Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR-21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo.
Background/Aims: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. Methods: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. Results: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. Conclusions: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC.
The TTS technique and RVIAT can both be performed with favorable cosmetic and acceptable clinical results for closing atrial septal defects. They are promising alternatives to SMS and merit additional study.
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