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BackgroundThis study was designed to investigate whether pretreatment of bone marrow mesenchymal stem cells (BMSCs) with 5-azacytidine (5-aza) or double intravenous infusion could enhance their therapeutic potential for dilated cardiomyopathy (DCM).Material/MethodsBMSCs were cultured for 2 weeks in the presence or absence of 5-aza and DCM serum. The cultured BMSCs (Groups 1 and 2), 5-aza-induced BMSCs (Groups 3 and 4), and medium alone (model control) were transplanted into 80 female Wistar rats by intravenous tail vein injection. Double infusion of BMSCs with 1-day time-interval was carried out in Groups 2 and 4. Postmortem histological analysis and evaluation of heart function were performed at 4 weeks post-transplantation.ResultsSome transplanted BMSCs engrafted into myocardial tissue and were positive for cardiac marker troponin T. The hearts containing transplanted BMSCs secreted a larger amount of vascular endothelial growth factor. Cardiac function parameters and serum level of brain natriuretic peptide (BNP) did not differ among Groups 1, 3, and the model control. As compared with model control, BMSC transplantation in Groups 2 and 4 significantly decreased the serum level of BNP and improved cardiac contractile function, as evidenced by reduced left ventricular end-diastolic and end-systolic diameter, elevated ejection fraction, and fractional shortening.ConclusionsBMSC transplantation is a promising strategy for the treatment of DCM. Pretreatment of BMSCs with 5-aza and DCM serum does not enhance their therapeutic efficacy, and the double intravenous BMSC infusion method is superior to single infusion for preserving cardiac contractile function in a rat model of DCM.

Highlights d Helminth-induced emphysema is IL-17-dependent and exacerbated in B cell-deficient mice d IL-4R signaling triggers activation of B cells that mitigate emphysematous pathology d These B cells express RELMa, which inhibits IL-17-producing gd T cells

Accumulating evidence indicates that microRNA-205 (miR-205) is involved in tumor initiation, development, and metastasis in various cancers. However, its functions in neuroblastoma (NB) remain largely unclear. Here we found that miR-205 was significantly downregulated in human NB tissue samples and cell lines. miR-205 expression was lower in poorly differentiated NB tissues and those of advanced International Neuroblastoma Staging System stage. In addition, restoration of miR-205 in NB cells suppressed proliferation, migration, and invasion and induced cell apoptosis in vitro, as well as impaired tumor growth in vivo. cAMP-responsive element-binding protein 1 () was identified as a direct target gene of miR-205. Expression of an miR-205 mimic in NB cells significantly diminished expression of CREB1 and the CREB1 targets BCL-2 and MMP9. CREB1 was also found to be upregulated in human NB tissues, its expression being inversely correlated with miR-205 expression ( = -0.554, = 0.003). Importantly, CREB1 upregulation partially rescued the inhibitory effects of miR-205 on NB cells. These findings suggest that miR-205 may function as a tumor suppressor in NB by targeting.

Cirrhosis-related immune dysfunction is well recognized and may contribute to early mortality following liver transplant (LT). The purpose of the present study was to identify pre-transplant biomarkers of immune dysfunction (i.e., immune frailty) that might accurately predict risk of early mortality following LT. Patient plasma was collected immediately prior to LT (T0) and analyzed via Luminex (N = 279). On multivariate analysis, HCV IgG, Fractalkine, and MMP3 were significant predictors of 1 year post-LT mortality and were utilized to comprise a novel Liver Immune Frailty Index (LIFI). The LIFI stratifies LT recipients into -low, -moderate, and –high risk tertiles. One year mortality was 1.5% for LIFI-low, 13.2% for LIFI-moderate, and 63.3% for LIFI-high. Internal validation through bootstrap resampling with 2000 replicates demonstrated the final LIFI model predicts early post-LT mortality with C-statistic = 0.84. This novel index may identify patients at risk for persistent severe immune dysfunction and early mortality following LT.