Liver is one of the vital organs in the human body and liver injury will have a very serious impact on human damage. Gypenoside XLIX is a PPAR-α activator that inhibits the activation of the NF-κB signaling pathway. The components of XLIX have pharmacological effects such as cardiovascular protection, antihypoxia, anti-tumor and anti-aging. In this study, we used cecum ligation and puncture (CLP) was used to induce in vivo mice hepatic injury, and lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells, evaluated whether Gypenoside XLIX could have a palliative effect on sepsis-induced acute liver injury via NF-κB/PPAR-α/NLRP3. In order to gain insight into these mechanisms, six groups were created in vivo: the Contol group, the Sham group, the CLP group, the CLP + XLIX group (40 mg/kg) and the Sham + XLIX (40 mg/kg) group, and the CLP + DEX (2 mg/kg) group. Three groups were created in vitro: Control, LPS, LPS + XLIX (40 μM). The analytical methods used included H&E staining, qPCR, reactive oxygen species (ROS), oil red O staining, and Western Blot. The results showed that XLIX attenuated hepatic inflammatory injury in mice with toxic liver disease through inhibition of the TLR4-mediated NF-κB pathway, attenuated lipid accumulation through activation of PPAR-α, and attenuated hepatic pyroptosis by inhibiting NLRP3 production. Regarding the imbalance between oxidative and antioxidant defenses due to septic liver injury, XLIX reduced liver oxidative stress-related biomarkers (ALT, AST), reduced ROS accumulation, decreased the amount of malondialdehyde (MDA) produced by lipid peroxidation, and increased the levels of antioxidant enzymes such as glutathione (GSH) and catalase (CAT). Our results demonstrate that XLIX can indeed attenuate septic liver injury. This is extremely important for future studies on XLIX and sepsis, and provides a potential pathway for the treatment of acute liver injury.

2023-10-01·Nature metabolism

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.

Article

作者: Song, Yongfeng ; Zhao, Jiajun ; Xu, Jiawen ; Yao, Zhenyu ; Wang, Dawei ; Yang, Rui ; Liu, Jun ; Wu, Yingjie ; Gao, Ling ; Gong, Ying ; Kong, Junjie ; Niu, Shaona ; Shao, Shanshan ; Fu, Lili ; Zhao, Xinya ; Wang, Xuemin ; Lin, Xiaoyan ; Xu, Yunyun ; Chen, Wenbin ; Zhang, Zhenhai ; Wan, Qiang ; Xuan, Qiuhui ; Proud, Christopher G ; Guo, Honglin ; Liu, Sijin ; Li, Qihang ; Bo, Tao ; Wang, Ximing ; Wang, Qian

Under normal conditions, insulin promotes hepatic de novo lipogenesis (DNL). However, during insulin resistance (IR), when insulin signalling is blunted and accompanied by hyperinsulinaemia, the promotion of hepatic DNL continues unabated and hepatic steatosis increases. Here, we show that WD40 repeat-containing protein 6 (WDR6) promotes hepatic DNL during IR. Mechanistically, WDR6 interacts with the beta-type catalytic subunit of serine/threonine-protein phosphatase 1 (PPP1CB) to facilitate PPP1CB dephosphorylation at Thr316, which subsequently enhances fatty acid synthases transcription through DNA-dependent protein kinase and upstream stimulatory factor 1. Using molecular dynamics simulation analysis, we find a small natural compound, XLIX, that inhibits the interaction of WDR6 with PPP1CB, thus reducing DNL in IR states. Together, these results reveal WDR6 as a promising target for the treatment of hepatic steatosis.

2019-07-01·Clinical Nuclear Medicine3区 · 医学

Mentoring, Coaching, and Burnout

3区 · 医学

Article

作者: Harolds, Jay A

AbstractMentoring and coaching are activities that are quite helpful in having doctors become happy, engaged, and successful in their work and also help prevent burnout. Coaching helps promote a better balance between work, rest, family, and fun pursuits. Coaching also helps the one being coached develop better emotional awareness, become more cognizant of the good he/she has done, develop a positive outlook on life, find more meaning in work, and be better able to overcome obstacles. In ways such as these, the coach helps his/her client become more resilient and recover from burnout.

100 项与 XLIX 相关的药物交易

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