CSS-LM

1
[{"sentiment": "PRODUCT-OF", "sentence": "Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer.", "aspect": "chemprot"}, {"sentiment": "PRODUCT-OF", "sentence": "In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the tetrahydrobiopterin ([[ BH4 ]]), the obligate cofactor for TPH.", "aspect": "chemprot"}, {"sentiment": "PRODUCT-OF", "sentence": "<< Cyclooxygenase(COX)-2 >>-derived [[ prostanoids ]] can influence several processes that are linked to carcinogenesis.", "aspect": "chemprot"}, {"sentiment": "PRODUCT-OF", "sentence": "Consistent with these results, the translocation of cPLA2 protein as well as the release of << arachidonic acid >>, a principal product of [[ phospholipase A2 ]], was rapidly induced by the addition of C2-ceramide in a Rac-dependent manner.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "Furthermore, << substance P >> (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "Improvements from baseline in mean << glycosylated haemoglobin >> (HbA(1c)) were significantly greater with [[ sitagliptin ]] monotherapy than with placebo in patients with type 2 diabetes.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "The << hemoglobin A1c >> (HbA1c) of all patients improved significantly from 8.1\u00b11.2% to 7.6\u00b11.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3\u00b115.8 U/day to 24.5\u00b116.5 U/day (p<0.001).", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing [[ Bim ]] expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "<< Statins >> increase [[ p21 ]] through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-UPREGULATOR", "sentence": "Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing [[ K18 ]] as well as an increase in the abundance of K18 mRNA.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of << phenformin >> on [[ complex I ]] respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Methods: Stabilized anaplastic thyroid cancer cell lines (BHT-101 and CAL-62) and primary cultures from patients who underwent thyroidectomy for anaplastic thyroid cancer were treated with the << histone deacetylase >> inhibitor [[ LBH589 ]].", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) << CaMPDE >> isozymes are inhibited by [[ felodipine ]] and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Rasagiline [N-propargyl-1R(+)-aminoindan; << TVP1012 >>] is a potent irreversible monoamine oxidase ([[ MAO ]]) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "<< TZDs >> also inhibited [[ alkaline phosphatase ]] activity (58-75%, p<0.046) and osteocalcin production (52-75%, p<0.031).", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Sodium salicylate and << aspirin >> also inhibited [[ NF-kappa B ]]-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Acetylcholinesterase (<< AChE >>) inhibited by the organophosphate [[ soman ]] (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Effects of inhibition of urokinase-type plasminogen activator (<< u-PA >>) by [[ amiloride ]] in the cornea and tear fluid of eyes irradiated with UVB.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Structural optimization of << 2,5-thiophene amides >> as highly potent and selective [[ 17\u03b2-hydroxysteroid dehydrogenase type 2 ]] inhibitors for the treatment of osteoporosis.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Effects of << felodipine >> (a dihydropyridine [[ calcium channel ]] blocker) and analogues on calmodulin-dependent enzymes.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "<< Rasagiline >> [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible [[ monoamine oxidase ]] (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "The potential for << ketoconazole >>, the archetypal strong inhibitor of [[ CYP3A4 ]], to alter the pharmacokinetic profile of ambrisentan and its oxidative metabolite, 4-hydroxymethyl ambrisentan, was assessed in an open-label, nonrandomized, 2-period, single-sequence study in 16 healthy men.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether << TZD >> inhibition of [[ aromatase ]] plays a role in their effects on bone metabolism.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only << PI3K >> vascular-targeted PI3K inhibitor prodrug, [[ SF1126 ]], which has now completed Phase I clinical trials.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2).", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Isometric contraction induced by a submaximal concentration of << Ang II >> (10(-7) mol/L) was reduced in a dose-dependent way by [[ torasemide ]] (IC(50)=0.5+/-0.04 micromol/L).", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific << renin >>-angiotensin-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Nitrogen-containing bisphosphonates (N-<< BPs >>) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]].", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Indomethacin abolished the inhibitory effect of << acetazolamide >> on CA I and [[ CA II ]].", "aspect": "chemprot"}, {"sentiment": "INHIBITOR", "sentence": "Activating glucocorticoid receptor-ERK signaling pathway contributes to << ginsenoside Rg1 >> protection against [[ \u03b2-amyloid peptide ]]-induced human endothelial cells apoptosis.", "aspect": "chemprot"}, {"sentiment": "UPREGULATOR", "sentence": "CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "aspect": "chemprot"}, {"sentiment": "UPREGULATOR", "sentence": "Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity.", "aspect": "chemprot"}, {"sentiment": "AGONIST", "sentence": "Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity.", "aspect": "chemprot"}, {"sentiment": "AGONIST", "sentence": "METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, << dexmedetomidine >>, were determined in mice deficient in [[ alpha2-receptor ]] subtypes.", "aspect": "chemprot"}, {"sentiment": "AGONIST", "sentence": "This inhibition was blocked when mice were pretreated with the selective << H3R >> agonist [[ R-(alpha)-methyl-histamine ]] (10\u00a0mg/kg).", "aspect": "chemprot"}, {"sentiment": "DOWNREGULATOR", "sentence": "The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]].", "aspect": "chemprot"}, {"sentiment": "DOWNREGULATOR", "sentence": "<< HSYA >> treatment also decreased NF-\u03baB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).", "aspect": "chemprot"}, {"sentiment": "DOWNREGULATOR", "sentence": "Expression of the dominant negative mutants rab5A-N133I or << rab7 >>-N125I blunted [[ U50,488H ]]-induced down-regulation.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "4.\u2002 At a substrate concentration of 20\u2009\u00b5M, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by [[ UGT1A6 ]] >UGT1A7 >UGT2A1, whereas at 300\u2009\u00b5M UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "The ratio between the << GDC >>/SHMT and C1-THF synthase/SHMT pathways of Ser synthesis from [[ [alpha-(13)C]Gly ]] and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, << EC 2.1.1.10 >>) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "Uptake of the radiolabeled model substrates estradiol 17\u03b2-glucuronide, estrone 3-sulfate, and dehydroepiandrosterone sulfate (<< DHEAS >>) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA).", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "<< zRetSat A >> also saturated the 13-14 or 7-8 double bonds of all-trans-3,4-didehydroretinol ([[ vitamin A2 ]]), a second endogenous form of vitamin A in zebrafish.", "aspect": "chemprot"}, {"sentiment": "SUBSTRATE", "sentence": "However, the loss of proliferative capacity of << hGSTA4 >> cells challenged with levels of [[ 4-HNE ]] associated with severe oxidative stress indicates a role of other aldehyde metabolizing enzymes, and/or GSH-electrophile transporter proteins, in providing full cellular protection against 4-HNE toxicity.", "aspect": "chemprot"}, {"sentiment": "ACTIVATOR", "sentence": "Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments.", "aspect": "chemprot"}, {"sentiment": "ACTIVATOR", "sentence": "These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that << phillyrin >> is a novel [[ AMPK ]] activator with a role in the prevention and treatment of obesity.", "aspect": "chemprot"}, {"sentiment": "ACTIVATOR", "sentence": "Recently, it has been shown that the activation of particular << T2R >> bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and [[ acesulfame-K ]].", "aspect": "chemprot"}, {"sentiment": "ACTIVATOR", "sentence": "<< DBDCT >> also caused the phosphorylation of JNK and [[ p38 ]](MAPK).", "aspect": "chemprot"}, {"sentiment": "ACTIVATOR", "sentence": "In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and << cytochrome P450 >>, compared to the [[ CCl4 ]] only group.", "aspect": "chemprot"}, {"sentiment": "AGONIST-ACTIVATOR", "sentence": "The results suggested that both the EtOAc extract and berberine were able to activate << PPAR\u03b1/\u03b2/\u03b3 >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].", "aspect": "chemprot"}, {"sentiment": "ANTAGONIST", "sentence": "Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.", "aspect": "chemprot"}, {"sentiment": "ANTAGONIST", "sentence": "The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect.", "aspect": "chemprot"}, {"sentiment": "ANTAGONIST", "sentence": "Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists.", "aspect": "chemprot"}, {"sentiment": "ANTAGONIST", "sentence": "EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "In all patients << loperamide >> induced a significant fall in plasma [[ ACTH ]] levels.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "There was no significant difference in TLR4, NF-\u03baB, and << IL-27 >> mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "The present studies were undertaken to determine whether stable analogues of << prostacyclin >>, a potent endothelium-derived platelet inhibitor and vasodilator, could inhibit [[ tissue factor ]] expression by human monocytic cells.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNF\u03b1, IL-1\u03b2 and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-\u03baB mRNA, IL-27 mRNA, [[ TLR4 ]] protein, NF-\u03baB p65 protein, and IL-27 p28 protein (p < 0.05).", "aspect": "chemprot"}, {"sentiment": "INDIRECT-DOWNREGULATOR", "sentence": "In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator [[ tumour necrosis factor-\u03b1 ]] (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells.", "aspect": "chemprot"}]