Our previous study demonstrated that angiogenesis increased during the recovery of heat-denatured endothelial cells. However, the mechanism is still unclear. This study aimed to investigate the relation of autophagy and angiogenesis during the recovery of heat-denatured endothelial cells. A rat deep partial-thickness burn model and heat-denatured human umbilical vein endothelial cells (HUVECs) model (52 °C for 35 s) were used. Autophagy increased significantly in the dermis and HUVECs in a time-dependent manner after heat denaturation and recovery for 2–5 days. Rapamycin-mediated autophagy enhanced the pro-angiogenic effect, evidenced by increased proliferation and migration of HUVECs, and formation of tube-like structures. Autophagy inhibition by 3-Methyladenine (3-MA) abolished the angiogenesis in heat-denatured HUVECs after recovery for 3–5 days. Moreover, heat denaturation augmented the phosphorylation of AMP-activated protein kinase (AMPK) but reduced the phosphorylation of Akt and mTOR in HUVECs. Furthermore, autophagy inhibition by antioxidant NAC, compound C or AMPK siRNA impaired cell proliferation, migration and tube formation heat-denatured HUVECs. At last, the in vivo experiments also showed that inhibition of autophagy by bafilomycin A1 could suppress angiogenesis and recovery of heat-denatured dermis.Taken together, we firstly revealed that autophagy promotes angiogenesis via AMPK/Akt/mTOR signaling during the recovery of heat-denatured endothelial cells and may provide a potential therapeutic target for the recovery of heat-denatured dermis.

Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2.

Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.