As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epid...As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.展开更多
Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2]....Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].展开更多
Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effec...Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effects of the compatibility of Paeoniae Radix Rubra(PRR)and Angelicae Sinensis Radix(ASR)on the metabolic level of rats,and observe the changes in body weight and behavior.Discover the mechanism of preventing the occurrence of diseases by using PRR and ASR.Methods:Two animal models were induced by levothyroxine and low-temperature stimulation,followed by 21 days of edible traditional Chinese medicine administration.The changes in the rats’water intake,food intake,body temperature,and thermotactic behavior were recorded.Results:The results showed that PRR could cause an increase in the body weight of rats,a decrease in body temperature,and a stronger preference for warm environments.PRR inhibited thyroid function,the excitability of the nervous system,and energy metabolism.PRR upregulated the expressions of mTOR and TRPM8 while downregulating the expressions of AMPK and TRPV1.Conclusion:Our research findings suggest that the cold-natured PRR can inhibit the material and energy metabolism of the body and lower the body temperature,increasing the thermophilic behavior of rats.In contrast,ASR exhibited an antagonistic effect against PRR.展开更多
Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progre...Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.展开更多
Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive component...Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive components of the essential oil derived from Curcuma species.Among these, curdione—one of the key active constituents—has been identified in 25 Curcuma species, with the highest concentration reported in the rhizome essential oil of Curcuma trichosantha Gagnep. Curdione can also be synthesized through chemical methods,and its regio-and stereo-selectivity can be further optimized via chemo-bio transformations.This compound demonstrates significant therapeutic potential, including anticancer, antithrombotic, anti-inflammatory, anti-viral, anti-fungal, anti-diabetic, and multi-organ protective properties. Despite these promising biological activities, its clinical application is hindered by poor water solubility and potential toxicity. This review summarizes current knowledge on the natural sources, chemical synthesis, chemo-bio transformations, metabolism, pharmacokinetics, pharmacological effects, potential toxicities, and molecular mechanisms of curdione. Furthermore, perspectives on future drug development are discussed with the aim of promoting the clinical translation of this promising natural compound.展开更多
Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva a...Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.展开更多
As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively ...As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively extensive,studies on the association between aging and related diseases remain limited.G.lucidum,a traditional medicinal fungus,has garnered significant attention due to its diverse bioactive properties.Recent studies have revealed that G.lucidum and its active components exhibit significant potential in anti-aging and regulating dysregulation of glucose and lipid metabolism.However,a comprehensive and detailed review of recent research findings has yet to be thoroughly explored.This paper summarizes and elucidates the latest advances in the pathological mechanisms of aging-related glucose and lipid metabolism disorders by retrieving data from databases such as X-mol and PubMed,provides a detailed account of the regulatory effects of G.lucidum’s primary active components on aging and lipid metabolism,and explores their potential mechanisms.Additionally,it discusses the application prospects of G.lucidum in the fields of anti-aging and metabolic regulation,aiming to provide a reference for research on aging-mediated lipid metabolism disorders and to lay a theoretical foundation for the further development and application of G.lucidum.展开更多
Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther developmen...Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.展开更多
The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to r...The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.展开更多
Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extr...Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.展开更多
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha...Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.展开更多
The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides hav...The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides have a certain intervention effect on disorders in glucose and lipid metabolism.This article reviewed the structure-function relationship of food-derived polysaccharides and elucidated their role in regulating glucose and lipid metabolism.Some new evidence suggests that secondary metabolites such as short-chain fatty acids,secondary bile acids,and lipopolysaccharide act as signaling molecules,activating pathways related to glucose and lipid metabolism,alleviating oxidative stress,inhibiting inflammation in the body,and regulating the homeostasis of glucose and lipid metabolism.These results indicated that food-derived polysaccharides have a positive impact on the regulation of glucose and lipid metabolism by improving the gut microbiota environment.On the other hand,gut microbiota disturbance can affect the host’s health through the gut-liver,gut-brain and gut-adipose tissue axes.Therefore,it is speculated that food-derived polysaccharides may intervene in glucose and lipid metabolism through the inter-organ crosstalk between gut,liver,adipose tissue,and nervous system.This essay provides a theoretical basis for the development and utilization of food-derived polysaccharides as prebiotics in intervening disorders in glucose and lipid metabolism.展开更多
Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which proc...Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.展开更多
High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We dem...High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.展开更多
Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine met...Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine metabolism.Methods:The Cancer Genome Atlas-Stomach Adenocarcinoma(TCGA-STAD),GSE19826,and GSE27342 datasets were analyzed by bioinformatics to identify key candidate genes in GC.The function of CENPF was assessed by flow cytometry,colony formation assays,and Cell Counting Kit-8(CCK-8).RNA sequencing,metabolic profiling,chromatin immunoprecipitation(ChIP),western blot(WB),and luciferase reporter assay were employed to investigate the fundamental mechanisms.Results:CENPF was upregulated in GC tumor samples and had a high diagnostic potential.CENPF knockdown declined cell proliferation,caused G2 arrest,and promoted apoptosis in GC cells.RNA sequencing revealed that CENPF was involved in glutamine metabolism.CENPF overexpression enhanced glutamine consumption and glutamate production,while glutamine deficiency reversed CENPF-mediated cell survival.CENPF stabilized cellular myelocytomatosis(c-Myc)by preventing proteasomal degradation,bound to the glutaminase(GLS)promoter,promoting glutamine metabolism.Overexpression of GLS or c-Myc rescued the CENPF knockdown’s inhibitory effect on GC cell growth.Conclusion:Our findings identify a new CENPF/c-Myc/GLS axis that affects glutamine metabolism and cell survival in GC,implying that CENPF might be a novel target for the treatment of GC.展开更多
Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chron...Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).展开更多
Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the undere...Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.展开更多
Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)r...Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.展开更多
Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We pr...Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.展开更多
Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivar...Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.展开更多
基金supported by grants from the Applied Basic Research Foundation of Yunnan Province(202301AT070095)the Candidate Talents Training Fund of Yunnan Province(H-2024069)。
文摘As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.
文摘Inborn errors of metabolism(IEMs)are a large group of disorders resulting from deficient activities in several metabolic pathways due to the dysfunction of a distinct enzyme associated with a biochemical pathway[1,2].Toxic intermediates will be produced due to the dysfunction of biochemical pathways.The liver is responsible for many essential metabolic processes,therefore it becomes one of the most severely affected organ by metabolic diseases[3].Early onset of liver disorders in IEMs includes jaundice,hepatomegaly,splenomegaly,ascites,hepatic encephalopathy,and liver failure[4].In infants and young children under 3 years old with acute liver failure(ALF),IEMs account for 18.9%-43%[5].
基金the preparation of this manuscript.This study was supported by the General Projects-Youth project(2022JQ-817)the Shaanxi University of Traditional Chinese Medicine Shaanxi Provincial Key Laboratory of Basic and New Drug Research Open Project(KF202303)+1 种基金the Research on process optimization and quality standard enhancement of five large varieties,including Four Seasons Antiviral Combination(2024CY-JJQ-36)the Shaanxi provincial science and technology department project(2025JC-YBMS-1033).
文摘Background:Disorders of metabolism can affect the food intake,weight changes,and behavioral alterations of the body.Metabolic disorders are usually accompanied by the occurrence of diseases.We aimed to study the effects of the compatibility of Paeoniae Radix Rubra(PRR)and Angelicae Sinensis Radix(ASR)on the metabolic level of rats,and observe the changes in body weight and behavior.Discover the mechanism of preventing the occurrence of diseases by using PRR and ASR.Methods:Two animal models were induced by levothyroxine and low-temperature stimulation,followed by 21 days of edible traditional Chinese medicine administration.The changes in the rats’water intake,food intake,body temperature,and thermotactic behavior were recorded.Results:The results showed that PRR could cause an increase in the body weight of rats,a decrease in body temperature,and a stronger preference for warm environments.PRR inhibited thyroid function,the excitability of the nervous system,and energy metabolism.PRR upregulated the expressions of mTOR and TRPM8 while downregulating the expressions of AMPK and TRPV1.Conclusion:Our research findings suggest that the cold-natured PRR can inhibit the material and energy metabolism of the body and lower the body temperature,increasing the thermophilic behavior of rats.In contrast,ASR exhibited an antagonistic effect against PRR.
文摘Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.
基金supported by the National Natural Science Foundation of China (Nos. 82192913 and 82304851)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (Nos. CI2023E002, CI2021B016, and CI2021A04801)the Fundamental Research Funds for the Central Public Welfare Research Institutes (Nos. ZZ13-YQ-055 and ZXKT22044)。
文摘Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive components of the essential oil derived from Curcuma species.Among these, curdione—one of the key active constituents—has been identified in 25 Curcuma species, with the highest concentration reported in the rhizome essential oil of Curcuma trichosantha Gagnep. Curdione can also be synthesized through chemical methods,and its regio-and stereo-selectivity can be further optimized via chemo-bio transformations.This compound demonstrates significant therapeutic potential, including anticancer, antithrombotic, anti-inflammatory, anti-viral, anti-fungal, anti-diabetic, and multi-organ protective properties. Despite these promising biological activities, its clinical application is hindered by poor water solubility and potential toxicity. This review summarizes current knowledge on the natural sources, chemical synthesis, chemo-bio transformations, metabolism, pharmacokinetics, pharmacological effects, potential toxicities, and molecular mechanisms of curdione. Furthermore, perspectives on future drug development are discussed with the aim of promoting the clinical translation of this promising natural compound.
文摘Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.
基金supported by grants from Natural Science Foundation of Jilin Province(No.23JQ08,No.YDZJ202502 CXJD077,No.JLARS-2025-0802-09 and No.YDZJ202501ZY TS706).
文摘As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively extensive,studies on the association between aging and related diseases remain limited.G.lucidum,a traditional medicinal fungus,has garnered significant attention due to its diverse bioactive properties.Recent studies have revealed that G.lucidum and its active components exhibit significant potential in anti-aging and regulating dysregulation of glucose and lipid metabolism.However,a comprehensive and detailed review of recent research findings has yet to be thoroughly explored.This paper summarizes and elucidates the latest advances in the pathological mechanisms of aging-related glucose and lipid metabolism disorders by retrieving data from databases such as X-mol and PubMed,provides a detailed account of the regulatory effects of G.lucidum’s primary active components on aging and lipid metabolism,and explores their potential mechanisms.Additionally,it discusses the application prospects of G.lucidum in the fields of anti-aging and metabolic regulation,aiming to provide a reference for research on aging-mediated lipid metabolism disorders and to lay a theoretical foundation for the further development and application of G.lucidum.
基金supported by the Science and Technology Major Program of Bingtuan,China (2023AA008)the National Natural Science Foundation of China (31960369)+1 种基金the Bingtuan Science and Technology Program,China (2025DA001)the Henan Provincial Science and Technology Research Project,China (222102110200)。
文摘Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the National Natural Science Foundation of China(82471925)。
文摘The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.
基金financially supported by the Natural Science Foundation of Zhejiang Province(LY22C010002)China Postdoctoral Science Foundation(2022M721732)+1 种基金the project of sending sci-tech experts to rural areas in Ningbo city(2022S205)the K.C.Wong Magna Fund of Ningbo University.
文摘Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.
基金supported and funded by the National Key Research and Development Program of China(2023YFD1300801)the Agricultural Science and Technology Innovation Program in Chinese Academy of Agricultural Sciences(ASTIP-IAS-08)。
文摘Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.
基金supported by the University Innovation Team of Shandong Province(2022KJ243)the National Natural Science Foundation of China(31901644)Natural Science Foundation of Shandong Province(ZR2025MS284).
文摘The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides have a certain intervention effect on disorders in glucose and lipid metabolism.This article reviewed the structure-function relationship of food-derived polysaccharides and elucidated their role in regulating glucose and lipid metabolism.Some new evidence suggests that secondary metabolites such as short-chain fatty acids,secondary bile acids,and lipopolysaccharide act as signaling molecules,activating pathways related to glucose and lipid metabolism,alleviating oxidative stress,inhibiting inflammation in the body,and regulating the homeostasis of glucose and lipid metabolism.These results indicated that food-derived polysaccharides have a positive impact on the regulation of glucose and lipid metabolism by improving the gut microbiota environment.On the other hand,gut microbiota disturbance can affect the host’s health through the gut-liver,gut-brain and gut-adipose tissue axes.Therefore,it is speculated that food-derived polysaccharides may intervene in glucose and lipid metabolism through the inter-organ crosstalk between gut,liver,adipose tissue,and nervous system.This essay provides a theoretical basis for the development and utilization of food-derived polysaccharides as prebiotics in intervening disorders in glucose and lipid metabolism.
基金supported by the project of National Natural Science Foundation of China(32272331 and 82560638)Guizhou Provincial Science and Technology Projects(Qiankehe[2024]youth 326)+1 种基金Zunyi Science and Technology Projects(Zunshikehe HZ zi 2024312 hao)Guizhou Provincial Health Commission Science and Technology Fund(gzwkj2025-512).
文摘Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Natural Science Foundation of China(32272364)Shanghai Engineering Research Center of food microbiology program(19DZ2281100).
文摘High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.
基金funded by the Medical and Health Technology Development Programin Shandong Province.Project number:202303031600.
文摘Background:Gastric cancer(GC)remains highly lethal,with metabolic reprogramming as a key hallmark.This study explores Centromere Protein F(CENPF)’s role in GC pathogenesis,specifically its regulation of glutamine metabolism.Methods:The Cancer Genome Atlas-Stomach Adenocarcinoma(TCGA-STAD),GSE19826,and GSE27342 datasets were analyzed by bioinformatics to identify key candidate genes in GC.The function of CENPF was assessed by flow cytometry,colony formation assays,and Cell Counting Kit-8(CCK-8).RNA sequencing,metabolic profiling,chromatin immunoprecipitation(ChIP),western blot(WB),and luciferase reporter assay were employed to investigate the fundamental mechanisms.Results:CENPF was upregulated in GC tumor samples and had a high diagnostic potential.CENPF knockdown declined cell proliferation,caused G2 arrest,and promoted apoptosis in GC cells.RNA sequencing revealed that CENPF was involved in glutamine metabolism.CENPF overexpression enhanced glutamine consumption and glutamate production,while glutamine deficiency reversed CENPF-mediated cell survival.CENPF stabilized cellular myelocytomatosis(c-Myc)by preventing proteasomal degradation,bound to the glutaminase(GLS)promoter,promoting glutamine metabolism.Overexpression of GLS or c-Myc rescued the CENPF knockdown’s inhibitory effect on GC cell growth.Conclusion:Our findings identify a new CENPF/c-Myc/GLS axis that affects glutamine metabolism and cell survival in GC,implying that CENPF might be a novel target for the treatment of GC.
基金supported by the Judith Jane Mason and Harold Stannett Williams Memorial Foundation National Medical Program(#Mason2210)to JX。
文摘Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).
基金supported by the Key Special Projects of the Ministry of Science and Technology(SQ2020YFF0404523)the North Anhui Soybean Advantageous Characteristic Industry Cluster Project(2023CYJQ013)+2 种基金the National Natural Science Foundation of China(32172162)the Key Genetic Technologies Research and Development Program of Hefei(2021GJ075)the Young Talents Program of Anhui Academy of Agricultural Science(QNYC-202122).
文摘Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.
基金supported by the National Natural Science Foundation of China(Nos.32371573 and 32171497)。
文摘Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.
基金supported by the National Natural Science Foundation of China(32172210)the Shandong Provincial Natural Science Foundation(ZR2025QC295).
文摘Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.
基金provided by the National Natural Sciences Foundation of China (82270979)High-Level Hospital Construction Project (0224C001,0224C050)Cultivation Program for Reserve Talents for Academic Leaders (2023A208) of Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University。
文摘Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.
