Metabolic dysfunction-associated steatohepatitis(MASH)is the progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD),and closely associated with a high risk of liver-related morbidity and m...Metabolic dysfunction-associated steatohepatitis(MASH)is the progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD),and closely associated with a high risk of liver-related morbidity and mortality.Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH,the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown.This clinicopathological study aimed to determine the association of neutrophilic crown-like structures(CLSs)in liver biopsies and evaluate their relevance to the histological diagnosis of MASH.A total of 483 morbidly obese adults who underwent bariatric surgery were recruited.Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3.All participants were classified into 4 histological subgroups:no MASLD(118,24.4%),MASLD(76,15.7%),borderline MASH(185,38.3%),and definite MASH(104,21.5%).In the discovery cohort(n=379),the frequency of neutrophilic CLSs increased in line with the severity of liver disease.The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH.At a cutoff value of<0.3 per 20×microscopic field,the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH;a cutoff at>1.3 per 20×microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups(no MASLD,MASLD,and borderline MASH).The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort(n=104).The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs.In conclusion,neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.展开更多
CCAAT/enhancer-binding proteins(C/EBPs)are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate tar...CCAAT/enhancer-binding proteins(C/EBPs)are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression.C/EBPs play important roles in various physiological processes,and their abnormal function can lead to various diseases.Recently,accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues.During fibrosis,various C/EBPs can exert distinct functions in the same organ,while the same C/EBP can exert distinct functions in different organs.Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs;therefore,novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention.In this review,we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.展开更多
基金financially supported by NSFC(82374171 and 81570701)the Natural Science Foundation of Guangdong Province(2024A1515012945)the Key Laboratory of Model Animal Phenotyping and Basic Research in Metabolic Diseases(2018KSYS003).
文摘Metabolic dysfunction-associated steatohepatitis(MASH)is the progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD),and closely associated with a high risk of liver-related morbidity and mortality.Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH,the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown.This clinicopathological study aimed to determine the association of neutrophilic crown-like structures(CLSs)in liver biopsies and evaluate their relevance to the histological diagnosis of MASH.A total of 483 morbidly obese adults who underwent bariatric surgery were recruited.Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3.All participants were classified into 4 histological subgroups:no MASLD(118,24.4%),MASLD(76,15.7%),borderline MASH(185,38.3%),and definite MASH(104,21.5%).In the discovery cohort(n=379),the frequency of neutrophilic CLSs increased in line with the severity of liver disease.The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH.At a cutoff value of<0.3 per 20×microscopic field,the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH;a cutoff at>1.3 per 20×microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups(no MASLD,MASLD,and borderline MASH).The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort(n=104).The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs.In conclusion,neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.
基金supported by the Major basic and applied basic research projects of Guangdong Province of China(2019B030302005)the Natural Science Foundation of China(81830113)+2 种基金the National Key Research and Development Program of China(2018YFC1704200)the Basic and applied basic research project of Guangdong Province of China(2020A1515010155)the“Innovation and Strengthening University Project”Subsidized Project of Guangdong Pharmaceutical University(2018KTSCX112).
文摘CCAAT/enhancer-binding proteins(C/EBPs)are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression.C/EBPs play important roles in various physiological processes,and their abnormal function can lead to various diseases.Recently,accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues.During fibrosis,various C/EBPs can exert distinct functions in the same organ,while the same C/EBP can exert distinct functions in different organs.Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs;therefore,novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention.In this review,we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.
