<< P505-15 >> (also known as PRT062607) is a novel, highly selective, and orally bioavailable small molecule [[ SYK ]] inhibitor (SYK IC(50) = 1 nM) with anti-SYK activity that is at least 80-fold greater than its affinity for other kinases.


<< P505-15 >> (also known as PRT062607) is a novel, highly selective, and orally bioavailable small molecule SYK inhibitor ([[ SYK ]] IC(50) = 1 nM) with anti-SYK activity that is at least 80-fold greater than its affinity for other kinases.


<< P505-15 >> (also known as PRT062607) is a novel, highly selective, and orally bioavailable small molecule SYK inhibitor (SYK IC(50) = 1 nM) with anti-[[ SYK ]] activity that is at least 80-fold greater than its affinity for other kinases.


P505-15 (also known as << PRT062607 >>) is a novel, highly selective, and orally bioavailable small molecule [[ SYK ]] inhibitor (SYK IC(50) = 1 nM) with anti-SYK activity that is at least 80-fold greater than its affinity for other kinases.


P505-15 (also known as << PRT062607 >>) is a novel, highly selective, and orally bioavailable small molecule SYK inhibitor ([[ SYK ]] IC(50) = 1 nM) with anti-SYK activity that is at least 80-fold greater than its affinity for other kinases.


P505-15 (also known as << PRT062607 >>) is a novel, highly selective, and orally bioavailable small molecule SYK inhibitor (SYK IC(50) = 1 nM) with anti-[[ SYK ]] activity that is at least 80-fold greater than its affinity for other kinases.


<< P505-15 >> successfully inhibited SYK-mediated [[ B-cell receptor ]] signaling and decreased cell viability in NHL and CLL.


<< P505-15 >> successfully inhibited [[ SYK ]]-mediated B-cell receptor signaling and decreased cell viability in NHL and CLL.


<< 17-Allylamino-17-demethoxygeldanamycin >> (17-AAG), an [[ Hsp90 ]] inhibitor, is currently under evaluation for its anticancer activity in clinical trials.


17-Allylamino-17-demethoxygeldanamycin (<< 17-AAG >>), an [[ Hsp90 ]] inhibitor, is currently under evaluation for its anticancer activity in clinical trials.


Although treatment with << 17-AAG >> reduced [[ AhR ]] levels and AhR-regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17-AAG.


Although treatment with << 17-AAG >> reduced AhR levels and [[ AhR ]]-regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17-AAG.


In addition, << 17-AAG >> treatment reduced cell viability, [[ CDK2 ]], CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.


In addition, << 17-AAG >> treatment reduced cell viability, CDK2, [[ CDK4 ]], cyclin E, cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.


In addition, << 17-AAG >> treatment reduced cell viability, CDK2, CDK4, [[ cyclin E ]], cyclin D1, and phosphorylated Rb levels in AhR-expressing lung AD cells.


In addition, << 17-AAG >> treatment reduced cell viability, CDK2, CDK4, cyclin E, [[ cyclin D1 ]], and phosphorylated Rb levels in AhR-expressing lung AD cells.


In addition, << 17-AAG >> treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and [[ phosphorylated Rb ]] levels in AhR-expressing lung AD cells.


<< Gemcitabine >> (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase ([[ DCK ]]), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


<< Gemcitabine >> (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by [[ cytidine deaminase ]] (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


<< Gemcitabine >> (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase ([[ CDA ]]) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


<< Gemcitabine >> (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and [[ deoxycytidine kinase ]] (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (<< dFdC >>, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase ([[ DCK ]]), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (<< dFdC >>, 2',2'-difluorodeoxycytidine) is metabolized by [[ cytidine deaminase ]] (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (<< dFdC >>, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase ([[ CDA ]]) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (<< dFdC >>, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and [[ deoxycytidine kinase ]] (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (dFdC, << 2',2'-difluorodeoxycytidine >>) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase ([[ DCK ]]), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (dFdC, << 2',2'-difluorodeoxycytidine >>) is metabolized by [[ cytidine deaminase ]] (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (dFdC, << 2',2'-difluorodeoxycytidine >>) is metabolized by cytidine deaminase ([[ CDA ]]) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Gemcitabine (dFdC, << 2',2'-difluorodeoxycytidine >>) is metabolized by cytidine deaminase (CDA) and [[ deoxycytidine kinase ]] (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.


Wild-type enzymes and variants of << CDA >> (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (<< Lys27Gln >> and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and << Ala70Thr >>) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and << DCK >> (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (<< Ile24Val >>, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, << Ala119Gly >>, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and << Pro122Ser >>) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ([[ Ara-C ]]), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of << CDA >> (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (<< Lys27Gln >> and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and << Ala70Thr >>) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and << DCK >> (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (<< Ile24Val >>, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, << Ala119Gly >>, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and << Pro122Ser >>) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), [[ dFdC ]], and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of << CDA >> (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (<< Lys27Gln >> and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and << Ala70Thr >>) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and << DCK >> (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (<< Ile24Val >>, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, << Ala119Gly >>, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and << Pro122Ser >>) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite [[ 2',2'-difluorodeoxyuridine ]] (dFdU) as substrates.


Wild-type enzymes and variants of << CDA >> (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine ([[ dFdU ]]) as substrates.


Wild-type enzymes and variants of << CDA >> (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (<< Lys27Gln >> and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and << Ala70Thr >>) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and << DCK >> (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (<< Ile24Val >>, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, << Ala119Gly >>, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and << Pro122Ser >>) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates.


All three << CDA >> proteins showed similar K(m) and V(max) for [[ Ara-C ]] and dFdC deamination, except for CDA70Thr, which had a 2.5-fold lower K(m) and 6-fold lower V(max) for Ara-C deamination.


All three << CDA >> proteins showed similar K(m) and V(max) for Ara-C and [[ dFdC ]] deamination, except for CDA70Thr, which had a 2.5-fold lower K(m) and 6-fold lower V(max) for Ara-C deamination.


All three CDA proteins showed similar K(m) and V(max) for Ara-C and dFdC deamination, except for << CDA >>70Thr, which had a 2.5-fold lower K(m) and 6-fold lower V(max) for [[ Ara-C ]] deamination.


All four << DCK >> proteins yielded comparable metabolic activity for [[ Ara-C ]] and dFdC monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K(m) (P < 0.05).


All four << DCK >> proteins yielded comparable metabolic activity for Ara-C and [[ dFdC ]] monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K(m) (P < 0.05).


All four DCK proteins yielded comparable metabolic activity for Ara-C and dFdC monophosphorylation, except for << DCK >>24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of [[ dFdC ]] monophosphorylation due to a 40% decrease in K(m) (P < 0.05).


In conclusion, the << Lys27Gln >> substitution does not significantly modulate CDA activity toward [[ dFdC ]], and therefore would not contribute to interindividual variability in response to gemcitabine.


In conclusion, the Lys27Gln substitution does not significantly modulate << CDA >> activity toward [[ dFdC ]], and therefore would not contribute to interindividual variability in response to gemcitabine.


The higher in vitro catalytic efficiency of << DCK >>24Val toward [[ dFdC ]] monophosphorylation may be relevant to dFdC clinical response.


The higher in vitro catalytic efficiency of << DCK >>24Val toward dFdC monophosphorylation may be relevant to [[ dFdC ]] clinical response.


Discovery of << 4-phenyl-2-phenylaminopyridine >> based [[ TNIK ]] inhibitors.


A series of compounds based on a << 4-phenyl-2-phenylaminopyridine >> scaffold that are potent and selective inhibitors of [[ Traf2- and Nck-interacting kinase ]] (TNIK) activity are described.


A series of compounds based on a << 4-phenyl-2-phenylaminopyridine >> scaffold that are potent and selective inhibitors of Traf2- and Nck-interacting kinase ([[ TNIK ]]) activity are described.


<< Boron >>-based inhibitors of [[ acyl protein thioesterases 1 and 2 ]].


Here we present << boronic >> and borinic acid derivatives as a new class of potent and nontoxic [[ APT ]] inhibitors.


Here we present boronic and << borinic acid >> derivatives as a new class of potent and nontoxic [[ APT ]] inhibitors.


Here, we report that << genistein >> at physiologically relevant concentrations (0.1-10 μM) significantly inhibited [[ thrombin ]]-induced increase in endothelial monolayer permeability.


<< Genistein >> also reduced the formation of stress fibers by [[ thrombin ]] and suppressed thrombin-induced phosphorylation of myosin light chain (MLC) on Ser(19)/Thr(18) in endothelial cells (ECs).


<< Genistein >> also reduced the formation of stress fibers by thrombin and suppressed [[ thrombin ]]-induced phosphorylation of myosin light chain (MLC) on Ser(19)/Thr(18) in endothelial cells (ECs).


<< Genistein >> also reduced the formation of stress fibers by thrombin and suppressed thrombin-induced phosphorylation of [[ myosin light chain ]] (MLC) on Ser(19)/Thr(18) in endothelial cells (ECs).


<< Genistein >> also reduced the formation of stress fibers by thrombin and suppressed thrombin-induced phosphorylation of myosin light chain ([[ MLC ]]) on Ser(19)/Thr(18) in endothelial cells (ECs).


Furthermore, << thrombin >> diminished cAMP production in ECs, which were prevented by treatment with [[ genistein ]].


Evaluation of drug interactions of << GSK1292263 >> (a [[ GPR119 ]] agonist) with statins: from in vitro data to clinical study design.


1. This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the << HMG-coA reductase >> inhibitors [[ simvastatin ]] and rosuvastatin.


1. This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the << HMG-coA reductase >> inhibitors simvastatin and [[ rosuvastatin ]].


1. This work investigated the drug interaction potential of << GSK1292263 >>, a novel [[ GPR119 ]] agonist, with the HMG-coA reductase inhibitors simvastatin and rosuvastatin.


2. In vitro experiments assessed the inhibition of << transporters >> and CYP enzymes by [[ GSK1292263 ]], and a clinical drug interaction study investigated the effect of GSK1292263 (300 mg BID) on the pharmacokinetic profile of simvastatin (40 mg single dose) and rosuvastatin (10 mg single dose).


2. In vitro experiments assessed the inhibition of transporters and << CYP >> enzymes by [[ GSK1292263 ]], and a clinical drug interaction study investigated the effect of GSK1292263 (300 mg BID) on the pharmacokinetic profile of simvastatin (40 mg single dose) and rosuvastatin (10 mg single dose).


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards [[ CYPs ]] (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs ([[ CYP1A2 ]], 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, [[ 2C9 ]], 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, [[ 2C19 ]], 2D6, 3A4), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, 2C19, [[ 2D6 ]], 3A4), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, [[ 3A4 ]]), Pgp, OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), [[ Pgp ]], OATP1B3, or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, [[ OATP1B3 ]], or OCT2.


3. In vitro, << GSK1292263 >> demonstrated little/weak inhibition (IC50 values >30 μM) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or [[ OCT2 ]].


However, << GSK1292263 >> inhibited [[ BCRP ]] and OATP1B1, which are transporters involved in statin disposition.


However, << GSK1292263 >> inhibited BCRP and [[ OATP1B1 ]], which are transporters involved in statin disposition.


4. In the clinical study, small increases in the AUC(0-inf) of simvastatin [mean ratio (90% CI) of 1.34 (1.22, 1.48)] and rosuvastatin [mean ratio (90% CI) of 1.39 (1.30, 1.49)] were observed when co-administered with << GSK1292263 >>, which is consistent with an inhibitory effect on intestinal BCRP and [[ CYP3A4 ]].


4. In the clinical study, small increases in the AUC(0-inf) of simvastatin [mean ratio (90% CI) of 1.34 (1.22, 1.48)] and rosuvastatin [mean ratio (90% CI) of 1.39 (1.30, 1.49)] were observed when co-administered with << GSK1292263 >>, which is consistent with an inhibitory effect on intestinal [[ BCRP ]] and CYP3A4.


This study provides a mechanistic understanding of the in vivo inhibition of << transporters >> and enzymes by [[ GSK1292263 ]].


The presence of << steroid >> hormones most probably causes the degradation of the [[ Tat2 ]] permease and impairment of tryptophan import.


Inhibition of Th1/Th17 responses via suppression of << STAT1 >> and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside [[ icariin ]].


Inhibition of Th1/Th17 responses via suppression of STAT1 and << STAT3 >> activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside [[ icariin ]].


Inhibition of Th1/Th17 responses via suppression of << STAT1 >> and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural [[ flavonoid ]] glucoside icariin.


Inhibition of Th1/Th17 responses via suppression of STAT1 and << STAT3 >> activation contributes to the amelioration of murine experimental colitis by a natural [[ flavonoid ]] glucoside icariin.


Further study showed that << icariin >> dose-dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro-inflammatory [[ cytokine ]] levels of activated T cells.


Moreover, << icariin >> treatment inhibited the phosphorylations of [[ STAT1 ]] and STAT3 in CD4(+) T cells, which were the crucial transcription factors for Th1 and Th17 respectively.


Moreover, << icariin >> treatment inhibited the phosphorylations of STAT1 and [[ STAT3 ]] in CD4(+) T cells, which were the crucial transcription factors for Th1 and Th17 respectively.


Pharmacological inhibition of MTORC1 with << rapamycin >> abrogated the [[ insulin ]]-induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, RPS6.


Pharmacological inhibition of << MTORC1 >> with [[ rapamycin ]] abrogated the insulin-induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, RPS6.


Pharmacological inhibition of MTORC1 with << rapamycin >> abrogated the insulin-induced phosphorylation of [[ EIF4EBP1 ]], RPS6KB1 and its downstream effector, RPS6.


Pharmacological inhibition of MTORC1 with << rapamycin >> abrogated the insulin-induced phosphorylation of EIF4EBP1, [[ RPS6KB1 ]] and its downstream effector, RPS6.


Pharmacological inhibition of MTORC1 with << rapamycin >> abrogated the insulin-induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, [[ RPS6 ]].


Furthermore, << insulin >>-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins CDK4, CCND3 and PCNA were also blocked by [[ rapamycin ]].


Furthermore, insulin-stimulated T-I cell proliferation and the expression of << cell cycle regulatory proteins >> CDK4, CCND3 and PCNA were also blocked by [[ rapamycin ]].


Furthermore, insulin-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins << CDK4 >>, CCND3 and PCNA were also blocked by [[ rapamycin ]].


Furthermore, insulin-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins CDK4, << CCND3 >> and PCNA were also blocked by [[ rapamycin ]].


Furthermore, insulin-stimulated T-I cell proliferation and the expression of cell cycle regulatory proteins CDK4, CCND3 and << PCNA >> were also blocked by [[ rapamycin ]].


Synthesis and evaluation of << 8-oxoadenine >> derivatives as potent [[ Toll-like receptor 7 ]] agonists with high water solubility.


We report the discovery of novel series of highly potent << TLR7 >> agonists based on 8-oxoadenines, 1 and 2 by introducing and optimizing various [[ tertiary amines ]] onto the N(9)-position of the adenine moiety.


We report the discovery of novel series of highly potent << TLR7 >> agonists based on 8-oxoadenines, 1 and 2 by introducing and optimizing various tertiary amines onto the [[ N ]](9)-position of the adenine moiety.


We report the discovery of novel series of highly potent << TLR7 >> agonists based on 8-oxoadenines, 1 and 2 by introducing and optimizing various tertiary amines onto the N(9)-position of the [[ adenine ]] moiety.


We report the discovery of novel series of highly potent << TLR7 >> agonists based on [[ 8-oxoadenines ]], 1 and 2 by introducing and optimizing various tertiary amines onto the N(9)-position of the adenine moiety.


The introduction of the << amino >> group resulted in not only improved water solubility but also enhanced [[ TLR7 ]] agonistic activity.


Inhibitors based on a << benzo-fused spirocyclic oxazepine >> scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 ([[ SCD1 ]]) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model.


Inhibitors based on a << benzo-fused spirocyclic oxazepine >> scaffold were discovered for [[ stearoyl-coenzyme A (CoA) desaturase 1 ]] (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model.


The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited << human Hsp60 >> chaperone activity (IC(50): 6.80 ± 0.25 μM) and this inhibition activity was higher than that of [[ ETB ]] (IC(50): 10.9 ± 0.63 μM).


<< Apocynin >> and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated [[ p66Shc ]] in rat testes.


Apocynin and << raisanberine >> alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated [[ p66Shc ]] in rat testes.


Apocynin and << raisanberine >> alleviate intermittent hypoxia induced abnormal StAR and [[ 3β-HSD ]] and low testosterone by suppressing endoplasmic reticulum stress and activated p66Shc in rat testes.


We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase (NOX), therefore, << APO >> (apocynin) an inhibitor of [[ NOX ]] and raisanberine (RS), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis.


We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase (NOX), therefore, APO (<< apocynin >>) an inhibitor of [[ NOX ]] and raisanberine (RS), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis.


<< APO >> and RS at least partially normalize hypoxia caused male hypogonadism by suppressing ER stress, and [[ p66Shc ]] in testes.


Here we found that << arsenic trioxide >>, a frontline agent for acute promyelocytic leukemia, inhibits [[ ΔNp63 ]] but not TAp63 expression in time- and dose-dependent manners.


In addition, we found that << arsenic trioxide >> decreases the stability of [[ ΔNp63 ]] protein via a proteasome-dependent pathway but has little effect on the level of ΔNp63 transcript.


Furthermore, we found that << arsenic trioxide >> activates the [[ Pirh2 promoter ]] and consequently induces Pirh2 expression.


Furthermore, we found that << arsenic trioxide >> activates the Pirh2 promoter and consequently induces [[ Pirh2 ]] expression.


Consistent with this, we found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, << arsenic >>-induced degradation of [[ ΔNp63 ]] protein.


Together, these data suggest that << arsenic >> degrades [[ ΔNp63 ]] protein at least in part via Pirh2-dependent proteolysis and that inhibition of ΔNp63 expression facilitates tumor cells to arsenic-induced death.


Together, these data suggest that << arsenic >> degrades ΔNp63 protein at least in part via Pirh2-dependent proteolysis and that inhibition of [[ ΔNp63 ]] expression facilitates tumor cells to arsenic-induced death.


<< Jaceosidin >>, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating cdc25C-cdc2 via [[ ATM ]]-Chk1/2 activation.


<< Jaceosidin >>, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating [[ cdc25C ]]-cdc2 via ATM-Chk1/2 activation.


<< Jaceosidin >>, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating cdc25C-[[ cdc2 ]] via ATM-Chk1/2 activation.


Additional mechanistic studies revealed that << jaceosidin >> treatment resulted in an increase in phosphorylation of [[ Cdc25C ]] and ATM-Chk1/2.


Additional mechanistic studies revealed that << jaceosidin >> treatment resulted in an increase in phosphorylation of Cdc25C and [[ ATM ]]-Chk1/2.


Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the << ERK >> inhibitor, [[ PD98059 ]], attenuated cell growth inhibition by jaceosidin.


These data suggest that << jaceosidin >>, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the [[ Cdc2 ]]-cyclin B1 complex, followed by G2/M cell cycle arrest in endometrial cancer cells.


These data suggest that << jaceosidin >>, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cdc2-[[ cyclin B1 ]] complex, followed by G2/M cell cycle arrest in endometrial cancer cells.


Electrical Stimuli Release ATP to Increase << GLUT4 >> Translocation and [[ Glucose ]] Uptake via PI3Kγ-Akt-AS160 in Skeletal Muscle Cells.


Electrical stimulation, ATP, and insulin each increased fluorescent 2-NBD-Glucose (2-NBDG) uptake in primary myotubes, but only electrical stimulation and ATP-dependent 2-NBDG uptake were inhibited by << adenosine-phosphate phosphatase >> and by purinergic receptor blockade ([[ suramin ]]).


Electrical stimulation, ATP, and insulin each increased fluorescent 2-NBD-Glucose (2-NBDG) uptake in primary myotubes, but only electrical stimulation and ATP-dependent 2-NBDG uptake were inhibited by adenosine-phosphate phosphatase and by << purinergic receptor >> blockade ([[ suramin ]]).


Electrical stimulation transiently elevated extracellular ATP and caused << Akt >> phosphorylation that was additive to insulin and inhibited by [[ suramin ]].


Exogenous << ATP >> transiently activated [[ Akt ]] and, inhibiting phosphatidylinositol 3-kinase (PI3K) or Akt as well as dominant-negative Akt mutant, reduced ATP-dependent 2-NBDG uptake and Akt phosphorylation.


ATP-dependent 2-NBDG uptake was also inhibited by the G protein βγ subunit-interacting peptide βark-ct and by the << phosphatidylinositol 3-kinase-γ >> (PI3Kγ) inhibitor [[ AS605240 ]].


ATP-dependent 2-NBDG uptake was also inhibited by the G protein βγ subunit-interacting peptide βark-ct and by the phosphatidylinositol 3-kinase-γ (<< PI3Kγ >>) inhibitor [[ AS605240 ]].


Structure-based design, synthesis and evaluation of novel << anthra[1,2-d]imidazole-6,11-dione >> derivatives as [[ telomerase ]] inhibitors and potential for cancer polypharmacology.


A series of << anthra[1,2-d]imidazole-6,11-dione >> derivatives were synthesized and evaluated for [[ telomerase ]] inhibition, hTERT expression and suppression of cancer cell growth in vitro.


<< Trichostatin A >> inhibits transforming growth factor-β-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced [[ NF-E2-related factor 2 ]]-antioxidant response element signaling.


<< Trichostatin A >> inhibits transforming growth factor-β-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF-E2-related factor 2-[[ antioxidant response element ]] signaling.


<< Trichostatin A >> inhibits [[ transforming growth factor-β ]]-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF-E2-related factor 2-antioxidant response element signaling.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the << NF-E2-related factor 2 >>-antioxidant response element (Nrf2-ARE) activator [[ sulforaphane ]], or small interfering RNA.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-<< antioxidant response element >> (Nrf2-ARE) activator [[ sulforaphane ]], or small interfering RNA.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (<< Nrf2 >>-ARE) activator [[ sulforaphane ]], or small interfering RNA.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-<< ARE >>) activator [[ sulforaphane ]], or small interfering RNA.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the << NAD(P)H oxidase >> inhibitor [[ diphenyleneiodonium ]] (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA.


Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the << NAD(P)H oxidase >> inhibitor diphenyleneiodonium ([[ DPI ]]), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA.


Treatment with << TSA >> and the Nrf2-ARE activator resulted in increased inhibition of the [[ TGF-β ]]-induced myofibroblast differentiation as compared with treatment with DPI or NAC.


Furthermore, << TSA >> also decreased cellular ROS and H(2)O(2) accumulation induced by [[ TGF-β ]], whereas it elevated intracellular GSH level and cellular total antioxidant capacity.


In addition, << TSA >> induced Nrf2 nuclear translocation and up-regulated the expression of [[ Nrf2 ]]-ARE downstream antioxidant genes, whereas Nrf2 knockdown by RNA interference blocked the inhibition of TSA on myofibroblast differentiation.


In addition, << TSA >> induced Nrf2 nuclear translocation and up-regulated the expression of Nrf2-[[ ARE ]] downstream antioxidant genes, whereas Nrf2 knockdown by RNA interference blocked the inhibition of TSA on myofibroblast differentiation.


In conclusion, this study provides the first evidence implicating that << TSA >> inhibits TGF-β-induced ROS accumulation and myofibroblast differentiation via enhanced [[ Nrf2 ]]-ARE signaling.


In conclusion, this study provides the first evidence implicating that << TSA >> inhibits TGF-β-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-[[ ARE ]] signaling.


In conclusion, this study provides the first evidence implicating that << TSA >> inhibits [[ TGF-β ]]-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-ARE signaling.


<< Cannabinoid receptor 1 >> (CB(1)) inverse agonists (e.g., [[ rimonabant ]]) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications.


Cannabinoid receptor 1 (<< CB(1) >>) inverse agonists (e.g., [[ rimonabant ]]) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications.


In the present studies, the CB(1) inverse agonist SR141716A (rimonabant) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel << CB(1) >> full agonist [[ AM4054 ]].


In the present studies, the << CB(1) >> inverse agonist [[ SR141716A ]] (rimonabant) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054.


In the present studies, the << CB(1) >> inverse agonist SR141716A ([[ rimonabant ]]) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054.


In the present studies, the CB(1) inverse agonist SR141716A (rimonabant) and the << CB(1) >> neutral antagonist [[ AM4113 ]] were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054.


Results indicate that << AM4054 >> serves as an effective [[ CB(1) ]] discriminative stimulus, with an onset and time course of action comparable with that of the CB(1) agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.


Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist [[ Δ(9)-tetrahydrocannabinol ]], and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.


Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the [[ AM4054 ]] dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.


Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of [[ AM4054 ]].


Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist [[ rimonabant ]] and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.


Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist [[ AM4113 ]] produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.


<< FXa >> inhibitors, e.g. [[ rivaroxaban ]] and apixaban, are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free FXa.


FXa inhibitors, e.g. << rivaroxaban >> and apixaban, are potent, oral direct inhibitors of [[ prothrombinase ]]-bound, clot-associated or free FXa.


FXa inhibitors, e.g. << rivaroxaban >> and apixaban, are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free [[ FXa ]].


<< FXa >> inhibitors, e.g. rivaroxaban and [[ apixaban ]], are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free FXa.


FXa inhibitors, e.g. rivaroxaban and << apixaban >>, are potent, oral direct inhibitors of [[ prothrombinase ]]-bound, clot-associated or free FXa.


FXa inhibitors, e.g. rivaroxaban and << apixaban >>, are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free [[ FXa ]].


Although parenteral oral direct << thrombin >> inhibitors (DTIs), such as [[ argatroban ]] and bivalirudin, have been on the market for years, DTIs such as dabigatran are novel synthetic thrombin antagonists.


Although parenteral oral direct thrombin inhibitors (DTIs), such as argatroban and bivalirudin, have been on the market for years, DTIs such as << dabigatran >> are novel synthetic [[ thrombin ]] antagonists.


<< Dabigatran >> has an advantage over the indirect [[ thrombin ]] inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound thrombin.


<< Dabigatran >> has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and [[ fibrin ]]-bound thrombin.


<< Dabigatran >> has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound [[ thrombin ]].


The reversible binding of << dabigatran >> may provide safer and more predictable anticoagulant treatment than seen with irreversible, non-covalent [[ thrombin ]] inhibitors, e.g. hirudin.


<< Aldehyde dehydrogenase 1 >> (ALDH1A1) catalyzes the oxidation of toxic aldehydes to [[ carboxylic acids ]].


Aldehyde dehydrogenase 1 (<< ALDH1A1 >>) catalyzes the oxidation of toxic aldehydes to [[ carboxylic acids ]].


<< Aldehyde dehydrogenase 1 >> (ALDH1A1) catalyzes the oxidation of toxic [[ aldehydes ]] to carboxylic acids.


Aldehyde dehydrogenase 1 (<< ALDH1A1 >>) catalyzes the oxidation of toxic [[ aldehydes ]] to carboxylic acids.


Physiologic levels of << Mg(2+) >> ions decrease [[ ALDH1 ]] activity in part by increasing NADH binding affinity to the enzyme.


As the << Mg(2+) >> ion concentration was increased, there was a consistent decrease of the enzyme catalytic turnover from 0.31 s(-1) (0 μM Mg(2+)) to 0.050 s(-1) (6000 μM Mg(2+)) and a distinct shift in steady-state conformational population from one that favors the [[ ALDH1 ]]-NADH complex with the shorter fluorescence lifetime (33% excess) in the absence of magnesium ion to one that favors the ALDH1-NADH complex with the longer fluorescence lifetime (13% excess) at 6000 μM Mg(2+).


This shift in conformational population at higher << Mg(2+) >> ion concentrations and to lower enzyme activity may be due to longer residence time of the NADH in the [[ ALDH1 ]] pocket.


Interestingly, << Acrolein >> increased proteins' levels of [[ amyloid precursor protein ]] (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.


Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), [[ β-secretase ]] (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.


Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), β-secretase ([[ BACE-1 ]]) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.


Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the [[ amyloid β-peptide transporter ]] receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.


Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter [[ receptor for advanced glycation end products ]], and decreased A-disintegrin and metalloprotease (ADAM) 10 levels.


Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased [[ A-disintegrin and metalloprotease (ADAM) 10 ]] levels.


Moreover, << Acrolein >> resulted in activation of astrocytes, up-regulation of [[ BACE-1 ]] in cortex and down-regulation of ADAM-10 in hippocampus and cortex.


Moreover, << Acrolein >> resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of [[ ADAM-10 ]] in hippocampus and cortex.


Regulation of sexual reproduction by << estradiol >> involves the activation of [[ estrogen receptors ]] (ERs) in the hypothalamus.


Regulation of sexual reproduction by << estradiol >> involves the activation of estrogen receptors ([[ ERs ]]) in the hypothalamus.


Using surface biotinylation, we observed that treatment of N-38 neurons with estradiol or with a membrane impermeant << estradiol >> elevated plasma membrane [[ ERα ]] protein levels, indicating that membrane signaling increased receptor insertion into the cell membrane.


Using surface biotinylation, we observed that treatment of N-38 neurons with << estradiol >> or with a membrane impermeant estradiol elevated plasma membrane [[ ERα ]] protein levels, indicating that membrane signaling increased receptor insertion into the cell membrane.


Insertion of << ERα >> was blocked by the ER antagonist [[ ICI 182,780 ]] or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide (BIS).


Insertion of << ERα >> was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (PKC) pathway inhibitor [[ bisindolylmaleimide ]] (BIS).


Insertion of ERα was blocked by the ER antagonist ICI 182,780 or with the << protein kinase C >> (PKC) pathway inhibitor [[ bisindolylmaleimide ]] (BIS).


Insertion of ERα was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (<< PKC >>) pathway inhibitor [[ bisindolylmaleimide ]] (BIS).


Insertion of << ERα >> was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide ([[ BIS ]]).


Insertion of ERα was blocked by the ER antagonist ICI 182,780 or with the << protein kinase C >> (PKC) pathway inhibitor bisindolylmaleimide ([[ BIS ]]).


Insertion of ERα was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (<< PKC >>) pathway inhibitor bisindolylmaleimide ([[ BIS ]]).


Insertion of ERα was blocked by the << ER >> antagonist [[ ICI 182,780 ]] or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide (BIS).


These results indicate that membrane << ERα >> levels in N-38 neurons are dynamically autoregulated by [[ estradiol ]].


Reductions in striatal dopamine and << tyrosine hydroxylase >> content were also less pronounced with [[ EHT ]] treatment.


The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and << JNK >> activation were significantly prevented with [[ EHT ]].


In cultured primary microglia and astrocytes, << EHT >> had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced [[ NFκB ]] activation, iNOS induction, and nitric oxide production.


In cultured primary microglia and astrocytes, << EHT >> had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, [[ iNOS ]] induction, and nitric oxide production.


Additionally, in SH-SY5Y cells, MPP(+)-induced demethylation of << phosphoprotein phosphatase 2A >> (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by [[ EHT ]].


Additionally, in SH-SY5Y cells, MPP(+)-induced demethylation of phosphoprotein phosphatase 2A (<< PP2A >>), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by [[ EHT ]].


Additionally, in SH-SY5Y cells, << MPP(+) >>-induced demethylation of [[ phosphoprotein phosphatase 2A ]] (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT.


Additionally, in SH-SY5Y cells, << MPP(+) >>-induced demethylation of phosphoprotein phosphatase 2A ([[ PP2A ]]), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT.


Substantial evidence shows that << H(2)S >> is involved in aging by inhibiting free-radical reactions, activating [[ SIRT1 ]], and probably interacting with the age-related gene Klotho.


Induction of << HO-1 >> through p38 MAPK/Nrf2 signaling pathway by [[ ethanol ]] extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice.


Induction of HO-1 through << p38 >> MAPK/Nrf2 signaling pathway by [[ ethanol ]] extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice.


Induction of HO-1 through p38 << MAPK >>/Nrf2 signaling pathway by [[ ethanol ]] extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice.


The induction of << HO-1 >> by EIH was inhibited by [[ SB203580 ]] but not by SP600125, PD98059, nor LY294002.


We demonstrate that two << flavin mono-oxygenase >> family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to [[ TMAO ]].


We demonstrate that two flavin mono-oxygenase family members, << FMO1 >> and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to [[ TMAO ]].


We demonstrate that two flavin mono-oxygenase family members, FMO1 and << FMO3 >>, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to [[ TMAO ]].


We demonstrate that two << flavin mono-oxygenase >> family members, FMO1 and FMO3, oxidize [[ trimethylamine ]] (TMA), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two flavin mono-oxygenase family members, << FMO1 >> and FMO3, oxidize [[ trimethylamine ]] (TMA), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two flavin mono-oxygenase family members, FMO1 and << FMO3 >>, oxidize [[ trimethylamine ]] (TMA), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two << flavin mono-oxygenase >> family members, FMO1 and FMO3, oxidize trimethylamine ([[ TMA ]]), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two flavin mono-oxygenase family members, << FMO1 >> and FMO3, oxidize trimethylamine ([[ TMA ]]), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two flavin mono-oxygenase family members, FMO1 and << FMO3 >>, oxidize trimethylamine ([[ TMA ]]), derived from gut flora metabolism of choline, to TMAO.


We demonstrate that two << flavin mono-oxygenase >> family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of [[ choline ]], to TMAO.


We demonstrate that two flavin mono-oxygenase family members, << FMO1 >> and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of [[ choline ]], to TMAO.


We demonstrate that two flavin mono-oxygenase family members, FMO1 and << FMO3 >>, oxidize trimethylamine (TMA), derived from gut flora metabolism of [[ choline ]], to TMAO.


FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing << FMO3 >> decreases [[ TMAO ]] levels.


<< FMO3 >> overexpression in mice significantly increases plasma [[ TMAO ]] levels while silencing FMO3 decreases TMAO levels.


In mice, this reduction in << FMO3 >> expression is due primarily to downregulation by [[ androgens ]].


FMO3 expression is induced by dietary bile acids by a mechanism that involves the << farnesoid X receptor >> (FXR), a [[ bile acid ]]-activated nuclear receptor.


FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (<< FXR >>), a [[ bile acid ]]-activated nuclear receptor.


<< FMO3 >> expression is induced by dietary [[ bile acids ]] by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor.


Analysis of natural genetic variation among inbred strains of mice indicates that << FMO3 >> and [[ TMAO ]] are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis.


Synthesis of << quinoline >> derivatives: discovery of a potent and selective [[ phosphodiesterase 5 ]] inhibitor for the treatment of Alzheimer's disease.


Phosphodiesterase type 5 (<< PDE5 >>) mediates the degradation of [[ cGMP ]] in a variety of tissues including brain.


<< Phosphodiesterase type 5 >> (PDE5) mediates the degradation of [[ cGMP ]] in a variety of tissues including brain.


Fragment-based design, synthesis, and biological evaluation of << N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide >> derivatives as novel [[ Mcl-1 ]] inhibitors.


We have previously reported a nanomolar inhibitor of antiapoptotic << Mcl-1 >> protein, [[ 3-thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile ]] (S1).


A novel potent compound, << N-benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide >> (12c), which binds [[ Mcl-1 ]] with an IC(50) value of 54 nM was obtained.


<< Peginesatide >>, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the [[ erythropoietin receptor ]] dimer that governs erythropoiesis.


Peginesatide, a << polyethylene glycol >> (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the [[ erythropoietin receptor ]] dimer that governs erythropoiesis.


Peginesatide, a polyethylene glycol (<< PEG >>)ylated peptide-based erythropoiesis-stimulating agent, stimulates the [[ erythropoietin receptor ]] dimer that governs erythropoiesis.


LPA1-induced cytoskeleton reorganization therefore makes a previously unrecognized but critically important contribution to the profibrotic activities of << LPA >> by driving MRTF-dependent [[ CTGF ]] expression, which, in turn, drives fibroblast proliferation.-Sakai, N., Chun, J., Duffield, J. S., Wada, T., Luster, A.


<< Bile acids >> are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, pregnane X receptor, [[ constitutive androstane receptor ]], and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.


<< Bile acids >> are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and [[ vitamin D receptor ]], and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.


<< Bile acids >> are signaling molecules that activate [[ nuclear receptors ]], such as farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.


<< Bile acids >> are signaling molecules that activate nuclear receptors, such as [[ farnesoid X receptor ]], pregnane X receptor, constitutive androstane receptor, and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.


<< Bile acids >> are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, [[ pregnane X receptor ]], constitutive androstane receptor, and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism.


The peptide << YR-11 >> (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and [[ RANKL ]] induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.


The peptide << YR-11 >> (YLEIEFSLKHR), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced [[ TRAP ]] activity and formation of multinucleated osteoclasts without any cytotoxicity.


The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of << cysteine >> with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and [[ RANKL ]] induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.


The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of << cysteine >> with a serine residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced [[ TRAP ]] activity and formation of multinucleated osteoclasts without any cytotoxicity.


The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a << serine >> residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and [[ RANKL ]] induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.


The peptide YR-11 (YLEIEFSLKHR), obtained by direct substitution of cysteine with a << serine >> residue in the template sequence, significantly (p<0.05) inhibited RANK-RANKL binding, and RANKL induced [[ TRAP ]] activity and formation of multinucleated osteoclasts without any cytotoxicity.


Results confirmed that << YR-11 >> peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of [[ NF-κB ]].


Results confirmed that << YR-11 >> peptide inhibited pro-inflammatory [[ cytokines ]] in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of NF-κB.


Results confirmed that << YR-11 >> peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on [[ RANKL ]] induced nuclear translocation of NF-κB.


The activation of << Rac1 >> was induced by [[ silica ]] nanoparticles as well as BCG DNA and is suggested as the critical signaling event inducing both cytoskeleton changes as well as inflammatory cell activation.


Osteoblasts survive the << arsenic trioxide >> treatment by activation of [[ ATM ]]-mediated pathway.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, p53, and p21(waf1/cip1) were reduced by an [[ ATM ]] inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, [[ Chk1 ]], Chk2, p53, and p21(waf1/cip1) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, [[ Chk2 ]], p53, and p21(waf1/cip1) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, [[ p53 ]], and p21(waf1/cip1) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, p53, and [[ p21 ]](waf1/cip1) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, p53, and p21([[ waf1 ]]/cip1) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, p53, and p21(waf1/[[ cip1 ]]) were reduced by an ATM inhibitor.


Additionally, these effects of << ATO >> on γ-[[ H2AX ]], Chk1, Chk2, p53, and p21(waf1/cip1) were reduced by an ATM inhibitor.


Furthermore, a mixture of << isoflavonoid >> parent compounds, and a mixture of isoflavonoid metabolites were found to have [[ PPARγ ]] activating abilities.


Furthermore, a mixture of isoflavonoid parent compounds, and a mixture of << isoflavonoid >> metabolites were found to have [[ PPARγ ]] activating abilities.


Both << fatty acids >>, but DHA to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of [[ cytokine ]]-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells.


Both fatty acids, but << DHA >> to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of [[ cytokine ]]-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells.


Both fatty acids, but DHA to a lesser extent compared with << EPA >>, selectively and dose-dependently reduced the percentage of [[ cytokine ]]-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells.


In monocytes, both << EPA >> and DHA increased [[ interleukin (IL)-10 ]] without affecting tumor necrosis factor (TNF)-α and IL-6.


In monocytes, both EPA and << DHA >> increased [[ interleukin (IL)-10 ]] without affecting tumor necrosis factor (TNF)-α and IL-6.


In the in vitro model we observed high permeability of << imperatorin >> and isoimperatorin with the [[ P-gp ]]-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of cnidilin with 0.82.


In the in vitro model we observed high permeability of imperatorin and << isoimperatorin >> with the [[ P-gp ]]-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of cnidilin with 0.82.


In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the << P-gp >>-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of [[ cnidilin ]] with 0.82.


Treatment with << adenosine dialdehyde >> (AdOx), an inhibitor of transmethylation-suppressive [[ adenosylhomocysteine (SAH) hydrolase ]] (SAHH), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Treatment with << adenosine dialdehyde >> (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase ([[ SAHH ]]), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Treatment with adenosine dialdehyde (<< AdOx >>), an inhibitor of transmethylation-suppressive [[ adenosylhomocysteine (SAH) hydrolase ]] (SAHH), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Treatment with adenosine dialdehyde (<< AdOx >>), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase ([[ SAHH ]]), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive << adenosylhomocysteine (SAH) hydrolase >> (SAHH), enhanced the level of [[ SAH ]] and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase (<< SAHH >>), enhanced the level of [[ SAH ]] and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.


Through immunoblotting analysis, it was found that << AdOx >> was capable of indirectly diminishing the phosphorylation of oncogenic [[ Src ]] and its kinase activity.


Through immunoblotting analysis, it was found that << AdOx >> was capable of indirectly diminishing the phosphorylation of oncogenic Src and its [[ kinase ]] activity.


Interestingly, << AdOx >> disrupted actin cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of [[ Src ]] and p85/PI3K, which is linked to various tumorigenic responses.


Interestingly, << AdOx >> disrupted actin cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and [[ p85 ]]/PI3K, which is linked to various tumorigenic responses.


Interestingly, << AdOx >> disrupted actin cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and p85/[[ PI3K ]], which is linked to various tumorigenic responses.


Interestingly, << AdOx >> disrupted [[ actin ]] cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and p85/PI3K, which is linked to various tumorigenic responses.


In agreement with these data, the exogenous treatment of << SAH >> or inhibition of SAHH by specific siRNA or another type of inhibitor, 3-deazaadenosine (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on [[ Src ]], the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src.


In agreement with these data, the exogenous treatment of SAH or inhibition of << SAHH >> by specific siRNA or another type of inhibitor, [[ 3-deazaadenosine ]] (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on Src, the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src.


In agreement with these data, the exogenous treatment of SAH or inhibition of << SAHH >> by specific siRNA or another type of inhibitor, 3-deazaadenosine ([[ DAZA ]]), similarly resulted in antitumorigenic responses, suppressive activity on Src, the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src.


Synthesis of derivatives of << methyl rosmarinate >> and their inhibitory activities against matrix metalloproteinase-1 ([[ MMP-1 ]]).


Synthesis of derivatives of << methyl rosmarinate >> and their inhibitory activities against [[ matrix metalloproteinase-1 ]] (MMP-1).


A series of << MMP-1 >> inhibitors have been identified based upon a [[ methyl rosmarinate ]] scaffold using structure-based drug design methods.


All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as << cyclooxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line.


All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (<< COX-2 >>)-derived [[ prostaglandin E2 ]] (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line.


All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as << cyclooxygenase-2 >> (COX-2)-derived prostaglandin E2 ([[ PGE2 ]]) inhibitory activity of murine macrophage RAW 264.7 cell line.


All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as cyclooxygenase-2 (<< COX-2 >>)-derived prostaglandin E2 ([[ PGE2 ]]) inhibitory activity of murine macrophage RAW 264.7 cell line.


Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the << lipoxygenase >> (LOX)-pathway (one having as precursors the [[ polyunsaturated fatty acids ]] containing a cis-cis-1,4-pentadiene system).


Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the lipoxygenase (<< LOX >>)-pathway (one having as precursors the [[ polyunsaturated fatty acids ]] containing a cis-cis-1,4-pentadiene system).


Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the << lipoxygenase >> (LOX)-pathway (one having as precursors the polyunsaturated fatty acids containing a [[ cis-cis-1,4-pentadiene ]] system).


Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the lipoxygenase (<< LOX >>)-pathway (one having as precursors the polyunsaturated fatty acids containing a [[ cis-cis-1,4-pentadiene ]] system).


In general, antiproliferative activity is greatly enhanced by low levels of the << glutathione synthase >> inhibitor [[ l-buthionine sulfoxime ]].


Cellular << zinc >> is controlled by [[ zinc-chelating proteins ]] and by zinc transporters.


Cellular << zinc >> is controlled by zinc-chelating proteins and by [[ zinc transporters ]].


The recent identification of << zinc >> permeability of the lysosomal ion channel [[ TRPML1 ]] (transient receptor potential mucolipin 1), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for TRPML1 in zinc transport.


The recent identification of << zinc >> permeability of the lysosomal ion channel TRPML1 ([[ transient receptor potential mucolipin 1 ]]), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for TRPML1 in zinc transport.


The recent identification of zinc permeability of the lysosomal ion channel TRPML1 (transient receptor potential mucolipin 1), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for << TRPML1 >> in [[ zinc ]] transport.


These results underscore a role for << TRPML1 >> in [[ zinc ]] metabolism.


Furthermore, they suggest that << TRPML1 >> works in concert with ZnT4 to regulate [[ zinc ]] translocation between the cytoplasm and lysosomes.


Furthermore, they suggest that TRPML1 works in concert with << ZnT4 >> to regulate [[ zinc ]] translocation between the cytoplasm and lysosomes.


<< Serum amyloid A >> upsurge precedes standard biomarkers of hepatotoxicity in [[ ritodrine ]]-injected mice.


Importantly, expression of the acute-phase reactant << serum amyloid A >> (SAA) significantly increased after [[ ritodrine ]] injection, with values indicating the largest fold-change.


Importantly, expression of the acute-phase reactant serum amyloid A (<< SAA >>) significantly increased after [[ ritodrine ]] injection, with values indicating the largest fold-change.


The increase in << SAA >> expression is specific to [[ ritodrine ]]-induced liver damage, because SAA expression was not induced by other hepatotoxic drugs such as acetaminophen, valproic acid, or metformin.


Our in vitro studies showed that cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was not a primary cause of the << ritodrine >>-induced [[ SAA ]] increase.


<< Ceftazidime >>-avibactam: a novel cephalosporin/[[ β-lactamase ]] inhibitor combination.


Ceftazidime-<< avibactam >>: a novel cephalosporin/[[ β-lactamase ]] inhibitor combination.


Avibactam (formerly << NXL104 >>, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some [[ Ambler class D ]] enzymes.


Avibactam (formerly << NXL104 >>, AVE1330A) is a synthetic non-β-lactam, [[ β-lactamase ]] inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes.


<< Avibactam >> (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some [[ Ambler class D ]] enzymes.


<< Avibactam >> (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, [[ β-lactamase ]] inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes.


Avibactam (formerly NXL104, << AVE1330A >>) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some [[ Ambler class D ]] enzymes.


Avibactam (formerly NXL104, << AVE1330A >>) is a synthetic non-β-lactam, [[ β-lactamase ]] inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes.


The addition of << avibactam >> greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of [[ β-lactamase ]] enzyme(s).


The addition of avibactam greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of << ceftazidime >> versus most species of Enterobacteriaceae depending on the presence or absence of [[ β-lactamase ]] enzyme(s).


Pharmacodynamic data suggest that << ceftazidime >>-avibactam is rapidly bactericidal versus [[ β-lactamase ]]-producing Gram-negative bacilli that are not inhibited by ceftazidime alone.Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates.


Pharmacodynamic data suggest that ceftazidime-<< avibactam >> is rapidly bactericidal versus [[ β-lactamase ]]-producing Gram-negative bacilli that are not inhibited by ceftazidime alone.Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates.


Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.In conclusion, << avibactam >> serves to broaden the spectrum of ceftazidime versus [[ ß-lactamase ]]-producing Gram-negative bacilli.


Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.In conclusion, avibactam serves to broaden the spectrum of << ceftazidime >> versus [[ ß-lactamase ]]-producing Gram-negative bacilli.


Moreover, treatment of high-fat-diet-fed apelin-knockout mice with a selective << cyclooxygenase-2 >> inhibitor, [[ celecoxib ]], improved vascular function, and also attenuated obesity.


<< Upamostat >> (Mesupron®) is a new small molecule [[ serine protease ]] inhibitor.


Upamostat (<< Mesupron >>®) is a new small molecule [[ serine protease ]] inhibitor.


Interestingly, GPx1a was the most sensitive to selenium availability in non stressful conditions, whereas << GPx1b1 >> and GPx1b2 were highly induced by exposure to [[ selenium ]] levels that had some toxic effects on the cells.


Interestingly, GPx1a was the most sensitive to selenium availability in non stressful conditions, whereas GPx1b1 and << GPx1b2 >> were highly induced by exposure to [[ selenium ]] levels that had some toxic effects on the cells.


<< Mn >> exposure (20 mg/kg) increased [[ p38 ]](MAPK) and Akt phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation.


<< Mn >> exposure (20 mg/kg) increased p38([[ MAPK ]]) and Akt phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation.


<< Mn >> exposure (20 mg/kg) increased p38(MAPK) and [[ Akt ]] phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation.


<< Mn >> exposure (20 mg/kg) increased p38(MAPK) and Akt phosphorylation, but decreased [[ DARPP-32 ]]-Thr-34 phosphorylation.


<< Mn >> (10 and 20 mg/kg) increased [[ caspase ]] activity and F(2)-isoprostane production (a biological marker of lipid peroxidation).


Notably, the antioxidant Trolox™ reversed the << Mn >> (20 mg/kg)-dependent augmentation in [[ p38 ]](MAPK) phosphorylation and reduced the Mn (20 mg/kg)-induced caspase activity and F(2)-isoprostane production.


Notably, the antioxidant Trolox™ reversed the << Mn >> (20 mg/kg)-dependent augmentation in p38([[ MAPK ]]) phosphorylation and reduced the Mn (20 mg/kg)-induced caspase activity and F(2)-isoprostane production.


Notably, the antioxidant Trolox™ reversed the Mn (20 mg/kg)-dependent augmentation in p38(MAPK) phosphorylation and reduced the << Mn >> (20 mg/kg)-induced [[ caspase ]] activity and F(2)-isoprostane production.


Notably, the antioxidant << Trolox >>™ reversed the Mn (20 mg/kg)-dependent augmentation in [[ p38 ]](MAPK) phosphorylation and reduced the Mn (20 mg/kg)-induced caspase activity and F(2)-isoprostane production.


Notably, the antioxidant << Trolox >>™ reversed the Mn (20 mg/kg)-dependent augmentation in p38([[ MAPK ]]) phosphorylation and reduced the Mn (20 mg/kg)-induced caspase activity and F(2)-isoprostane production.


Notably, the antioxidant << Trolox >>™ reversed the Mn (20 mg/kg)-dependent augmentation in p38(MAPK) phosphorylation and reduced the Mn (20 mg/kg)-induced [[ caspase ]] activity and F(2)-isoprostane production.


These findings are the first to show that long-term exposure to << Mn >> during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, [[ p38 ]](MAPK) phosphorylation and caspase activity in the striatum.


These findings are the first to show that long-term exposure to << Mn >> during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, p38([[ MAPK ]]) phosphorylation and caspase activity in the striatum.


These findings are the first to show that long-term exposure to << Mn >> during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, p38(MAPK) phosphorylation and [[ caspase ]] activity in the striatum.


<< Nocapyrone H >> (1) reduced the pro-inflammatory factor such as nitric oxide (NO), prostaglandin E2 (PGE2) and [[ interleukin-1β ]] (IL-1β).


<< Nocapyrone H >> (1) reduced the pro-inflammatory factor such as nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-1β ([[ IL-1β ]]).


Investigating the enteroenteric recirculation of << apixaban >>, a [[ factor Xa ]] inhibitor: administration of activated charcoal to bile duct-cannulated rats and dogs receiving an intravenous dose and use of drug transporter knockout rats.


The fecal elimination, IC, and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with << GF-120918 >>, a dual [[ BCRP ]] and P-gp inhibitor).


The fecal elimination, IC, and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with << GF-120918 >>, a dual BCRP and [[ P-gp ]] inhibitor).


<< BCRP >> appeared to play a more important role for absorption and intestinal and renal elimination of [[ apixaban ]] than P-gp in transporter-KO rats after oral and i.v. dosing, which led to a higher level of active renal excretion in rat than other species.


BCRP appeared to play a more important role for absorption and intestinal and renal elimination of << apixaban >> than [[ P-gp ]] in transporter-KO rats after oral and i.v. dosing, which led to a higher level of active renal excretion in rat than other species.


Cloning, Characterization, and << Sulfonamide >> and Thiol Inhibition Studies of an [[ α-Carbonic Anhydrase ]] from Trypanosoma cruzi, the Causative Agent of Chagas Disease.


Cloning, Characterization, and Sulfonamide and << Thiol >> Inhibition Studies of an [[ α-Carbonic Anhydrase ]] from Trypanosoma cruzi, the Causative Agent of Chagas Disease.


The enzyme (TcCA) has a very high catalytic activity for the << CO(2) >> hydration reaction, being similar kinetically to the human (h) isoform [[ hCA II ]], although it is devoid of the His64 proton shuttle.


The enzyme (<< TcCA >>) has a very high catalytic activity for the [[ CO(2) ]] hydration reaction, being similar kinetically to the human (h) isoform hCA II, although it is devoid of the His64 proton shuttle.


A large number of << aromatic/heterocyclic sulfonamides >> and some 5-mercapto-1,3,4-thiadiazoles were investigated as [[ TcCA ]] inhibitors.


A large number of aromatic/heterocyclic sulfonamides and some << 5-mercapto-1,3,4-thiadiazoles >> were investigated as [[ TcCA ]] inhibitors.


The mRNA level for << nestin >> (Nes, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-[[ EDS ]], but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes.


The mRNA level for nestin (<< Nes >>, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-[[ EDS ]], but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes.


<< GnRH >> pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of PKA and [[ CREB ]].


<< GnRH >> pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of [[ PKA ]] and CREB.


<< GnRH >> pulse frequency-dependent stimulation of [[ FSHβ ]] transcription is mediated via activation of PKA and CREB.


cAMP response element-binding protein (CREB) has been implicated in the regulation of FSHβ gene expression, but the molecular mechanisms by which pulsatile << GnRH >> regulates [[ CREB ]] activation remain poorly understood.


We hypothesized that << CREB >> is activated by a distinct signaling pathway in response to pulsatile [[ GnRH ]] in a frequency-dependent manner to dictate the FSHβ transcriptional response.


<< GnRH >> stimulation of [[ CREB ]] phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89.


<< GnRH >> stimulation of CREB phosphorylation ([[ pCREB ]]) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89.


GnRH stimulation of << CREB >> phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, [[ H89 ]].


GnRH stimulation of CREB phosphorylation (<< pCREB >>) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, [[ H89 ]].


GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a << protein kinase A >> (PKA) inhibitor, [[ H89 ]].


GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (<< PKA >>) inhibitor, [[ H89 ]].


A dominant negative PKA (DNPKA) reduced << GnRH >>-stimulated [[ pCREB ]] and markedly decreased GnRH stimulation of FSHβ mRNA and FSHβLUC activity, but had little effect on LHβLUC activity, indicating relative specificity of this pathway.


A dominant negative PKA (DNPKA) reduced GnRH-stimulated pCREB and markedly decreased << GnRH >> stimulation of FSHβ mRNA and [[ FSHβ ]]LUC activity, but had little effect on LHβLUC activity, indicating relative specificity of this pathway.


A dominant negative PKA (DNPKA) reduced GnRH-stimulated pCREB and markedly decreased << GnRH >> stimulation of [[ FSHβ ]] mRNA and FSHβLUC activity, but had little effect on LHβLUC activity, indicating relative specificity of this pathway.


In perifusion studies, FSHβ mRNA levels and << FSHβ >>LUC activities were increased by pulsatile [[ GnRH ]], with significantly greater increases at low compared with high pulse frequencies.


In perifusion studies, << FSHβ >> mRNA levels and FSHβLUC activities were increased by pulsatile [[ GnRH ]], with significantly greater increases at low compared with high pulse frequencies.


DNPKA markedly reduced these << GnRH >>-stimulated [[ FSHβ ]] responses at both low and high pulse frequencies.


Correlating with << FSHβ >> activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high [[ GnRH ]] pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies.


Correlating with FSHβ activation, both << PKA >> activity and levels of pCREB were increased to a greater extent by low compared with high [[ GnRH ]] pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies.


Correlating with FSHβ activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high << GnRH >> pulse frequencies, and the induction of [[ pCREB ]] was also attenuated by overexpression of DNPKA at both low and high pulse frequencies.


Correlating with FSHβ activation, both PKA activity and levels of << pCREB >> were increased to a greater extent by low compared with high [[ GnRH ]] pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies.


Taken together, these data indicate that a PKA-mediated signaling pathway mediates << GnRH >> activation of [[ CREB ]] at low-pulse frequencies, playing a significant role in the decoding of the hypothalamic GnRH signal to result in frequency-dependent FSHβ activation.


Taken together, these data indicate that a PKA-mediated signaling pathway mediates GnRH activation of CREB at low-pulse frequencies, playing a significant role in the decoding of the hypothalamic << GnRH >> signal to result in frequency-dependent [[ FSHβ ]] activation.


<< Sophocarpine >> alleviates hepatocyte steatosis through activating [[ AMPK ]] signaling pathway.


While << sophocarpine >> treatment resulted in: significant improvement of steatosis (>50% decrease), decrease of leptin expression (<0.57-fold) and increase of [[ adiponectin ]] expression (>1.48-fold).


While << sophocarpine >> treatment resulted in: significant improvement of steatosis (>50% decrease), decrease of [[ leptin ]] expression (<0.57-fold) and increase of adiponectin expression (>1.48-fold).


Moreover, compared with the model group, << sophocarpine >> could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and [[ ACC ]] (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and HNF-4α (<0.20-fold) protein expression.


Moreover, compared with the model group, << sophocarpine >> could significantly increase [[ P-AMPKα ]] (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and HNF-4α (<0.20-fold) protein expression.


Moreover, compared with the model group, << sophocarpine >> could significantly increase P-AMPKα (>5.82-fold), [[ AMPKα ]] (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and HNF-4α (<0.20-fold) protein expression.


Moreover, compared with the model group, << sophocarpine >> could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce [[ P-ACC ]] (<0.30-fold) and HNF-4α (<0.20-fold) protein expression.


Moreover, compared with the model group, << sophocarpine >> could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and [[ HNF-4α ]] (<0.20-fold) protein expression.


We concluded that << sophocarpine >> could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of [[ AMPK ]].


To evaluate to what extent the regional differences in expression of << P-gp >> and P450 enzymes affect the absorption of a dual substrate, we investigated the transport of [[ darunavir ]] across different small intestinal segments (duodenum, proximal jejunum and ileum).


To evaluate to what extent the regional differences in expression of P-gp and << P450 enzymes >> affect the absorption of a dual substrate, we investigated the transport of [[ darunavir ]] across different small intestinal segments (duodenum, proximal jejunum and ileum).


The involvement of P-gp in the absorption of darunavir was clearly shown by coperfusion of darunavir with the << P-gp >> inhibitor [[ zosuquidar ]].


The involvement of << P-gp >> in the absorption of [[ darunavir ]] was clearly shown by coperfusion of darunavir with the P-gp inhibitor zosuquidar.


Involvement of << P450 >> mediated metabolism in the absorption of [[ darunavir ]] could not be demonstrated in this rat model.


Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of << ketoconazole >> on [[ P-gp ]] as the main mechanism for the increased transport of darunavir across the small intestine.


Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on << P-gp >> as the main mechanism for the increased transport of [[ darunavir ]] across the small intestine.


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including [[ cyclooxygenase-2 ]] (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 ([[ COX-2 ]]), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), [[ inducible nitric oxide synthase ]] (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase ([[ iNOS ]]), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and [[ tumor necrosis factor-α ]] (TNF- α).


In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α ([[ TNF- α ]]).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including [[ cyclooxygenase-2 ]] (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 ([[ COX-2 ]]), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), [[ inducible nitric oxide synthase ]] (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase ([[ iNOS ]]), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and [[ tumor necrosis factor-α ]] (TNF- α).


In HaCaT cells, buthanol and << ethylacetate >> fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α ([[ TNF- α ]]).


In HaCaT cells, buthanol and ethylacetate fractions of 80% << methanol >> C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including [[ cyclooxygenase-2 ]] (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and ethylacetate fractions of 80% << methanol >> C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 ([[ COX-2 ]]), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and ethylacetate fractions of 80% << methanol >> C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), [[ inducible nitric oxide synthase ]] (iNOS), and tumor necrosis factor-α (TNF- α).


In HaCaT cells, buthanol and ethylacetate fractions of 80% << methanol >> C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase ([[ iNOS ]]), and tumor necrosis factor-α (TNF- α).