Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic f...Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic fatty liver disease.With the rise of intensive poultry farming,the incidence of FLHS has markedly increased,resulting in significant economic losses in the poultry industry.The gut microbiota plays a crucial role in host digestion,metabolism,and immune regulation,particularly in liver diseases.Gut microbiota and its metabolites influence liver health via the gut-liver axis.This review aims to explore metabolite-mediated interactions between the laying hens and the gut microbiota,elucidating their role in the pathogenesis of FLHS.Host-derived metabolites,such as lipids,bile acids,amino acids,and carbohydrates,regulate the structure and function of the gut microbiota through the gut-liver axis,playing a role in FLHS progression.Concurrently,microbial metabolites,including short-chain fatty acids,bile acids,and amino acid derivatives,influence hepatic lipid metabolism,inflammation,and oxidative stress,driving the development of FLHS.Key microbes,such as Bacteroides,Lactobacillus,and Akkermansia muciniphila,are considered potential therapeutic targets due to their involvement in metabolite production.By integrating multi-omics data and mechanistic studies,this review highlights the central role of host–gut microbiota communication in FLHS and provides a theoretical basis and research direction for the development of microbiota-based intervention strategies.展开更多
Changes in intestinal microecology play a crucial role in the pathogenesis and progression of metabolic diseases.Lycium barbarum polysaccharide(LBP)and quinoa ultrafine powder diet is a promising sources of prebiotics...Changes in intestinal microecology play a crucial role in the pathogenesis and progression of metabolic diseases.Lycium barbarum polysaccharide(LBP)and quinoa ultrafine powder diet is a promising sources of prebiotics.However,the potential synergistic effects of combining them as a microbiota-targeted dietary supplement to mitigate lipid accumulation in nonalcoholic fatty liver disease(NAFLD)remain unclear.Our study aims to provide evidence for the application food/nutrient synergy interventions in NAFLD management,and also to support the clarification of these mechanisms.Following 12 weeks of a high-fat diet(HFD)-inducing NAFLD and an 11-week intervention in rats,the combination of LBP and quinoa ultrafine powder significantly decreased hepatocyte lipid accumulation and improved lipid metabolism disorders compared with those using either LBP or quinoa ultrafine powder alone.The combination increased beneficial intestinal microbiota,such as Lactobacillus acidophilus,Roseburia,Ruminococcus 2,and Prevotella,promoting the production of short-chain fatty acids,notably butyric acid,and then activated AMP-activated protein kinase/sterol regulatory element-binding protein 1C/stearoyl-CoA desaturase 1(AMPK/SREBP-1C/SCD-1)signaling.Combining LBP with quinoa ultrafine powder is a promising microbiota-targeted dietary supplement for ameliorating lipid disorders in NAFLD.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as...Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as a comprehensive intervention on human health and immune status.This study used a 14-day continuous drinking intervention consisting of 5 beers,namely white beer,India pale ale(IPA),Pilsner,non-alcoholic beer,and premium lager beer.Surprisingly,our findings indicate that consuming white beer has little impact on the gut microbiota and physiological condition of mice,whereas consuming other types of beer leads to an increase in Lactobacillus and a decrease in Lachnospiraceae.In addition,we devised an extended feeding experiment to investigate the comparative safety and health benefits of consuming white beer.The research showed that when mice drank excessive quantities of white beer over 42 days,the intestines of the mice had more Prevotellaceae and the Firmicutes to Bacteroidetes ratio(F/B ratio)had a decline from 1.29 to 0.38.The levels of acetic acid,propionic acid,and isobutyric acid increased from 1.0,0.27,and 0.015 mg/g to 1.28,0.38,and 0.037 mg/g,respectively(P<0.05).There were no significant changes observed in the levels of most measured cytokines in the colon tissue of mice that consumed beer,however,there was an increase in the concentration of the inflammatory factor tumor nesrosis factor-α(TNF-α)from 135.86 pg/mL in the control group to 189.78 pg/mL in the white beer group(P<0.01).These results give us real-world proof that we can use to study how different beers affect the host’s health and satisfaction in future research.展开更多
Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has l...Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.展开更多
Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of ...Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of fatty acids.Recent findings from nonruminant studies revealed that long chain fatty acyl-CoA ligase 4(ACSL4)could play a role in the regulation of cellular fatty acid metabolism,but the mechanisms by which ACSL4 mediates cellular lipid metabolism in response to BHB remains unclear.To achieve the aims,we conducted in vivo or in vitro analyses using bovine mammary gland biopsies and the immortalized mammary epithelial cell line(MAC-T).The in vivo study(n=6 cows per group)involved healthy cows(plasma BHB<0.60 mmol L^(–1))or ketotic cows(plasma BHB>2.0 mmol L^(–1))from which mammary gland tissue was biopsied.In vitro,MAC-T cells were challenged with 0,0.3,0.6,1.2,or 2.4 mmol L^(–1)BHB for 24 h to determine an optimal dose.Subsequently,MAC-T were incubated with 1.2 mmol L^(–1)BHB for 0,3,6,12,24,or 48 h.Furthermore,MAC-T cells were treated with small interfering ACSL4(siACSL4)for 24 h or ACSL4 overexpression plasmid(pcACSL4)for 36 h followed by a challenge with 1.2 mmol L^(–1)BHB for 24 h.Results showed that increased mRNA and protein abundance of lipogenic genes were linked to both mammary gland and in vitro challenge with BHB.BHB increased fatty acid content by activating ACSL4 expression,whereas inhibition of ACSL4 reduced BHB-induced reactive oxygen species(ROS)overproduction,enhancement of mitochondrial membrane potential,increase in fatty acid content,and lipid droplet accumulation.Furthermore,we also elevated ACSL4 expression with an overexpression plasmid to clarify its molecular role in response to BHB challenge.ACSL4 overexpression enhances BHB-induced lipid droplet accumulation by increased fatty acid content.Overall,the information showed that ACSL4 is crucial for the process of producing fatty acids from exogenous BHB.Reduced ACSL4 decreased fatty acid content and lipid droplet accumulation,improved mitochondrial function,directed more fatty acids towards oxidation.Thus,ACSL4 plays an important role in determining the fate of intracellular fatty acids and BHB in BMECs.展开更多
The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pat...The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.展开更多
Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial re...Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial research has reported the therapeutic potential of Omega-3 fatty acids for the central nervous system,particularly after traumatic SCI.Omega-3 fatty acids may contribute to improving SCI recovery through their anti-inflammatory,anti-oxidative,neurotrophic,and membrane integrity-preserving properties.These functions of Omega-3 fatty acids are primarily mediated via the activation of G protein-coupled receptor 120(GPR120),commonly known as the fish oil-specific receptor.Advancements in understanding of the molecular mechanisms of GPR120’s recognition of Omega-3 fatty acids and its downstream signaling mechanisms has significantly promoted research on the pharmacological potential of Omega-3 fatty acids and the development of highly selective and high-affinity alternatives.This review aims to provide in-depth analysis of the comprehensive therapeutic potential of Omega-3 fatty acids for SCI and its accompanying complications,and the prospects for developing novel drugs based on the recognition of Omega-3 fatty acids by GPR120.展开更多
Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in rece...Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwid...Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.展开更多
Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,n...Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,non-NAFLD patients with MA,and patients with NAFLD without MA underwent liver biopsy.Homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride/high-density lipoprotein cholesterol(TG/HDL-C),visceral obesity index(VAI),lipid accumulation product(LAP),and triglyceride glucose(TyG)index were analyzed.The diagnostic efficacy of these indicators of NAFLD was also evaluated.Results In the NAFLD-MA group,BMI,HOMA-IR,LAP,VAI,TyG index,and TG/HDL-C ratio were higher than those in the non-NAFLD-MA group(P<0.001).Logistic regression indicated that BMI and TyG index were independent risk factors for NAFLD.Receiver Operating Characteristic(ROC)curves analysis revealed that the Area Under the ROC Curve(AUC)for TyG-BMI was 0.819,and the optimal cutoff for NAFLD was TyG-BMI 39.77.For patients with NAFLD with or without MA,logistic regression analysis suggested that age,TG level,and TyG index were independent risk factors.The area under the ROC curve showed that AUC for the TyG index was 0.724.The optimal cutoff for NAFLD-non MA was a TyG index of 1.580.Conclusion TyG index has diagnostic value in both types of NAFLD;however,TyG-BMI is better in patients with NAFLD with MA and may be an effective screening indicator alone in patients with NAFLD without MA.展开更多
Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.L...Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.Lipid and free fatty acid contents in grains correlate positively with cooking and eating quality of rice.This study examined Yangdao 6(YD6,a conventional taste indica inbred)and Nanjing 9108(NJ9108,a superior taste japonica inbred)cultivated under conventional irrigation(CI),alternate wetting and moderate drying irrigation(AWMD),and alternate wetting and severe drying irrigation(AWSD)from 10 days after transplanting to maturity.The research investigated the relationship between lipid and free fatty acid biosynthesis in grains and the cooking and eating quality of rice.Compared to CI treatment,AWMD significantly enhanced the contents of lipid,total free fatty acids(TFFAs),free unsaturated fatty acids(FUFAs),linoleic acid,and oleic acid in milled rice by increasing activities of enzymes associated with lipid synthesis,while AWSD produced opposite effects.Correlation analysis revealed that elevated levels of lipid,TFFAs,FUFAs,linoleic acid,and oleic acid contribute to improved rice cooking and eating quality.The findings demonstrate that AWMD enhances cooking and eating quality of milled rice through optimization of lipid and fatty acid synthesis in rice grains.展开更多
Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose d...Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose degradation by pancreatic lipase generates different free fatty acids,which can exacerbate pancreatitis.Saturated fatty acids(SFAs)play an inflammatory role in human metabolic syndrome and obesity,whereas unsaturated fatty acids(UFAs)are“good fats”that are thought to enhance overall health status.However,it appears that serum UFAs correlate with severe acute pancreatitis.Additionally,the“obesity paradox”suggests that UFAs potentially minimize direct harm to the organ.This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.展开更多
Non-alcoholic fatty liver disease(NAFLD),also referred to as metabolic-associated fatty liver disease,is among the most prevalent chronic liver conditions.In some cases,NAFLD may lead to liver inflammation and non-alc...Non-alcoholic fatty liver disease(NAFLD),also referred to as metabolic-associated fatty liver disease,is among the most prevalent chronic liver conditions.In some cases,NAFLD may lead to liver inflammation and non-alcoholic steatohepatitis,which can eventually progress to liver cirrhosis and hepatocellular carcinoma.The pathophysiology of NAFLD is complex,involving both genetic and environmental factors.NAFLD is a multisystem disease linked to a higher likelihood of developing metabolic disorders such as type 2 diabetes,obesity,and cardiovascular and chronic kidney diseases.The gut-liver axis represents a key connection between the gut microbiota and the liver,and its disruption has been linked to NAFLD.Growing evidence underscores the significant role of gut microbiota in the onset and progression of NAFLD,with alterations in the gut microbiome and impaired gut barrier function.Studies have identified key microbiota signatures and metabolites linked to NAFLD,implicating oxidative stress,endotoxemia,and inflammatory pathways that further strengthen the connection between gut microbiota and NAFLD.Modulation of gut microbiota through diet and microbiota-centered therapies,such as next-generation probiotics and fecal microbiota transplantation,holds promise for treating NAFLD.In this review,we explore the key link between gut microbiota and the development and progression of NAFLD,as well as its potential applications in the diagnosis and treatment of the disease.展开更多
Metabolic-associated fatty liver disease(MAFLD),formerly known as nonalcoho-lic fatty liver disease,is an increasing global health challenge with substantial implications for metabolic and cardiovascular health(CVH).A...Metabolic-associated fatty liver disease(MAFLD),formerly known as nonalcoho-lic fatty liver disease,is an increasing global health challenge with substantial implications for metabolic and cardiovascular health(CVH).A recent study by Fu et al investigated the relationship between CVH metrics,specifically Life’s Simple 7 and Life’s Essential 8,and the prevalence of MAFLD.While this study offered important insights into the relationship between CVH and MAFLD,several me-thodological limitations,unaddressed confounding factors,and potential biases that could impact the interpretation of their findings should be considered.The study’s cross-sectional nature restricted the ability to draw causal conclusions,and it did not fully account for potential confounding factors such as dietary habits,genetic predispositions,and medication use.Furthermore,relying on tran-sient elastography to diagnose MAFLD introduces certain diagnostic limitations.Longitudinal study designs,advanced statistical modeling techniques,and diverse population groups should be utilized to strengthen future research.Exploring the mechanistic pathways that link CVH metrics to MAFLD through multi-omics approaches and interventional studies will be essential in formulating targeted prevention and treatment strategies.Structural equation modeling and machine learning techniques could provide a more refined analysis of these interrelated factors.Additionally,future research should employ longitudinal study designs and explore genetic and epigenetic influences to enhance our un-derstanding of CVH and MAFLD interactions.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease,including cirrhosis and liver cancer.It is projected th...Non-alcoholic fatty liver disease(NAFLD)is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease,including cirrhosis and liver cancer.It is projected that more than fifty percent of the adult population,including women,smokers,and individuals without metabolic syndrome,will have NAFLD by 2040.Various mechanisms linking the gut microbiome to NAFLD and the consequent fibrosis have been discerned,which suggest the dysbiosis-induced impairment of gut endothelial barrier function,leading to hepatic inflammation through the translocation of bacterial components.NAFLD is progressively associated with environmental variables,especially exposure to heavy metals that impair liver metabolism,produce oxidative stress,and exacerbate inflammation,hence accelerating its progression.These toxicants also modify the composition of gut microbiota,hence intensifying liver damage.Comprehending the processes by which heavy metals contribute to NAFLD is essential for formulating tailored therapies.This review examines strategies to alleviate liver toxicity caused by heavy metals,including chelation therapy,dietary modifications(antioxidants and hepatoprotective nutrients),gut microbiome modulation via probiotics and postbiotics like short-chain fatty acids to restore intestinal barrier function and use of essential minerals like selenium,with potent antioxidant characteristics.Employing these measures may offer an integrated approach for addressing NAFLD in individuals subjected to heavy metal poisoning.展开更多
Non-alcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally,with its incidence rising annually.It can progress to cirrhosis and even hepatocellular carcinoma,posing a serious t...Non-alcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally,with its incidence rising annually.It can progress to cirrhosis and even hepatocellular carcinoma,posing a serious threat to human health.Stress can participate in the pathological process of NAFLD by activating inflammatory responses and regulating levels of inflammatory mediators,with hepatocyte injury being a core component of NAFLD progression.This paper focuses on three key stress-related inflammatory mediators:tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and C-reactive protein(CRP),elucidating their core mechanisms in the pathway related to stress signal,followed by inflammatory activation and hepatocyte injury respectively,and reviewing current research.Research indicates that certain inflammatory mediators can damage hepatocytes by directly inducing apoptosis or indirectly regulating metabolic disorders and fibrosis progression.However,questions regarding causal relationships,target specificity for intervention,and quantification of psychological stress remain unresolved.This paper aims to provide theoretical support for NAFLD intervention strategies targeting inflammatory mediators,clarifying future research directions to advance clinical translation.展开更多
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
With the shift in the definition of disease from non-alcoholic fatty liver disease(NAFLD)to metabolism-associated fatty liver disease(MAFLD),as well as the rapid evolution of pathological classification and therapeuti...With the shift in the definition of disease from non-alcoholic fatty liver disease(NAFLD)to metabolism-associated fatty liver disease(MAFLD),as well as the rapid evolution of pathological classification and therapeutic targets,traditional clinical teaching models face challenges such as outdated guideline updates,disjointed translation of scientific research,and limited skill training.This study proposes a dynamic training model integrating“guidelines,clinical practice,and scientific research.”Through stratified case-based teaching(e.g.,FibroScan simulator and metabolic sand table),dynamic guideline analysis(comparing old and new evidence),and the integration of scientific thinking(visualization of CAND1 protein mechanism),a teaching system that integrates theory and practice is constructed.Innovatively developed smart assistant tools(AI decision support system,VR liver biopsy simulator)and a multi-dimensional evaluation system(deviation analysis of diagnosis and treatment pathways,milestone assessment)are used while emphasizing metabolic medicine integration(continuous glucose monitoring and digital therapy)and ethical privacy protection(federated learning framework).This model aims to cultivate students’evidence-based decision-making skills and scientific research transformation thinking through dynamic knowledge base construction and interdisciplinary collaboration,providing sustainable teaching solutions to cope with the rapid iteration of NAFLD diagnosis and treatment.展开更多
The evolving nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic dysfunction-associated steatotic liver disease(MASLD)aims to better encompass the metabolic context of the disease.This change has si...The evolving nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic dysfunction-associated steatotic liver disease(MASLD)aims to better encompass the metabolic context of the disease.This change has significant implications for patients with type 2 diabetes mellitus(T2DM),given the frequent overlap between these conditions.This minireview explores the rationale behind the change,compares diagnostic criteria,and evaluates the impact of the MASLD framework on disease prevalence,characterization,and outcomes in T2DM patients.The updated MASLD criteria include all individuals with T2DM and hepatic steatosis,emphasizing metabolic dysfunction as the primary driver.In contrast,the NAFLD definition necessitates excluding other chronic liver diseases and verifying the absence of significant alcohol consumption,leading to a narrower diagnostic framework.Both metabolic dysfunction-associated fatty liver disease and MASLD identify a higher prevalence of steatotic liver disease,particularly among T2DM patients,compared to NAFLD.Notably,the MASLD framework introduces metabolic and alcohol-associated liver disease to account for dual etiologies involving alcohol use,which is common in T2DM populations but previously excluded under NAFLD criteria.While the new definitions enhance clinical relevance and inclusivity,they also highlight challenges such as unrecognized medication-induced steatosis and the need for reclassification in ongoing T2DM clinical trials.Emerging evidence supports enhanced screening strategies(e.g.,fibrosis-4)and metabolic-targeted treatments for MASLD in T2DM patients.The successful integration of MASLD into clinical practice will require system-wide reeducation,standardization,and multidisciplinary collaboration to improve outcomes for T2DM patients.展开更多
基金supported by the Science Research Project of Hebei Education Department(BJK2024077)Key Research and Development Projects of Hebei Province(22326619D)the National Natural Science Foundation of China(No.32473073 and No.32503085)。
文摘Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic fatty liver disease.With the rise of intensive poultry farming,the incidence of FLHS has markedly increased,resulting in significant economic losses in the poultry industry.The gut microbiota plays a crucial role in host digestion,metabolism,and immune regulation,particularly in liver diseases.Gut microbiota and its metabolites influence liver health via the gut-liver axis.This review aims to explore metabolite-mediated interactions between the laying hens and the gut microbiota,elucidating their role in the pathogenesis of FLHS.Host-derived metabolites,such as lipids,bile acids,amino acids,and carbohydrates,regulate the structure and function of the gut microbiota through the gut-liver axis,playing a role in FLHS progression.Concurrently,microbial metabolites,including short-chain fatty acids,bile acids,and amino acid derivatives,influence hepatic lipid metabolism,inflammation,and oxidative stress,driving the development of FLHS.Key microbes,such as Bacteroides,Lactobacillus,and Akkermansia muciniphila,are considered potential therapeutic targets due to their involvement in metabolite production.By integrating multi-omics data and mechanistic studies,this review highlights the central role of host–gut microbiota communication in FLHS and provides a theoretical basis and research direction for the development of microbiota-based intervention strategies.
基金funded by the Key Research Project of Ningxia(2021BEG03031)National Natural Science Foundation(82560643)Scientific Research Funding Project of Ningxia Medical University(XT2025025).
文摘Changes in intestinal microecology play a crucial role in the pathogenesis and progression of metabolic diseases.Lycium barbarum polysaccharide(LBP)and quinoa ultrafine powder diet is a promising sources of prebiotics.However,the potential synergistic effects of combining them as a microbiota-targeted dietary supplement to mitigate lipid accumulation in nonalcoholic fatty liver disease(NAFLD)remain unclear.Our study aims to provide evidence for the application food/nutrient synergy interventions in NAFLD management,and also to support the clarification of these mechanisms.Following 12 weeks of a high-fat diet(HFD)-inducing NAFLD and an 11-week intervention in rats,the combination of LBP and quinoa ultrafine powder significantly decreased hepatocyte lipid accumulation and improved lipid metabolism disorders compared with those using either LBP or quinoa ultrafine powder alone.The combination increased beneficial intestinal microbiota,such as Lactobacillus acidophilus,Roseburia,Ruminococcus 2,and Prevotella,promoting the production of short-chain fatty acids,notably butyric acid,and then activated AMP-activated protein kinase/sterol regulatory element-binding protein 1C/stearoyl-CoA desaturase 1(AMPK/SREBP-1C/SCD-1)signaling.Combining LBP with quinoa ultrafine powder is a promising microbiota-targeted dietary supplement for ameliorating lipid disorders in NAFLD.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金financially supported by the National Key R&D Program of China(2022YFA1304103)Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(CXGC2024A04)SKLMT Frontiers&Challenges Project.
文摘Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as a comprehensive intervention on human health and immune status.This study used a 14-day continuous drinking intervention consisting of 5 beers,namely white beer,India pale ale(IPA),Pilsner,non-alcoholic beer,and premium lager beer.Surprisingly,our findings indicate that consuming white beer has little impact on the gut microbiota and physiological condition of mice,whereas consuming other types of beer leads to an increase in Lactobacillus and a decrease in Lachnospiraceae.In addition,we devised an extended feeding experiment to investigate the comparative safety and health benefits of consuming white beer.The research showed that when mice drank excessive quantities of white beer over 42 days,the intestines of the mice had more Prevotellaceae and the Firmicutes to Bacteroidetes ratio(F/B ratio)had a decline from 1.29 to 0.38.The levels of acetic acid,propionic acid,and isobutyric acid increased from 1.0,0.27,and 0.015 mg/g to 1.28,0.38,and 0.037 mg/g,respectively(P<0.05).There were no significant changes observed in the levels of most measured cytokines in the colon tissue of mice that consumed beer,however,there was an increase in the concentration of the inflammatory factor tumor nesrosis factor-α(TNF-α)from 135.86 pg/mL in the control group to 189.78 pg/mL in the white beer group(P<0.01).These results give us real-world proof that we can use to study how different beers affect the host’s health and satisfaction in future research.
基金supported by grants from the National Natural Science Foundation of China(82270924)the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-016)the National High Level Hospital Clinical Research Funding(2022-PUMCH-C-014,2025-PUMCH-C-041).
文摘Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.
基金supported by the grants from the National Key Research and Development Program of China(2023YFD1800804 and 2023YFD1801100)the National Natural Science Foundation of China(32172926)the China Agriculture Research System(CARS-36)。
文摘Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of fatty acids.Recent findings from nonruminant studies revealed that long chain fatty acyl-CoA ligase 4(ACSL4)could play a role in the regulation of cellular fatty acid metabolism,but the mechanisms by which ACSL4 mediates cellular lipid metabolism in response to BHB remains unclear.To achieve the aims,we conducted in vivo or in vitro analyses using bovine mammary gland biopsies and the immortalized mammary epithelial cell line(MAC-T).The in vivo study(n=6 cows per group)involved healthy cows(plasma BHB<0.60 mmol L^(–1))or ketotic cows(plasma BHB>2.0 mmol L^(–1))from which mammary gland tissue was biopsied.In vitro,MAC-T cells were challenged with 0,0.3,0.6,1.2,or 2.4 mmol L^(–1)BHB for 24 h to determine an optimal dose.Subsequently,MAC-T were incubated with 1.2 mmol L^(–1)BHB for 0,3,6,12,24,or 48 h.Furthermore,MAC-T cells were treated with small interfering ACSL4(siACSL4)for 24 h or ACSL4 overexpression plasmid(pcACSL4)for 36 h followed by a challenge with 1.2 mmol L^(–1)BHB for 24 h.Results showed that increased mRNA and protein abundance of lipogenic genes were linked to both mammary gland and in vitro challenge with BHB.BHB increased fatty acid content by activating ACSL4 expression,whereas inhibition of ACSL4 reduced BHB-induced reactive oxygen species(ROS)overproduction,enhancement of mitochondrial membrane potential,increase in fatty acid content,and lipid droplet accumulation.Furthermore,we also elevated ACSL4 expression with an overexpression plasmid to clarify its molecular role in response to BHB challenge.ACSL4 overexpression enhances BHB-induced lipid droplet accumulation by increased fatty acid content.Overall,the information showed that ACSL4 is crucial for the process of producing fatty acids from exogenous BHB.Reduced ACSL4 decreased fatty acid content and lipid droplet accumulation,improved mitochondrial function,directed more fatty acids towards oxidation.Thus,ACSL4 plays an important role in determining the fate of intracellular fatty acids and BHB in BMECs.
基金supported by the National Natural Science Foundation of China(82574477)the Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan(QN202426)+5 种基金Jiangsu Province“333 High-level Talents Training Project”((2024)3-0189)Youth Talent Support Project of the Jiangsu Association for Science and Technology(TJ-2023-053)Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials(KF202401)Fundamental Research Program of Shanxi Province(202403021221211)the research project supported by the Shanxi Scholarship Council of China(No.2023-158)Open Project of Key Laboratory of Tibetan Medicine Basic Research,Ministry of Education.
文摘The global prevalence of metabolic-associated fatty liver disease(MAFLD)is on the rise,seriously threatening human health.Currently,no specific approved drugs are available for its treatment.This paper reviews the pathogenesis of MAFLD,covering aspects like lipid accumulation and insulin resistance,oxidative stress,endoplasmic reticulum stress(ERS),lipotoxicity-induced hepatocyte damage,and fibrosis.It also elaborates on multiple treatment approaches for MAFLD,including metabolic regulation,improvement of the gut-liver axis interaction,modulation of immune and inflammatory pathways,enhancement of the adipose tissue-liver interaction,alleviation of fibrosis,prevention of hepatocyte injury,and traditional Chinese medicine(TCM)external therapies.Additionally,natural product research advancements,individual Chinese medicine components,and mixed herbal formulas for MAFLD treatment is provided.Many natural products and traditional Chinese medicines exhibit favorable effects in regulating lipid metabolism,anti-inflammation,and anti-oxidation,offering new directions and potential drug options for MAFLD treatment.This is expected to provide a reference for future clinical treatment and drug development.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)Taishan Scholars Programof Shandong Province-Young Taishan Scholars(tsqn201909197)+1 种基金Cutting Edge Development Fund of Advanced Medical Research Institute(Shandong University)National Natural Science Foundation of China(82220108005)。
文摘Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial research has reported the therapeutic potential of Omega-3 fatty acids for the central nervous system,particularly after traumatic SCI.Omega-3 fatty acids may contribute to improving SCI recovery through their anti-inflammatory,anti-oxidative,neurotrophic,and membrane integrity-preserving properties.These functions of Omega-3 fatty acids are primarily mediated via the activation of G protein-coupled receptor 120(GPR120),commonly known as the fish oil-specific receptor.Advancements in understanding of the molecular mechanisms of GPR120’s recognition of Omega-3 fatty acids and its downstream signaling mechanisms has significantly promoted research on the pharmacological potential of Omega-3 fatty acids and the development of highly selective and high-affinity alternatives.This review aims to provide in-depth analysis of the comprehensive therapeutic potential of Omega-3 fatty acids for SCI and its accompanying complications,and the prospects for developing novel drugs based on the recognition of Omega-3 fatty acids by GPR120.
文摘Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.
基金supported by Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(Grant No.HB2023008)Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)+2 种基金Medical Key Discipline Program ofWuxi Health.Commission(Grant Nos.ZDXK2021007 and CXTD2021005)Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.
基金Beijing Research Ward Excellence Program(BRWEP2024W102170101)The National Key Research and Development Program(2022YFC2603500,2022YFC2603505)+5 种基金Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader-03-26,discipline backbone-02-28)Capital’s Funds for Health Improvement and Research(2022-1-2172)Beijing Hospitals Authority Clinical medicine Development of special funding support(ZLRK202301)Beijing Hospitals Authority"peak"talent training program(DFL20241803)National Key Research and Development Program of China(2023YFC2306900)National Key Research and Development Program of Ministry of Science and Technology(2023YFC2308105).
文摘Objective To analyze the diagnostic efficacy of lipid-related insulin resistance(IR)markers in patients with non-alcoholic fatty liver disease(NAFLD)and metabolic abnormalities(MA).Method Patients with NAFLD with MA,non-NAFLD patients with MA,and patients with NAFLD without MA underwent liver biopsy.Homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride/high-density lipoprotein cholesterol(TG/HDL-C),visceral obesity index(VAI),lipid accumulation product(LAP),and triglyceride glucose(TyG)index were analyzed.The diagnostic efficacy of these indicators of NAFLD was also evaluated.Results In the NAFLD-MA group,BMI,HOMA-IR,LAP,VAI,TyG index,and TG/HDL-C ratio were higher than those in the non-NAFLD-MA group(P<0.001).Logistic regression indicated that BMI and TyG index were independent risk factors for NAFLD.Receiver Operating Characteristic(ROC)curves analysis revealed that the Area Under the ROC Curve(AUC)for TyG-BMI was 0.819,and the optimal cutoff for NAFLD was TyG-BMI 39.77.For patients with NAFLD with or without MA,logistic regression analysis suggested that age,TG level,and TyG index were independent risk factors.The area under the ROC curve showed that AUC for the TyG index was 0.724.The optimal cutoff for NAFLD-non MA was a TyG index of 1.580.Conclusion TyG index has diagnostic value in both types of NAFLD;however,TyG-BMI is better in patients with NAFLD with MA and may be an effective screening indicator alone in patients with NAFLD without MA.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20241931 and BK 20221371)the National Natural Science Foundation of China(32071943,32372214,and 31901444)the National Key Research and Development Program of China(2022YFD2300304)。
文摘Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.Lipid and free fatty acid contents in grains correlate positively with cooking and eating quality of rice.This study examined Yangdao 6(YD6,a conventional taste indica inbred)and Nanjing 9108(NJ9108,a superior taste japonica inbred)cultivated under conventional irrigation(CI),alternate wetting and moderate drying irrigation(AWMD),and alternate wetting and severe drying irrigation(AWSD)from 10 days after transplanting to maturity.The research investigated the relationship between lipid and free fatty acid biosynthesis in grains and the cooking and eating quality of rice.Compared to CI treatment,AWMD significantly enhanced the contents of lipid,total free fatty acids(TFFAs),free unsaturated fatty acids(FUFAs),linoleic acid,and oleic acid in milled rice by increasing activities of enzymes associated with lipid synthesis,while AWSD produced opposite effects.Correlation analysis revealed that elevated levels of lipid,TFFAs,FUFAs,linoleic acid,and oleic acid contribute to improved rice cooking and eating quality.The findings demonstrate that AWMD enhances cooking and eating quality of milled rice through optimization of lipid and fatty acid synthesis in rice grains.
文摘Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose degradation by pancreatic lipase generates different free fatty acids,which can exacerbate pancreatitis.Saturated fatty acids(SFAs)play an inflammatory role in human metabolic syndrome and obesity,whereas unsaturated fatty acids(UFAs)are“good fats”that are thought to enhance overall health status.However,it appears that serum UFAs correlate with severe acute pancreatitis.Additionally,the“obesity paradox”suggests that UFAs potentially minimize direct harm to the organ.This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.
文摘Non-alcoholic fatty liver disease(NAFLD),also referred to as metabolic-associated fatty liver disease,is among the most prevalent chronic liver conditions.In some cases,NAFLD may lead to liver inflammation and non-alcoholic steatohepatitis,which can eventually progress to liver cirrhosis and hepatocellular carcinoma.The pathophysiology of NAFLD is complex,involving both genetic and environmental factors.NAFLD is a multisystem disease linked to a higher likelihood of developing metabolic disorders such as type 2 diabetes,obesity,and cardiovascular and chronic kidney diseases.The gut-liver axis represents a key connection between the gut microbiota and the liver,and its disruption has been linked to NAFLD.Growing evidence underscores the significant role of gut microbiota in the onset and progression of NAFLD,with alterations in the gut microbiome and impaired gut barrier function.Studies have identified key microbiota signatures and metabolites linked to NAFLD,implicating oxidative stress,endotoxemia,and inflammatory pathways that further strengthen the connection between gut microbiota and NAFLD.Modulation of gut microbiota through diet and microbiota-centered therapies,such as next-generation probiotics and fecal microbiota transplantation,holds promise for treating NAFLD.In this review,we explore the key link between gut microbiota and the development and progression of NAFLD,as well as its potential applications in the diagnosis and treatment of the disease.
文摘Metabolic-associated fatty liver disease(MAFLD),formerly known as nonalcoho-lic fatty liver disease,is an increasing global health challenge with substantial implications for metabolic and cardiovascular health(CVH).A recent study by Fu et al investigated the relationship between CVH metrics,specifically Life’s Simple 7 and Life’s Essential 8,and the prevalence of MAFLD.While this study offered important insights into the relationship between CVH and MAFLD,several me-thodological limitations,unaddressed confounding factors,and potential biases that could impact the interpretation of their findings should be considered.The study’s cross-sectional nature restricted the ability to draw causal conclusions,and it did not fully account for potential confounding factors such as dietary habits,genetic predispositions,and medication use.Furthermore,relying on tran-sient elastography to diagnose MAFLD introduces certain diagnostic limitations.Longitudinal study designs,advanced statistical modeling techniques,and diverse population groups should be utilized to strengthen future research.Exploring the mechanistic pathways that link CVH metrics to MAFLD through multi-omics approaches and interventional studies will be essential in formulating targeted prevention and treatment strategies.Structural equation modeling and machine learning techniques could provide a more refined analysis of these interrelated factors.Additionally,future research should employ longitudinal study designs and explore genetic and epigenetic influences to enhance our un-derstanding of CVH and MAFLD interactions.
基金Supported by DHR Women Scientist Fellowship,No.12013/53/2024.
文摘Non-alcoholic fatty liver disease(NAFLD)is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease,including cirrhosis and liver cancer.It is projected that more than fifty percent of the adult population,including women,smokers,and individuals without metabolic syndrome,will have NAFLD by 2040.Various mechanisms linking the gut microbiome to NAFLD and the consequent fibrosis have been discerned,which suggest the dysbiosis-induced impairment of gut endothelial barrier function,leading to hepatic inflammation through the translocation of bacterial components.NAFLD is progressively associated with environmental variables,especially exposure to heavy metals that impair liver metabolism,produce oxidative stress,and exacerbate inflammation,hence accelerating its progression.These toxicants also modify the composition of gut microbiota,hence intensifying liver damage.Comprehending the processes by which heavy metals contribute to NAFLD is essential for formulating tailored therapies.This review examines strategies to alleviate liver toxicity caused by heavy metals,including chelation therapy,dietary modifications(antioxidants and hepatoprotective nutrients),gut microbiome modulation via probiotics and postbiotics like short-chain fatty acids to restore intestinal barrier function and use of essential minerals like selenium,with potent antioxidant characteristics.Employing these measures may offer an integrated approach for addressing NAFLD in individuals subjected to heavy metal poisoning.
基金Science Research Project of Hebei Education Department(Project No.:QN2022013)。
文摘Non-alcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally,with its incidence rising annually.It can progress to cirrhosis and even hepatocellular carcinoma,posing a serious threat to human health.Stress can participate in the pathological process of NAFLD by activating inflammatory responses and regulating levels of inflammatory mediators,with hepatocyte injury being a core component of NAFLD progression.This paper focuses on three key stress-related inflammatory mediators:tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and C-reactive protein(CRP),elucidating their core mechanisms in the pathway related to stress signal,followed by inflammatory activation and hepatocyte injury respectively,and reviewing current research.Research indicates that certain inflammatory mediators can damage hepatocytes by directly inducing apoptosis or indirectly regulating metabolic disorders and fibrosis progression.However,questions regarding causal relationships,target specificity for intervention,and quantification of psychological stress remain unresolved.This paper aims to provide theoretical support for NAFLD intervention strategies targeting inflammatory mediators,clarifying future research directions to advance clinical translation.
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
文摘With the shift in the definition of disease from non-alcoholic fatty liver disease(NAFLD)to metabolism-associated fatty liver disease(MAFLD),as well as the rapid evolution of pathological classification and therapeutic targets,traditional clinical teaching models face challenges such as outdated guideline updates,disjointed translation of scientific research,and limited skill training.This study proposes a dynamic training model integrating“guidelines,clinical practice,and scientific research.”Through stratified case-based teaching(e.g.,FibroScan simulator and metabolic sand table),dynamic guideline analysis(comparing old and new evidence),and the integration of scientific thinking(visualization of CAND1 protein mechanism),a teaching system that integrates theory and practice is constructed.Innovatively developed smart assistant tools(AI decision support system,VR liver biopsy simulator)and a multi-dimensional evaluation system(deviation analysis of diagnosis and treatment pathways,milestone assessment)are used while emphasizing metabolic medicine integration(continuous glucose monitoring and digital therapy)and ethical privacy protection(federated learning framework).This model aims to cultivate students’evidence-based decision-making skills and scientific research transformation thinking through dynamic knowledge base construction and interdisciplinary collaboration,providing sustainable teaching solutions to cope with the rapid iteration of NAFLD diagnosis and treatment.
文摘The evolving nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic dysfunction-associated steatotic liver disease(MASLD)aims to better encompass the metabolic context of the disease.This change has significant implications for patients with type 2 diabetes mellitus(T2DM),given the frequent overlap between these conditions.This minireview explores the rationale behind the change,compares diagnostic criteria,and evaluates the impact of the MASLD framework on disease prevalence,characterization,and outcomes in T2DM patients.The updated MASLD criteria include all individuals with T2DM and hepatic steatosis,emphasizing metabolic dysfunction as the primary driver.In contrast,the NAFLD definition necessitates excluding other chronic liver diseases and verifying the absence of significant alcohol consumption,leading to a narrower diagnostic framework.Both metabolic dysfunction-associated fatty liver disease and MASLD identify a higher prevalence of steatotic liver disease,particularly among T2DM patients,compared to NAFLD.Notably,the MASLD framework introduces metabolic and alcohol-associated liver disease to account for dual etiologies involving alcohol use,which is common in T2DM populations but previously excluded under NAFLD criteria.While the new definitions enhance clinical relevance and inclusivity,they also highlight challenges such as unrecognized medication-induced steatosis and the need for reclassification in ongoing T2DM clinical trials.Emerging evidence supports enhanced screening strategies(e.g.,fibrosis-4)and metabolic-targeted treatments for MASLD in T2DM patients.The successful integration of MASLD into clinical practice will require system-wide reeducation,standardization,and multidisciplinary collaboration to improve outcomes for T2DM patients.
