MiRNA (miR)-128, which is a well-recognized inhibitor of tumor growth, is involved in the anti-tumor function of dendritic cells (DCs). However, the association between miR-128 and the DC-mediated anti-tumor immunity remains to be elucidated. Murine B16 melanoma cells and C57BL/6 male mice were used to obtain marrow-derived DCs. DCs were treated with B16 cell suspension. miR-128 mimic, miR-128 inhibitor, p38 inhibitor or negative control oligonucleotides were transfected into DCs. After transfection, mRNA and protein expression of p38 in DCs was detected via reverse transcription-quantitative polymerase chain reaction and western blotting. The present study demonstrated that the miR-128 abundance in DCs was significantly attenuated by B16 (a melanoma cell line) stimulation and the protein expression level of p38 was increased. Additionally, miR-128 inhibited the protein expression of p38 in DCs in a dose-dependent manner, however no significant effect on the p38 mRNA level was observed. Furthermore, miR-128 mimic or p38 inhibitor decreased the mRNA expression and secretion of interleukin (IL)-6 and IL-10 cytokines and increased the level of IL-12 in DCs, whereas an miR-128 inhibitor exhibited the opposite effects. These findings suggested that miR-128 regulated the immune response of DCs via p38-downstream cytokines. Furthermore, the tumor growth rate, size and weight were markedly decreased and the survival time prolonged, following injection of DCs harboring miR-128 mimic or p38 inhibitor in C57BL/6 mice bearing B16 melanoma. The results therefore suggest that miR-128 enhances the anti-tumor immunity response of DCs via targeting of the p38 mitogen activated protein kinase signaling pathway.
Objective:Myocardial ischemia affects mitochondrial functions, leading to ionic imbalance and susceptibility to ventricular fibrillation. Trimetazidine, a metabolic agent, is clinically used in anti-anginal therapy.Methods:In this study, the rats were orally treated by gavage with trimetazidine 10 mg/kg/d for 7 days, and the effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia were evaluated.Results:It has been suggested that acute myocardial ischemia leads to a damage to mitochondrial functions. However, compared with ischemia group without trimetazidine administration, a significant reduction in the infarct size was observed in trimetazidine-treated ischemia group (31.24±3.02% vs. 52.87±4.89%). Trimetazidine preserved the mitochondrial structure and improved respiratory control ratio and complex I activity. Furthermore, trimetazidine improved mitochondrial biosynthesis and fission/fusion, as demonstrated by the promotion of peroxisome prolifera-tor-activated receptor gamma (PPARg) co-activator 1a (PGC-1a), mitofusins 1 (Mfn1), dynamin-related protein 1 (Drp1), and optic atrophy 1 (Opa1) expressions in rats with acute myocardial ischemia.Conclusion:Taken together, it was suggested that in this rat model of myocardial ischemia, trimetazidine demonstrated cardioprotective effects attributing to the preservation of mitochondrial respiratory function, biosynthesis, and fission/fusion and, thus, could be considered as an agent for cardioprotection.
Refractory ventricular tachycardia (VT) often occurs in the context of organic heart disease. It is associated with significantly high mortality and morbidity rates. Antiarrhythmic drugs and catheter ablation represent the two main treatment options for refractory VT, but their use can be associated with inadequate therapeutic responses and procedure-related complications. Stereotactic body radiotherapy (SBRT) is extensively applied in the precision treatment of solid tumors, with excellent therapeutic responses. Recently, this highly precise technology has been applied for radioablation of VT, and its early results demonstrate a favorable safety profile. This review presents the potential value of SBRT in refractory VT.
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