Objective To investigate the impacts of neferine on cellular autophagy and apoptosis,and the silent mating type information regulation 2 homolog-1/5'-AMP activated protein kinase activated protein kinase/mammalian target of rapamycin(SIRT1/AMPK/mTOR)signaling path-way in acute myocardial infarction(AMI)rats.Methods A rat model of AMI was constructed on male SD rats,and then 72 successfully modeled rats were randomly divided into model group,low-and high-dose neferine groups,and high-dose neferine+SIRT1 inhibitor(EX-527)group,with 18 rats in each group.Another 18 normal rats served as the Control group.The area of myocardial infarction,expression of myocardocyte autophagy related proteins,myocardocyte apoptosis,and expression of SIRT1/AMPK/mTOR signaling pathway-related proteins were observed and detec-ted in above groups of rats.Results When compared with the model group,the low-and high-dose neferine groups exhibited milder pathological injuries,higher left ventricular ejection frac-tion,enhanced left ventricular fractional shortening,increased optical densities of microtubule associated protein 1 light chain 3(LC3)Ⅱ and Beclin-1,and elevated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),and shorten left ventricular end-systolic diameter,lessened area of myocardial infarction,lower apoptotic rate,and reduced expres-sion of Bax and p-mTOR/mTOR(P＜0.05).While,in comparison to high-dose neferine treat-ment,addition of SIRT1 inhibitor,EX-527 resulted in more severe myocardial injuries,decreased left ventricular ejection fraction and left ventricular fractional shortening values,reduced optical densities of LC3 Ⅱ and Beclin-1,and down-regulated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),but increased left ventricular end-systolic diame-ter,larger myocardial infarction area,increased apoptotic rate,and increased expression levels of Bax and p-mTOR/mTOR(P＜0.05).Conclusion Neferine can inhibit apoptosis and promote autophagy in AMI rats and exert myocardial protective effects,which may be related to the activa-tion of the SIRT1/AMPK/mTOR signaling pathway.

Objective To investigate the impacts of neferine on cellular autophagy and apoptosis,and the silent mating type information regulation 2 homolog-1/5'-AMP activated protein kinase activated protein kinase/mammalian target of rapamycin(SIRT1/AMPK/mTOR)signaling path-way in acute myocardial infarction(AMI)rats.Methods A rat model of AMI was constructed on male SD rats,and then 72 successfully modeled rats were randomly divided into model group,low-and high-dose neferine groups,and high-dose neferine+SIRT1 inhibitor(EX-527)group,with 18 rats in each group.Another 18 normal rats served as the Control group.The area of myocardial infarction,expression of myocardocyte autophagy related proteins,myocardocyte apoptosis,and expression of SIRT1/AMPK/mTOR signaling pathway-related proteins were observed and detec-ted in above groups of rats.Results When compared with the model group,the low-and high-dose neferine groups exhibited milder pathological injuries,higher left ventricular ejection frac-tion,enhanced left ventricular fractional shortening,increased optical densities of microtubule associated protein 1 light chain 3(LC3)Ⅱ and Beclin-1,and elevated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),and shorten left ventricular end-systolic diameter,lessened area of myocardial infarction,lower apoptotic rate,and reduced expres-sion of Bax and p-mTOR/mTOR(P＜0.05).While,in comparison to high-dose neferine treat-ment,addition of SIRT1 inhibitor,EX-527 resulted in more severe myocardial injuries,decreased left ventricular ejection fraction and left ventricular fractional shortening values,reduced optical densities of LC3 Ⅱ and Beclin-1,and down-regulated protein levels of LC3 Ⅱ/LC3 Ⅰ,Beclin-1,Bcl-2,SIRT1,and p-AMPK/AMPK(P＜0.05),but increased left ventricular end-systolic diame-ter,larger myocardial infarction area,increased apoptotic rate,and increased expression levels of Bax and p-mTOR/mTOR(P＜0.05).Conclusion Neferine can inhibit apoptosis and promote autophagy in AMI rats and exert myocardial protective effects,which may be related to the activa-tion of the SIRT1/AMPK/mTOR signaling pathway.

Objective:To investigate the effect of afatinib, a tyrosine kinase inhibitor, on the proliferation, cell cycle, and apoptosis of human breast cell lines, and compare its effects with those of gefitinib. Methods:Three human breast cell lines, MCF-7, T47D, and MDA-MB-231, were cultured as cell models. A methyl thiazolyl tetrazolium assay was utilized to measure cell viability. Flow cytometer was used to analyze the cell cycle arrest (PI staining) and apoptosis rates (Annexin-V/PI staining). The protein expression was detected by Western blot analysis. Results:The proliferation of three human breast cell lines was significantly inhibited by afatinib, and the IC50 levels of MCF-7, T47D, and MDA-MB-231 were 0.101, 0.141, and 0.887μmol/L, respectively. The G0/G1 phase cell ratio increased con-siderably 24 h after afatinib was added to T47D or MDA-MB-231. The cell apoptosis rate also increased in the two cell lines (88.9%and 58.1%). The cleavage of apoptosis pathway proteins PARP and caspase-3 was also promoted by afatinib. Phosphorylation of EGFR was significantly inhibited by afatinib in the MDA-MB-231 cell line. Finally, the inhibition effect of afatinib was stronger than that of gefi-tinib. Conclusion: Afatinib could significantly inhibit the proliferation of breast cancer cells and promote apoptosis. The effect was dose-dependent. Afatinib was a more effective tyrosine kinase inhibitor as compared with gefitinib.