Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Objective To investigate the expression and clinical significance of microRNA-148a-3p (miR-148a-3p) in lung adenocarcinoma and analyze the effect and mechanism of miR-148a-3p on radiotherapy sensitivity of lung adenocarcinoma cells by targeting the protein core 1β13-galactosyltransferase 1(C1GALT1). Methods Seventy-six patients' tumor tissues from lung adenocarcinoma tissue microarrays and lung adenocarcinoma A549 cell line were selected for the study. The miR-148a-3p in situ hybridizations (ISH) and C1GALT1 immunohistochemical staining were performed on the tissue microarrays to analyze the correlations of miR-148a-3p expression with clinical pathology, prognosis and C1GALT1 expression in the tumor tissues of the 76 patients with lung adenocarcinoma. A549 cells were transfected with miR-148a-3p overexpression plasmid by using cell transfection technique; the clone formation assay was used to detect the sensitivity of the transfected cells for radiotherapy after receiving 2 Gy radiotherapy; the protein expression level of cellular C1GALT1 was detected by western blot; the targeted regulatory relationship between miR-148a-3p and C1GALT1 was verified by dual-luciferase reporter gene experiment; the mechanism of miR-148a-3p regulating the sensitivity of A549 cells to radiotherapy was analyzed by co-transfection technique. Results Low expression of miR-148a-3p in 76 cases of lung adenocarcinoma tissues was significantly associated with lymph node metastasis (P=0.012); the prognosis of patients with high expression of miR-148a-3p was significantly better than that of patients with low expression of miR-148a-3p (P=0.005); there was a significant negative correlation between the expression of miR-148a-3p and C1GALT1 in lung adenocarcinoma tissues (P=0.023). Multivariate analysis showed that low expression of miR-148a-3p, T staging and lymph node metastasis were the independent risk factors for prognosis. Clone formation experiment showed that the number of clone formation in the miR-148a-3p overexpression group was significantly lower than that in the control group (P < 0.001); western blot result showed that overexpression of miR-148a-3p was able to significantly down-regulate the level of C1GALT1 protein in cells (P < 0.001). Dual luciferase reporter gene experiment showed that miR-148a-3p was able to regulate the expression of C1GALT1 by binding to the 3'UTR of C1GALT1. Functional rescue experiment showed that C1GALT1 could partially offset the radiosensitization effect of miR-148a-3p. Conclusion Low expression of miR-148a-3p in lung adenocarcinoma is significantly associated with lymph node metastasis, high expression of C1GALT1 and poor prognosis, and miR-148a-3p can enhance the radiosensitivity of lung adenocarcinoma cells by negatively regulating the expression of C1GALT1.