Anti-HMGB1 monoclonal antibody

Previous studies demonstrated the effect of Trimetazidine (TMZ) on alleviating cardiomyocytes Hypoxia/Reoxygenation (H/R) injuries and the protective effect of autophagy on Ischemia-Reperfusion (I/R) cell injuries. However, whether the protection mechanism of TMZ was also involved in autophagy remained unclear. Our study introduces the role of HMGB1 to examine the regulation of TMZ on autophagy against cardiomyocytes H/R injuries. After cell extraction and identification through anti-alpha-actin staining, the cardiomyocytes were made hypoxic and reoxygenated, each for 3 h, and then treated with various concentrations of TMZ and transfected with siHMGB1. Cell viability and apoptosis were measured by the MTS method and flow cytometry, respectively. The expressions of autophagy-related factors (LC3-I, LC3-II, Beclin-1) and HMGB1 were detected by Western blot and qPCR. Lactate dehydrogenase (LDH) release was assessed by ELISA kit. The cardiomyocytes were extracted. H/R decreased the cell viability and increased the LDH level and apoptosis of cardiomyocytes. TMZ had no effect on untreated cardiomyocytes, but it reversed the adverse impact of H/R on cardiomyocytes. The expressions of LC3-II, Beclin-1, and HMGB1 and the ratio of LC3-II/LC3-I were increased in H/R-processed cardiomyocytes and further raised by TMZ pretreatment. However, siHMGB1 transfection aggravated the impact of H/R on cardiomyocytes and suppressed the protective effects of TMZ on H/R damaged cardiomyocytes by increasing the LDH level and apoptosis and reducing the viability of cardiomyocytes. Autophagy was inhibited by siHMGB1 in TMZ-pretreated and H/R-processed cardiomyocytes. TMZ protected cardiomyocytes against H/R injuries may through regulating HMGB1 to increase the impact of autophagy.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HNIGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HNIGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HNIGB1. The miR-142-3p/HNIGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.