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Background: Oxidative stress is crucial for the development of ionizing radiation-induced intestinal injuries and inflammation. Taurine is a sulfur-containing amino acid distributed in tissues and organs throughout the body. It possesses several important physiological functions, including anti-oxidative activity and anti-inflammatory effects. Aims: To investigate the therapeutic effect and underlying mechanism of taurine against radiation-induced intestinal injuries. Methods: CCK-8 assay and DCFH-DA, a fluorescence probe of intracellular reactive oxygen species (ROS) were applied to determine the effects of taurine on radiation-induced inhibition of cell viability and ROS accumulation in human intestinal epithelial cell line HIEC-6. The modulatory effects of taurine on expressions of oxidative stress-related genes in intestinal cells after exposure to radiation were measured by real-time PCR in in vitro and in vivo studies. The roles of taurine in maintenance of intestinal morphology and suppression of cell apoptosis in mice receiving whole body radiation were assessed by HE staining and TUNEL staining. Results: In in vitro study, taurine improved the radiation-induced inhibition of cell viability and reduced intracellular ROS accumulation in HIEC-6 cells. The expression levels of catalase (CAT) and glutathione peroxidase 1 (GPx1) in HIEC-6 cells were up-regulated by taurine treatment. In vivo study showed that taurine activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway, alleviated intestinal villi disorganization and loss of crypt cells, and suppressed cell apoptosis in mice after radiation. Conclusions: Taurine can reduce the intracellular ROS accumulation via activating Nrf2/HO-1 antioxidant signaling pathway, and thereby, exerts protective effect against radiation-induced intestinal injuries. It might be a candidate for treatment of intestinal injuries in patients undergoing radiotherapy.
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Background: Studies showed that aberrant activation of JAK/STAT3 signaling pathway promoted the tumorigenesis and progression of hepatocellular carcinoma (HCC), and transforming growth factor-β1 (TGF-β1) has either tumor-suppressing or tumor-promoting effect in regulation of tumor progression.Aims: To investigate the effect of specific inhibition of JAK/STAT3 signaling pathway on HCC and whether TGF-β1 signaling pathway is involved in this process or not.Methods: Thirty Wistar rats were randomly divided into three groups: control group, HCC group, and HCC+AG490 group.In the latter two groups, diethylnitrosamine was administered in drinking water to induce HCC model, and in HCC+AG490 group, AG490, a specific inhibitor of JAK was injected intraperitoneally in the first week of model establishment.At the end of the 16th week, all rats were sacrificed.The maximum diameter of tumor nodules in the liver was recorded and the number of tumors with maximum diameter greater than 1 cm was counted.Expression and distribution of STAT3 and TGF-β1 in liver tissue were determined by real-time PCR, immunohistochemistry, and immunofluorescence.Results: Compared with the control group, expressions of STAT3 and TGF-β1 mRNA in liver tissue were significantly increased in HCC group (P<0.05).Phosphorylated STAT3 (p-STAT3) and TGF-β1 proteins were absent in liver tissue in control group, and both were up-regulated and co-expressed in HCC group.While in HCC+AG490 group, expressions of STAT3 and TGF-β1 mRNA were significantly lower than those in HCC group (P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-β1 proteins, and the number of tumor nodules greater than 1 cm and the maximum diameter were markedly reduced when compared with the HCC group [1.20±1.03 and (1.14±0.18) cm vs.4.30±1.06 and (1.78±0.27) cm, P all<0.05].Conclusions: Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-β1 signaling pathway.
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Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their own features and become mesenchymal cells, and more and more studies have shown that EMT plays an important role in the invasion and metastasis of hepatocellular carcinoma (HCC). This article reviews the signaling pathways involved in the progression of HCC and molecules involved in the regulation of EMT, in order to provide a new direction for the treatment of HCC.
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ObjectiveTo investigate the risk genes for predicting the development of chronic hepatitis B (CHB) cirrhosis using gene chip technology. MethodsA total of 40 CHB patients who visited Shanghai First People′s Hospital from April 2008 to December 2010 were enrolled as a clinical cohort and were divided into S0, S1, S2, S3, and S4 groups, with 8 patients in each group. Liver biopsy was performed to determine fibrosis stage with the Scheuer pathological score as the criteria, and clinical data and liver tissue samples were reserved. The Human Affymetrix GeneChip was used to establish the gene expression profiles of liver tissues in CHB patients, and the significance analysis of microarrays (SAM) and prediction analysis of microarrays (PAM) were used to screen out the risk genomes for predicting the development of CHB cirrhosis. Quantitative real-time PCR was used to measure the mRNA expression of risk genes in liver tissue. The chi-square test was used for comparison of categorical data. The t-test and a one-way analysis of variance were used for comparison of normally distributed continuous data, and SNK-q test was used for further comparison between any two groups; the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data. ResultsA total of 1674 differentially expressed genes were screened out by Affymetrix GeneChip. A cluster analysis of these genes showed that gene expression showed differences between groups with different fibrosis stages, which suggested that the gene expression profile was well consistent with fibrosis stage. Four different classification methods were used for analysis, and 87 significant genes were screened out by SAM and 14 “high-risk” genes were screened out by PAM. The quantitative real-time PCR showed the expression of 6 risk genes (CD24, CXCL6, EHF, ITGBL1, LUM, and SOX9) differed significantly between groups S0, S1-3, and S4 (P＜0.05), and the S1-3 and S4 groups showed significantly upregulated expression of these genes compared with the S0 group (all P＜0.05). ConclusionThe 6 high-risk factors screened out and verified by gene chip technology help to predict the probability of developing liver cirrhosis in CHB patients and can be used as the diagnostic genes for predicting hepatitis B cirrhosis.
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Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.
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Atherosclerosis (AS) is pathologically important basis of many kinds of coronary atherosclerosis disease (CAD). It can be substantially protected by raising high-density lipoprotein (HDL).In view of mechanism, drugs for raising HDL include: cholesterol ester transfer protein inhibitors, peroxisomal proliferator-activated receptor agonists, liver X-activated receptor agonists, farnesoid X receptor antagonists or agonists, lipoprotein lipase activators, niacin, and phenytoin and lecin : cholesterol acyltransferase activators, etc. This review aimed to the progress of drugs for regulating high-density lipoprotein and their mechanism, in view of clinical and preclinical aspects.