AdaptLLM/ChemProt · Datasets at Hugging Face

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Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]].	SUBSTRATE	[]
To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor [[ N(omega)-hydroxy-nor-L-arginine ]] (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).	INHIBITOR	[]
To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor N(omega)-hydroxy-nor-L-arginine ([[ Nor-NOHA ]]) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).	INHIBITOR	[]
To determine whether << arginases >> modulate the endothelial [[ NO ]] synthesis, we investigated the effects of the competitive arginase inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).	PRODUCT-OF	[]
In unstimulated cells, << Nor-NOHA >> dose-dependently reduced the [[ arginase ]] activity with maximal inhibition at 20 microM.	INHIBITOR	[]
When HUVECs were stimulated by thrombin without extracellular L-arginine, << Nor-NOHA >> dose-dependently increased the [[ NOS ]] activity and the NO release with maximal effects at 20 microM.	ACTIVATOR	[]
Extracellular << L-arginine >> also dose-dependently increased NO release and [[ arginase ]] activity.	ACTIVATOR	[]
However, despite activation of L-arginine uptake, the inhibition of << arginase >> activity by [[ Nor-NOHA ]] was still significant.	INHIBITOR	[]
These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane.	PRODUCT-OF	[]
However, pretreatment with agents that block late I(Na), like lidocaine, mexiletine, and << RSD1235 >>, a novel mixed [[ ion channel ]] blocker for the rapid pharmacologic conversion of atrial fibrillation, significantly attenuates the prolonging effects of Class III agents or those induced by ATX-II, a specific toxin that delays Na channel inactivation and amplifies late I(Na) greatly, mimicking LQT3.	INHIBITOR	[]
The << Na channel >> block caused by [[ lidocaine ]] and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.	INHIBITOR	[]
The << Na channel >> block caused by lidocaine and [[ RSD1235 ]] can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.	INHIBITOR	[]
Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	INHIBITOR	[]
Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	INHIBITOR	[]
Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	INHIBITOR	[]
Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	INHIBITOR	[]
Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.	PRODUCT-OF	[]
Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity.	UPREGULATOR	[]
Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [[[ diethylglyoxal bis-(guanylhydrazone) ]]; DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.	INHIBITOR	[]
Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); [[ DEGBG ]]] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.	INHIBITOR	[]
Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC.	PRODUCT-OF	[]
Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC.	PRODUCT-OF	[]
The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that << polyamines >> might be involved in the [[ caspase ]] activating signal cascade.	INDIRECT-UPREGULATOR	[]
On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.	DOWNREGULATOR	[]
On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start of<< carvedilol >> therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.	INDIRECT-DOWNREGULATOR	[]
Two mechanisms of action have been identified for << A77 1726 >>: inhibition of [[ dihydroorotate dehydrogenase ]] (DHODH) and inhibition of tyrosine kinases.	INHIBITOR	[]
Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase ([[ DHODH ]]) and inhibition of tyrosine kinases.	INHIBITOR	[]
Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase (DHODH) and inhibition of [[ tyrosine kinases ]].	INHIBITOR	[]
<< DHODH >> inhibition occurs at lower concentrations of [[ A77 1726 ]] than that of tyrosine kinases and is currently considered the major mode of action.	INHIBITOR	[]
DHODH inhibition occurs at lower concentrations of << A77 1726 >> than that of [[ tyrosine kinases ]] and is currently considered the major mode of action.	INHIBITOR	[]
<< L-proline >> accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding [[ gamma-glutamyl kinase ]].	PRODUCT-OF	[]
Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.	PRODUCT-OF	[]
Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.	PRODUCT-OF	[]
Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.	SUBSTRATE	[]
Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.	SUBSTRATE	[]
When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene.	PRODUCT-OF	[]
These results suggest that the altered << gamma-glutamyl kinase >> results in stabilization of the complex or has an indirect effect on gamma-glutamyl phosphate reductase activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.	PRODUCT-OF	[]
These results suggest that the altered gamma-glutamyl kinase results in stabilization of the complex or has an indirect effect on << gamma-glutamyl phosphate reductase >> activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.	PRODUCT-OF	[]
Structural optimization of << 2,5-thiophene amides >> as highly potent and selective [[ 17β-hydroxysteroid dehydrogenase type 2 ]] inhibitors for the treatment of osteoporosis.	INHIBITOR	[]
We report here the optimization of << human 17β-HSD2 >> inhibitors in the [[ 2,5-thiophene amide ]] class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group.	INHIBITOR	[]
While none of the phenethylamides (n = 2) were active, most of the << anilides >> (n = 0) turned out to moderately or strongly inhibit [[ 17β-HSD2 ]].	INHIBITOR	[]
Multiple exposure to << theophylline >>, a phosphodiesterase ([[ PDE ]]) inhibitor, induces acinar hypertrophy in the salivary gland.	INHIBITOR	[]
Multiple exposure to << theophylline >>, a [[ phosphodiesterase ]] (PDE) inhibitor, induces acinar hypertrophy in the salivary gland.	INHIBITOR	[]
<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for [[ CysS ]] and PDE3A, but PDE4D gene expression was unchanged.	INDIRECT-UPREGULATOR	[]
<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for CysS and [[ PDE3A ]], but PDE4D gene expression was unchanged.	INDIRECT-UPREGULATOR	[]
Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.	AGONIST	[]
Terbutaline (Bricanyl) and its prodrug Bambuterol (<< Bambec >>) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.	AGONIST	[]
<< Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.	AGONIST	[]
Terbutaline (<< Bricanyl >>) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.	AGONIST	[]
<< (+/-)-tamsulosin >>, an [[ alpha 1A-adrenoceptor ]] antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart.	ANTAGONIST	[]
The influence of << (+/-)-tamsulosin >>, a selective [[ alpha 1A-adrenoceptor ]] antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium.	ANTAGONIST	[]
<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.	AGONIST-ACTIVATOR	[]
(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of << alpha 1B-adrenoceptors >> by treatment with [[ chlorethylclonidine ]], which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.	INHIBITOR	[]
(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of << phenylephrine >> even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.	AGONIST	[]
<< (+/-)-Tamsulosin >> effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.	ANTAGONIST	[]
<< (+/-)-Tamsulosin >>, over the range of concentrations at which it antagonized the positive inotropic effect mediated by [[ alpha 1-adrenoceptors ]], did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine.	ANTAGONIST	[]
These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.	AGONIST	[]
These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.	ANTAGONIST	[]
<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the [[ JAK2 ]]/STAT3 signaling pathway.	INHIBITOR	[]
<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/[[ STAT3 ]] signaling pathway.	INHIBITOR	[]
Furthermore, << PTE >> treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of [[ STAT3 ]].	INDIRECT-DOWNREGULATOR	[]
Furthermore, << PTE >> treatment directly inhibited the phosphorylation of [[ JAK2 ]] at Tyr 1007 and the downstream activation of STAT3.	INHIBITOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, [[ Bak ]], cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic [[ Cytochrome c ]], and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved [[ Caspase3 ]]) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as [[ p21 ]] and p27.	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and [[ p27 ]].	INDIRECT-UPREGULATOR	[]
<< PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-DOWNREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins [[ Bcl-xL ]] and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-DOWNREGULATOR	[]
<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and [[ Mcl-1 ]], leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.	INDIRECT-DOWNREGULATOR	[]
PTE, used in combination with a known << JAK2 >>/STAT3 inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.	INHIBITOR	[]
PTE, used in combination with a known JAK2/<< STAT3 >> inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.	INHIBITOR	[]
Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the [[ JAK2 ]]/STAT3 signaling pathway.	INHIBITOR	[]
Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/[[ STAT3 ]] signaling pathway.	INHIBITOR	[]
These data suggest that inhibition of << JAK2 >>/STAT3 signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.	INHIBITOR	[]
These data suggest that inhibition of JAK2/<< STAT3 >> signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.	INHIBITOR	[]
Furthermore, << sinapic acid >> reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of [[ type I collagen ]] mRNA and histological analysis of collagen in liver tissue.	INDIRECT-DOWNREGULATOR	[]
Additionally, the expression of hepatic fibrosis-related factors such as << α-smooth muscle actin >> and transforming growth factor-β1 (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].	INDIRECT-DOWNREGULATOR	[]
Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and << transforming growth factor-β1 >> (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].	INDIRECT-DOWNREGULATOR	[]
Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (<< TGF-β1 >>), were reduced in rats treated with [[ sinapic acid ]].	INDIRECT-DOWNREGULATOR	[]
In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells.	INDIRECT-DOWNREGULATOR	[]
<< Thalidomide >> inhibits growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.	INHIBITOR	[]
<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased [[ cytochrome c ]], but had no effect on that of COX-1, in MCF-7 and HL-60.	INDIRECT-UPREGULATOR	[]
<< Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.	INDIRECT-DOWNREGULATOR	[]
<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of [[ bcl-2 ]] protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.	INDIRECT-DOWNREGULATOR	[]
<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, [[ TNFalpha ]], VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.	INDIRECT-DOWNREGULATOR	[]
<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, [[ VEGF ]], GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.	INDIRECT-DOWNREGULATOR	[]
These results demonstrated that << thalidomide >> might inhibit growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.	INHIBITOR	[]
Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, [[ hemoglobin ]], packed cell volume, platelets, mean corpuscular volume, and mean corpuscular hemoglobin in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.	INDIRECT-UPREGULATOR	[]
Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular [[ hemoglobin ]] in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.	INDIRECT-UPREGULATOR	[]
Gene expression profiling (GEP) of GIST-S, GIST-R cells and two << IM >> resistant GIST patients demonstrated that [[ KIT ]] is downregulated implying a major role in IM resistance.	INDIRECT-DOWNREGULATOR	[]
Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that << KIT >> is downregulated implying a major role in [[ IM ]] resistance.	INDIRECT-DOWNREGULATOR	[]
Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel [[ c-Kit ]]/AXL kinase inhibitor.	INHIBITOR	[]
Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel c-Kit/[[ AXL ]] kinase inhibitor.	INHIBITOR	[]

Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]].

SUBSTRATE

[]

To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor [[ N(omega)-hydroxy-nor-L-arginine ]] (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).

INHIBITOR

[]

To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor N(omega)-hydroxy-nor-L-arginine ([[ Nor-NOHA ]]) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).

INHIBITOR

[]

To determine whether << arginases >> modulate the endothelial [[ NO ]] synthesis, we investigated the effects of the competitive arginase inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs).

PRODUCT-OF

[]

In unstimulated cells, << Nor-NOHA >> dose-dependently reduced the [[ arginase ]] activity with maximal inhibition at 20 microM.

INHIBITOR

[]

When HUVECs were stimulated by thrombin without extracellular L-arginine, << Nor-NOHA >> dose-dependently increased the [[ NOS ]] activity and the NO release with maximal effects at 20 microM.

ACTIVATOR

[]

Extracellular << L-arginine >> also dose-dependently increased NO release and [[ arginase ]] activity.

ACTIVATOR

[]

However, despite activation of L-arginine uptake, the inhibition of << arginase >> activity by [[ Nor-NOHA ]] was still significant.

INHIBITOR

[]

These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane.

PRODUCT-OF

[]

However, pretreatment with agents that block late I(Na), like lidocaine, mexiletine, and << RSD1235 >>, a novel mixed [[ ion channel ]] blocker for the rapid pharmacologic conversion of atrial fibrillation, significantly attenuates the prolonging effects of Class III agents or those induced by ATX-II, a specific toxin that delays Na channel inactivation and amplifies late I(Na) greatly, mimicking LQT3.

INHIBITOR

[]

The << Na channel >> block caused by [[ lidocaine ]] and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.

INHIBITOR

[]

The << Na channel >> block caused by lidocaine and [[ RSD1235 ]] can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells.

INHIBITOR

[]

Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

INHIBITOR

[]

Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

INHIBITOR

[]

Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

INHIBITOR

[]

Depletion of putrescine, spermidine, and spermine by DL-alpha-difluoromethylornithine (<< DFMO >>), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

INHIBITOR

[]

Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.

PRODUCT-OF

[]

Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity.

UPREGULATOR

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Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [[[ diethylglyoxal bis-(guanylhydrazone) ]]; DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.

INHIBITOR

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Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); [[ DEGBG ]]] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC.

INHIBITOR

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Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC.

PRODUCT-OF

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Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC.

PRODUCT-OF

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The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that << polyamines >> might be involved in the [[ caspase ]] activating signal cascade.

INDIRECT-UPREGULATOR

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On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.

DOWNREGULATOR

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On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start of<< carvedilol >> therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l.

INDIRECT-DOWNREGULATOR

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Two mechanisms of action have been identified for << A77 1726 >>: inhibition of [[ dihydroorotate dehydrogenase ]] (DHODH) and inhibition of tyrosine kinases.

INHIBITOR

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Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase ([[ DHODH ]]) and inhibition of tyrosine kinases.

INHIBITOR

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Two mechanisms of action have been identified for << A77 1726 >>: inhibition of dihydroorotate dehydrogenase (DHODH) and inhibition of [[ tyrosine kinases ]].

INHIBITOR

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<< DHODH >> inhibition occurs at lower concentrations of [[ A77 1726 ]] than that of tyrosine kinases and is currently considered the major mode of action.

INHIBITOR

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DHODH inhibition occurs at lower concentrations of << A77 1726 >> than that of [[ tyrosine kinases ]] and is currently considered the major mode of action.

INHIBITOR

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<< L-proline >> accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding [[ gamma-glutamyl kinase ]].

PRODUCT-OF

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Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.

PRODUCT-OF

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Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo.

PRODUCT-OF

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Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.

SUBSTRATE

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Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.

SUBSTRATE

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When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene.

PRODUCT-OF

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These results suggest that the altered << gamma-glutamyl kinase >> results in stabilization of the complex or has an indirect effect on gamma-glutamyl phosphate reductase activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.

PRODUCT-OF

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These results suggest that the altered gamma-glutamyl kinase results in stabilization of the complex or has an indirect effect on << gamma-glutamyl phosphate reductase >> activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae.

PRODUCT-OF

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Structural optimization of << 2,5-thiophene amides >> as highly potent and selective [[ 17β-hydroxysteroid dehydrogenase type 2 ]] inhibitors for the treatment of osteoporosis.

INHIBITOR

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We report here the optimization of << human 17β-HSD2 >> inhibitors in the [[ 2,5-thiophene amide ]] class by varying the size of the linker (n equals 0 and 2) between the amide moiety and the phenyl group.

INHIBITOR

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While none of the phenethylamides (n = 2) were active, most of the << anilides >> (n = 0) turned out to moderately or strongly inhibit [[ 17β-HSD2 ]].

INHIBITOR

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Multiple exposure to << theophylline >>, a phosphodiesterase ([[ PDE ]]) inhibitor, induces acinar hypertrophy in the salivary gland.

INHIBITOR

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Multiple exposure to << theophylline >>, a [[ phosphodiesterase ]] (PDE) inhibitor, induces acinar hypertrophy in the salivary gland.

INHIBITOR

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<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for [[ CysS ]] and PDE3A, but PDE4D gene expression was unchanged.

INDIRECT-UPREGULATOR

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<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for CysS and [[ PDE3A ]], but PDE4D gene expression was unchanged.

INDIRECT-UPREGULATOR

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Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.

AGONIST

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Terbutaline (Bricanyl) and its prodrug Bambuterol (<< Bambec >>) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.

AGONIST

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<< Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.

AGONIST

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Terbutaline (<< Bricanyl >>) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.

AGONIST

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<< (+/-)-tamsulosin >>, an [[ alpha 1A-adrenoceptor ]] antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart.

ANTAGONIST

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The influence of << (+/-)-tamsulosin >>, a selective [[ alpha 1A-adrenoceptor ]] antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium.

ANTAGONIST

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<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.

AGONIST-ACTIVATOR

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(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of << alpha 1B-adrenoceptors >> by treatment with [[ chlorethylclonidine ]], which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.

INHIBITOR

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(+/-)-Tamsulosin effectively antagonized the positive inotropic effect of << phenylephrine >> even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.

AGONIST

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<< (+/-)-Tamsulosin >> effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine.

ANTAGONIST

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<< (+/-)-Tamsulosin >>, over the range of concentrations at which it antagonized the positive inotropic effect mediated by [[ alpha 1-adrenoceptors ]], did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine.

ANTAGONIST

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These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.

AGONIST

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These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.

ANTAGONIST

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<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the [[ JAK2 ]]/STAT3 signaling pathway.

INHIBITOR

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<< Pterostilbene >> exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/[[ STAT3 ]] signaling pathway.

INHIBITOR

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Furthermore, << PTE >> treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of [[ STAT3 ]].

INDIRECT-DOWNREGULATOR

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Furthermore, << PTE >> treatment directly inhibited the phosphorylation of [[ JAK2 ]] at Tyr 1007 and the downstream activation of STAT3.

INHIBITOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, [[ Bak ]], cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic [[ Cytochrome c ]], and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved [[ Caspase3 ]]) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as [[ p21 ]] and p27.

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and [[ p27 ]].

INDIRECT-UPREGULATOR

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<< PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-DOWNREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins [[ Bcl-xL ]] and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-DOWNREGULATOR

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<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and [[ Mcl-1 ]], leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27.

INDIRECT-DOWNREGULATOR

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PTE, used in combination with a known << JAK2 >>/STAT3 inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.

INHIBITOR

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PTE, used in combination with a known JAK2/<< STAT3 >> inhibitor, [[ AG490 ]], further decreased the viability of osteosarcoma cells.

INHIBITOR

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Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the [[ JAK2 ]]/STAT3 signaling pathway.

INHIBITOR

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Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/[[ STAT3 ]] signaling pathway.

INHIBITOR

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These data suggest that inhibition of << JAK2 >>/STAT3 signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.

INHIBITOR

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These data suggest that inhibition of JAK2/<< STAT3 >> signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers.

INHIBITOR

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Furthermore, << sinapic acid >> reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of [[ type I collagen ]] mRNA and histological analysis of collagen in liver tissue.

INDIRECT-DOWNREGULATOR

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Additionally, the expression of hepatic fibrosis-related factors such as << α-smooth muscle actin >> and transforming growth factor-β1 (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].

INDIRECT-DOWNREGULATOR

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Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and << transforming growth factor-β1 >> (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].

INDIRECT-DOWNREGULATOR

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Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (<< TGF-β1 >>), were reduced in rats treated with [[ sinapic acid ]].

INDIRECT-DOWNREGULATOR

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In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells.

INDIRECT-DOWNREGULATOR

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<< Thalidomide >> inhibits growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.

INHIBITOR

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<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased [[ cytochrome c ]], but had no effect on that of COX-1, in MCF-7 and HL-60.

INDIRECT-UPREGULATOR

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<< Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.

INDIRECT-DOWNREGULATOR

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<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of [[ bcl-2 ]] protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.

INDIRECT-DOWNREGULATOR

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<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, [[ TNFalpha ]], VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.

INDIRECT-DOWNREGULATOR

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<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, [[ VEGF ]], GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60.

INDIRECT-DOWNREGULATOR

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These results demonstrated that << thalidomide >> might inhibit growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis.

INHIBITOR

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Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, [[ hemoglobin ]], packed cell volume, platelets, mean corpuscular volume, and mean corpuscular hemoglobin in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.

INDIRECT-UPREGULATOR

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Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular [[ hemoglobin ]] in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h.

INDIRECT-UPREGULATOR

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Gene expression profiling (GEP) of GIST-S, GIST-R cells and two << IM >> resistant GIST patients demonstrated that [[ KIT ]] is downregulated implying a major role in IM resistance.

INDIRECT-DOWNREGULATOR

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Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that << KIT >> is downregulated implying a major role in [[ IM ]] resistance.

INDIRECT-DOWNREGULATOR

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Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel [[ c-Kit ]]/AXL kinase inhibitor.

INHIBITOR

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Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to << MP470 >>, a novel c-Kit/[[ AXL ]] kinase inhibitor.

INHIBITOR

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