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 another experiment, topical application of CFB, CFE or << CLS >> prior to UVB irradiation (200mJ/cm(2)) on BALB/c mice, inhibited the UVB-elevated protein levels of [[ COX-2 ]], iNOS, and TNF-α.


In another experiment, topical application of CFB, CFE or << CLS >> prior to UVB irradiation (200mJ/cm(2)) on BALB/c mice, inhibited the UVB-elevated protein levels of COX-2, [[ iNOS ]], and TNF-α.


In another experiment, topical application of CFB, CFE or << CLS >> prior to UVB irradiation (200mJ/cm(2)) on BALB/c mice, inhibited the UVB-elevated protein levels of COX-2, iNOS, and [[ TNF-α ]].


In overexpressing cell lines, << OATP1B1 >>- and OATP1B3-mediated estradiol-17β-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin [[ flavonolignans ]] investigated.


In overexpressing cell lines, OATP1B1- and << OATP1B3 >>-mediated estradiol-17β-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin [[ flavonolignans ]] investigated.


In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17β-glucuronide uptake and << OATP2B1 >>-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin [[ flavonolignans ]] investigated.


In overexpressing cell lines, << OATP1B1 >>- and OATP1B3-mediated [[ estradiol-17β-glucuronide ]] uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated.


In overexpressing cell lines, OATP1B1- and << OATP1B3 >>-mediated [[ estradiol-17β-glucuronide ]] uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated.


In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17β-glucuronide uptake and << OATP2B1 >>-mediated [[ estrone-3-sulfate ]] uptake were inhibited by most of the silymarin flavonolignans investigated.


<< OATP1B1 >>-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), [[ silybin A ]] (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, << OATP1B3 >>-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), [[ silybin A ]] (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, OATP1B3-, and << OATP2B1 >>-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), [[ silybin A ]] (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


<< OATP1B1 >>-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), [[ silybin B ]] (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, << OATP1B3 >>-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), [[ silybin B ]] (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, OATP1B3-, and << OATP2B1 >>-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), [[ silybin B ]] (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


<< OATP1B1 >>-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and [[ silychristin ]] (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, << OATP1B3 >>-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and [[ silychristin ]] (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


OATP1B1-, OATP1B3-, and << OATP2B1 >>-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and [[ silychristin ]] (IC50 values of 9.0, 36.4, and 3.6 µM, respectively).


Furthermore, silymarin, << silybin A >>, and silybin B (100 µM) significantly inhibited [[ OATP ]]-mediated estradiol-17β-glucuronide and rosuvastatin uptake into human hepatocytes.


Furthermore, silymarin, silybin A, and << silybin B >> (100 µM) significantly inhibited [[ OATP ]]-mediated estradiol-17β-glucuronide and rosuvastatin uptake into human hepatocytes.


Furthermore, silymarin, silybin A, and silybin B (100 µM) significantly inhibited << OATP >>-mediated [[ estradiol-17β-glucuronide ]] and rosuvastatin uptake into human hepatocytes.


Furthermore, silymarin, silybin A, and silybin B (100 µM) significantly inhibited << OATP >>-mediated estradiol-17β-glucuronide and [[ rosuvastatin ]] uptake into human hepatocytes.


Further investigation demonstrated that 8k reduced << H2O2 >>-induced activation of mitochondrial apoptosis by inhibiting the expression of [[ Bax ]] and elevating the expression of Bcl-2.


Further investigation demonstrated that 8k reduced << H2O2 >>-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of [[ Bcl-2 ]].


Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of << insulin >> (achieved by administering insulin plus [[ glucose ]], glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine).


Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of << insulin >> (achieved by administering insulin plus glucose, [[ glucose ]] only, glucose and GLP-1, and glucose and GLP-1 combined with arginine).


Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of << insulin >> (achieved by administering insulin plus glucose, glucose only, [[ glucose ]] and GLP-1, and glucose and GLP-1 combined with arginine).


Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of << insulin >> (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and [[ glucose ]] and GLP-1 combined with arginine).


Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of << insulin >> (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with [[ arginine ]]).


The << CRF(1) receptor >> antagonist [[ SSR125543 ]] prevents stress-induced cognitive deficit associated with hippocampal dysfunction: Comparison with paroxetine and D-cycloserine.


RATIONALE: The selective << CRF(1) (corticotropin releasing factor type 1) receptor >> antagonist [[ SSR125543 ]] has been previously shown to attenuate the long-term cognitive deficit produced by traumatic stress exposure.


Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10 mg/kg/day), and the partial << N-methyl-D-aspartate (NMDA) receptor >> agonist, [[ D-cycloserine ]] (10 mg/kg/day), two compounds which have demonstrated clinical efficacy against PTSD.


CONCLUSIONS: These findings confirm that the << CRF(1) receptor >> antagonist [[ SSR125543 ]] is able to attenuate the behavioral effects of traumatic stress exposure and indicate that these effects are associated with a normalization of hippocampal neuronal excitability impaired by stress.


A series of << indazole arylsulfonamides >> were synthesized and examined as [[ human CCR4 ]] antagonists.


Repeated Low Dose Administration of the << Monoacylglycerol Lipase >> Inhibitor [[ JZL184 ]] Retains CB1 Receptor Mediated Antinociceptive and Gastroprotective Effects.


The monoacylglycerol lipase (<< MAGL >>) inhibitor [[ JZL184 ]] produces antinociceptive and anti-inflammatory effects.


The << monoacylglycerol lipase >> (MAGL) inhibitor [[ JZL184 ]] produces antinociceptive and anti-inflammatory effects.


Mice given daily injections of high dose << JZL184 >> (≥16 mg/kg) for six days displayed decreased [[ CB(1) ]] receptor density and function in brain, as assessed in [(3)H]SR141716A binding and CP55,940-stimulated [(35)S]GTPγS binding assays, respectively.


Design and synthesis of << bicyclic pyrazinone and pyrimidinone amides >> as potent [[ TF ]]-FVIIa inhibitors.


Design and synthesis of << bicyclic pyrazinone and pyrimidinone amides >> as potent TF-[[ FVIIa ]] inhibitors.


<< Bicyclic pyrazinone and pyrimidinone amides >> were designed and synthesized as potent TF-[[ FVIIa ]] inhibitors.


<< Bicyclic pyrazinone and pyrimidinone amides >> were designed and synthesized as potent [[ TF ]]-FVIIa inhibitors.


Fragment-based drug design and identification of << HJC0123 >>, a novel orally bioavailable [[ STAT3 ]] inhibitor for cancer therapy.


The most potent compound 5 (<< HJC0123 >>) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved [[ caspase-3 ]], inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values.


The most potent compound 5 (<< HJC0123 >>) has demonstrated to inhibit [[ STAT3 promoter ]] activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values.


The most potent compound 5 (<< HJC0123 >>) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of [[ STAT3 ]], increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values.


The effects of the << phosphodiesterase type 5 >> inhibitor [[ vardenafil ]] on cognitive performance in healthy adults: a behavioral- electroencephalography study.


Therefore, we examined whether the << PDE5 >>-I [[ vardenafil ]] improves memory and executive functioning and affect electroencephalography (EEG) in healthy young adults.


Statins are inhibitors of the enzyme << 3-hydroxy-3-methylglutaryl coenzyme A reductase >>, the rate-limiting step in [[ cholesterol ]] biosynthesis.


We found that atorvastatin withdrawal decreased levels of nitric oxide and mitochondrial superoxide dismutase activity, whereas increased << NADPH oxidase >> activity and immunoreactivity for the protein nitration marker [[ 3-nitrotyrosine ]] in the cerebral cortex.


Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a << peroxisome proliferator-activated receptor alpha >> agonist [[ bezafibrate ]] (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition.


Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a << peroxisome proliferator-activated receptor alpha >> agonist bezafibrate ([[ Bzf ]]; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition.


Moreover, the effects of the << DRD3 >> agonist [[ 7-hydroxy-N,N-dipropyl-2-aminotetralin ]] (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant.


Moreover, the effects of the DRD3 agonist << 7-hydroxy-N,N-dipropyl-2-aminotetralin >> (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when [[ DRD3 ]] proteins were abundant.


Moreover, the effects of the << DRD3 >> agonist 7-hydroxy-N,N-dipropyl-2-aminotetralin ([[ 7-OH-DPAT ]])-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant.


Moreover, the effects of the DRD3 agonist 7-hydroxy-N,N-dipropyl-2-aminotetralin (<< 7-OH-DPAT >>)-induced locomotor hypoactivity were significantly increased when [[ DRD3 ]] proteins were abundant.


Studies on an (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid << (AMPA) receptor >> antagonist [[ IKM-159 ]]: asymmetric synthesis, neuroactivity, and structural characterization.


<< IKM-159 >> was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as [[ AMPA receptor ]]-selective antagonists.


IKM-159 was developed and identified as a member of a new class of heterotricyclic << glutamate >> analogues that act as [[ AMPA receptor ]]-selective antagonists.


<< (2R)-IKM-159 >> locks the [[ GluA2 ]] in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.


<< (2R)-IKM-159 >> locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of [[ AMPA receptors ]].


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, [[ flavanone ]], chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by [[ 2'-methoxy-5,7-dihydroxyflavone ]], 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, [[ 2-ethynylnaphthalene ]], 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, [[ 2'-methoxyflavone ]], 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, [[ 2-naphththalene propargyl ether ]], acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, [[ acenaphthene ]], acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, [[ chrysin ]], 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, [[ acenaphthylene ]], naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, [[ naphthalene ]], 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, [[ 1-acetylpyrene ]], flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, [[ 3-ethynylphenanthrene ]], flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, [[ flavone ]], and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and [[ 7-hydroxyflavone ]]; these chemicals induced Type I spectral changes with low Ks values.


<< Coumarin >> 7-hydroxylation, catalyzed by [[ P450 2A13 ]], was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.


Full agonists to the << peroxisome proliferator-activated receptor (PPAR)γ >>, such as [[ Rosiglitazone ]], have been associated with a series of undesired side effects, such as weight gain, fluid retention, cardiac hypertrophy, and hepatotoxicity.


The << (R)-omeprazole >> hydroxylation index reflects [[ CYP2C19 ]] activity in healthy Japanese volunteers.


PURPOSE: << Omeprazole >> has (R)- and (S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with [[ cytochrome P450 (CYP) 2C19 ]] genotype groups.


Additionally, there was a significant difference in plasma concentrations of << (R)-5-hydroxyomeprazole >> among [[ CYP2C19 ]] genotype groups, whereas no significant differences were observed in that of (S)-5-hydroxyomeprazole.


Additionally, there was a significant difference in plasma concentrations of (R)-5-hydroxyomeprazole among << CYP2C19 >> genotype groups, whereas no significant differences were observed in that of [[ (S)-5-hydroxyomeprazole ]].


CONCLUSION: Our findings demonstrate that << (R)-omeprazole >> HI correlated better with [[ CYP2C19 ]] genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.


CONCLUSION: Our findings demonstrate that (R)-omeprazole HI correlated better with << CYP2C19 >> genotype groups than [[ racemic-omeprazole ]] HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, << all-trans retinoic acid >> (atRA), which regulates the expression of a battery of target genes through several families of [[ nuclear receptors ]] (RARs, RXRs and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, << all-trans retinoic acid >> (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors ([[ RARs ]], RXRs and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, << all-trans retinoic acid >> (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, [[ RXRs ]] and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, << all-trans retinoic acid >> (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPARβ/δ), [[ polymorphic retinoic acid (RA) response elements ]] and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (<< atRA >>), which regulates the expression of a battery of target genes through several families of [[ nuclear receptors ]] (RARs, RXRs and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (<< atRA >>), which regulates the expression of a battery of target genes through several families of nuclear receptors ([[ RARs ]], RXRs and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (<< atRA >>), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, [[ RXRs ]] and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators.


The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (<< atRA >>), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPARβ/δ), [[ polymorphic retinoic acid (RA) response elements ]] and multiple coregulators.


Interestingly, << miR-21 >> expression positively correlated with urine albumin [[ creatine ]] ratio (ACR), TIMP1, collagen IV (ColIV), and fibronectin (FN); while negatively correlated with creatine clearance ratio (Ccr) and MMP-9 protein.


Interestingly, << miR-21 >> expression positively correlated with urine albumin creatine ratio (ACR), TIMP1, collagen IV (ColIV), and fibronectin (FN); while negatively correlated with [[ creatine ]] clearance ratio (Ccr) and MMP-9 protein.


The << human cytosolic sulfotransferase hSULT2A1 >> catalyzes the sulfation of a broad range of xenobiotics, as well as endogenous [[ hydroxysteroids ]] and bile acids.


The << human cytosolic sulfotransferase hSULT2A1 >> catalyzes the sulfation of a broad range of xenobiotics, as well as endogenous hydroxysteroids and [[ bile acids ]].


Studies on the kinetics of the << hSULT2A1 >>-catalyzed sulfation of [[ dehydroepiandrosterone ]] (DHEA) showed the effects of disulfide bond formation on the substrate inhibition characteristics of the enzyme.


Studies on the kinetics of the << hSULT2A1 >>-catalyzed sulfation of dehydroepiandrosterone ([[ DHEA ]]) showed the effects of disulfide bond formation on the substrate inhibition characteristics of the enzyme.


Computational docking analysis was conducted to model the interaction of these antagonists with the human ERα and showed that they could tightly bind to the ERα in a manner similar to that of << ICI-182,780 >>, a pure [[ ER ]] antagonist.


These results provide an example that attachment of a bulky side chain to the C-7α position of E2 can produce ER antagonists with << ER >> affinity comparable to that of [[ ICI-182,780 ]].


Discovery of << 7-methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole >> (TASP0382088): a potent and selective [[ transforming growth factor-β type I receptor ]] inhibitor as a topical drug for alopecia.


Discovery of 7-methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole (<< TASP0382088 >>): a potent and selective [[ transforming growth factor-β type I receptor ]] inhibitor as a topical drug for alopecia.


<< 7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole >> 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as [[ activin receptor-like kinase 5 ]] or ALK5) inhibitor.


<< 7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole >> 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or [[ ALK5 ]]) inhibitor.


<< 7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole >> 11 (TASP0382088) was synthesized and evaluated as [[ transforming growth factor-β (TGF-β) type I receptor ]] (also known as activin receptor-like kinase 5 or ALK5) inhibitor.


7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (<< TASP0382088 >>) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as [[ activin receptor-like kinase 5 ]] or ALK5) inhibitor.


7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (<< TASP0382088 >>) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or [[ ALK5 ]]) inhibitor.


7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (<< TASP0382088 >>) was synthesized and evaluated as [[ transforming growth factor-β (TGF-β) type I receptor ]] (also known as activin receptor-like kinase 5 or ALK5) inhibitor.


In non-pre-treated cells, only << efflux transporters >> were down-regulated by [[ 7-ketosterols ]], showing a greater influence upon ABCG5 expression.


Cell-pre-incubation with bradykinin induced changes in ABCG expression levels after 7-ketostigmasterol-incubation; however, the energetic metabolism inhibition reduced << NPC1L1 >> expression only in [[ 7-ketocholesterol ]]-incubated cells.


In non-pre-treated cells, << HMG-CoA >> was up-regulated by both [[ 7-ketosterols ]].


In lymphocytes, the NTPDase and << ADA >> activities were increased in all groups treated with [[ caffeic acid ]] when compared to control (P<0.05).


In lymphocytes, the << NTPDase >> and ADA activities were increased in all groups treated with [[ caffeic acid ]] when compared to control (P<0.05).


Currently, the most important insecticides are << neonicotinoids >>, which are metabolized in vitro by [[ AOX ]] on reduction of the nitroimino group and by CYPs via oxidation reactions.


Currently, the most important insecticides are << neonicotinoids >>, which are metabolized in vitro by AOX on reduction of the nitroimino group and by [[ CYPs ]] via oxidation reactions.


Currently, the most important insecticides are neonicotinoids, which are metabolized in vitro by << AOX >> on reduction of the [[ nitroimino ]] group and by CYPs via oxidation reactions.


The procedure was to reduce liver << AOX >> activity by providing [[ tungsten ]] or hydralazine in the drinking water or to use the AOX-deficient DBA/2 mouse strain.


The procedure was to reduce liver << AOX >> activity by providing tungsten or [[ hydralazine ]] in the drinking water or to use the AOX-deficient DBA/2 mouse strain.


Liver << AOX >> activity was reduced by 45% with [[ tungsten ]] and 61% with hydralazine and 81% in AOX-deficient mice relative to controls.


Liver << AOX >> activity was reduced by 45% with tungsten and 61% with [[ hydralazine ]] and 81% in AOX-deficient mice relative to controls.


When mice were treated ip with the major neonicotinoid imidacloprid (IMI), metabolism by CYP oxidation reactions was not appreciably affected, whereas the << AOX >>-generated nitrosoguanidine metabolite was decreased by 30% with [[ tungsten ]] and 56% with hydralazine and 86% in the AOX-deficient mice.


When mice were treated ip with the major neonicotinoid imidacloprid (IMI), metabolism by CYP oxidation reactions was not appreciably affected, whereas the << AOX >>-generated nitrosoguanidine metabolite was decreased by 30% with tungsten and 56% with [[ hydralazine ]] and 86% in the AOX-deficient mice.


When mice were treated ip with the major neonicotinoid imidacloprid (IMI), metabolism by CYP oxidation reactions was not appreciably affected, whereas the << AOX >>-generated [[ nitrosoguanidine ]] metabolite was decreased by 30% with tungsten and 56% with hydralazine and 86% in the AOX-deficient mice.


Thus, decreasing liver << AOX >> activity by three quite different procedures gave a corresponding decrease for in vivo reductive metabolites in the liver of [[ IMI ]]-treated mice.


Possible << AOX >> involvement in [[ IMI ]] metabolism in insects was evaluated using AOX-expressing and AOX-deficient Drosophila, but no differences were found in IMI nitroreduction or sensitivity between the two strains.


Possible AOX involvement in << IMI >> metabolism in insects was evaluated using [[ AOX ]]-expressing and AOX-deficient Drosophila, but no differences were found in IMI nitroreduction or sensitivity between the two strains.


This is the first study to establish the in vivo relevance of << AOX >> in [[ neonicotinoid ]] metabolism in mammals and one of the first for xenobiotics in general.


Recommended management may include use of << acetylcholinesterase >> inhibitors (e.g. [[ neostigmine ]]) and wound care on a case-by-case basis.


Of the compounds active in the present assay system, the most potent compound 7, << platyphyllonol-5-O-β-d-xylopyranoside >>, significantly suppressed the induction of peroxisome proliferator activated receptor γ (PPARγ and [[ CCAAT/enhancer binding protein α ]] (C/EBPα) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist.


Of the compounds active in the present assay system, the most potent compound 7, << platyphyllonol-5-O-β-d-xylopyranoside >>, significantly suppressed the induction of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer binding protein α ([[ C/EBPα ]]) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist.


Of the compounds active in the present assay system, the most potent compound 7, << platyphyllonol-5-O-β-d-xylopyranoside >>, significantly suppressed the induction of [[ peroxisome proliferator activated receptor γ ]] (PPARγ and CCAAT/enhancer binding protein α (C/EBPα) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist.


Of the compounds active in the present assay system, the most potent compound 7, << platyphyllonol-5-O-β-d-xylopyranoside >>, significantly suppressed the induction of peroxisome proliferator activated receptor γ ([[ PPARγ ]] and CCAAT/enhancer binding protein α (C/EBPα) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist.


Of the compounds active in the present assay system, the most potent compound 7, platyphyllonol-5-O-β-d-xylopyranoside, significantly suppressed the induction of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer binding protein α (C/EBPα) protein expression, and inhibited adipocyte differentiation induced by << troglitazone >>, a [[ PPARγ ]] agonist.


<< Benzenesulfonamides >>: a unique class of [[ chemokine receptor type 4 ]] inhibitors.


Based on our previously published work on CXCR4 antagonists, we have synthesized a series of << aryl sulfonamides >> that inhibit the [[ CXCR4 ]]/CXCL12 interaction.


Based on our previously published work on CXCR4 antagonists, we have synthesized a series of << aryl sulfonamides >> that inhibit the CXCR4/[[ CXCL12 ]] interaction.


These data demonstrate that << benzenesulfonamides >> are a unique class of [[ CXCR4 ]] inhibitors with high potency.


Measurement of Transport Activities of << 3β-Hydroxy-Δ(5)-bile Acids >> in [[ Bile Salt Export Pump ]] and Multidrug Resistance-Associated Proteins Using LC-MS/MS.


Measurement of Transport Activities of << 3β-Hydroxy-Δ(5)-bile Acids >> in Bile Salt Export Pump and [[ Multidrug Resistance-Associated Proteins ]] Using LC-MS/MS.


The analytical method was applied to measurements of transport activities in membrane vesicles obtained from human multidrug resistance-associated protein 2-, 3-, and << human bile salt export pump >>-expressing Sf9 cells for conjugated [[ 3β-hydroxy-Δ(5)-bile acids ]].


The present study demonstrated that << human multidrug resistance-associated protein 3 >> vesicles accepted conjugated [[ 3β-hydroxy-Δ(5)-bile acids ]] along with common bile acids such as glycocholic acid and taurolithocholic acid 3-sulfate.


The present study demonstrated that << human multidrug resistance-associated protein 3 >> vesicles accepted conjugated 3β-hydroxy-Δ(5)-bile acids along with common [[ bile acids ]] such as glycocholic acid and taurolithocholic acid 3-sulfate.


The present study demonstrated that << human multidrug resistance-associated protein 3 >> vesicles accepted conjugated 3β-hydroxy-Δ(5)-bile acids along with common bile acids such as [[ glycocholic acid ]] and taurolithocholic acid 3-sulfate.


The present study demonstrated that << human multidrug resistance-associated protein 3 >> vesicles accepted conjugated 3β-hydroxy-Δ(5)-bile acids along with common bile acids such as glycocholic acid and [[ taurolithocholic acid 3-sulfate ]].


Synthesis and evaluation of << 3-(benzylthio)-5-(1H-indol-3-yl)-1,2,4-triazol-4-amines >> as [[ Bcl-2 ]] inhibitory anticancer agents.


A series of substituted << 3-(benzylthio)-5-(1H-indol-3-yl)-4H-1,2,4-triazol-4-amines >> has been synthesised and tested in vitro as potential pro-apoptotic [[ Bcl-2 ]]-inhibitory anticancer agents.


Active compounds, such as the << nitrobenzyl >> analogue 6c, were found to exhibit sub-micromolar IC50 values in [[ Bcl-2 ]] expressing human cancer cell lines.


<< Glutathione-S-transferase >>, a phase II enzyme, was inhibited by both [[ arsenic ]] and nicotine but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine.


<< Glutathione-S-transferase >>, a phase II enzyme, was inhibited by both arsenic and [[ nicotine ]] but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine.


Upon << nicotine >> pre-exposure, brain [[ acetylcholinesterase ]] increased, while monoamine oxidase (MAO) decreased.


Upon << nicotine >> pre-exposure, brain acetylcholinesterase increased, while [[ monoamine oxidase ]] (MAO) decreased.


Upon << nicotine >> pre-exposure, brain acetylcholinesterase increased, while monoamine oxidase ([[ MAO ]]) decreased.


The toxic effects of << MAO >> significantly attenuated with [[ nicotine ]] pre-exposure.


We developed a computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC) behaviors for endocrine effects of the << aromatase >> inhibitor, [[ fadrozole ]] (FAD).


We developed a computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC) behaviors for endocrine effects of the << aromatase >> inhibitor, fadrozole ([[ FAD ]]).


Although naturally occurring electrophilic plant compounds, such as mustard oil and << cinnamaldehyde >>, are [[ TRPA1 ]] agonists, it is unknown whether arthropod-produced electrophiles activate mammalian TRPA1.


We found that << pBQN >> activates [[ TRPA1 ]] starting at 10 nM and peaking at 300 nM; higher concentrations caused rapid activation followed by a fast decline.


Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist << carvacrol >>, whereas the triple cysteine mutant [[ TRPA1 ]] retained its full response.


Interestingly, following pBQN desensitization, wild-type << TRPA1 >> had dramatically reduced response to the nonelectrophile agonist [[ carvacrol ]], whereas the triple cysteine mutant TRPA1 retained its full response.


Synthesis and in-silico studies of some << diaryltriazole >> derivatives as potential [[ cyclooxygenase ]] inhibitors.


A highly potent inhibition of the << peroxidase >> catalytic reaction by [[ NO ]]/SNO was seen in assays employing the coupled Prx-Trx system.


A highly potent inhibition of the << peroxidase >> catalytic reaction by NO/[[ SNO ]] was seen in assays employing the coupled Prx-Trx system.


In this setting, << S-nitrosocysteine >> (10 μm) effectively blocked the [[ Trx ]]-mediated regeneration of oxidized Prx1.


In this setting, << S-nitrosocysteine >> (10 μm) effectively blocked the Trx-mediated regeneration of [[ oxidized Prx1 ]].


CK significantly inhibited << DMN >>-induced increases in serum [[ alanine aminotransferase ]] (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content.


CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase ([[ ALT ]]) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content.


CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase (ALT) and [[ aspartate aminotransferase ]] (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content.


CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase ([[ AST ]]) activities, fibrosis score, and hepatic malondialdehyde and collagen content.


CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and [[ collagen ]] content.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in [[ matrix metalloproteinase-13 ]] (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 ([[ MMP-13 ]]), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), [[ tissue inhibitor of metalloproteinase-1 ]] (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 ([[ TIMP-1 ]]), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and [[ tumor necrosis factor-α ]] (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α ([[ TNF-α ]]) mRNA, and collagen type I and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and [[ collagen type I ]] and α-smooth muscle actin protein.


Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and [[ α-smooth muscle actin ]] protein.


<< DMN >>-induced cyclooxygenase-2 (COX-2) expression and [[ nuclear factor-kappa B ]] (NF-κB) activation was reduced by CK treatment.


<< DMN >>-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B ([[ NF-κB ]]) activation was reduced by CK treatment.


<< DMN >>-induced [[ cyclooxygenase-2 ]] (COX-2) expression and nuclear factor-kappa B (NF-κB) activation was reduced by CK treatment.


<< DMN >>-induced cyclooxygenase-2 ([[ COX-2 ]]) expression and nuclear factor-kappa B (NF-κB) activation was reduced by CK treatment.


Extrinsic apoptotic pathway markers such as Fas levels and << caspase-8 >> activity increased as a result of [[ CdTe ]]-QD exposure.


Extrinsic apoptotic pathway markers such as << Fas >> levels and caspase-8 activity increased as a result of [[ CdTe ]]-QD exposure.


Our findings reveal that << CdTe >>-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein [[ kinases ]], leading to apoptosis via both extrinsic and intrinsic pathways.


<< Puerarin >> administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and [[ PI3K ]]/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.


<< Puerarin >> administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and PI3K/[[ Akt ]] pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.


<< Puerarin >> administration enhanced glutathione (GSH) activity, [[ glial cell line-derived neurotrophic factor ]] (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.


<< Puerarin >> administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor ([[ GDNF ]]) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.


In addition to the effect on ROS, << puerarin >> ameliorated MPTP-reduced lysosome-associated membrane protein type 2A ([[ Lamp 2A ]]) expression.


In addition to the effect on ROS, puerarin ameliorated << MPTP >>-reduced [[ lysosome-associated membrane protein type 2A ]] (Lamp 2A) expression.


In addition to the effect on ROS, puerarin ameliorated << MPTP >>-reduced lysosome-associated membrane protein type 2A ([[ Lamp 2A ]]) expression.


Taken together, our data demonstrate that << puerarin >> attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of [[ Lamp 2A ]] expression.


Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate << MPTP >>-induced ROS formation and decrease of [[ Lamp 2A ]] expression.


Instead, radiolabeled << nucleosides >> resulting from [[ nuclease ]] hydrolysis were observed.


A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3)H]dihydrotetrabenazine binding affinity at the << vesicular monoamine transporter >> and for their inhibition of vesicular [[ [(3)H]dopamine ]] uptake.


<< IPI-926 >> is both a substrate and inhibitor (IC50 = 1.9 µM) of [[ P-glycoprotein ]].


Oral << lorcaserin >> (BELVIQ(®)), a selective serotonin [[ 5-HT2C ]] receptor agonist, is indicated in the US as an adjunct to diet and exercise in the chronic weight management of obese adults, or overweight adults with at least one weight-related comorbidity (e.g. dyslipidaemia, hypertension, type 2 diabetes).


Oral lorcaserin (<< BELVIQ >>(®)), a selective serotonin [[ 5-HT2C ]] receptor agonist, is indicated in the US as an adjunct to diet and exercise in the chronic weight management of obese adults, or overweight adults with at least one weight-related comorbidity (e.g. dyslipidaemia, hypertension, type 2 diabetes).


Design, Synthesis, Biological Evaluation, and Docking Studies of (S)-Phenylalanine Derivatives with a << 2-Cyanopyrrolidine >> Moiety as Potent [[ Dipeptidyl Peptidase 4 ]] Inhibitors.


Design, Synthesis, Biological Evaluation, and Docking Studies of << (S)-Phenylalanine >> Derivatives with a 2-Cyanopyrrolidine Moiety as Potent [[ Dipeptidyl Peptidase 4 ]] Inhibitors.


Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 (DPP-4) inhibitors, among them, the << cyclopropyl-substituted phenylalanine >> derivative 11h displayed the most potent [[ DPP-4 ]] inhibitory activity with an IC50 value of 0.247 μM.


<< TCPOBOP >>, a CAR ligand, modestly induced [[ mdr1a ]].fLUC in pxr(+/+) and pxr(-/-) strains, consistent with CAR's minor role in mdr1a regulation.


<< Galangin >> decreased expression of pro-inflammatory [[ cytokines ]], such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8.


<< Galangin >> decreased expression of pro-inflammatory cytokines, such as [[ tumor necrosis factor (TNF)-α ]], interleukin (IL)-6, IL-1β, and IL-8.


<< Galangin >> decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, [[ interleukin ]] (IL)-6, IL-1β, and IL-8.


<< Galangin >> decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin [[ (IL)-6 ]], IL-1β, and IL-8.


<< Galangin >> decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, [[ IL-1β ]], and IL-8.


<< Galangin >> decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and [[ IL-8 ]].


The inhibitory effect of << galangin >> on theses pro-inflammatory [[ cytokines ]] was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1.


Furthermore, << galangin >> attenuated [[ IgE ]]-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue.


Furthermore, << galangin >> attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of [[ histamine receptor 1 ]] at the inflamed tissue.


Our results showed that << galangin >> down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory [[ cytokines ]].


<< Nobiletin >> attenuates metastasis via both [[ ERK ]] and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells.


<< Nobiletin >> attenuates metastasis via both ERK and [[ PI3K ]]/Akt pathways in HGF-treated liver cancer HepG2 cells.


<< Nobiletin >> attenuates metastasis via both ERK and PI3K/[[ Akt ]] pathways in HGF-treated liver cancer HepG2 cells.


Among them, << nobiletin >> markedly inhibited [[ HGF ]]-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations.


Data also showed << nobiletin >> inhibited [[ HGF ]]-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia.


Furthermore, << nobiletin >> could inhibit [[ HGF ]]-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38.


Furthermore, << nobiletin >> could inhibit HGF-induced the membrane localization of phosphorylated [[ c-Met ]], ERK2, and Akt, but not phosphorylated JNK1/2 and p38.


Furthermore, << nobiletin >> could inhibit HGF-induced the membrane localization of phosphorylated c-Met, [[ ERK2 ]], and Akt, but not phosphorylated JNK1/2 and p38.


Furthermore, << nobiletin >> could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and [[ Akt ]], but not phosphorylated JNK1/2 and p38.


Next, << nobiletin >> significantly decreased the levels of [[ phospho-ERK2 ]] and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.


Next, << nobiletin >> significantly decreased the levels of phospho-ERK2 and [[ phospho-Akt ]] in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.


Next, << nobiletin >> significantly decreased the levels of phospho-ERK2 and phospho-Akt in [[ ERK2 ]] or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.


Next, << nobiletin >> significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or [[ Akt ]] siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration.


In conclusion, << nobiletin >> attenuates [[ HGF ]]-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.


In conclusion, << nobiletin >> attenuates HGF-induced HepG2 cells metastasis involving both [[ ERK ]] and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.


In conclusion, << nobiletin >> attenuates HGF-induced HepG2 cells metastasis involving both ERK and [[ PI3K ]]/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.


In conclusion, << nobiletin >> attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/[[ Akt ]] pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma.


<< Cholesterol >> also increases [[ Amyloid β ]] (Aβ) deposition and tau pathology.


<< Cholesterol >> also increases Amyloid β ([[ Aβ ]]) deposition and tau pathology.


<< Cholesterol >> also increases Amyloid β (Aβ) deposition and [[ tau ]] pathology.


Excess of << cholesterol >> converted into 24OHC may up-regulate [[ ApoE ]] synthesis which is a scavenger for Aβ and Tau.


Excess of cholesterol converted into << 24OHC >> may up-regulate [[ ApoE ]] synthesis which is a scavenger for Aβ and Tau.


In the current study, we extend these findings to show that the ability of astrocytes to buffer extracellular << glutamate >> is reduced when [[ CaMKII ]] is inhibited.


<< 3-Hydroxypyridin-2-thione >> as Novel Zinc Binding Group for Selective [[ Histone Deacetylase ]] Inhibition.


3-Hydroxypyridin-2-thione as Novel << Zinc >> Binding Group for Selective [[ Histone Deacetylase ]] Inhibition.


Small molecules bearing hydroxamic acid as the << zinc >> binding group (ZBG) have been the most effective [[ histone deacetylase ]] inhibitors (HDACi) to date.


Small molecules bearing hydroxamic acid as the << zinc >> binding group (ZBG) have been the most effective histone deacetylase inhibitors ([[ HDAC ]]i) to date.


We have identified << 3-hydroxypyridin-2-thione >> (3-HPT) as a novel ZBG that is compatible with [[ HDAC ]] inhibition.


We have identified 3-hydroxypyridin-2-thione (<< 3-HPT >>) as a novel ZBG that is compatible with [[ HDAC ]] inhibition.


<< 3-HPT >> inhibits [[ HDAC 6 ]] and HDAC 8 with an IC50 of 681 and 3675 nM, respectively.


<< 3-HPT >> inhibits HDAC 6 and [[ HDAC 8 ]] with an IC50 of 681 and 3675 nM, respectively.


Subsequent optimization led to several novel << 3HPT >>-based [[ HDAC ]]i that are selective for HDAC 6 and HDAC 8.


Subsequent optimization led to several novel << 3HPT >>-based HDACi that are selective for [[ HDAC 6 ]] and HDAC 8.


Subsequent optimization led to several novel << 3HPT >>-based HDACi that are selective for HDAC 6 and [[ HDAC 8 ]].


Maqui berry (Aristotelia chilensis) and the constituent << delphinidin glycoside >> inhibit [[ photoreceptor ]] cell death induced by visible light.


These findings indicate that MBE and its << anthocyanidins >> suppress the light-induced photoreceptor cell death by inhibiting ROS production, suggesting that the inhibition of [[ phosphorylated-p38 ]] may be involved in the underlying mechanism.


Moreover, << curcumin >> could also down-regulate the expression and activity of [[ matrix metalloproteinase-9 ]] (MMP-9).


Moreover, << curcumin >> could also down-regulate the expression and activity of matrix metalloproteinase-9 ([[ MMP-9 ]]).


Treatment with << EVn-50 >> or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of [[ Histone 3 ]] at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.


Treatment with << EVn-50 >> or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of [[ Cdk1 ]] at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.


Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of [[ Histone 3 ]] at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.


Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of [[ Cdk1 ]] at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c.


Treatment with << EVn-50 >> or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of [[ cyclin B1 ]], and decreased expression of Cdc25c.


Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of [[ cyclin B1 ]], and decreased expression of Cdc25c.


Treatment with << EVn-50 >> or VB1 resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of [[ Cdc25c ]].


Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of cyclin B1, and decreased expression of [[ Cdc25c ]].


<< Xanthohumol >> and 2-hydroxychalcone induced apoptosis by [[ Bcl-2 ]] downregulation.


Xanthohumol and << 2-hydroxychalcone >> induced apoptosis by [[ Bcl-2 ]] downregulation.


Importantly, << 2-hydroxychalcone >> and xanthohumol exerted more potent inhibitory effects on the proliferation, [[ MMP-9 ]] expression and invasive phenotype of MDA-MB-231 than chalcone.


Importantly, 2-hydroxychalcone and << xanthohumol >> exerted more potent inhibitory effects on the proliferation, [[ MMP-9 ]] expression and invasive phenotype of MDA-MB-231 than chalcone.


<< 4-Hydroxypyridazin-3(2H)-one >> Derivatives as Novel [[ d-Amino Acid Oxidase ]] Inhibitors. d-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including d-serine, a coagonist of the N-methyl-d-aspartate receptor.


4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. d-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including << d-serine >>, a coagonist of the [[ N-methyl-d-aspartate receptor ]].


4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. << d-Amino acid oxidase >> (DAAO) catalyzes the oxidation of d-amino acids including [[ d-serine ]], a coagonist of the N-methyl-d-aspartate receptor.


4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. d-Amino acid oxidase (<< DAAO >>) catalyzes the oxidation of d-amino acids including [[ d-serine ]], a coagonist of the N-methyl-d-aspartate receptor.


4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. << d-Amino acid oxidase >> (DAAO) catalyzes the oxidation of [[ d-amino acids ]] including d-serine, a coagonist of the N-methyl-d-aspartate receptor.


4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. d-Amino acid oxidase (<< DAAO >>) catalyzes the oxidation of [[ d-amino acids ]] including d-serine, a coagonist of the N-methyl-d-aspartate receptor.


We identified a series of << 4-hydroxypyridazin-3(2H)-one >> derivatives as novel [[ DAAO ]] inhibitors with high potency and substantial cell permeability using fragment-based drug design.


<< 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one >> exhibited the predicted binding mode and demonstrated high inhibitory activity for [[ human DAAO ]] in enzyme- and cell-based assays.


Fourteen of 17 << parabens >> exhibited [[ hERα ]] and/or hERβ agonistic activity at concentrations of ⩽1×10(-5)M, whereas none of the 17 parabens showed AR agonistic or antagonistic activity.


Fourteen of 17 << parabens >> exhibited hERα and/or [[ hERβ ]] agonistic activity at concentrations of ⩽1×10(-5)M, whereas none of the 17 parabens showed AR agonistic or antagonistic activity.


Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, << heptylparaben >> (C7) and pentylparaben (C5) showed the most potent [[ ERα ]] and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, << heptylparaben >> (C7) and pentylparaben (C5) showed the most potent ERα and [[ ERβ ]] agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, heptylparaben (C7) and << pentylparaben >> (C5) showed the most potent [[ ERα ]] and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, heptylparaben (C7) and << pentylparaben >> (C5) showed the most potent ERα and [[ ERβ ]] agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 << parabens >> with linear alkyl chains ranging in length from C1 to C12, heptylparaben (C7) and pentylparaben (C5) showed the most potent [[ ERα ]] and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 << parabens >> with linear alkyl chains ranging in length from C1 to C12, heptylparaben (C7) and pentylparaben (C5) showed the most potent ERα and [[ ERβ ]] agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 parabens with linear << alkyl >> chains ranging in length from C1 to C12, heptylparaben (C7) and pentylparaben (C5) showed the most potent [[ ERα ]] and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Among 12 parabens with linear << alkyl >> chains ranging in length from C1 to C12, heptylparaben (C7) and pentylparaben (C5) showed the most potent ERα and [[ ERβ ]] agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.


Most << parabens >> showing estrogenic activity exhibited [[ ERβ ]]-agonistic activity at lower concentrations than those inducing ERα-agonistic activity.


Most << parabens >> showing estrogenic activity exhibited ERβ-agonistic activity at lower concentrations than those inducing [[ ERα ]]-agonistic activity.


These results indicate that << parabens >> are selective agonists for [[ ERβ ]] over ERα; their interactions with ERα/β are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by carboxylesterases, leading to attenuation of their estrogenic activity.


These results indicate that << parabens >> are selective agonists for ERβ over [[ ERα ]]; their interactions with ERα/β are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by carboxylesterases, leading to attenuation of their estrogenic activity.


These results indicate that << parabens >> are selective agonists for ERβ over ERα; their interactions with ERα/β are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by [[ carboxylesterases ]], leading to attenuation of their estrogenic activity.


Wattakaka volubilis << steroidal glycoside >> mixture (WVSM) and PPG (1-50μM) significantly inhibited the [[ COX-2 ]] and iNOS enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264.7 macrophage cells.


Wattakaka volubilis << steroidal glycoside >> mixture (WVSM) and PPG (1-50μM) significantly inhibited the COX-2 and [[ iNOS ]] enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264.7 macrophage cells.


Wattakaka volubilis steroidal glycoside mixture (WVSM) and << PPG >> (1-50μM) significantly inhibited the [[ COX-2 ]] and iNOS enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264.7 macrophage cells.


Wattakaka volubilis steroidal glycoside mixture (WVSM) and << PPG >> (1-50μM) significantly inhibited the COX-2 and [[ iNOS ]] enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264.7 macrophage cells.


<< Quercetin >> suppressed [[ CYP2E1 ]]-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO.


However, the precise mechanism by which << quercetin >> counteracts [[ CYP2E1 ]]-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear.


Our data showed that chronic << ethanol >> over-activated [[ CYP2E1 ]] but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.).


Our data showed that chronic << ethanol >> over-activated CYP2E1 but suppressed [[ HO-1 ]] with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.).


<< Quercetin >> (100μM) induced [[ HO-1 ]] and depleted heme pool when incubated to human hepatocytes.


<< Ethanol >>-stimulated (100mM) [[ CYP2E1 ]] upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation.


Ethanol-stimulated (100mM) << CYP2E1 >> upregulation was suppressed by [[ quercetin ]] but further enhanced by HO-1 inhibition with resultant heme accumulation.


<< Ethanol >>-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by [[ HO-1 ]] inhibition with resultant heme accumulation.


Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by << HO-1 >> inhibition with resultant [[ heme ]] accumulation.


<< CO >> scavenging blocked the suppression of quercetin only on [[ CYP2E1 ]] activity.


CO donor dose-dependently inactivated << CYP2E1 >> of [[ ethanol ]]-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger.


<< CO >> donor dose-dependently inactivated [[ CYP2E1 ]] of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger.


CO donor dose-dependently inactivated << CYP2E1 >> of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by [[ CO ]] scavenger.


Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by << quercetin >> through [[ HO-1 ]] induction.


Depleted heme pool and << CO >> releasing limited protein synthesis and inhibited enzymatic activity of [[ CYP2E1 ]], respectively.


Novel racemic << tetrahydrocurcuminoid dihydropyrimidinone >> analogues as potent [[ acetylcholinesterase ]] inhibitors.


Agonistic activity of << ICI 182 780 >> on activation of GSK 3β/[[ AKT ]] pathway in the rat uterus during the estrous cycle.


Agonistic activity of << ICI 182 780 >> on activation of [[ GSK 3β ]]/AKT pathway in the rat uterus during the estrous cycle.


Both << ICI >> treatments, induced a significant decrease (p<0.01) in uterine [[ estrogen receptor alpha ]] (ERα) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals.


Both << ICI >> treatments, induced a significant decrease (p<0.01) in uterine estrogen receptor alpha ([[ ERα ]]) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals.


Furthermore, we detected that << ICI >> treatment induced [[ glycogen synthase kinase ]] (Gsk3-β) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization.


Furthermore, we detected that << ICI >> treatment induced glycogen synthase kinase ([[ Gsk3-β ]]) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization.


We observed that the administration of << ICI >> at 08:00h on proestrus day produced a 15% inhibition of luminal epithelial cell proliferation, reduced uterine wet weight by 21% and caused reduction of [[ Akt ]] phosphorylation at Ser 473 as compared to vehicle-treated animals, whereas ICI treatment at 00:00h on estrus day had no effect on these parameters.


The overall results indicate that << ICI >> may exert agonistic and antagonistic effects on uterine cell proliferation through differential activation of the [[ Akt ]] pathway depending on the administration period during the estrous cycle, and indicates that the mechanism of cell proliferation during the physiological conditions of the estrous cycle, is under a different and more complex regulation than in the ovariectomized +E2 animal model.


<< Aminopropylindenes >> derived from Grundmann's ketone as a novel chemotype of [[ oxidosqualene cyclase ]] inhibitors.


Aminopropylindenes derived from << Grundmann's ketone >> as a novel chemotype of [[ oxidosqualene cyclase ]] inhibitors.


A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (<< OSC >>)-mediated cyclization of 2,3-oxidosqualen to [[ lanosterol ]] was prepared from Grundmann's ketone.


A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the << oxidosqualene cyclase(1) >> (OSC)-mediated cyclization of 2,3-oxidosqualen to [[ lanosterol ]] was prepared from Grundmann's ketone.


A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (<< OSC >>)-mediated cyclization of [[ 2,3-oxidosqualen ]] to lanosterol was prepared from Grundmann's ketone.


A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the << oxidosqualene cyclase(1) >> (OSC)-mediated cyclization of [[ 2,3-oxidosqualen ]] to lanosterol was prepared from Grundmann's ketone.


A << N,N-dimethylaminopropyl >> derivative showed promising inhibition of [[ Trypanosoma cruzi OSC ]] in combination with low cytotoxicity, and showed significant reduction of cholesterol biosynthesis in a human cell line.


A N,N-dimethylaminopropyl derivative showed promising inhibition of << Trypanosoma cruzi OSC >> in combination with low cytotoxicity, and showed significant reduction of [[ cholesterol ]] biosynthesis in a human cell line.


The << ATP >> required for potentiation of skeletal muscle contraction is released via [[ pannexin ]] hemichannels.


During repetitive stimulation of skeletal muscle, extracellular << ATP >> levels raise, activating [[ purinergic receptors ]], increasing Ca(2+) influx, and enhancing contractile force, a response called potentiation.


Consistent with two << glucose >> uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or [[ glucose transporter ]] (GLUT4), and blocked by dual blockade.


Consistent with two << glucose >> uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter ([[ GLUT4 ]]), and blocked by dual blockade.


Consistent with two glucose uptake pathways, induced uptake of << 2-NBDG >>, a fluorescent glucose derivative, was decreased by inhibition of HCs or [[ glucose transporter ]] (GLUT4), and blocked by dual blockade.


Consistent with two glucose uptake pathways, induced uptake of << 2-NBDG >>, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter ([[ GLUT4 ]]), and blocked by dual blockade.


MRS2179, a P2Y1R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles << ATP >> activates [[ P2Y1 ]] but not P2X receptors.


Opening of << Panx1 >> HCs during repetitive activation allows efflux of [[ ATP ]], influx of glucose and possibly Ca(2+) too, which are required for potentiation of contraction.


Opening of << Panx1 >> HCs during repetitive activation allows efflux of ATP, influx of [[ glucose ]] and possibly Ca(2+) too, which are required for potentiation of contraction.


Opening of << Panx1 >> HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly [[ Ca(2+) ]] too, which are required for potentiation of contraction.


The rate limiting enzyme of beta-oxidation (<< ACOX1 >>) was significantly over-expressed in the liver with [[ tBHQ ]] treatment.


These results indicate that << tBHQ >> suppresses body weight gain in mice, possibly at least related to the up-regulation of [[ ACOX1 ]] gene expression.


When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the << VEGF >> release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core [[ PLGA ]] and more than 45% with HMW core PLGA.


When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of << PDGF >>, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core [[ PLGA ]] and more than 45% with HMW core PLGA.


When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the << VEGF >> release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core [[ PLGA ]].


When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of << PDGF >>, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core [[ PLGA ]].


Potency switch between CHK1 and << MK2 >>: Discovery of [[ imidazo[1,2-a]pyrazine ]]- and imidazo[1,2-c]pyrimidine-based kinase inhibitors.


Potency switch between CHK1 and MK2: Discovery of << imidazo[1,2-a]pyrazine >>- and imidazo[1,2-c]pyrimidine-based [[ kinase ]] inhibitors.


Potency switch between << CHK1 >> and MK2: Discovery of [[ imidazo[1,2-a]pyrazine ]]- and imidazo[1,2-c]pyrimidine-based kinase inhibitors.


Potency switch between CHK1 and << MK2 >>: Discovery of imidazo[1,2-a]pyrazine- and [[ imidazo[1,2-c]pyrimidine ]]-based kinase inhibitors.


Potency switch between CHK1 and MK2: Discovery of imidazo[1,2-a]pyrazine- and << imidazo[1,2-c]pyrimidine >>-based [[ kinase ]] inhibitors.


Potency switch between << CHK1 >> and MK2: Discovery of imidazo[1,2-a]pyrazine- and [[ imidazo[1,2-c]pyrimidine ]]-based kinase inhibitors.


Discovery of << aryl ureas >> and aryl amides as potent and selective [[ histamine H3 receptor ]] antagonists for the treatment of obesity (Part I).


Discovery of aryl ureas and << aryl amides >> as potent and selective [[ histamine H3 receptor ]] antagonists for the treatment of obesity (Part I).


A series of structurally novel << aryl ureas >> was derived from optimization of the HTS lead as selective [[ histamine H3 receptor ]] (H3R) antagonists.


A series of structurally novel << aryl ureas >> was derived from optimization of the HTS lead as selective histamine H3 receptor ([[ H3R ]]) antagonists.


In terms of the mechanisms, we found that fatty acid amide hydrolase (<< FAAH >>) which degrades [[ anandamide ]], was upregulated after nerve injury at both ages, so that this upregulation likely did not account for the age-dependent differences.


In terms of the mechanisms, we found that << fatty acid amide hydrolase >> (FAAH) which degrades [[ anandamide ]], was upregulated after nerve injury at both ages, so that this upregulation likely did not account for the age-dependent differences.


However, enzymes contributing to oxidative metabolism of << anandamide >>, namely [[ cyclooxygenase-1 ]] and Cyp2D6, were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of anandamide.


However, enzymes contributing to oxidative metabolism of << anandamide >>, namely cyclooxygenase-1 and [[ Cyp2D6 ]], were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of anandamide.


However, enzymes contributing to oxidative metabolism of anandamide, namely << cyclooxygenase-1 >> and Cyp2D6, were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of [[ anandamide ]].


However, enzymes contributing to oxidative metabolism of anandamide, namely cyclooxygenase-1 and << Cyp2D6 >>, were increased in the brain of aged mice, possibly enhancing the oxidative breakdown of [[ anandamide ]].


<< 24(S)-hydroxycholesterol >> is actively eliminated from neuronal cells by [[ ABCA1 ]].


High << cholesterol >> turnover catalyzed by [[ cholesterol 24-hydroxylase ]] is essential for neural functions, especially learning.


Because << 24(S)-hydroxycholesterol >> (24-OHC), produced by [[ 24-hydroxylase ]], induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells.


Because 24(S)-hydroxycholesterol (<< 24-OHC >>), produced by [[ 24-hydroxylase ]], induces apoptosis of neuronal cells, it is vital to eliminate it rapidly from cells.


The expression of << ABCA1 >> and ABCG1 was induced by 24-OHC, as well as TO901317 and [[ retinoic acid ]], which are ligands of the nuclear receptors LXR/RXR.


The expression of ABCA1 and << ABCG1 >> was induced by 24-OHC, as well as TO901317 and [[ retinoic acid ]], which are ligands of the nuclear receptors LXR/RXR.


The expression of << ABCA1 >> and ABCG1 was induced by [[ 24-OHC ]], as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.


The expression of ABCA1 and << ABCG1 >> was induced by [[ 24-OHC ]], as well as TO901317 and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.


The expression of << ABCA1 >> and ABCG1 was induced by 24-OHC, as well as [[ TO901317 ]] and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.


The expression of ABCA1 and << ABCG1 >> was induced by 24-OHC, as well as [[ TO901317 ]] and retinoic acid, which are ligands of the nuclear receptors LXR/RXR.


To confirm the role of each transporter, we analyzed HEK293 cells stably expressing << human ABCA1 >> or ABCG1; we clearly observed [[ 24-OHC ]] efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A-I was marginal.


To confirm the role of each transporter, we analyzed HEK293 cells stably expressing human ABCA1 or << ABCG1 >>; we clearly observed [[ 24-OHC ]] efflux in the presence of HDL, whereas efflux in the presence of apolipoprotein A-I was marginal.


These results suggest that << ABCA1 >> actively eliminates [[ 24-OHC ]] in the presence of HDL as a lipid acceptor and protects neuronal cells.


The selective << CaMKIIα >> inhibitor [[ KN-62 ]] reversed the blockade produced by ionomycin and K(+)-depolarization.


The selective << CaMKIIα >> inhibitor KN-62 reversed the blockade produced by [[ ionomycin ]] and K(+)-depolarization.


In K(+)-depolarized tissues, D3 receptors potentiated D1 receptor-induced stimulation of [(3)H]GABA release only when << CaMKIIα >> was blocked with [[ KN-62 ]].


In the presence of this inhibitor, the selective << D3 >> agonist [[ PD 128,907 ]] reduced the ED50 for the D1 agonist SKF 38393 from 56 to 4 nM.


In the presence of this inhibitor, the selective D3 agonist PD 128,907 reduced the ED50 for the << D1 >> agonist [[ SKF 38393 ]] from 56 to 4 nM.


The << Bcl2 >>/Bax ratio increased and Mfn2 expression decreased in MIN6 cells after [[ glucose ]] stimulation.


The Bcl2/<< Bax >> ratio increased and Mfn2 expression decreased in MIN6 cells after [[ glucose ]] stimulation.


The Bcl2/Bax ratio increased and << Mfn2 >> expression decreased in MIN6 cells after [[ glucose ]] stimulation.


Additionally, treatment with << glucose >>/iron showed a higher [[ HO ]] activity.


Additionally, treatment with glucose/<< iron >> showed a higher [[ HO ]] activity.


Our study revealed that high << glucose >>/Fe concentrations in MIN6 cells induced an increase of the [[ Bcl2 ]]/Bax ratio, an indicator of increased cell apoptosis.


Our study revealed that high << glucose >>/Fe concentrations in MIN6 cells induced an increase of the Bcl2/[[ Bax ]] ratio, an indicator of increased cell apoptosis.


Our study revealed that high glucose/<< Fe >> concentrations in MIN6 cells induced an increase of the [[ Bcl2 ]]/Bax ratio, an indicator of increased cell apoptosis.


Our study revealed that high glucose/<< Fe >> concentrations in MIN6 cells induced an increase of the Bcl2/[[ Bax ]] ratio, an indicator of increased cell apoptosis.


This includes << nonribosomal peptide synthetases >> (NRPS) and polyketide synthases (PKS) required for the formation of the [[ benzopyranopyrrole ]] core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (<< NRPS >>) and polyketide synthases (PKS) required for the formation of the [[ benzopyranopyrrole ]] core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (NRPS) and << polyketide synthases >> (PKS) required for the formation of the [[ benzopyranopyrrole ]] core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (NRPS) and polyketide synthases (<< PKS >>) required for the formation of the [[ benzopyranopyrrole ]] core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) required for the formation of the << benzopyranopyrrole >> core unit, as well as a suite of tailoring enzymes (e.g., four [[ halogenases ]], an O-methyltransferase, and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) required for the formation of the << benzopyranopyrrole >> core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an [[ O-methyltransferase ]], and an N-glycosyltransferase) necessary for further modifications of the core structure.


This includes nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) required for the formation of the << benzopyranopyrrole >> core unit, as well as a suite of tailoring enzymes (e.g., four halogenases, an O-methyltransferase, and an [[ N-glycosyltransferase ]]) necessary for further modifications of the core structure.


Targeted disruption of the gene encoding the << N-glycosyltransferase >>, prlH, abolished [[ pyralomicin ]] production, and recombinant expression of PrlA confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the C7-cyclitol moiety.


Targeted disruption of the gene encoding the N-glycosyltransferase, << prlH >>, abolished [[ pyralomicin ]] production, and recombinant expression of PrlA confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the C7-cyclitol moiety.


Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of << PrlA >> confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the [[ C7 ]]-cyclitol moiety.


Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a << sugar phosphate cyclase >> involved in the formation of the [[ C7 ]]-cyclitol moiety.


Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of << PrlA >> confirms the activity of this enzyme as a sugar phosphate cyclase involved in the formation of the C7-[[ cyclitol ]] moiety.


Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a << sugar phosphate cyclase >> involved in the formation of the C7-[[ cyclitol ]] moiety.


To examine receptor mediation of estradiol effects, Ovx mice replaced for 2 days with either the << ERα >>-selective agonist [[ PPT ]] or the ERβ-selective agonist DPN were compared to Sham mice, and mice lacking either ERα (αERKO) or ERβ (βERKO) were compared to WT littermates.


To examine receptor mediation of estradiol effects, Ovx mice replaced for 2 days with either the ERα-selective agonist PPT or the << ERβ >>-selective agonist [[ DPN ]] were compared to Sham mice, and mice lacking either ERα (αERKO) or ERβ (βERKO) were compared to WT littermates.


The << Intermediate-conductance Calcium-activated Potassium Channel KCa3.1 >> Regulates Vascular Smooth Muscle Cell Proliferation via Controlling [[ Calcium ]]-dependent Signaling.


Reactive Metabolite Trapping Studies on << Imidazo- and 2-Methylimidazo[2,1-b]thiazole >>-based Inverse Agonists of the [[ Ghrelin Receptor ]].


The current study examined the bioactivation potential of << ghrelin receptor >> inverse agonists, 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone (1) and [[ 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone ]] (2), containing a fused imidazo[2,1-b]thiazole motif in the core structure.


The current study examined the bioactivation potential of << ghrelin receptor >> inverse agonists, 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone (1) and 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone (2), containing a fused [[ imidazo[2,1-b]thiazole ]] motif in the core structure.


The current study examined the bioactivation potential of << ghrelin receptor >> inverse agonists, [[ 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(imidazo[2,1-b]thiazol-6-yl)ethanone ]] (1) and 1-(2-(2-chloro-4-(2H-1,2,3-triazol-2-yl)benzyl)-2,7-diazaspiro[3.5]nonan-7-yl)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)ethanone (2), containing a fused imidazo[2,1-b]thiazole motif in the core structure.


Processing of polysialylated NCAM was reproduced in a mouse model by << bleomycin >> administration leading to an activation of the inflammasome and secretion of [[ interleukin (IL)-1β ]].


<< 4-Hydroxytamoxifen >>-stimulated processing of [[ cyclin E ]] is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells.


<< 17β-Estradiol >> (E2) has been recently shown to induce [[ cyclin E ]] processing in breast cancer cells.


Collectively, our data indicate that << OHT >> contributes to the production of proteolyzed [[ cyclin E ]] via GPR30 with augmented migration in MCF-7 cells.


We have recently reported that a mono-hydroxylated metabolite of the synthetic << aminoalkylindole >> cannabinoid JHW-073 (3) exhibits neutral antagonist activity at [[ CB1Rs ]] and thus may serve as a promising lead for the development of novel alcohol abuse therapies.


We have recently reported that a mono-hydroxylated metabolite of the synthetic aminoalkylindole cannabinoid << JHW-073 >> (3) exhibits neutral antagonist activity at [[ CB1Rs ]] and thus may serve as a promising lead for the development of novel alcohol abuse therapies.


In the current study, we show that systematic modification of an << aminoalkylindole >> scaffold identifies two new compounds with dual CB1R antagonist/[[ CB2R ]] agonist activity.


In the current study, we show that systematic modification of an << aminoalkylindole >> scaffold identifies two new compounds with dual [[ CB1R ]] antagonist/CB2R agonist activity.


Collectively, these initial findings suggest that design and systematic modification of << aminoalkylindoles >> such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/[[ CB2R ]] agonist activity with potential for use as treatments of alcohol abuse.


Collectively, these initial findings suggest that design and systematic modification of << aminoalkylindoles >> such as 3 may lead to development of novel cannabinoid ligands with dual [[ CB1R ]] antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.


Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the << dipeptidyl peptidase-4 >> inhibitor [[ vildagliptin ]] in an advanced-aged diet-induced obesity mouse model.


METHODS: After 1 month of HFD alone, the mice were given the << DPP4 >> inhibitor [[ vildagliptin ]] for a further 11 months.


The improved survival rates for obese mice chronically treated with << vildagliptin >> suggest that chronic [[ DPP4 ]] inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy.


Protein levels of the << glucose transporter >> (GLUT4) involved in [[ glucose ]] transport via these two pathways were also increased.


Protein levels of the glucose transporter (<< GLUT4 >>) involved in [[ glucose ]] transport via these two pathways were also increased.


<< Puerarin >> stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent [[ MEK ]]/ERK and PI3K/Akt activation.


<< Puerarin >> stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/[[ ERK ]] and PI3K/Akt activation.


<< Puerarin >> stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and [[ PI3K ]]/Akt activation.


<< Puerarin >> stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/[[ Akt ]] activation.


Puerarin promotes proliferation by altering cell cycle distribution whereas << puerarin >>-mediated survival may be associated with up-regulation of [[ Bcl-xL ]] expression.


Treatment with the << ER >> antagonist [[ ICI 182,780 ]] abolishes the above actions of puerarin on osteoblast-derived cells.


Moreover, we also demonstrate that << puerarin >> functions at least partially through activation of [[ MEK ]]/ERK and PI3K/Akt signaling.


Moreover, we also demonstrate that << puerarin >> functions at least partially through activation of MEK/[[ ERK ]] and PI3K/Akt signaling.


Moreover, we also demonstrate that << puerarin >> functions at least partially through activation of MEK/ERK and [[ PI3K ]]/Akt signaling.


Moreover, we also demonstrate that << puerarin >> functions at least partially through activation of MEK/ERK and PI3K/[[ Akt ]] signaling.


RESULTS: Pretreatment of ucOC (30ng/ml) prevented LA-induced apoptosis in insulin-stimulated endothelial cells; effects were abolished by pretreatment with the << phosphatidylinositol 3-kinase >> (PI3-kinase) inhibitor, [[ wortmannin ]].