DHA induced cytotoxicity in NSCLC cells via inhibiting PI3K pathway activation and GLUT2 expression / 中国病理生理杂志

[ ABSTRACT ] AIM: To investigate the molecular mechanisms of cytotoxicity induced by dihydroartemisinin ( DHA) in non-small cell lung cancer ( NSCLC) cells.METHODS:NSCLC cell lines A549 and NCI-H1650 were treated with various concentrations of DHA for indicated time.Subsequently, the effects of DHA on the cell activity, colony forma-tion ability and apoptosis were determined by MTT assay, colony formation assay, Annexin V-FITC/PI staining and flow cy-tometry, respectively.At the same time, the effects of DHA on glucose, ATP and lactate levels were assessed, and the PI3K pathway activation and glucose transporter 2 ( GLUT2) expression were detected by Western blot in the A549 cells and NCI-H1650 cells.Overexpression of GLUT2 and Rheb was established in A549 and NCI-H1650 cells by transfection with GST-GLUT2 and GST-Rheb plasmids, respectively, and the effects of DHA on cell activity, apoptosis, glucose level, ATP content and PI3K pathway activation were analyzed in A549 cells and NCI-H1650 cells.The effect of glucose depriva-tion on the cytotoxicity triggered by DHA in NSCLC cells was also determined.RESULTS:Compared with control group, DHA significantly inhibited cell activity and colony formation ability, and induced remarkable cell apoptosis in the A549 cells and NCI-H1650 cells.At the same time, DHA reduced ATP and lactate contents, and hindered glucose uptake in a time-and dose-dependent manner in A549 cells and NCI-H1650 cells.The activity of PI3K pathway and GLUT2 expression were downregulated, while upregulated GLUT2 expression and activated PI3K pathway reduced the cytotoxicity induced by DHA in NSCLC cells.Glucose deprivation increased DHA-mediated cytotoxicity in NSCLC cells.On the contrary, high levels of glucose inhibited DHA-mediated cytotoxicity in NSCLC cells.CONCLUSION: DHA restrains cell activity and colony formation, and induces apoptosis.DHA induces cytotoxicity via inhibiting PI3K pathway activation and GLUT2 ex-pression, leading to inhibit glycolytic metabolism in NSCLC cells.

Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus

Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.

Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure.</p><p><b>METHODS</b>Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing.</p><p><b>RESULTS</b>LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group.</p><p><b>CONCLUSION</b>RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.</p>

Neuregulin-1? inhibits cardiomyocyte apoptosis in adriamycin-induced rat cardiomyopathy by regulating bcl-2 and bax / 第三军医大学学报

Objective To investigate the cardiomyocyte apoptosis and protein expressions of bcl-2 and bax in adriamycin (ADM)-induced myocardial damage in rats treated with neuregulin-1? (NRG-1?).Methods Sixty male SD rats weighing 200 to 250 g were randomly divided into 3 groups:control,ADR-DCM and ADR+NRG groups.ADR-DCM group (n=20) was weekly injected 2.0 mg/kg of ADR via tail vein once a week for 8 weeks to produce cardiomyopathy.The rats of ADR+NRG group (n=20) was given an injection of NRG-1? at 10 ?g/(kg?d) via tail vein for 5 d after the establishment of cardiomyopathy by ADR injection.The animals from control group (n=20) received 2 ml/kg normal saline by injection,once a week for 8 weeks.Nine weeks later,rats were executed under anesthesia and their heart was resected.Apoptotic cardiomyocytes were detected by using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method.The expressions of bcl-2 and bax protein were determined by Western blotting.Results The index of apoptotic cardiomyocytes was increased significantly in ADR-DCM group and ADR+NRG group compared with control group (P

Expression of ErbB4 in and apoptosis of cardiac muscle cells of rats with dilated cardiomyopathy and their intervention with neuregulin-1? / 第三军医大学学报

Objective To study the adriamycin(ADR)-induced expression of ErbB4 in and apoptosis of cardiac muscle cells of rats with dilated cardiomyopathy and their intervention with neuregulin-1?.Methods Sixty male SD rats,weighing 200-250 g,were randomly divided into ADR 1 group(n=10),ADR 2 group(n=20),ADR+neuregulin-1? group(n=20),and normal control(NC) group(n=10).Rats in ADR1 and ADR2 groups were injected with 2.0 mg/kg of ADR through the tail vein,once a week for 8 and 12 weeks,respectively.Rats in ADR+neuregulin-1? group were injected with 2.0mg/kg of ADR through the tail vein,once a week for 8 weeks,followed by neuregulin-1? [10 ?g/(kg?d)],once a day for 5 d.Rats in NC group received normal saline [2 ml/(kg?d)],once a week for 8 weeks.Expression of ErbB4 was detected by Wes-tern blotting.Lesions of cardiac muscle were scored with HE staining.Apoptosis of cardiac muscle cells was detected with the TUNEL method.Results The apoptotic index of cardiac muscle cells was significantly lower in ADR+neuregulin-1? group than in ADR 1 group(P