| 1 | Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis显示文摘Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine(DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium(DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine,the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota. | Chenjie Qin Huilu Zhang Linghao Zhao Min Zeng Weijian Huang Gongbo Fu Weiping Zhou Hongyang Wang Hexin Yan | 2018 | Science China(Life Sciences)2018，61，12： | 8 |
| 2 | Conversion of hepatoma cells to hepatocyte-like cells by defined hepatocyte nuclear factors显示文摘Normal cells become cancer cells after a malignant transformation,but whether cancer cells can be reversed to normal status remains elusive.Here,we report that the combination of hepatocyte nuclear factor IA (HNFIA),HNF4A and forkhead box protein A3 (FOXA3)synergistically reprograms hepatocellular carcinoma (HCC)cells to hepatocyte-like cells (reprogrammed hepatocytes, rHeps).Our results show that rHeps lose the malignant phenotypes of cancer cells and retrieve hepatocyte-specific characteristics including hepatocyte-like morphology;global expression pattern of genes and specific biomarkers of hepatocytes;and the unique hepatic functions of albumin (ALB)secretion,glycogen synthesis,low-density lipoprotein (LDL)uptake,urea production, cytochrome P450 enzymes induction and drug metabolism.Intratumoral injection of these three factors efficiently shrank patientderived tumor xenografts and reprogrammed HCC cells in vivo.Most importantly,transplantation of rHeps in the liver of fumarylacetoacetate hydrolase-deficient (Fah^-/-)mice led to the reconstruction of hepatic lobules and the restoration of hepatic function.Mechanistically,exogenous expression of HNF1A,HNF4A and FOXA3 in HCC cells initiated the endogenous expression of numerous hepatocyte nuclear factors,which promoted the conversion of HCC cells to hepatocyte-like cells.Collectively,our results indicate the successful conversion of hepatoma cells to hepatocyte-like cells,not only extending our current knowledge of cell reprogramming but also providing a route towards a novel therapeutic strategy for cancer. | Zhuo Cheng Zhiying He Yongchao Cai Cheng Zhang Gongbo Fu Hengyu Li Wen Sun Changcheng Liu Xiuliang Cui Beifang Ning Daimin Xiang Tengfei Zhou Xiaofeng Li Weifen Xie Hongyang Wang Jin Ding | 2019 | Cell Research2019，29，2： | 3 |
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