Bone-derived mesenchymal stem cell (BMSC) transplantation has been reported to be effective for the treatment of ischemic heart disease, but whether BMSCs are the optimal cell type remains under debate. Increasing numbers of studies have shown that Nestin, an intermediate filament protein, is a potential marker for MSCs, which raises the question of whether Nestin+ cells in BMSCs may play a more crucial role in myocardial repair. Nestin+ cells were isolated using flow cytometry by gating for CD45− Ter119− CD31− cells from the compact bone of Nestin-GFP transgenic mice, expressing GFP driven by the Nestin promoter. Colony-forming and proliferative curve assays were conducted to determine the proliferative capacity of these cells, while qRT-PCR was used to analyze the mRNA levels of relative chemokines and growth factors. Cardiac endothelial cell (CEC) recruitment was assessed via a transwell assay. Moreover, permanent ligation of the left anterior descending (LAD) coronary artery was performed to establish an acute myocardial infarction (AMI) mouse model. After cell transplantation, conventional echocardiography was conducted 1 and 4 weeks post-MI, and hearts were harvested for hematoxylin-and-eosin (HE) staining and immunofluorescence staining 1 week post-MI. Further evaluation of paracrine factor levels and administration of a neutralizing antibody (TIMP-1, TIMP-2, and CXCL12) or a CXCR4 antagonist (AMD3100) in MI hearts were performed to elucidate the mechanism involved in the chemotactic effect of Nestin+ BMSCs in vivo. Compared with Nestin− BMSCs, a greater proliferative capacity of Nestin+ BMSCs was observed, which further exhibited moderately high expression of chemokines instead of growth factors. More CEC recruitment in the Nestin+ BMSC-cocultured group was observed in vitro, while this effect was obviously abolished after treatment with neutralizing antibodies against TIMP-1, TIMP-2, or CXCL12, and more importantly, blocking the CXCL12/CXCR4 axis with a AMD3100 significantly reduced the chemotactic effect of Nestin+ BMSCs. After transplantation into mice exposed to myocardial infarction (MI), Nestin+ BMSC-treated mice showed significantly improved survival and left ventricular function compared with Nestin− BMSC-treated mice. Moreover, endogenous CECs were markedly increased, and chemokine levels were significantly higher, in the infarcted border zone with Nestin+ BMSC treatment. Meanwhile, neutralization of each TIMP-1, TIMP-2, or CXCL12 in vivo could reduce the left ventricular function at 1 and 4 weeks post-MI; importantly, the combined use of these three neutralizing antibodies could make a higher significance on cardiac function. Finally, blocking the CXCL12/CXCR4 axis with AMD3100 significantly reduced the left ventricular function and greatly inhibited Nestin+ BMSC-induced CEC chemotaxis in vivo. These results suggest that Nestin+ BMSC transplantation can improve cardiac function in an AMI model by recruiting resident CECs to the infarcted border region via the CXCL12/CXCR4 chemokine pathway. And we demonstrated that Nestin+BMSC-secreted TIMP-1/2 enhances CXCL12(SDF1α)/CXCR4 axis-driven migration of endogenous Sca-1+ endothelial cells in ischemic heart post-AMI. Taken together, our results show that Nestin is a useful marker for the identification of functional BMSCs and indicate that Nestin+ BMSCs could be a better therapeutic candidate for cardiac repair.

Probiotic Lactobacillus plantarum BFS1243 improved gut dysbiosis and then decreased systemic inflammation, ultimately improving frailty-associated phenotypes to varying degrees, which were caused by transplantation of fecal microbiota from frailty patients.

Background: Handgrip strength (HGS) weakness and asymmetry are both abnormal conditions of upper-limb muscle strength. The association between HGS weakness and physical performance is controversial, and the link between HGS asymmetry and physical performance remains unclear. Aims: This study aimed to investigate the associations of HGS weakness and asymmetry separately and concurrently with low physical performance among Chinese older people. Methods: The study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2013 and 2015. HGS weakness and asymmetry were defined according to the maximal HGS and the HGS ratio, respectively. Participants were classified into 4 groups according to HGS status: normal, asymmetry only, weakness only, and concurrent weakness and asymmetry. The logistic regression model was used to investigate the cross-sectional association between low physical performance and each of maximal HGS, HGS ratio, and HGS status, as well as the prospective association between baseline HGS status and new-onset physical performance decline after two years. Results: Participants with HGS asymmetry only, weakness only, and two abnormalities showed a higher prevalence of low physical performance when asymmetry defined as an HGS ratio exceeding 1.20 and 1.30 (all, p < 0.001), with the greatest odds in those with two abnormalities (20% threshold: OR 3.83; 30% threshold: OR 5.41). The longitudinal analysis found that HGS weakness can predict the new-onset low physical performance over a two-year period, with concurrent HGS asymmetry further increased the future risk of physical performance decline. Conclusions: Both HGS weakness and asymmetry were associated with a higher prevalence of low physical performance, in an additive way. This study will help screen older people with low physical performance more efficiently, and identify those at higher risk of developing new-onset physical performance decline within two years.

Background: Some studies have shown that genetic polymorphisms in the 15 kDa selenoprotein (SEP15) gene can alter the interaction of Sep15 protein with selenium (Se), which is associated with increased susceptibility to cancer. However, the results of other studies are conflicting and ambiguous. Methods: To evaluate the associations between two common SEP15 polymorphisms (rs5859 and rs5845) and susceptibility to cancer, we conducted a comprehensive literature research of several electronic database, including PubMed, EMBASE, Cochrane Library, and Web of Science. We enrolled all relevantly eligible studies that were published by December 17, 2016. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Results: A total of nine publications comprising 10 case-control studies were enrolled for two SEP15 polymorphisms (rs5859 and rs5845). For the rs5859 polymorphism, we enrolled 5,802 cases and 7,035 controls from seven case-control studies, whereas for the rs5845 polymorphism, three case-control studies comprising 1,168 cases and 1,397 controls were included. Overall, the results demonstrated that neither the rs5859 nor rs5845 polymorphism was related to cancer susceptibility. In addition, stratification analyses based on ethnicity, cancer type, Hardy Weinberg equilibrium (HWE) status, and source of control generated null results. Conclusions: The results of this study show that SEP15 polymorphisms (rs5859 and rs5845) are not risk factors for cancer. Future well-designed studies with larger sample sizes are needed to validate these findings.