Background Cardiomyocyte apoptosis is a primary cause for coronary microembolization （CME）-induced cardiac dysfunction, p53induces cell growth retardation and apoptosis through stress pathway. The present study inve...Background Cardiomyocyte apoptosis is a primary cause for coronary microembolization （CME）-induced cardiac dysfunction, p53induces cell growth retardation and apoptosis through stress pathway. The present study investigated the mechanism of p53-induced myocar-dial apoptosis and cardiac dysfunction by activating the mitochondrion apoptotic pathway following CME. Methods Forty SD rats wereequally divided into microembolization （CME）, sham operation （sham）, CME＋siRNA-p53, and CME＋control-p53 groups. The CME ratmodel was established by injecting microembolization spheres via the left ventricle. Cardiac ultrasound, TUNEL, fluorescence quantitativePCR, and Western blot were used to assess the cardiac function indicators, cardiomyocyte apoptosis, and the expressions of mRNA and pro-tein in myocardial tissues, respectively. Results Echocardiography revealed a significantly reduced cardiac function of the CME group thanthe sham group while the CME-induced cardiac dysfunction was improved in the CME＋siRNA-p53 group. The indicators of myocardialapoptosis in the CME group increased significantly than the sham group; those of the CME＋siRNA-p53 group decreased significantly thanthe CME group. Fluorescence quantitative PCR and Western blot demonstrated that p53, Bbc3 （PUMA）, and cleaved caspase-3 expressionswere significantly increased, and BCL-2 expression was declined in myocardial tissues of the CME group compared to the sham group. Acontrasting result was observed in the CME＋siRNA-p53 group as compared to the CME group. Conclusions P53 is involved in theCME-induced cardiac dysfunction, which may up-regulate Bbc3 to activate BCL-2/caspase3 mitochondrial apoptotic pathway and inducemyocardial apoptosis. Inhibiting the p53 expression can effectively suppress this pathway, thereby reducing myocardial apoptosis and car-diac dysftmction.展开更多
Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential ...Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.展开更多
文摘Background Cardiomyocyte apoptosis is a primary cause for coronary microembolization （CME）-induced cardiac dysfunction, p53induces cell growth retardation and apoptosis through stress pathway. The present study investigated the mechanism of p53-induced myocar-dial apoptosis and cardiac dysfunction by activating the mitochondrion apoptotic pathway following CME. Methods Forty SD rats wereequally divided into microembolization （CME）, sham operation （sham）, CME＋siRNA-p53, and CME＋control-p53 groups. The CME ratmodel was established by injecting microembolization spheres via the left ventricle. Cardiac ultrasound, TUNEL, fluorescence quantitativePCR, and Western blot were used to assess the cardiac function indicators, cardiomyocyte apoptosis, and the expressions of mRNA and pro-tein in myocardial tissues, respectively. Results Echocardiography revealed a significantly reduced cardiac function of the CME group thanthe sham group while the CME-induced cardiac dysfunction was improved in the CME＋siRNA-p53 group. The indicators of myocardialapoptosis in the CME group increased significantly than the sham group; those of the CME＋siRNA-p53 group decreased significantly thanthe CME group. Fluorescence quantitative PCR and Western blot demonstrated that p53, Bbc3 （PUMA）, and cleaved caspase-3 expressionswere significantly increased, and BCL-2 expression was declined in myocardial tissues of the CME group compared to the sham group. Acontrasting result was observed in the CME＋siRNA-p53 group as compared to the CME group. Conclusions P53 is involved in theCME-induced cardiac dysfunction, which may up-regulate Bbc3 to activate BCL-2/caspase3 mitochondrial apoptotic pathway and inducemyocardial apoptosis. Inhibiting the p53 expression can effectively suppress this pathway, thereby reducing myocardial apoptosis and car-diac dysftmction.
文摘Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.
