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The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.

microRNA-210 (miR-210) has generally been reported to be associated with cell survival under hypoxia. However, there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells (MSCs) under oxidative stress conditions. Thus, we sought to investigate whether miR-210 over-expression could protect MSCs against oxidative stress injury and what the primary mechanisms involved are. The results showed that over-expression of miR-210 significantly reduced the apoptosis of MSCs under oxidative stress, accompanied by obvious increases in cell viability and superoxide dismutase activity and remarkable decreases in malonaldehyde content and reactive oxygen species production, resulting in a noticeable reduction of apoptotic indices when compared with the control. Moreover, the above beneficial effects of miR-210 could be significantly reduced by c-Met pathway repression. Collectively, these results showed that miR-210 over-expression improved MSC survival under oxidative stress through antioxidation and c-Met pathway activation, indicating the potential development of a novel approach to enhance the efficacy of MSC-based therapy for injured myocardium. microRNAs, stem cells, oxidative stress, signal transduction Citation:Xu JF, Huang ZY, Lin L, Fu MQ, Gao YH, Shen YL, Zou YZ, Sun AJ, Qian JY, Ge JB. miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation. Sci China Life Sci, 2014, 57: 989 -997,

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Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague‐Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary‐like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase‐3 activity. Neuregulin‐1 (NRG‐1) siRNA and LY294002 were administrated to block NRG‐1/ErbB and PI3K/Akt signalling, respectively. As a result, anoxia inhibited cell migration, capillary‐like tube formation and angiogenesis, and increased cell apoptosis. QL significantly reversed these anoxia‐induced injuries and up‐regulated expressions of NRG‐1, phospho‐ErbB2, phospho‐ErbB4, phospho‐Akt, phospho‐mammalian target of rapamycin (mTOR), hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) in CMECs, while NRG‐1 knockdown abolished the protective effects of QL with suppressed NRG‐1, phospho‐ErbB2, phospho‐ErbB4, phospho‐Akt, phospho‐mTOR, HIF‐1α and VEGF expressions. Similarly, LY294002 interrupted the beneficial effects of QL with down‐regulated phospho‐Akt, phospho‐mTOR, HIF‐1α and VEGF expressions. However, it had no impact on NRG‐1/ErbB signalling. Our data indicated that QL could attenuate anoxia‐induced injuries in CMECs via NRG‐1/ErbB signalling which was most probably dependent on PI3K/Akt/mTOR pathway.

ObjectiveThe predictors of in-hospital mortality for intensive care units (ICUs)-admitted heart failure (HF) patients remain poorly characterised. We aimed to develop and validate a prediction model for all-cause in-hospital mortality among ICU-admitted HF patients.DesignA retrospective cohort study.Setting and participantsData were extracted from the Medical Information Mart for Intensive Care (MIMIC-III) database. Data on 1177 heart failure patients were analysed.MethodsPatients meeting the inclusion criteria were identified from the MIMIC-III database and randomly divided into derivation (n=825, 70%) and a validation (n=352, 30%) group. Independent risk factors for in-hospital mortality were screened using the extreme gradient boosting (XGBoost) and the least absolute shrinkage and selection operator (LASSO) regression models in the derivation sample. Multivariate logistic regression analysis was used to build prediction models in derivation group, and then validated in validation cohort. Discrimination, calibration and clinical usefulness of the predicting model were assessed using the C-index, calibration plot and decision curve analysis. After pairwise comparison, the best performing model was chosen to build a nomogram according to the regression coefficients.ResultsAmong the 1177 admissions, in-hospital mortality was 13.52%. In both groups, the XGBoost, LASSO regression and Get With the Guidelines-Heart Failure (GWTG-HF) risk score models showed acceptable discrimination. The XGBoost and LASSO regression models also showed good calibration. In pairwise comparison, the prediction effectiveness was higher with the XGBoost and LASSO regression models than with the GWTG-HF risk score model (p<0.05). The XGBoost model was chosen as our final model for its more concise and wider net benefit threshold probability range and was presented as the nomogram.ConclusionsOur nomogram enabled good prediction of in-hospital mortality in ICU-admitted HF patients, which may help clinical decision-making for such patients.

Background: Until now there was no systematic review concerning the chronic effects of intracoronary bone marrow-derived cell (BMC) transplantation in patients with acute myocardial infarction (MI). Hypothesis: Improvement of cardiac function in patients with acute MI post BMC transplantation might last longer than 12 months. Methods: We searched MEDLINE, EMBASE, and the Cochrane database through June 2009. Eligible studies were randomized controlled trials of intracoronary BMC transfer in acute MI patients with follow-up duration equal to or longer than 12 months. Results: A total of 8 trials involving 725 participants were identified. Compared with controls, BMC transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.37% (95% confidence interval [CI]: 2.66%-6.08%; P < 0.00001), reduced left ventricular end-diastolic volume (LVEDV) by 5.71 mL (95% CI: 2.03-9.40 mL; P = 0.002), left ventricular end-systolic volume (LVESV) by 8.94 mL (95% CI: 4.22-13.66 mL; P = 0.0002), and infarct size by 2.42% (95% CI: 1.33%-3.51%, P < 0.00001). Bone marrowderived cell treatment also significantly reduced the risk of death (relative risk [RR]: 0.33, 95% CI: 0.13-0.89; P = 0.03), while the risk of reinfarction was similar between the 2 groups (RR: 0.62, 95% CI: 0.09-4.12; P = 0.62). Subgroup analysis showed that the BMC transplantation-induced LVEF increase was more significant in patients age <55 and with cells transferred 6 or 7 days after MI. Conclusion: Beneficial effects of intracoronary BMC transplantation could last more than 12 months in acute MI patients.