The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide...The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.展开更多
Ovarian cancer,particularly high-grade serous ovariancancer(HGSOC),remains the most lethal gynecologicalmalignancy,with a 5-year survival rate of around 40%due to late diagnosis,recurrence,and the developmentof chemor...Ovarian cancer,particularly high-grade serous ovariancancer(HGSOC),remains the most lethal gynecologicalmalignancy,with a 5-year survival rate of around 40%due to late diagnosis,recurrence,and the developmentof chemoresistance[1,2].Mutations in tumor protein 53(TP53)occur in over 96%of HGSOC cases,impairing itstumor-suppressive functions,including cell cycle control,DNA repair,and apoptosis.Mutant TP53 promotes tumorprogression,genomic instability,and resistance to stan-dard therapies,thereby worsening patient outcomes[3,4].Death-associated protein kinase 1(DAPK1)is a key reg-ulator of apoptosis and autophagy[5,6].展开更多
基金Federal Ministry of Education and Research(Q-HCC,01KD2214)the Sino-German Center for Research Promotion(GZ-1546 and C-0012)+5 种基金the State Ministry of Baden-Wuerttemberg for Sciences,Research and Arts supporting the Clinical Cooperation Unit Healthy Metabolism at the Center for Preventive Medicine and Digital Health(CCU Healthy Metabolism)the Baden-Wuerttemberg Center for Digital Early Disease Detection and Prevention(BW-ZDFP)the Foundation for Biomedical Alcohol Research,Schriesheim,Germanyfunded by the Federal Ministry of Education and Research(BMBF)the Ministry of Culture and Science of the German State of North Rhine-Westphalia(MKW)(NRW Rueckkehrprogramm)under the Excellence Strategy of the Federal Government and the Länderthe German Research Foundation(DFG,403224013-SFB1382,gut-liver axis).
文摘The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.
基金supported by grants from Deutsche Kreb-shilfe(70116875)the German Cancer Consortium(DKTK,Heidelberg).
文摘Ovarian cancer,particularly high-grade serous ovariancancer(HGSOC),remains the most lethal gynecologicalmalignancy,with a 5-year survival rate of around 40%due to late diagnosis,recurrence,and the developmentof chemoresistance[1,2].Mutations in tumor protein 53(TP53)occur in over 96%of HGSOC cases,impairing itstumor-suppressive functions,including cell cycle control,DNA repair,and apoptosis.Mutant TP53 promotes tumorprogression,genomic instability,and resistance to stan-dard therapies,thereby worsening patient outcomes[3,4].Death-associated protein kinase 1(DAPK1)is a key reg-ulator of apoptosis and autophagy[5,6].
