Search

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p’s role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p’s pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

Background: Rheumatic heart disease (RHD) is an autoimmune disease caused by rheumatic fever following infection with Group A Streptococcus (GAS) that primarily affects the mitral valve, and our previous study has shown that endothelial-mesenchymal transition (EndMT) plays an important role in mitral valve damage due to RHD. TGF-β1 is an important profibrotic factor, but its role has not been explored in RHD. The current study is aimed to investigate the role of TGF-β1 in mitral valve damage due to RHD. Methods: RHD rats were established using inactivated GAS. Successful modelling of the RHD rat was verified in mitral valve pathology sections. Echocardiography and running test were used to detect the cardiac function of rats. And immunohistochemistry, RT-qPCR and Western blotting were used to detect activation of the TGF-β1/Smad signalling pathway and EndMT in mitral valve. Wounding healing and cell counting Kit-8 assay were conducted to figure out the function of TGF-β1 in vitro. Results: The TGF-β1/Smad signalling pathway was activated, and significant EndMT of the mitral valve occurred in RHD rats. And TGF-β type I receptor (TGF-βRI) inhibitor SB431542 inhibited the TGF-β1/Smad signalling pathway and EndMT of the mitral valve. Conclusion: EndMT was involved in mitral valve damage, and inhibition of TGF-βRI alleviated EndMT of mitral valve damage due to RHD.

Concurrent with the growth of the application of the seismic isolation technique to civil structures, a large variety of isolation systems has been developed during the past two decades. This paper investigates the seismic behavior of a 1/7.5 scaled bridge model isolated by rolling-type bearings. Shaking table tests of the scaled bridge model have been conducted to verify the effectiveness of the rolling-type bearing as a seismic isolation device. Test results reveal that the seismic force transmitted by the rolling-type bearing is independent of the earthquake intensities when the sloped rolling mechanism is completely triggered. An approximate expression is derived for predicting the peak acceleration response of a structure isolated by the rolling-type bearing. It is shown that the maximum structural acceleration may be estimated by the proposed formula. As an appropriate option, viscous dampers may be incorporated to reduce the larger displacement and eliminate unfavorable oscillation of the bridge deck, which may occur under strong earthquakes.