BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on...This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.展开更多
This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two ...In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.展开更多
Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MAS...Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.展开更多
Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comme...Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.展开更多
The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized...The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.展开更多
Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the w...Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.展开更多
Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely intertwined.Sarcopenia,traditionally a disease of the older adult and chronic disease population,has been closely studied as on...Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely intertwined.Sarcopenia,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD.They share similar risk factors of insulin resistance and physical inactivity.Given similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice versa.Current research suggests a bidirectional relationship.Given the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver.However,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study.However,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet.Future studies are needed to reach a consensus and reduce diagnostic variation.With similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.展开更多
The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been ful...The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.展开更多
Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD ...Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.展开更多
The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver en...The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.展开更多
Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver diseas...Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.展开更多
Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates ...Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates that junk food disrupts lipid metabolism,alters gut microbiota,and triggers chronic inflammation,leading to systemic metabolic dysfunction.Traditional Chinese medicine(TCM),rooted in holistic regulation of organ systems,blood circulation,and energy balance,offers multi-target plant-based strategies for modulating obesity.This review summarizes key mechanisms through which Chinese medicinal plants counteract obesity,including appetite suppression,regulation of lipid metabolism,activation of thermogenesis,modulation of gut microbiota,and anti-oxidative and anti-inflammatory actions.Representative herbs such as Panax ginseng,Nelumbo nucifera,Cinnamomum cassia,Gynostemma pentaphyllum,and Pueraria lobata exhibit lipid-lowering,glucose-regulating,and inflammation-modulating activity in experimental and clinical studies.Overall,TCM herbal therapies provide a holistic and safe approach to correcting metabolic imbalance through multi-pathway regulation.However,standardized formulation,mechanistic validation,and large-scale clinical trials are urgently required to establish their efficacy and translational value.Future work integrating traditional knowledge with biomedical research will help position TCM-based phytotherapy as a scientifically grounded strategy for obesity prevention and management.展开更多
Objective To analyze the occurrence of metabolic dysfunction-associated fatty liver disease(MAFLD)and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome(OSAHS)and explore the risk factors of ...Objective To analyze the occurrence of metabolic dysfunction-associated fatty liver disease(MAFLD)and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome(OSAHS)and explore the risk factors of MAFLD.Methods This is a cross-sectional study.From January 2022 to October 2024,172 patients with sleep disorders were enrolled in the First Affiliated Hospital of Soochow University,including 38 patients with non-OSAHS,53 patients with mild OSAHS,37 patients with moderate OSAHS,and 44 patients with severe OSAHS.The occurrence of MAFLD was comprehensively judged from three aspects:metabolic dysfunction-associated fatty liver(MAFL),elevated liver enzymes,and liver fibrosis.The situation of MAFLD and the level of related inflammatory markers were compared among the four groups.Binary logistic regression was used to analyze the risk factors for MAFLD in OSAHS.Results There were significant differences in the prevalence of MAFL,the percentage of elevated liver enzymes,and interleukin-6 and tumor necrosis factoralpha levels among the four groups(P<0.05).The differences of fibrosis-4 index and C-reactive protein among the four groups were not statistically significant(P>0.05).Binary logistic regression showed that BMI,triglycerides,longest time of sleep apnea and tumor necrosis factor-alpha were the risk factors for MAFL(P<0.05).BMI,glucose,and apnea-hypopnea index were the risk factors for elevated liver enzymes(P<0.05).Conclusion OSAHS is strongly associated with MAFLD,and the involvement of OSAHS in the occurrence and development of MAFLD may be related to obesity,lipid metabolism disorders,insulin resistance,inflammatory responses,and intermittent hypoxia.展开更多
Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs.However,whether there are microbial markers associated with post-weaning diarrhea remains unknown.In the current study,we c...Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs.However,whether there are microbial markers associated with post-weaning diarrhea remains unknown.In the current study,we compared the microbial community,functions and metabolites between healthy weaned piglets(group H,n=7)and piglets with post-weaning diarrhea(group D,n=7),in order to find out diarrhea associated microbial markers.Each of 7 fecal samples was collected from H and D piglets(weaned at 21 d and sampled at 26 d).The metagenomic and untargeted metabolomic analysis revealed that the microbial composition,function and metabolic profile in D pigs was considerably reshaped,including the reduced abundance and number of Bacteroides,which significantly correlated with the diarrhea status of host.The carbohydrate metabolism,biosynthesis and metabolism,lipid metabolism,amino acid metabolism,and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs.Diarrhea significantly changed the metabolic profiles of fecal microbiota,and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides.In conclusion,the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets.展开更多
Background and aim Metabolic dysfunction-associated fatty liver disease(MAFLD)is an alternative description and classification of non-alcoholic fatty liver disease(NAFLD)that may have better utility than NAFLD in clin...Background and aim Metabolic dysfunction-associated fatty liver disease(MAFLD)is an alternative description and classification of non-alcoholic fatty liver disease(NAFLD)that may have better utility than NAFLD in clinical practice.We performed a meta-analysis to quantify the magnitude of the association between MAFLD and risk of both prevalent and incident chronic kidney disease(CKD).Methods We systematically searched PubMed,Medline(OVID),Embase(OVID),Web of Science and Cochrane Library from database inception until 29 May 2022.We included observational studies examining the association between MAFLD and risk of CKD,defined by estimated glomerular filtration rate≤60 mL/min/1.73 m2 or presence of abnormal albuminuria.Meta-analysis was performed using random-effects models to obtain summary HRs or ORs with 95%CIs.Results Seventeen observational studies with aggregate data on 845753 participants were included in meta-analysis.In the 7 cohort studies,the pooled random-effects HR for incident CKD in patients with MAFLD was 1.29(95%CI 1.17 to 1.41,I2=87.0%).In the 10 cross-sectional studies,the pooled random-effects OR for prevalent CKD in patients with MAFLD was 1.35(95%CI 1.11 to 1.64,I2=92.6%).Conclusion MAFLD is significantly associated with an increased prevalence and incidence of CKD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution o...Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.展开更多
Polycystic ovary syndrome(PCOS)is a prevalent endocrine disorder among women of reproductive age,with a global prevalence ranging from 5%to 18%(Shrivastava and Conigliaro,2023).Currently,a total of 12.13 million cases...Polycystic ovary syndrome(PCOS)is a prevalent endocrine disorder among women of reproductive age,with a global prevalence ranging from 5%to 18%(Shrivastava and Conigliaro,2023).Currently,a total of 12.13 million cases of infertility(Liu et al.,2024)and 0.24 million cases of cardiovascular disease(Wan et al.,2024)are attributable to PCOS worldwide,and nearly 8 billion US dollars are spent in the USA and Europe for the management of PCOS every year.However,there are still many challenges in understanding and treatment of PCOS.展开更多
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
基金Supported by National Natural Science Foundation of China,No.82270594.
文摘This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
文摘In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.
文摘Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.
文摘Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.
文摘The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.
文摘Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.
文摘Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely intertwined.Sarcopenia,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD.They share similar risk factors of insulin resistance and physical inactivity.Given similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice versa.Current research suggests a bidirectional relationship.Given the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver.However,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study.However,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet.Future studies are needed to reach a consensus and reduce diagnostic variation.With similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.
文摘The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.
基金The animal protocols were approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University(SYDW2019-258).
文摘Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.
文摘The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.
文摘Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.
文摘Obesity driven by high-sugar and high-fat dietary patterns has become a major global health challenge and is closely associated with metabolic syndrome,diabetes,and cardiovascular disorders.Growing evidence indicates that junk food disrupts lipid metabolism,alters gut microbiota,and triggers chronic inflammation,leading to systemic metabolic dysfunction.Traditional Chinese medicine(TCM),rooted in holistic regulation of organ systems,blood circulation,and energy balance,offers multi-target plant-based strategies for modulating obesity.This review summarizes key mechanisms through which Chinese medicinal plants counteract obesity,including appetite suppression,regulation of lipid metabolism,activation of thermogenesis,modulation of gut microbiota,and anti-oxidative and anti-inflammatory actions.Representative herbs such as Panax ginseng,Nelumbo nucifera,Cinnamomum cassia,Gynostemma pentaphyllum,and Pueraria lobata exhibit lipid-lowering,glucose-regulating,and inflammation-modulating activity in experimental and clinical studies.Overall,TCM herbal therapies provide a holistic and safe approach to correcting metabolic imbalance through multi-pathway regulation.However,standardized formulation,mechanistic validation,and large-scale clinical trials are urgently required to establish their efficacy and translational value.Future work integrating traditional knowledge with biomedical research will help position TCM-based phytotherapy as a scientifically grounded strategy for obesity prevention and management.
文摘Objective To analyze the occurrence of metabolic dysfunction-associated fatty liver disease(MAFLD)and related inflammatory indicators in obstructive sleep apnea hypopnea syndrome(OSAHS)and explore the risk factors of MAFLD.Methods This is a cross-sectional study.From January 2022 to October 2024,172 patients with sleep disorders were enrolled in the First Affiliated Hospital of Soochow University,including 38 patients with non-OSAHS,53 patients with mild OSAHS,37 patients with moderate OSAHS,and 44 patients with severe OSAHS.The occurrence of MAFLD was comprehensively judged from three aspects:metabolic dysfunction-associated fatty liver(MAFL),elevated liver enzymes,and liver fibrosis.The situation of MAFLD and the level of related inflammatory markers were compared among the four groups.Binary logistic regression was used to analyze the risk factors for MAFLD in OSAHS.Results There were significant differences in the prevalence of MAFL,the percentage of elevated liver enzymes,and interleukin-6 and tumor necrosis factoralpha levels among the four groups(P<0.05).The differences of fibrosis-4 index and C-reactive protein among the four groups were not statistically significant(P>0.05).Binary logistic regression showed that BMI,triglycerides,longest time of sleep apnea and tumor necrosis factor-alpha were the risk factors for MAFL(P<0.05).BMI,glucose,and apnea-hypopnea index were the risk factors for elevated liver enzymes(P<0.05).Conclusion OSAHS is strongly associated with MAFLD,and the involvement of OSAHS in the occurrence and development of MAFLD may be related to obesity,lipid metabolism disorders,insulin resistance,inflammatory responses,and intermittent hypoxia.
基金supported by the National Natural Science Foundation of China(31730091,31872369 and 31672436)。
文摘Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs.However,whether there are microbial markers associated with post-weaning diarrhea remains unknown.In the current study,we compared the microbial community,functions and metabolites between healthy weaned piglets(group H,n=7)and piglets with post-weaning diarrhea(group D,n=7),in order to find out diarrhea associated microbial markers.Each of 7 fecal samples was collected from H and D piglets(weaned at 21 d and sampled at 26 d).The metagenomic and untargeted metabolomic analysis revealed that the microbial composition,function and metabolic profile in D pigs was considerably reshaped,including the reduced abundance and number of Bacteroides,which significantly correlated with the diarrhea status of host.The carbohydrate metabolism,biosynthesis and metabolism,lipid metabolism,amino acid metabolism,and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs.Diarrhea significantly changed the metabolic profiles of fecal microbiota,and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides.In conclusion,the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets.
基金supported by grants from the National Natural Science Foundation of China(82070588 and 82000690)High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032)+1 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT is supported in part by grants from the University School of Medicine of Verona,Verona,ItalyCDB is supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004),UK.
文摘Background and aim Metabolic dysfunction-associated fatty liver disease(MAFLD)is an alternative description and classification of non-alcoholic fatty liver disease(NAFLD)that may have better utility than NAFLD in clinical practice.We performed a meta-analysis to quantify the magnitude of the association between MAFLD and risk of both prevalent and incident chronic kidney disease(CKD).Methods We systematically searched PubMed,Medline(OVID),Embase(OVID),Web of Science and Cochrane Library from database inception until 29 May 2022.We included observational studies examining the association between MAFLD and risk of CKD,defined by estimated glomerular filtration rate≤60 mL/min/1.73 m2 or presence of abnormal albuminuria.Meta-analysis was performed using random-effects models to obtain summary HRs or ORs with 95%CIs.Results Seventeen observational studies with aggregate data on 845753 participants were included in meta-analysis.In the 7 cohort studies,the pooled random-effects HR for incident CKD in patients with MAFLD was 1.29(95%CI 1.17 to 1.41,I2=87.0%).In the 10 cross-sectional studies,the pooled random-effects OR for prevalent CKD in patients with MAFLD was 1.35(95%CI 1.11 to 1.64,I2=92.6%).Conclusion MAFLD is significantly associated with an increased prevalence and incidence of CKD.
基金supported by Seed Fund for Basic Science(2302101604),the University of Hong Kong.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.
基金supported by the National Key Research and Development Program of China(2021YFC2700403)Shanghai Municipal Science and Tech-nology Major Project(2023SHZDZX02)+1 种基金the National Natural Science Foundation of China(81873660 and 32371333)the Science and Technology Commission of Shanghai Municipality(23XD1423300 and 23ZR1411000).
文摘Polycystic ovary syndrome(PCOS)is a prevalent endocrine disorder among women of reproductive age,with a global prevalence ranging from 5%to 18%(Shrivastava and Conigliaro,2023).Currently,a total of 12.13 million cases of infertility(Liu et al.,2024)and 0.24 million cases of cardiovascular disease(Wan et al.,2024)are attributable to PCOS worldwide,and nearly 8 billion US dollars are spent in the USA and Europe for the management of PCOS every year.However,there are still many challenges in understanding and treatment of PCOS.
