBITOR", "metadata": []}
{"text": "While none of the phenethylamides (n = 2) were active, most of the << anilides >> (n = 0) turned out to moderately or strongly inhibit [[ 17β-HSD2 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Multiple exposure to << theophylline >>, a phosphodiesterase ([[ PDE ]]) inhibitor, induces acinar hypertrophy in the salivary gland.", "label": "INHIBITOR", "metadata": []}
{"text": "Multiple exposure to << theophylline >>, a [[ phosphodiesterase ]] (PDE) inhibitor, induces acinar hypertrophy in the salivary gland.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for [[ CysS ]] and PDE3A, but PDE4D gene expression was unchanged.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for CysS and [[ PDE3A ]], but PDE4D gene expression was unchanged.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.", "label": "AGONIST", "metadata": []}
{"text": "Terbutaline (Bricanyl) and its prodrug Bambuterol (<< Bambec >>) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.", "label": "AGONIST", "metadata": []}
{"text": "<< Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.", "label": "AGONIST", "metadata": []}
{"text": "Terbutaline (<< Bricanyl >>) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.", "label": "AGONIST", "metadata": []}
{"text": "<< (+/-)-tamsulosin >>, an [[ alpha 1A-adrenoceptor ]] antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart.", "label": "ANTAGONIST", "metadata": []}
{"text": "The influence of << (+/-)-tamsulosin >>, a selective [[ alpha 1A-adrenoceptor ]] antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.", "label": "AGONIST-ACTIVATOR", "metadata": []}
{"text": "(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of << alpha 1B-adrenoceptors >> by treatment with [[ chlorethylclonidine ]], which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.", "label": "INHIBITOR", "metadata": []}
{"text": "(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of << phenylephrine >> even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.", "label": "AGONIST", "metadata": []}
{"text": "<< (+/-)-Tamsulosin >> effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< (+/-)-Tamsulosin >>, over the range of concentrations at which it antagonized the positive inotropic effect mediated by [[ alpha 1-adrenoceptors ]], did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine.", "label": "ANTAGONIST", "metadata": []}
{"text": "These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.", "label": "AGONIST", "metadata": []}
{"text": "These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.", "label": "ANTAGONIST", "metadata": []}
{"text": "<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the [[ JAK2 ]]/STAT3 signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/[[ STAT3 ]] signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << PTE >> treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of [[ STAT3 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, << PTE >> treatment directly inhibited the phosphorylation of [[ JAK2 ]] at Tyr 1007 and the downstream activation of STAT3.", "label": "INHIBITOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, [[ Bak ]], cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic [[ Cytochrome c ]], and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved [[ Caspase3 ]]) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as [[ p21 ]] and p27.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and [[ p27 ]].", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins [[ Bcl-xL ]] and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and [[ Mcl-1 ]], leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "PTE, used in combination with a known << JAK2 >>/STAT3 inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.", "label": "INHIBITOR", "metadata": []}
{"text": "PTE, used in combination with a known JAK2/<< STAT3 >> inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the [[ JAK2 ]]/STAT3 signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/[[ STAT3 ]] signaling pathway.", "label": "INHIBITOR", "metadata": []}
{"text": "These data suggest that inhibition of << JAK2 >>/STAT3 signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.", "label": "INHIBITOR", "metadata": []}
{"text": "These data suggest that inhibition of JAK2/<< STAT3 >> signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.", "label": "INHIBITOR", "metadata": []}
{"text": "Furthermore, << sinapic acid >> reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of [[ type I collagen ]] mRNA and histological analysis of collagen in liver tissue.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the expression of hepatic fibrosis-related factors such as << α-smooth muscle actin >> and transforming growth factor-β1 (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and << transforming growth factor-β1 >> (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (<< TGF-β1 >>), were reduced in rats treated with [[ sinapic acid ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Thalidomide >> inhibits growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased [[ cytochrome c ]], but had no effect on that of COX-1, in MCF-7 and HL-60.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of [[ bcl-2 ]] protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, [[ TNFalpha ]], VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, [[ VEGF ]], GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "These results demonstrated that << thalidomide >> might inhibit growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.", "label": "INHIBITOR", "metadata": []}
{"text": "Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, [[ hemoglobin ]], packed cell volume, platelets, mean corpuscular volume, and mean corpuscular hemoglobin in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular [[ hemoglobin ]] in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Gene expression profiling (GEP) of GIST-S, GIST-R cells and two << IM >> resistant GIST patients demonstrated that [[ KIT ]] is downregulated implying a major role in IM resistance.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that << KIT >> is downregulated implying a major role in [[ IM ]] resistance.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel [[ c-Kit ]]/AXL kinase inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel c-Kit/[[ AXL ]] kinase inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel c-Kit/AXL [[ kinase ]] inhibitor.", "label": "INHIBITOR", "metadata": []}
{"text": "INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors acarbose and [[ voglibose ]] on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus.", "label": "INHIBITOR", "metadata": []}
{"text": "INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors [[ acarbose ]] and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus.", "label": "INHIBITOR", "metadata": []}
{"text": "INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors acarbose and voglibose on postprandial plasma [[ glucose ]] and serum triglyceride levels in patients with type 2 diabetes mellitus.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of << JAK >> and ERK pathways with [[ AG490 ]] and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH.", "label": "INHIBITOR", "metadata": []}
{"text": "Blockade of JAK and << ERK >> pathways with AG490 and [[ U0126 ]], respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH.", "label": "INHIBITOR", "metadata": []}
{"text": "The << COX >> pathway generates inflammatory [[ prostaglandins ]], while the 5-LOX pathway generates inflammatory leukotrienes.", "label": "PRODUCT-OF", "metadata": []}
{"text": "The COX pathway generates inflammatory prostaglandins, while the << 5-LOX >> pathway generates inflammatory [[ leukotrienes ]].", "label": "PRODUCT-OF", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the << 5-LOX >> inhibitor [[ REV 5901 ]]; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "label": "INHIBITOR", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the << 5-LOX activating protein >> (FLAP) inhibitor [[ MK-886 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (<< FLAP >>) inhibitor [[ MK-886 ]].", "label": "INHIBITOR", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the << COX-2 >> inhibitor [[ NS-398 ]]; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "label": "INHIBITOR", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed << COX-1 >>/COX-2 inhibitor [[ ibuprofen ]]; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "label": "INHIBITOR", "metadata": []}
{"text": "They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/<< COX-2 >> inhibitor [[ ibuprofen ]]; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (FLAP) inhibitor MK-886.", "label": "INHIBITOR", "metadata": []}
{"text": "Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in [[ Bax ]] expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, andcleaved-[[ caspase-3 ]] expression, whereas these were inhibited by CRE or EB treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Additionally, << MPTP >> significantly down-regulated [[ Bcl-2 ]] expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Add-on therapy with the << DPP-4 >> inhibitor [[ sitagliptin ]] improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus.", "label": "INHIBITOR", "metadata": []}
{"text": "The << hemoglobin A1c >> (HbA1c) of all patients improved significantly from 8.1±1.2% to 7.6±1.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3±15.8 U/day to 24.5±16.5 U/day (p<0.001).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The hemoglobin A1c (<< HbA1c >>) of all patients improved significantly from 8.1±1.2% to 7.6±1.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3±15.8 U/day to 24.5±16.5 U/day (p<0.001).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In the present study, we have evaluated possible participation of << monocarboxylate transporters >> (MCTs) responsible for the bidirectional membrane transport of [[ pyruvate ]] in the cytoprotective property in osteoblasts.", "label": "SUBSTRATE", "metadata": []}
{"text": "In the present study, we have evaluated possible participation of monocarboxylate transporters (<< MCTs >>) responsible for the bidirectional membrane transport of [[ pyruvate ]] in the cytoprotective property in osteoblasts.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Mammalian ALDH1B1 >>, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2.", "label": "SUBSTRATE", "metadata": []}
{"text": "Mammalian ALDH1B1, another mitochondrial enzyme sharing 72% identity with << ALDH2 >>, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2.", "label": "SUBSTRATE", "metadata": []}
{"text": "<< Aspirin >> (ASA) and other non-steroidal anti-inflammatory drugs, which are [[ cyclooxygenase ]] (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Aspirin >> (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase ([[ COX ]]) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients.", "label": "INHIBITOR", "metadata": []}
{"text": "Aspirin (<< ASA >>) and other non-steroidal anti-inflammatory drugs, which are [[ cyclooxygenase ]] (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients.", "label": "INHIBITOR", "metadata": []}
{"text": "Aspirin (<< ASA >>) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase ([[ COX ]]) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients.", "label": "INHIBITOR", "metadata": []}
{"text": "However, salicylate moiety appears to interfere with << aspirin >> inhibitory action on platelets and vascular [[ COX ]].", "label": "INHIBITOR", "metadata": []}
{"text": "Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between << salicylate >> and ASA on [[ cyclo-oxygenase ]] locus in the respiratory tract in ASA-intolerant patients.", "label": "INHIBITOR", "metadata": []}
{"text": "Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and << ASA >> on [[ cyclo-oxygenase ]] locus in the respiratory tract in ASA-intolerant patients.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Minocycline >> inhibits [[ cytochrome c ]] release and delays progression of amyotrophic lateral sclerosis in mice.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "We find that << minocycline >> inhibits mitochondrial permeability-transition-mediated [[ cytochrome c ]] release.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "<< Minocycline >>-mediated inhibition of [[ cytochrome c ]] release is demonstrated in vivo, in cells, and in isolated mitochondria.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Here we studied the effects of the recently developed << monoacylglycerol lipase >> inhibitor [[ JZL184 ]] on basal and stress-induced corticosterone levels in male CD1 mice, and found that this compound dramatically increased basal levels without affecting stress responses.", "label": "INHIBITOR", "metadata": []}
{"text": "Considerable attention has focused on the antitumor effect of << histone deacetylase >> inhibitor ([[ Trichostatin A ]], TSA) as well as the coding gene expression-induced apoptosis of cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Considerable attention has focused on the antitumor effect of << histone deacetylase >> inhibitor (Trichostatin A, [[ TSA ]]) as well as the coding gene expression-induced apoptosis of cancer cells.", "label": "INHIBITOR", "metadata": []}
{"text": "Among these differentially expressed lncRNAs, the greatest change was noted for << uc002mbe.2 >>, which had more than 300 folds induction upon [[ TSA ]] treatment.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< TSA >> selectively induced [[ uc002mbe.2 ]] in four studied HCC cell lines.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "The << TSA >>-induced [[ uc002mbe.2 ]] expression was positively correlated with the apoptotic effect of TSA in HCC cells.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Orlistat >>, a new [[ lipase ]] inhibitor for the management of obesity.", "label": "INHIBITOR", "metadata": []}
{"text": "<< Orlistat >> treatment also results in modest improvements in total cholesterol, [[ low-density lipoprotein ]], blood pressure, and fasting glucose and insulin concentrations.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "<< Orlistat >> treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and [[ insulin ]] concentrations.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis.", "label": "UPREGULATOR", "metadata": []}
{"text": "TSH and << cAMP >> also increase the levels of the specific mRNA for [[ TPO ]] in thyroid cells from different species.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "A novel << benzo[d]imidazole >> derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of [[ NLRP3 ]] inflammasome.", "label": "INHIBITOR", "metadata": []}
{"text": "In addition, the disease activity index, histopathologic scores and << myeloperoxidase >> activity were also significantly reduced by [[ Fc11a-2 ]] treatment.", "label": "INHIBITOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory << cytokines >> in colon, including TNF-α, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including << TNF-α >>, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, << IL-1β >>, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, << IL-18 >>, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, << IL-17A >> and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, IL-17A and << IFN-γ >>, were markedly suppressed by [[ Fc11a-2 ]].", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "Furthermore, a decreased CD11c(+) macrophage infiltration in colons and inactivation of << caspase-1 >> in peritoneal macrophages were detected in [[ Fc11a ]]-2-treated mice.", "label": "INHIBITOR", "metadata": []}
{"text": "The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of [[ pro-caspase-1 ]], pro-IL-1β and pro-IL-18 which in turn suppressed the activation of NLRP3 inflammasome.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, [[ pro-IL-1β ]] and pro-IL-18 which in turn suppressed the activation of NLRP3 inflammasome.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and [[ pro-IL-18 ]] which in turn suppressed the activation of NLRP3 inflammasome.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and pro-IL-18 which in turn suppressed the activation of [[ NLRP3 ]] inflammasome.", "label": "INHIBITOR", "metadata": []}
{"text": "Taken together, our results demonstrate the ability of << Fc11a-2 >> to inhibit [[ NLRP3 ]] inflammasome activation and its potential use in the treatment of inflammatory bowel diseases.", "label": "INHIBITOR", "metadata": []}
{"text": "At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker [[ tyrosine hydroxylase ]] (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase ([[ TH ]]), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less [[ norepinephrine transporter ]] (NET)-ir density.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter ([[ NET ]])-ir density.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In hippocampal dentate gyrus, << MPH >>-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of [[ neural cell adhesion molecule ]]).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In hippocampal dentate gyrus, << MPH >>-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-[[ NCAM ]] (polysialylated form of neural cell adhesion molecule).", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In hippocampal dentate gyrus, << MPH >>-receiving rats showed a 51% decrease in [[ NET ]]-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule).", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}
{"text": "In medial striatum, TH-ir decreased by 21%, and in hypothalamus << neuropeptide Y >>-ir increased by 10% in [[ MPH ]]-exposed rats.", "label": "INDIRECT-UPREGULATOR", "metadata": []}
{"text": "In medial striatum, << TH >>-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in [[ MPH ]]-exposed rats.", "label": "INDIRECT-DOWNREGULATOR", "metadata": []}