Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(H...Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.展开更多
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
文摘Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
