Objective:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy as it has unique capacity to selectively trigger apoptosis in cancer cells. We reported here that paclitaxel sensitized gastric cancer cells to TRAIL-induced apoptosis.Methods: After drug exposure, apoptosis rate and caspase activation were examined. Various proteins were detected by western blot. Several interventions, including pharmacological inhibitors and siRNA transfection were used. hTe growth inhibition of tumors was evaluated in SGC-7901-implanted nude mice model.Results:We found gastric cancer cellsshowed a mixed response to TRAIL. Combined treatment with paclitaxel markedly enhanced TARIL-induced apoptosis in vitro and in vivo. The underlying mechanisms involved in synergistical activation of caspase proteins, up-regulation of receptors, down-regulation of antiapoptotic proteins and inactivation of MAPKs.Conclusion:TRAIL-induced cytotoxicity and apoptosis can be synergistically enhanced by paclitaxel, suggesting the therapeutic potential of combining TARIL plus paclitaxel in gastric cancer treatment.

Angiotensin-converting enzyme 2 (ACE2)-angiotensin (1-7) [Ang (1-7)]-Mas constitutes the vasoprotective axis and is demon-strated to antagonize the vascular pathophysiological effects of the classical renin -angiotensin system .We hypothesize that upregulation of ACE2-Ang (1-7) signaling protects endothelial function through reducing oxidative stress , thus resulting in beneficial outcome in di-abetes.Ex vivo treatment with Ang (1-7) augmented endothelium-dependent relaxation (EDR) in renal arteries from diabetic patients . Both Ang (1-7) infusion via osmotic pump (500 ng? kg -1? min-1 ) for 2 weeks and exogenous ACE 2 overexpression mediated by ad-enoviral ACE2 via tail vein injection rescued the impaired EDR and flow-mediated dilatation ( FMD) in db/db mice.Diminazene acetu-rate treatment (15 mg? kg-1? d-1 ) activated ACE2, increased the circulating Ang (1-7) level, and augmented EDR and FMD in db/db mouse arteries.In addition, activation of the ACE2-Ang (1-7) axis reduced reactive oxygen species (ROS) overproduction de-termined by dihydroethidium staining , CM-H2DCFDA fluorescence imaging , and chemiluminescence assay in db/db mouse aortas and also in high-glucose-treated endothelial cells .Pharmacological benefits of ACE 2-Ang ( 1-7 ) upregulation on endothelial function were confirmed in ACE2 knockout mice both ex vivo and in vitro.We elucidate that the ACE2-Ang (1-7)-Mas axis serves as an important signal pathway in endothelial cell protection in diabetic mice , especially in diabetic human arteries .In summary, endogenous ACE2-Ang (1-7) activation or ACE2 overexpression preserves endothelial function in diabetic mice through increasing nitric oxide bioavail -ability and inhibiting oxidative stress , suggesting the therapeutic potential of ACE 2-Ang(1-7) axis activation against diabetic vasculop-athy.

Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine .In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia /reperfusion injury based on the reports pub-lished between January 2000 and September 2015 and indexed in the PubMed and Web of Science databases .The effect of exosomes on heart function was evaluated according to the following parameters:the area at risk as a percentage of the left ventricle , infarct size as a percentage of the area at risk , infarct size as a percentage of the left ventricle , left ventricular ejection fraction , left ventricular frac-tion shortening , end-diastolic volume , and end-systolic volume .Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function .However , further mechanis-tic studies, therapeutic safety and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury .