Babao Dan attenuates acute ethanol-induced liver injury via Nrf2 activation and autophagy.

BACKGROUND: Babao Dan (BBD), a traditional Chinese medicine, has been used as a complementary and alternative medicine to treat multifarious liver diseases. In this study, we aimed to observe its protective effect on ethanol-induced liver injury and explore potential mechanisms. METHODS: Mice pretreated with BBD (0.125, 0.25 and 0.5 g/kg BW) were administrated by ethanol gavage (5 g/kg BW). Liver injury biomarkers and hepatic redox parameters were evaluated by histopathology as well as serum and hepatic content analysis. AML-12 cell was also utilized to determine the efficacy of BBD against ethanol-induced hepatotoxicity. RESULTS: Drunkenness experiment showed that the latency was significantly increased and the drunken sleep time was decreased in mice pretreated with BBD. We then found that BBD could reduce hepatic lipid peroxidation and steatosis induced by ethanol exposure. BBD could also suppress ethanol-induced depletion of hepatic antioxidant enzyme. Besides that, BBD treatment lessened the induction of hepatic cytochrome P450 2E1, a major contributor to ethanol-mediated oxidative stress, and up-regulated the expression of nuclear factor erythroid 2-related factor 2 and its two transcriptional targets hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit. Furthermore, autophagy induced by BBD contributed to hepatoprotection activity. CONCLUSIONS: Our results suggest that BBD can markedly dispel acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy.

Awareness and associated factors of tobacco hazards among middle school personnel in Shanghai / 中国学校卫生

Objective@#To understand current situation of the awareness of tobacco hazards among middle school personnel in Shanghai and to explore its influencing factors,and to provide reference for making targeted measures to control tobacco hazards in schools.@*Methods@#A total of 30 middle schools in Shanghai were selected by stratified cluster sampling method. The questionnaires were used to investigate the smoking prevalence and tobacco hazard awareness of 3 007 faculty members.@*Results@#The total smoking rate of school personnel in Shanghai was 8.25%; the complete correct rate on the harm of smoking and second-hand smoke was only 19.72% and 23.74%, respectively. The correct awareness rate of harm caused by tobacco, such as stroke, osteoporosis and heart disease, was less than 50%. Gender, education level, smoking behavior and tobacco control training were related with tobacco hazards perception level.@*Conclusion@#The smoking rate among middle school personnel in Shanghai has been generally improved, but the faculty and staff have an unbalanced understanding of tobacco hazards. The school's tobacco control education should be targeted. Smoking, men and personnel with relatively low education levels are the key groups in school tobacco control education.

Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway.

Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1ß has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1ß promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1ß in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1ß indicated poor prognosis. We overexpressed HNF-1ß in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1ß than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1ß. More importantly, HNF-1ß promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1ß not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-κB/HIF-1α pathway.

Due to the existence of cancer stem cells (CSCs), persistence and relapse of human hepatocellular carcinoma (HCC) are common after treatment with existing anti-cancer therapies. Emerging evidence indicates that lipopolysaccharide (LPS) plays a crucial role in aggravating HCC, but information about the effect of LPS on CSCs of HCC remains scant. Here, we report that the stemness of CD133(+) CSCs sorted from the human HCC cell line Huh7 was maintained well when cells were cultured with LPS. The reduction of CD133 expression was much lesser in cultured CSCs in the presence of LPS. In response to LPS stimulation, CSCs showed an increase in their activity of clonogenesis and tumorigenesis. LPS also supported maintaining CSC abilities of migration, invasion, and chemo-resistance. Treatment with HIF-1α-specific siRNA significantly reduced CD133 expression by CSCs at both mRNA and protein levels. Further, the expression of HIF-1α and CD133 was reduced in LPS-stimulated CSCs when the NF-κB inhibitor was added to the cell culture. HIF-1α-specific siRNA also effectively counteracted the effect of LPS on maintaining CSC abilities of migration and invasion. These data indicate that LPS, an important mediator in the liver tumor microenvironment, supports the maintenance of CSC stemness through signaling of the NF-κB/HIF-1α pathway. Our current study highlights LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC.