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CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes.
Publication Year: Unknown Source: The Journal of clinical investigation PMID: 12697733
Azathioprine and its metabolite 6-mercaptopurine (6-MP) are immunosuppressive drugs that are used in organ transplantation and autoimmune and chronic inflammatory diseases such as Crohn disease. However, their molecular mechanism of action is unknown. In the present study, we have identified a unique and unexpected role for azathioprine and its metabolites …
NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population.
Publication Year: Unknown Source: Alimentary pharmacology & therapeutics PMID: 12823148
BACKGROUND: Crohn's disease affects people world-wide, but the incidence in Asia is lower than in Western countries. This difference may be due to genetic and/or environmental factors. Three single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene have been identified to be independently associated with the development of Crohn's disease in …
Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.
Publication Year: Unknown Source: Alimentary pharmacology & therapeutics PMID: 12950415
A series of epidemiological, experimental and preliminary clinical trials strongly suggest that mesalazine or 5-aminosalicyclic acid (5-ASA) may have antineoplastic and potentially prophylactic chemopreventive properties. It is assumed that mesalazine may have similar genetic and molecular targets as nonsteroidal anti-inflammatory drugs (NSAIDs), which is further supported by its close similarity …
Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse.
Publication Year: Unknown Source: Molecular genetics and metabolism PMID: 11914033
We hypothesized that liver fatty acid oxidation (FAO) is compromised in the leptin-deficient obese (Lep(ob)/Lep(ob)) mouse model, and that this would be further challenged when these mice were fed a high-fat diet. Obese mice had a 3.8-fold increased body fat content and a 9-fold increased liver fat content as compared …
Lack of common NOD2 variants in Japanese patients with Crohn's disease.
Publication Year: Unknown Source: Gastroenterology PMID: 12105836
BACKGROUND & AIMS: Previous studies have linked Crohn's disease (CD) to the pericentromeric region of chromosome 16 (IBD1). Three independent studies of Western populations have recently shown that 3 variants of NOD2, a gene located at 16q12, are associated with susceptibility to CD. Here, we have evaluated the 3 NOD2 …
Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.
Publication Year: Unknown Source: The Journal of clinical investigation PMID: 15199412
PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePten(flox/flox) mice). AlbCrePten(flox/flox) mice showed massive hepatomegaly and steatohepatitis with triglyceride …
Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin.
Publication Year: Unknown Source: American journal of physiology. Gastrointestinal and liver physiology PMID: 15256362
Obesity and type 2 diabetes are associated with nonalcoholic steatohepatitis (NASH), but an obese/diabetic animal model that mimics human NASH remains undefined. We examined the induction of steatohepatitis and liver fibrosis in obese and type 2 diabetic db/db mice in a nutritional model of NASH and determined the relationship of …
Fat-loaded HepG2 spheroids exhibit enhanced protection from Pro-oxidant and cytokine induced damage.
Publication Year: Unknown Source: Journal of cellular biochemistry PMID: 17211854
The mechanisms by which steatosis renders hepatocytes susceptible to damage in non-alcoholic steatohepatitis (NASH) are unclear although fat accumulation is believed to increase hepatocyte susceptibility to inflammatory cytokines and oxidative stress. We therefore investigated the susceptibility of steatotic, hepatocyte-derived cells to TNFalpha and the pro-oxidant, t-butylhydroperoxide (TBH). HepG2 spheroids rendered …
Liver fibrosis in vitro: cell culture models and precision-cut liver slices.
Publication Year: Unknown Source: Toxicology in vitro : an international journal published in association with BIBRA PMID: 17289342
Chronic liver injury of various etiologies can cause liver fibrosis, which is characterized by the progressive accumulation of connective tissue in the liver. As no effective treatment for liver fibrosis is available yet, extensive research is ongoing to further study the mechanisms underlying the development of disease- or toxicity-induced liver …
A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.
Publication Year: Unknown Source: Science (New York, N.Y.) PMID: 17068223
The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene …
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