Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions th...Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive micro...Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal ...1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.展开更多
Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review ...Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short...Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and ...Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.展开更多
Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have esta...Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.展开更多
The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic...The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its glo...Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.展开更多
Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-asso...Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.展开更多
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of mi...Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of microorganisms in aquatic ecosystems.To understand the influences of ecological floating beds on size-fractionated microorganisms,we investigated the community assembly and nitrogen metabolic characteristics of three size-fractionated microorganism groups in the ecological floating bed area,using 18S rDNA,16S rDNA metabarcoding,and metagenomic sequencing techniques.Firstly,we discovered substantial differences between size-fractionated groups in the diversity and compositions of both microeukaryotic and bacterial communities,as well as the influences of floating beds on specific groups.The floating beds appeared to provide more habitats for heterotrophs and symbiotes while potentially inhibiting the growth of certain phytoplankton(cyanobacteria).Secondly,we observed that microeukaryotic and bacterial communities were predominantly influenced by stochastic and deterministic processes,respectively,and they both exhibited distinct patterns across different size-fractionated groups.Notably,microeukaryotic community assembly demonstrated a greater sensitivity to ecological floating beds,as indicated by an increase in dispersal limitation processes.Finally,the nitrogen metabolism functional genes revealed that microbes associated with large-sized particles played a crucial role in dissimilatory nitrate reduction to ammonium(DNRA)and denitrification processes within the floating bed area,thereby facilitating the removal of excess nitrogen nutrients from the water.In contrast,freeliving microorganisms from small-sized groups were linked mainly to the genes involved in nitrogen assimilation and assimilatory nitrate reduction to ammonium(ANRA)processes.These findings help understand the impact of ecological floating beds on the diversity and functional characteristics of microorganism communities in different size-fractionated groups.展开更多
基金support held by JPA,Collaborative Network Award BRAVEinMS,Grant/Award Number:PA-1604-08492(MG)from the Multiple Sclerosis Society of Canada,Grant/Award Number:1038154(to TEK).
文摘Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金funded by National Natural Science Foundation of China(82360801).
文摘Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
文摘1.Introduction The field of exercise science is experiencing a renaissance,with recent research illuminating the molecular,cellular,and systemic effects of physical activity.This is largely due to the now unequivocal evidence that a lack of physical activity,not only has direct effects on the prevalence of non-contagious diseases(NCDs)but has profound additive effects of other risk factors for NCD such as obesity and hypertension.1 The articles in this special topic of Journal of Sport and Health Science(JSHS)are dedicated to research on Exercise biochemistry&metabolism.
基金supported by Government of the Principado de Asturias through the Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y a la Tecnologia(FICYT)and also co-founded by the European Union,GRUPIN(IDI/2024/000719).
文摘Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
基金supported by the National Research Foundation of Korea(2020R1F1A1074155).
文摘Recently,Prevotella spp.,a major genus of gram-negative commensal bacteria in humans,have emerged as a key microbial contributor to host metabolism due to its ability to ferment dietary fibers,produce beneficial short-chain fatty acids,and influence immune responses.However,their diversity and functional differences have created challenges for their development and therapeutic use.Recent studies have shown that specific Prevotella species,such as P.copri,P.intestinalis,and P.histicola,can strengthen gut barrier integrity and reduce metabolic imbalances.Notably,Prevotella populations can be increased through high-fiber or herbal-based treatments.Traditional herbal medicines,including fiber-rich decoctions,also demonstrate the potential to boost endogenous Prevotella communities,enhance microbial fermentation,and improve glucose and lipid balance.This perspective examines the context-dependent roles of Prevotella spp.,with emphasis on the functional heterogeneity of key species such as P.copri,suggests a framework for combining herbal modulation with species-level microbiota profiling,and outlines a research plan to explore microbe-herb synergy in treating obesity,type 2 diabetes,and related metabolic disorders.This strategy offers a new,ecology-based approach to complement standard metabolic interventions.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金supported by the Natural Science Foundation of Beijing Municipality(Grant No.7234401)the Postdoctoral Research Foundation of China(Grant No.88014Y0226)。
文摘Cardiovascular disease(CVD)is often accompanied by chronic kidney disease(CKD)and metabolic disorders such as obesity and type 2 diabetes^([1]).The coexistence of these conditions can lead to systemic dysfunction and substantially increase adverse cardiovascular outcomes.To describe this interplay,the American Heart Association(AHA)recently proposed the concept of cardiovascular-kidney-metabolic(CKM)syndrome^([1]).However,its risk-enhancing factors and underlying mechanisms remain unclear.
基金supported by NIH awards R01 DK101043 to LJG and P30 DK036836 to Joslin Diabetes Centersupported by American Diabetes Association Grant No.1-17-PMF-009+1 种基金supported by American Diabetes Association(Grant No.1-25-PDF-67)supported by fellowships from Sunstar Foundation,Japan Society for the Promotion of Science(JSPS),Kanae Foundation,and Meiji Yasuda Life Foundation of Health and Welfare.
文摘Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.
基金financial support from the National Natural Science Foundation of China (Nos.82473887 and 21927808)the Scientific and Technological Innovation Program of Shanghai (No.23DZ2202500)the CAMS Innovation Fund for Medical Sciences (No.2021-1-I2M-026)。
文摘The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
文摘Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.
文摘Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease,particularly metabolic dysfunction-associated steatohep-atitis(MASH),a progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD).With the rising global prevalence of MASLD—affecting over one-third of the adult population—and its close association with obesity,insulin resistance,and metabolic syndrome,there is an urgent need for inno-vative,minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma.Traditional management of MASLD relies on lifestyle modifications and bariatric surgery,yet these app-roaches are hampered by issues of adherence,invasiveness,and accessibility.This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty(ESG),intragastric balloons(IGB),duodenal mucosal resur-facing(DMR),and duodeno-jejunal bypass liners(DJBL),as well as revisional procedures like endoscopic revisional gastroplasty(ERG)and transoral outlet reduction(TORe).Clinical studies and meta-analyses indicate that metabolic en-doscopy is safe and effective for liver fibrosis in MASH.ESG appears to offer the greatest fibrosis reduction,while IGB and DJBL yield modest improvements,and DMR shows no significant effect.Among revisional therapies,ERG has dem-onstrated fibrosis reduction,although the benefits of TORe remain to be fully evaluated.
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
基金Supported by the National Natural Science Foundation of China(Nos.42141003,42176147)the National Key Research and Development Program of China(No.2022YFF0802204)the Xiamen Key Laboratory of Urban Sea Ecological Conservation and Restoration(USER)(Nos.USER2021-1,USER2021-5)。
文摘Ecological floating bed is an important biological remediation method for water pollution control.During the removal of excess nutrients and pollutants,changes in environmental factors affect the characteristics of microorganisms in aquatic ecosystems.To understand the influences of ecological floating beds on size-fractionated microorganisms,we investigated the community assembly and nitrogen metabolic characteristics of three size-fractionated microorganism groups in the ecological floating bed area,using 18S rDNA,16S rDNA metabarcoding,and metagenomic sequencing techniques.Firstly,we discovered substantial differences between size-fractionated groups in the diversity and compositions of both microeukaryotic and bacterial communities,as well as the influences of floating beds on specific groups.The floating beds appeared to provide more habitats for heterotrophs and symbiotes while potentially inhibiting the growth of certain phytoplankton(cyanobacteria).Secondly,we observed that microeukaryotic and bacterial communities were predominantly influenced by stochastic and deterministic processes,respectively,and they both exhibited distinct patterns across different size-fractionated groups.Notably,microeukaryotic community assembly demonstrated a greater sensitivity to ecological floating beds,as indicated by an increase in dispersal limitation processes.Finally,the nitrogen metabolism functional genes revealed that microbes associated with large-sized particles played a crucial role in dissimilatory nitrate reduction to ammonium(DNRA)and denitrification processes within the floating bed area,thereby facilitating the removal of excess nitrogen nutrients from the water.In contrast,freeliving microorganisms from small-sized groups were linked mainly to the genes involved in nitrogen assimilation and assimilatory nitrate reduction to ammonium(ANRA)processes.These findings help understand the impact of ecological floating beds on the diversity and functional characteristics of microorganism communities in different size-fractionated groups.
