Abstract:
:Hyperactivated macrophages play a key role in the initiation and perpetuation of mucosal inflammation in Crohn's disease (CD). Increasing evidence suggests that the basic helix-loop-helix (bHLH) repressor Twist1 can suppress activation of nuclear factor-κB (NF-κB) and the subsequent production of TNF-α, which are both essential elements of macrophage activation. Thus, developing novel therapeutic strategies to enhance Twist1 expression and to inhibit macrophage activation may be beneficial for CD treatment. In the present study, a series of trifluoroethyl thiazolo[3,2-b][1,2,4]triazole derivatives were used to investigate their potential anti-inflammatory activities and the underlying mechanism. In a biological activity screen, compound 7# (Thiazolo[3,2-b][1,2,4]triazole-5-methanamine, 6-phenyl-α-(trifluoromethyl)-, (αR)-, TT-TFM) suppressed the activation of macrophages. Consistent with the in vitro data, TT-TFM protected against 2,4,6-trinitrobenzene sulfonic acid (TNBS), dextran sulfate sodium (DSS)-induced acute colitis and IL-10 knockout (KO) chronic colitis, as judged by body weight changes and colonic pathological damage. A mechanistic study based on microarray analysis and gene interference experiments indicated that TT-TFM exerted anti-inflammatory effects by enhancing Twist1 expression and subsequently blocking the NF-κB/TNF-α pathway. In addition, pretreatment with lentiviruses encoding shRNA targeting Twist1 could abolish the therapeutic effect of TT-TFM in TNBS colitis. Ultimately, TT-TFM showed anti-colitis activity by reducing NF-κB activation and the TNF-α level by promoting Twist1 expression; thus, TT-TFM may offer a therapeutic strategy for CD patients.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Tu T,Yu M,Zhang Y,Shi X,Xu J,Hu J,Gan J,He W,Dong L,Han J,Huang Z,Pan Y,Zhang Jdoi
10.1016/j.bcp.2018.07.020subject
Has Abstractpub_date
2018-09-01 00:00:00pages
275-287eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30288-0journal_volume
155pub_type
杂志文章abstract::The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was re...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90341-0
更新日期:1982-03-15 00:00:00
abstract::Stroke is a neurological condition and may cause changes in hepatic drug-metabolizing enzymes. Hepatic CYP2B is involved in the metabolism of a variety of centrally active substances. The purpose of this study was to investigate the possible down-regulation mechanism of hepatic CYP2B after acute stroke. Using a rat mo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.12.011
更新日期:2014-02-15 00:00:00
abstract::The biotransformation and the hepato- and nephrotoxicity of the mercapturic acids (N-acetyl-1-cysteine S-conjugates) of three structurally related 2,2-difluoroethylenes were investigated in vivo in the rat. All mercapturic acids appeared to cause nephrotoxicity, without any measureable effect on the liver. The mercapt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90665-x
更新日期:1988-12-01 00:00:00
abstract::The structure and membrane interactions of lipophilic glucosyl phosphotriester derivatives of thymidine and 5-fluoro-deoxy thymidine are investigated by NMR spectroscopy. The self-association of these molecules, found in different solvents, presents a diastereoisomeric effect which is also observed in the transmembran...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90108-w
更新日期:1990-06-01 00:00:00
abstract::To test the association between flavin-containing monooxygenases (FMOs) and osmoregulation, saltwater-adapted euryhaline flounder (Platichthys flesus) were statically exposed to 34 (ambient), 25, and 15 parts per thousand (/1000) salinity for 1 or 2 weeks. FMO activity (thiourea S-oxidase) was assayed in gill and live...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00358-9
更新日期:1996-09-13 00:00:00
abstract::BAY X 1005 ((R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid) has been demonstrated to be a potent inhibitor of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) synthesis in various in vitro systems. Using mainly human polymorphonuclear leukocytes (PMNL) this study elucidates the mech...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90382-7
更新日期:1993-01-07 00:00:00
abstract::Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90158-7
更新日期:1982-02-15 00:00:00
abstract::Administration of pentylenetetrazol (PTZ) (60 mg/kg, s.c.) to normal or carbaryl (200 mg/kg, p.o.) treated adult male albino rats produced characteristic changes in the steady-state levels of striatal dopamine (DA), noradrenaline (NA) and homovanillic acid (HVA) at different time intervals (0.5, 1.0 and 2.0 hr). The e...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90189-3
更新日期:1985-02-15 00:00:00
abstract::Rat brain P2Y(1) (rP2Y(1)) receptor-transfected human embryonic kidney cells (HEK 293) were recently shown to have enhanced reactivity to both ATP and ADP (Vöhringer C, Schäfer R, Reiser G. Biochem Pharmacol 2000;59:791-800). Here, we demonstrated the usefulness of this cell line as a system for further studying novel...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00593-7
更新日期:2001-05-15 00:00:00
abstract::These in vitro studies indicate that N-oxidation of N-hydroxyamphetamine (NOHA) by rat liver homogenates yields phenylacetone oxime (PAOx) as the major metabolite. This oxidation was NADPH and oxygen dependent but was not appreciably increased in microsomes from phenobarbital-pretreated animals. The addition to micros...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90244-1
更新日期:1982-01-01 00:00:00
abstract::The relationship between DNA crosslinks and cell death as a result of exposure to melphalan (MLN) was studied in the F1 variant of B16 melanoma cells. The formation of DNA crosslinks is believed to represent the lethal lesion following exposure of cells to bifunctional alkylating agents. The production of DNA crosslin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90319-x
更新日期:1988-08-15 00:00:00
abstract::During receptor-mediated endocytosis (RME), extracellular molecules are internalized after being recognized and bound to specific cell surface receptors. In previous studies of the asialoglycoprotein receptor (ASGPR) in rats, we showed that ethanol impairs RME at multiple ASGPR sites. Ethanol administration has been s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01555-1
更新日期:2003-02-15 00:00:00
abstract::Innovative crystallographic techniques have resulted in an exponential growth in the number of solved G-protein coupled receptor (GPCR) structures and a better understanding of the mechanisms of class A receptor activation and G protein binding. The recent release of the type 1 receptor for the corticotropin-releasing...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.05.015
更新日期:2015-08-01 00:00:00
abstract::The bactericidal effect of metronidazole on Escherichia coli and Bacteroides fragilis can be partially reversed by cysteamine under conditions that lead to the formation of an adduct, the thioether, 4-(2-aminoethyl)thio-2-methylimidazole-1-ethanol (4-ATME). This adduct, which is not mutagenic for the Ames histidine au...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90196-x
更新日期:1983-11-01 00:00:00
abstract::It was shown recently that the antiaggregating agent ticlopidine and some of its analogues inhibit the energy-conserving mechanism in mitochondria [Abou-Khalil et al., Biochem. Pharmac. 33, 3893 (1984)]. In the present investigation, the mechanism of inhibition by these drugs was investigated by studying their effects...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90303-5
更新日期:1986-06-01 00:00:00
abstract::7-Ketocholesterol (7-KC) is found at an elevated level in patients with cancer and chronic liver disease. The up-regulation of an efflux pump, P-glycoprotein (P-gp) leads to drug resistance. To elucidate the effect of 7-KC on P-gp, P-gp function and expression were investigated in hepatoma cell lines Huh-7 and HepG2 a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.06.006
更新日期:2013-08-15 00:00:00
abstract::The aim of this study was to find the peptide ligands to inhibit Candida albicans secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300 different peptides, was constructed, and their interaction with Sap2 was separately calculated by molecular dynamic software. Second, 10 peptide ligands with ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.05.020
更新日期:2014-08-15 00:00:00
abstract::We have shown previously that Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, A(II)) inhibits human breast cancer cell proliferation regardless of estrogen receptor status or estrogen sensitivity, and that its cellular targets include microtubules. In the present study, we investigated the apoptosis-inducin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00289-5
更新日期:1999-01-01 00:00:00
abstract::We have examined chromosome damage caused by a wide range of bleomycin (BLM) concentrations in Chinese hamster ovary (CHO-K1) cells reversibly porated by the bacterial cytotoxin streptolysin-O (SLO). Chromosome damage was measured using the micronucleus cytokinesis block technique (employing cytochalasin-B). Treatment...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90128-j
更新日期:1993-02-09 00:00:00
abstract::Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; M...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.02.023
更新日期:2018-04-01 00:00:00
abstract::An intestinal active transport system specific to small peptides and peptide-like drugs such as beta-lactam antibiotics was functionally expressed in Xenopus laevis oocytes after microinjection of messenger RNA (mRNA) derived from rat intestinal mucosal cells. The transport activity was evaluated by measuring the upta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90358-1
更新日期:1994-08-30 00:00:00
abstract::Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are local...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.06.030
更新日期:2013-09-15 00:00:00
abstract::Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regula...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90385-1
更新日期:1988-10-01 00:00:00
abstract::A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90562-y
更新日期:1990-08-01 00:00:00
abstract::Amodiaquine, a 4-aminoquinoline antimalarial, has been associated with hepatitis and agranulocytosis in humans. Drug hypersensitivity reactions, especially agranulocytosis, have been attributed to reactive intermediates generated by the oxidants discharged from stimulated polymorphonuclear leucocytes (PMN). The metabo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00236-s
更新日期:1995-09-28 00:00:00
abstract::To provide a background for future studies on neurodegenerative changes in the spinal cord, the present study analysed the distribution of the activity of methionine adenosyltransferase (ATP:L-methionine S-adenosyltransferase, EC 2.5.1.6, MAT), an enzyme that catalyses the synthesis of the biological methyl group dono...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00316-6
更新日期:2000-08-01 00:00:00
abstract::The reduction of penicillamine disulfide by reductants in aqueous solutions has been studied and compared with that for captopril disulfide. Whereas near quantitative reduction for captopril disulfide was achieved with tributyl phosphine (200 mM), no detectable penicillamine was formed from penicillamine disulfide. Th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90070-0
更新日期:1987-04-15 00:00:00
abstract::Isothiazole dioxides have been shown to inhibit Trypanosoma brucei protein farnesyltransferase (PFTase) in isolated enzyme, but elicited only a minor effect on mammalian PFTase. In the present study we have evaluated the effect of 3-diethylamino-4-(4-methoxyphenyl)-isothiazole 1,1-dioxides with different substituents ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.09.022
更新日期:2005-12-05 00:00:00
abstract::On the basis of previous electrophysiological studies, it has been proposed that there are three main classes of excitatory amino acid receptor in the mammalian central nervous system, which are activated preferentially by kainic acid, quisqualic acid and N-methyl-D-aspartate respectively. Although the pharmacology of...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90213-3
更新日期:1986-02-01 00:00:00
abstract::Interleukin (IL)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. IL-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. UTTR1147A is a recombinant fusion prot...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.03.031
更新日期:2018-06-01 00:00:00