1.The status quo, problems and reform proposals on salary system of medical personnel in Shanghai
Xueli DU ; Su XU ; Tiefeng XU ; Yanhua NI ; Xiliang LENG ; Lu CHEN ; Guangwen GAO ; Chen FU
Chinese Journal of Health Policy 2015;(8):4-9
The establishment of a scientific salary system is a key measure to improve the incentive and re-straint mechanisms, adjust and optimize the relations of the production, release the reform “bonus”, and is also an important health care reform today. In order to establish a scientific salary system of medical personnel adapting to the health industry characteristics, the paper makes an investigation on the salary level in the years of 2010—2012 in Shanghai, and analyzes the main problems of the present performance pay policy. On this basis, starting from the point of the health industry characteristics, the paper builds the salary system of medical personnel containing the comprehensive budget management, theoretical workload for approval, authorized personnel, performance appraisal and distribution, structural proportion within the industry, fund distribution management through the establishment of the salary level’s average wage and social linkage mechanism, and builds a theoretical framework on salary system of medical personnel in Shanghai.
2.The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.
Yiwei ZHU ; Lin LEI ; Xinghui WANG ; Linfang CHEN ; Wei LI ; Jinxia LI ; Chenchen ZHAO ; Xiliang DU ; Yuxiang SONG ; Wenwen GAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2023;13(4):1616-1630
Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.
3.Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway.
Xiliang DU ; Chiara DI MALTA ; Zhiyuan FANG ; Taiyu SHEN ; Xiaodi NIU ; Meng CHEN ; Bo JIN ; Hao YU ; Lin LEI ; Wenwen GAO ; Yuxiang SONG ; Zhe WANG ; Chuang XU ; Zhijun CAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2022;12(6):2869-2886
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.