The aim of this study was to research the effects of microRNA-10a (miR-10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF-TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR-10a mimics, miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT-qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR-10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR-10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a inhibitors group presented an opposite trend to the miR-10a mimics and K252a groups. The synapse was complete and abundant in the miR-10a inhibitors group while disappeared in the miR-10a mimics and K252a groups. The results indicated that miR-10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway.

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Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA‐135b (miR‐135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR‐135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR‐135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR‐135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR‐135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR‐135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR‐135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR‐135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.

Coronary artery spasm (CAS) is an intense vasoconstriction of coronary arteries that cause total or subtotal vessel occlusion. The cardioprotective effect of sirtuin-1 (SIRT1) has been extensively highlighted in coronary artery diseases. The aims within this study include the investigation of the molecular mechanism by which SIRT1 alleviates CAS. SIRT1 expression was first determined by RT-qPCR and Western blot analysis in an endothelin-1 (ET-1)-induced rat CAS model. Interaction among SIRT1, nuclear factor-kappaB (NF-κB), myosin light chain kinase/myosin light chain-2 (MLCK/MLC2), and ET-1 was analyzed using luciferase reporter assay, RT-qPCR and Western blot analysis. After ectopic expression and depletion experiments in vascular smooth muscle cells (VSMCs), contraction and proliferation VSMCs, and expression of contraction-related proteins (α-SMA, calponin, and SM22α) were measured by collagen gel contraction, EdU assay, RT-qPCR and Western blot analysis. The obtained results showed that SIRT1 expression was reduced in rat CAS models. However, overexpression of SIRT1 inhibited the contraction and proliferation of VSMCs in vitro. Mechanistic investigation indicated that SIRT1 inhibited NF-κB expression through deacetylation. Moreover, NF-κB could activate the MLCK/MLC2 pathway and up-regulate ET-1 expression by binding to their promoter regions, thus inducing VSMC contraction and proliferation in vitro. In vivo experimental results also revealed that SIRT1 alleviated CAS through regulation of the NF-κB/MLCK/MLC2/ET-1 signaling axis. Collectively, our data suggested that SIRT1 could mediate the deacetylation of NF-κB, disrupt the MLCK/MLC2 pathway and inhibit the expression of ET-1 to relieve CAS, providing a theoretical basis for the prospect of CAS treatment and prevention.

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