Study on expression of ASC and Caspase-1 in peripheral blood of patients with primary biliary cirrhosis / 重庆医学

Objective To explore the influence of apoptosis-associated speck-like protein containing a caspase recruitment do-main(ASC)and Caspase-1 on the pathogenesis of primary biliary cirrhosis(PBC).Methods The real-time PCR,Western blot,py-rophosphate sequencing and ELISA were adopted to respectively detect the relative expressions of mRNA and protein of peripheral blood mononuclear cells(PBMS)Caspase-1 and ASC as well as the methylation status of ASC promoter region and plasma Caspase-1 and IL-18 expression levels in 30 cases of PBC and healthy controls.Results The mRNA and protein expressions of PBMC Caspase-1 and ASC in the PBC group were significantly higher than those in the control group(P<0.05).The methylation rate of ASC promoter Island1(ISI)was significantly lower than that of the control group(P<0.05),which of Island 2(IS2)was smaller than the background value and had no methylation occurrence.The levels of plasma Caspase-1 and IL-18 in the PBC group were sig-nificantly higher than those in the control group(P<0.05).The ASC mRNA in the PBC group was significantly correlated with the Caspase-1 mRNA expression(P<0.05);the methylation rates at loci 1,2,4,5 of ASC promoter region CpG island were nega-tively correlated with ASC mRNA expression(P< 0.05),and which at loci 3,6 had no correlation with their expressions(P>0.05);plasma Caspase-1 and IL-18 levels showed the obviously positive correlation.Conclusion ASC and Caspase-1 are involved in the immune inflammatory response in PBC.

Correlation analysis of NF-κB signaling pathway activated by IL-18 in CD4+ T cells and the pathogenesis of PBC / 重庆医学

Objective To explore the correlation between NF-κB signaling pathways activated by IL-18 in CD4+ T cells and the pathogenesis of PBC.Methods We detected the expression of IL-18 mRNA in PBMCs,IL-18 level in plasma,receptor IL-18R on surface of CD4+ T cell,proliferation rate of CD4+T cell and its NF-κB signaling pathway protein IκBα and NF-κB p65 by qRT-PCR,ELISA,flow cytometry,MACS and Western blot on 32 cases of patients with PBC (PBC group) and 32 healthy people (control group) in Guizhou provincial people′s hospital.Results The level of IL-18 in PBC group was significantly higher than that in control group (P<0.05).The relative expression of IL-18 mRNA in PBC group was significantly higher than that in control group (P<0.05).The percentage of CD4+T cells expressing IL-18Rα in PBC group was higher than that in control group (P<0.05).The proliferation rate of CD4+T cells stimulated by IL-18 in PBC group was significantly higher than that in healthy control group (P<0.01).The relative expression levels of NF-κB p65 protein were up-regulated in IL-18,and the expression of IκBα protein in each group was significantly increased,especially in PBC group (P<0.01).Conclusion IL-18 can activate NF-κB signal pathway in CD4+ T cells and participate in the pathogenesis of primary biliary cirrhosis.

Discussion on the relationship between H-type hypertension and left ventricular remodeling / 天津医药

Objective To investigate the effects of homocysteinemia (HHcy) and hypertension on left ventricular re?modeling. Methods A total of 275 patients with coronary heart disease were divided into four groups including H-type hy? pertension group (n=96), non-H-type hypertension group (n=44), HHcy+non-hypertension group (n=53) and control group (n=65) based on their blood pression levels and plasma HHcy levels. The serum levels of glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) were compared between groups. The left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT), ventricular septal thickness (IVST) and left ventricular mass index (LVMI) were observed in four groups. The proportion of patients with left ventricular remodeling was also compared between four groups. The influence fac?tors of left ventricular remodeling were analysed. Results There were no significant differences in biochemical parameters except Hcy level between frour groups. The values of LVMI, left ventricular wall thickness and the proportion of patients with left ventricular remodeling were significantly higher in H-type hypertension group than those of other three groups ( P<0.05). The Hcy level was positively correlated with LVMI and left ventricular wall thickness. Logistic regression analysis showed that HHcy and hypertension were the risk factors of left ventricular remodeling (OR=7.443, 7.754 and 9.948,P<0.05). The risk factors of left ventricular remodeling were higher in patients with both HHcy and hypertension than those in patients with HHcy or hypertension. Conclusion Homocysteine and higher systolic pressure are independent risk factors for left ventricular remodeling and they have a synergistic effect on leading to left ventricular remodeling.

HER-2 promotes breast cancer cell epithelial-mesenchymal transition by regulating ZEB1 / 中国癌症杂志

Background and purpose:Human epidermal growth factor receptor-2 (HER-2), a member of epidermal growth factor receptor family, initiates a diverse set of signaling pathways that ultimately affect such fun-damental processes as cell proliferation, cell motility and cell apoptosis. It is reported that HER-2 was associated with epithelial-mesenchymal transition (EMT) process. However, the mechanism needs further investigation. The purpose of this study was to investigate the mechanism of HER-2 on regulating EMT process.Methods:Transwell assay was used to determine the motility of breast cancer cells; Real-time lfuorescence quantitative polymerase chain reaction (RT-FQ-PCR) was employed to determine the expression of genes of interest, and reactive oxygen species production was measured by reactive oxygen species detection kit.Results:HER-2 overexpression in breast cancer cells could promote cell migration and invasion. Mechanistic study showed that HER-2 overexpression could upregulate ZEB1 expression. ZEB1 silencing by siRNA reduced cell motility of HER-2-overexpressing breast cancer cells. Furthermore, reactive oxygen species produced in HER-2-overexpressing breast cancer cells were less than those produced in corresponding control cells.Conclusion:Our study demonstrated that HER-2 overexpression endowed breast cancer cells with EMT related properties by upregulating ZEB1 expression. ZEB1 could be a candidate target for further study of the relation-ship between HER-2 and EMT.