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silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

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World Journal of Gastroenterology 2024年第11期30卷 1588-1608页

作者： Xing-Nian Zhou Quan Zhang Hong Peng Yu-Jie Qin Yu-Hong Liu Lu Wang Ming-Liang Cheng Xin-Hua Luo Hong Li Department of Infectious Diseases The Affiliated Hospital of Guizhou Medical UniversityGuizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina Department of Infectious Diseases Guizhou Provincial People's HospitalGuiyang 550001Guizhou ProvinceChina

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and *** silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and *** To investigate the association between ferroptosis and pyroptosis and the upstream regulatory *** This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce *** D(GSDMD)^(-/-)mice were used as an experimental *** changes in liver tissue were monitored by hematoxylin and eosin ***,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial ***-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain ***1,p53,and GSDMD were assessed by immunofluorescence *** Serum AST and ALT levels were elevated in patients with ***1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver *** the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was *** mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were *** vitro,knockdown of p53 and overexpression of GPX

关键词： silent information regulator sirtuin 1 Ferroptosis Pyroptosis p53/glutathione peroxidase 4/gasdermin D Acute liver failure

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Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

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World Journal of Gastroenterology 2024年第23期30卷 2931-2933页

作者： Chun-Yao Cheng Wen-Rui Hao Tzu-Hurng Cheng Department of Medical Education National Taiwan University HospitalTaipei 100225Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan Department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404333Taiwan

In this editorial we comment on the article published in a recent issue of the World Journal of *** liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient *** research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of *** is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue *** comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin *** from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these *** across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

关键词： silent information regulator sirtuin 1 Ferroptosis Pyroptosis P53/glutathione peroxidase 4/gasdermin D Acute liver failure

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Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

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World Journal of Gastroenterology 2024年第27期30卷 3273-3277页

作者： Tsvetelina Velikova Milena Gulinac Medical Faculty Sofia University St Kliment OhridskiSofia 1407Bulgaria Department of General and Clinical Pathology Medical University of PlovdivPlovdiv 4002Bulgaria

In this editorial,we comment on three articles published in a recent issue of World Journal of *** is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains ***,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further ***,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly *** studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

关键词： Gastrointestinal diseases Autophagy Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level silent information regulator sirtuin 1 Acute liver failure

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