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
As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to pr...As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.展开更多
With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis...With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.展开更多
Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological...Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.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
AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 p...AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 patients with DME treated with IVC with 3+PRN regimen.Based on the estimated glomerular filtration rate(eGFR),the patients were divided into normal renal function group(n=37),impaired renal function group(n=27),and renal insufficiency group(n=36).The main outcome measures were best-corrected visual acuity(BCVA)and central subfield macular thickness(CST).Clinical parameters included blood urea nitrogen,serum creatinine,serum uric acid,glycosylated hemoglobin(HbA1c),and hemoglobin.RESULTS:The mean follow-up time was 3.9mo.The mean number of IVCs was 2.07±1.22 in the three groups.Mean BCVA improved significantly from 0.81±0.49 logMAR at baseline to 0.72±0.52 logMAR in the three groups at the final visit(P<0.001).Mean CST decreased significantly from 427.85±148.99μm at baseline to 275.31±108.31μm at final visit(P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).The three groups had no differences in baseline HbA1c levels(P>0.05).Good baseline BCVA(logMAR,P=0.001)and thicker baseline CST(P=0.041)were associated with visual acuity improvement.Higher eGFR(P<0.001),hemoglobin(P=0.032)and thicker baseline CST(P=0.017)were associated with macular edema retrogression in the conbercept-treated diabetic patients,which showed better anatomical response to IVC.CONCLUSION:Our results indicate that the renal dysfunction is the risk factor associated with the efficacy of IVC for DME.展开更多
ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted usin...ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted using PubMed and Cochrane databases for relevant articles published in English between 2008 and 2023. Keywords used included “ketamine” and “upper urinary tract”.ResultsA total of 22 papers were included. Relatively few studies have focused on ketamine-associated UUT dysfunction. Exclusion criteria included lack of hydronephrosis, or pathological findings. After careful screening and exclusion, we finally adopted 11 of these papers and analyzed them. Ketamine-associated UUT dysfunction may be a concern in this field.ConclusionKetamine abuse can lead to UUT impairment and dysfunction, with symptoms such as bladder dysfunction and contracted bladder with vesicoureteral reflux, direct damage and barrier dysfunction, inflammation, apoptosis, fibrosis and stricture, and papillary necrosis. Oxidative stress, autophagy, and microvascular injury are also potential pathogenic mechanisms. The detection of these symptoms largely depends on laboratory and imaging examinations. The treatment principles of ketamine-associated UUT dysfunction are protecting the UUT, improving bladder dysfunction, and resuming normal social life. More investigations are needed to clarify the mechanisms and shed light on the treatment of ketamine-associated UUT damage.展开更多
BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is ...BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.展开更多
BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)...BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.展开更多
BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systo...BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.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
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
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
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
Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial f...Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovas...Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbl...Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
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.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82430018 to Q.C.,82270361 and 82570402 to H.Z.)the Nanjing Medical University Undergraduate Innovation and Entrepreneurship Training Program Fund(Grant No.202410312138Y to C.Z.)the Basic Sciences of Jiangsu Higher Education Institutions(Grant No.22KJA310002 to H.Z.)。
文摘As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.
基金supported by grants from the Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)Medical Key Discipline Program of Wuxi Health Commission(Grant Nos.ZDXK2021007 and CXTD2021005)+1 种基金Top Talent Support Program for Young and MiddleAged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.
基金Supported by Russian Science Foundation,No.23-45-10030.
文摘Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.
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.
基金Supported by Basic and Applied Basic Research Project of Guangzhou Science and Technology Plan(No.202201020008,No.2023A03J0584).
文摘AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 patients with DME treated with IVC with 3+PRN regimen.Based on the estimated glomerular filtration rate(eGFR),the patients were divided into normal renal function group(n=37),impaired renal function group(n=27),and renal insufficiency group(n=36).The main outcome measures were best-corrected visual acuity(BCVA)and central subfield macular thickness(CST).Clinical parameters included blood urea nitrogen,serum creatinine,serum uric acid,glycosylated hemoglobin(HbA1c),and hemoglobin.RESULTS:The mean follow-up time was 3.9mo.The mean number of IVCs was 2.07±1.22 in the three groups.Mean BCVA improved significantly from 0.81±0.49 logMAR at baseline to 0.72±0.52 logMAR in the three groups at the final visit(P<0.001).Mean CST decreased significantly from 427.85±148.99μm at baseline to 275.31±108.31μm at final visit(P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).The three groups had no differences in baseline HbA1c levels(P>0.05).Good baseline BCVA(logMAR,P=0.001)and thicker baseline CST(P=0.041)were associated with visual acuity improvement.Higher eGFR(P<0.001),hemoglobin(P=0.032)and thicker baseline CST(P=0.017)were associated with macular edema retrogression in the conbercept-treated diabetic patients,which showed better anatomical response to IVC.CONCLUSION:Our results indicate that the renal dysfunction is the risk factor associated with the efficacy of IVC for DME.
文摘ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted using PubMed and Cochrane databases for relevant articles published in English between 2008 and 2023. Keywords used included “ketamine” and “upper urinary tract”.ResultsA total of 22 papers were included. Relatively few studies have focused on ketamine-associated UUT dysfunction. Exclusion criteria included lack of hydronephrosis, or pathological findings. After careful screening and exclusion, we finally adopted 11 of these papers and analyzed them. Ketamine-associated UUT dysfunction may be a concern in this field.ConclusionKetamine abuse can lead to UUT impairment and dysfunction, with symptoms such as bladder dysfunction and contracted bladder with vesicoureteral reflux, direct damage and barrier dysfunction, inflammation, apoptosis, fibrosis and stricture, and papillary necrosis. Oxidative stress, autophagy, and microvascular injury are also potential pathogenic mechanisms. The detection of these symptoms largely depends on laboratory and imaging examinations. The treatment principles of ketamine-associated UUT dysfunction are protecting the UUT, improving bladder dysfunction, and resuming normal social life. More investigations are needed to clarify the mechanisms and shed light on the treatment of ketamine-associated UUT damage.
基金supported by the National High Level Hospital Clinical Research Funding (2022-NHLHCRF-YS-03)the National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.
基金Supported by the National Natural Science Foundation of China,No.82300894.
文摘BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.
基金Supported by the Italian Ministry for Education,University and Research under the Programme“Dipartimenti di Eccellenza 2018-2022”Project,No.D15D18000410001Novo Nordisk“Gestione delle complicanze croniche del diabete:From bedside to bench?”,No.n1/2021.
文摘BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.
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.
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.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by China Scholarship Council(No.202106380078 to HL)the Netherlands Cardiovascular Research Initiative:The Dutch Heart Foundation(CVON 2018-28 and 2012-06 Heart Brain Connection to AMT)。
文摘Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
