ABSTRACT
Objective:To investigate the association of nonalcoholic fatty liver disease (NAFLD) and obesity with risk of atherosclerotic cardiovascular disease (ASCVD).Methods:A total of 1 486 individuals, including 1 051 males and 635 women aged (56.0±9.0) years, who underwent health check-up at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from January 2020 to November 2021 were enrolled. The participants were divided into non-NAFLD group ( n=564), NAFLD without obesity group ( n=689), and NAFLD with obesity group ( n=233) according to the presence of NAFLD and body mass index. The general information, smoking history, alcohol consumption, medical history and results of physical examination, laboratory tests and liver ultrasound of participants were collected from the electronic medical record system. Body mass index≥28.0 kg/m 2 was defined as obesity, fatty liver was diagnosed by ultrasonography, and ASCVD risk was assessed according to the criteria of the Chinese guideline on the primary prevention of cardiovascular diseases( 2020). Multivariate logistic regression model was used to analyse the relationship of NAFLD and obesity with risk of ASCVD. Results:The proportions of individuals at high risk for ASCVD in the non-NAFLD group, the NAFLD without obesity group and the NAFLD with obesity group were 27.5%(155/564), 50.1%(345/689) and 61.8%(144/233), respectively, and the proportions of individuals at high ASCVD risk in the NAFLD without obesity group and the NAFLD with obesity group were higher than that in the non-NAFLD group (all P<0.05), and the proportion in the NAFLD with obesity group was higher than the NAFLD without obesity group ( P<0.05). Multivariate logistic regression analysis showed that NAFLD was significantly associated with a higher risk of ASCVD after correction for sex, alcohol consumption and alanine aminotransferase, and the association was stronger in the NAFLD with obesity, and the results were unchanged after further correction for uric acid, fasting glucose and systolic blood pressure (all P<0.001). Conclusion:NAFLD is strongly associated with the risk of ASCVD with or without obesity, and obesity may strengthen this association.
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Objective To investigate the protective mechanism of MEK1/2 inhibitor PD98059 on ox-LDL induced injury of human umbilical vein endothelial cells (HUVEC),and its influence on the expression of LOX-1.Methods HUVEC damage models were established by using ox-LDL and were treated with PD98059 later,divided into the negative control group,the ox-LDL group,the positive control group and the PD98059+ox-LDL group.The effect of inhibition of MEK1/2 on ox-LDL induced HUVEC damage was measured.Results Compared with the negative control group,the levels in the ox-LDL group of LOX-1,pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were increased significantly,the proliferations of HUVEC and the productions of NO were decreased (P＜0.05).Compared with the ox-LDL group,the levels in the positive control group and the PD98059+ox-LDL group of pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were decreased,the proliferation of HUVEC and the production of NO were increased (P＜0.05).Conclusion PD98059 inhibit the MEK1/2 signaling pathway to suppress the ox-LDL induced damage of HUVEC by decreasing the expression of LOX-1.
ABSTRACT
Objective:To investigate the effect of hypoxia on the expression of forkhead box P3 (FOXP3) in human oral squamous cell carcinoma (OSCC) cells,and to clarify its possible epigenetic mechanism.Methods:Two kinds of OSCC cell lines,FaDu and OECM-1,were cultured under normoxic or hypoxic conditions for 18 h.The relative expression levels of FOXP3 mRNA and protein in the cells were detected by Real-time RT-PCR and Western blotting method.The histone modification levels on the FOXP3 gene promoter,including acetylation of histone 3 lysine 4 (H3K4ac),trimethylation of histone 3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3),were analyzed by Chromatin Immunocipitation (ChIP) and quantitative PCR (ChIP-qPCR).The relative expression levels of histone deacetylase 3 (HDAC3) mRNA and inhibitory rates of FOXP3 mRNA expression in the HDAC3-knockdown FaDu cells were investigated by Real-time qPCR and ChIP-qPCR.Results:Compared with normoxic condition,the relative expression levels of FOXP3 mRNA in FaDu and OECM-1 cells under hypoxic condition were decreased by 65.6% and 75.7% (P<0.01).The Western blotting results indicated that compared with normoxic condition,the expression levels of FOXP3 protein in FaDu and OECM-1 cells under hypoxic condition were decreased.The ChIP experiment results showed that compared with normoxic condition,the levels of H3K4ac and H3K4me3 on FOXP3 gene promoter in FaDu cells were decreased under hypoxic condition (P<0.01),while the H3K27me3 level was not changed.In HDAC3-knockdown FaDu cells,compared with control cells,the inhibitory rates of the expressions of H3K4ac and H3K4me3 on FOXP3 gene promoter under hypoxia condition were decreased (P<0.05),so did expressions the FOXP3 mRNA expression (P<0.05).Conclusion:Hypoxia could suppress the expression of FOXP3 by HDAC3-mediated down-regulation of H3K4ac on FOXP3 gene promoter in the human OSCC cells.