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Objective: Myocardial infarction (MI), which causes irreversible damage and loss of cardiomyocytes, is the most important cause of death in the world. MicroRNA is an important regulator of physiological and pathological activities of cardiovascular system. The aim of this research was to study the effect of microRNA-323-3p (miR-323-3p) on MI and its underlying mechanisms of action., Materials and Methods: A rat model of MI was established to measure the expression of miR-323-3p, Bax, Bcl-2, SOD1, and SOD2 in ischemic myocardial tissue, and the cardiac function of rats were tested at seventh day after MI. H9c2 cells were divided into control group, miRNA negative control (NC) transfection group, miR-323-3p mimic (miR-323-3p min) transfection group, and then, treated with H2O2. Oxidative stress and apoptosis of H9c2 cells were observed by Western blot, Real Time-Polymerase Chain Reaction (RT-PCR), flow cytometry, SOD activity assay, TUNEL staining, DHR dye assay, etc. RESULTS: The level of miR-323-3p was decreased in ischemic myocardium, as well as H2O2-treated H9c2 cells. MiR-323-3p overexpression greatly decreased the level of Bax and increased the levels of SOD1, SOD2, and Bcl-2. After treated with miR-323-3p mimic, TUNEL positive cells were greatly reduced, and apoptosis rate of H9c2 cells was greatly decreased. Moreover, SOD levels significantly increased, while ROS production decreased after treatment of miR-323-3p. After intravenous injection of miR-323-3p agomir in rats with MI, the cardiac function of the rats was significantly improved. Western blot and Luciferase reporter gene experiments illustrated that miR-323-3p acts by targeting TGF-β2., Conclusions: MiR-323-3p was downregulated in ischemic myocardium and H2O2-treated H9c2 cells, and miR-323-3p overexpression reduced oxidative stress and apoptosis of cardiomyocytes. The protective function was achieved via regulation of TGF-β2/JNK pathway.

Neddylation is a post-translational protein modification process associated with carcinogenesis and cancer development. MLN4924, a pharmaceutical neddylation inhibitor, induces potent anti-cancer effects in multiple types of cancers. In this study, we investigated the effects of MLN4924 on human osteosarcoma (OS). Levels of both NEDD8 activating enzyme E1 (NAE1) and ubiquitin-conjugating enzyme E2M (Ube2M), two critical components of the neddylation pathway, were much higher in OS tissues and cells than in normal osseous tissues and cells. MLN4924 treatment led to DNA damage, reduced cell viability, senescence and apoptosis in OS cells. Moreover, MLN4924 inhibited OS xenograft tumor growth in mice. Mechanistically, MLN4924 blocked the neddylation of cullins and induced accumulation of several tumor-suppressive substrates of Cullin-RING E3 ubiquitin ligases (CRLs), including CDT1, Wee1, p21, p27, Noxa, and p16. These results suggest clinical studies investigating the utility of MLN4924 for the treatment of OS are warranted., Competing Interests: The authors declare no conflicts of interest.

Children undergoing cardiopulmonary bypass (CPB) operations have an increased risk for the development of immunosuppression and severe infection. Lymphocyte apoptosis plays an important role in regulating immune responses. This study aimed to investigate the effect of open heart surgery with CPB on peripheral blood lymphocyte (PBL) apoptosis and the possible mechanism of lymphocyte apoptosis in infants and young children. This study enrolled 20 consecutive infants and children as a CPB group and 20 age-matched children who underwent patent arterial duct closure without CPB as control subjects. Samples were taken from peripheral blood after induction of anesthesia (preoperatively) and again 24 h after the operations. The degree of apoptosis and the expression level of Fas (CD95) on PBL were measured using flow cytometry. The percentage of lymphocyte apoptosis significantly increased after surgery in both groups, but it was much higher in the children with CPB than in those without CPB (14.46%+/-4.83% vs. 7.33%+/-1.43%; p<0.01). The expression level of Fas in the individuals with CPB was significantly higher than in those without CPB (52.80%+/-8.80% vs. 37.82%+/-6.32%; p<0.01). As shown by the study findings, both surgical stress and CPB can induce PBL apoptosis, which may lead to lymphopenia after open heart surgery with CPB for infants and young children.