1.Molecular mechanism of pyroptosis in sepsis
Jian GONG ; Fanbo QIN ; Chunmu MIAO ; Jianping GONG
International Journal of Surgery 2019;46(3):203-207
Sepsis is a disease with a high mortality rate worldwide,which seriously threatens human life and health.Due to the complexity of its pathogenesis,diagnosis and treatment are often very difficult.Pyroptosis is a newly discovered pro-inflammatory form of programmed cell death,which occurs predominantly in professional phagocytes.During sepsis,appropriate pyroptosis is required for defense against bacterial infection,however,excessive pyroptosis will also aggravate the inflammatory reaction of sepsis.Therefore,the study of the signaling pathways and regulatory mechanisms of pyroptosis in sepsis may contribute to identify potential therapeutic targets.Hence,the study provide an overview of the recent advances which focus on the two signaling pathway of pyroptosis,some caspases which have found new effects,GSDM family and the crosstalk between different form of cell death.
2.Wortmannin inhibits the activity of NLRP3 in Kupffer cells through the Chemerin/CMKLR1 pathway and relieves nonalcoholic fatty liver in mice
Mingbing WU ; Wenfeng ZHANG ; Jianping GONG ; Chunmu MIAO
Chongqing Medicine 2018;47(17):2279-2284
Objective To investigate the role and mechanism of inflammatory response of Kupffer cells induced by Chemerin in the progression of non-alcoholic fatty liver disease (NAFLD) in mice.Methods Wortmannin was used to treated on KCs which pre-treated with Chemerin in vitro for two hours,and treated on C57BL/6J mice which was fed with a high-fat die.Levels of cytokines in supernatant/serum were tested by enzyme-linked immunosorbent assays(ELISA);mRNA and protein levels of KCs' Chemokine-like receptor 1 (CMKLR) and nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in vivo and vitrowere detected by real time polymerase chain reaction(real time-PCR) and Western blot;changes of mouse weight were recorded;insulin resistance and glucose tolerance were detected;the severity of liver steatosis was evaluated by HE staining combined with NAS score.Results The levels of interleukin 1β (IL-1β) and IL-18 in the KCs and mice treated with wortmannin were significantly lower than the KCs treated with Chemerin only and mice fed with high fat diet only.The mRNA and protein levels of CMKLR1 and inflammasome 3 (NLRP3) were significantly lower in the KCs and mice treated with Wortmannin than the KCs treated with Chemerin only and mice fed with high fat diet only.In addition,changes in mouse weight,hepatic steatosis,liver function,insulin resistance and glucose tolerance were much milder in mice treated with Wortmannin than those mice fed with high fat diet.Conclusion Wortmannin alleviates liver steatosis and inflammation mediated by KCs via down-regulating the expression of CMKLR1 and NLRP3 in high fat diet fed mice.
3.Advance on surgical treatment of hepatolithiasis
Peng CHEN ; Zheyu ZHU ; Feifan WU ; Siyu WANG ; Yiyu HU ; Weimin WANG ; Chunmu MIAO ; Yunbing WANG ; Xiong DING
The Journal of Practical Medicine 2023;39(21):2857-2860
Hepatolithiasis is a common biliary tract disease in China and other Asian countries.It has insidious onset,recurrent disease,and may lead to biliary cirrhosis or even cancer in the late stage without inter-vention.At present,surgery is considered to be the best choice for treatment.In the 21st century of minimally inva-sive surgery,traditional procedures such as partial hepatectomy,choledochotomy,cholangioenterostomy and liver transplantation can be performed with the assistance of laparoscopy and da Vinci robots,and emerging endoscopic techniques such as endoscopic retrograde cholangiopancreatography(ERCP)and percutaneous transhepatic cho-ledochoscopic lithotripsy(PTCSL)have also been developed,bringing better treatment for patients with hepatoli-thiasis.As treatment options are becoming more varied,there are also some clinical problems that need to be addressed.In this article,we would like to briefly review the current surgical treatment modalities in order to provide a theoretical basis for optimizing the treatment modalities.