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
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
This study employed integrated multi-omics approaches to elucidate,from the perspective of amino acid metabolism,the adaptive mechanism of Penicillium digitatum under modified atmosphere packaging(MAP)conditions.Compa...This study employed integrated multi-omics approaches to elucidate,from the perspective of amino acid metabolism,the adaptive mechanism of Penicillium digitatum under modified atmosphere packaging(MAP)conditions.Comparative analysis of natural air(Air),controlled atmosphere(CA),and MAP treatments revealed that MAP upregulated the expression of the hercynylcysteine S-oxide synthase(HCSOS),aldehyde dehydrogenase(ALDH),and monoamine oxidase(MAO)genes,thereby enhancing histidine-derived ergothioneine and methionine levels,and subsequently boosting glutathione-mediated redox homeostasis.Meanwhile,MAP induced the expression of the dihydroxyacid dehydratase(DHAD),saccharopine dehydrogenase(SDH),and arginosuccinate lyase(ASL)genes,redirecting valine,lysine,and arginine into the tricarboxylic acid(TCA)cycle to fuel ATP production.MAP also enhanced ASL-mediated arginine degradation and urea cycle activity,reducing arginine accumulation when compared to CA treatment.In contrast,while MAP induced upregulated expression of the pyrroline-5-carboxylate dehydrogenase(P5CDH)and D-amino acid oxidase(DAAO)genes,CA treatment promoted proline accumulation,reflecting stress-specific metabolic flexibility.Collectively,these findings demonstrate that MAP triggers transcriptional reprogramming of amino acid metabolism to coordinate oxidative defense,energy generation,and osmotic balance.By modulating these metabolic pathways and regulatory genes under MAP conditions,fungal adaptability can be disrupted.Hence,this study provides a promising strategy for suppressing green mold development,extending the postharvest shelf life,and improving the quality of fruits and vegetables.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
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
Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodelin...Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.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
Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In t...Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.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
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
This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.L...This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.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
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
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
Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective e...Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective effects against liver diseases.However,its effects on hepatic lipid metabolism in pigs fed a low-net energy(NE)diet and the underlying mechanisms remain unclear.Thirty-two pigs(85.52±2.27 kg)were randomly assigned to four treatments:N-NE group(normal NE diet,2,475 kcal/kg NE),N-NEB group(normal NE diet+1,500 mg/kg BET,2,475 kcal/kg NE),R100-NE group(low-NE diet,2,375 kcal/kg NE),and R100-NEB group(low-NE diet+1,500 mg/kg BET,2,375 kcal/kg NE).The experiment lasted 35 d.Results There was no significant difference in growth performance among the groups(P>0.05).Reducing dietary NE levels caused liver dysfunction and increased total glyceride concentration,accompanied by lipid metabolism disorders.BET supplementation in a low-NE diet exhibited hepatoprotective roles,as evidenced by increased TP concentration and reduced ALT level in serum(P<0.05),as well as decreased fat content,adipocyte size,and total glyceride concentration in the liver(P<0.05).Meanwhile,dietary BET alleviated low-NE diet-induced hepatic lipid metabolism disorder by downregulating mRNA expressions of genes related to fatty acid transport(FABP3 and CD36)and lipogenesis(SREBP1c and FASN),while upregulating mRNA expressions involved in lipolysis(CPT1 and HSL)(P<0.05).Furthermore,dietary BET increased serum SAM concentration and the SAM/SAH ratio in pigs fed low-NE diets(P<0.05),thereby providing sufficient methyl groups through regulating the activities of enzymes participated in BET metabolism.Mechanistically,BET increased m^(6)A modification level and regulated mRNA and protein expressions of m^(6)A modified proteins including METTL3,METTL14,WTAP,YTHDF1,and ALKBH5.Correlation analysis showed a significant association between m^(6)A RNA methylation and hepatic lipid metabolism,suggesting that m^(6)A RNA methylation may play a critical role in mediating hepatic lipid metabolism.Conclusions Dietary BET supplementation in low-NE diets alleviated hepatic lipid metabolism disorders by regulating m^(6)A RNA methylation,ultimately reducing hepatic lipid accumulation in finishing pigs.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
Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The ...Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.展开更多
Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role i...Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.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 majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in th...The majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in the brain.This interpretation has the benefit of providing a level of constancy to what we experience as vision but also limits our ability to perceive subtle decline in our own vision.展开更多
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.
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This study employed integrated multi-omics approaches to elucidate,from the perspective of amino acid metabolism,the adaptive mechanism of Penicillium digitatum under modified atmosphere packaging(MAP)conditions.Comparative analysis of natural air(Air),controlled atmosphere(CA),and MAP treatments revealed that MAP upregulated the expression of the hercynylcysteine S-oxide synthase(HCSOS),aldehyde dehydrogenase(ALDH),and monoamine oxidase(MAO)genes,thereby enhancing histidine-derived ergothioneine and methionine levels,and subsequently boosting glutathione-mediated redox homeostasis.Meanwhile,MAP induced the expression of the dihydroxyacid dehydratase(DHAD),saccharopine dehydrogenase(SDH),and arginosuccinate lyase(ASL)genes,redirecting valine,lysine,and arginine into the tricarboxylic acid(TCA)cycle to fuel ATP production.MAP also enhanced ASL-mediated arginine degradation and urea cycle activity,reducing arginine accumulation when compared to CA treatment.In contrast,while MAP induced upregulated expression of the pyrroline-5-carboxylate dehydrogenase(P5CDH)and D-amino acid oxidase(DAAO)genes,CA treatment promoted proline accumulation,reflecting stress-specific metabolic flexibility.Collectively,these findings demonstrate that MAP triggers transcriptional reprogramming of amino acid metabolism to coordinate oxidative defense,energy generation,and osmotic balance.By modulating these metabolic pathways and regulatory genes under MAP conditions,fungal adaptability can be disrupted.Hence,this study provides a promising strategy for suppressing green mold development,extending the postharvest shelf life,and improving the quality of fruits and vegetables.
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.
基金Shanghai Municipal Health Commission,No.20224Z0008(to PY)the National Natural Science Foundation of China,No.82101412(to MZ)+1 种基金the Science Foundation of Naval Medical Center of PLA,No.23M2702(to MZ)National Key Research and Development Program of China,No.2023YFC2506506(QL)。
文摘Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.
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 Shanghai Shenkang Center Demonstration Research Ward Construction,No.SHDC2022CRW010(to MF)Shanghai Shenkang Center Medical Enterprise Integration and Innovation Collaborative Special Project,No.SHDC2022CRT018(to MF)+4 种基金Shanghai Health System Key Supported Discipline-Rehabilitation Medicine,No.2023ZDFC0301(to JT)Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine,No.23KFL009(to JT)Shanghai Postdoctoral Excellence Program,No.2022515(to CY)Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan,No.23YF1447600(to CY)China Postdoctoral Science Foundation,No.2023M732338(to CY).
文摘Ischemic stroke,which is characterized by hypoxia and ischemia,triggers a cascade of injury responses,including neurotoxicity,inflammation,oxidative stress,disruption of the blood-brain barrier,and neuronal death.In this context,tryptophan metabolites and enzymes,which are synthesized through the kynurenine and 5-hydroxytryptamine pathways,play dual roles.The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke.Neuroprotective metabolites,such as kynurenic acid,exert their effects through various mechanisms,including competitive blockade of N-methyl-D-aspartate receptors,modulation ofα7 nicotinic acetylcholine receptors,and scavenging of reactive oxygen species.In contrast,neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins,induce neurotoxicity mediated by reactive oxygen species,and disrupt mitochondrial function.Additionally,the enzymes involved in tryptophan metabolism play major roles in these processes.Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis.Consequently,the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke.Stroke treatment aims to restore the balance of various metabolite levels;however,precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke.Therefore,this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.
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.
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National Nature Science Foundation of China,No.81870944(to FL).
文摘This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.
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 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.
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 Key Research and Development Program of China(2022YFD1300502)Sichuan Science and Technology Program(2021ZDZX0009)。
文摘Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective effects against liver diseases.However,its effects on hepatic lipid metabolism in pigs fed a low-net energy(NE)diet and the underlying mechanisms remain unclear.Thirty-two pigs(85.52±2.27 kg)were randomly assigned to four treatments:N-NE group(normal NE diet,2,475 kcal/kg NE),N-NEB group(normal NE diet+1,500 mg/kg BET,2,475 kcal/kg NE),R100-NE group(low-NE diet,2,375 kcal/kg NE),and R100-NEB group(low-NE diet+1,500 mg/kg BET,2,375 kcal/kg NE).The experiment lasted 35 d.Results There was no significant difference in growth performance among the groups(P>0.05).Reducing dietary NE levels caused liver dysfunction and increased total glyceride concentration,accompanied by lipid metabolism disorders.BET supplementation in a low-NE diet exhibited hepatoprotective roles,as evidenced by increased TP concentration and reduced ALT level in serum(P<0.05),as well as decreased fat content,adipocyte size,and total glyceride concentration in the liver(P<0.05).Meanwhile,dietary BET alleviated low-NE diet-induced hepatic lipid metabolism disorder by downregulating mRNA expressions of genes related to fatty acid transport(FABP3 and CD36)and lipogenesis(SREBP1c and FASN),while upregulating mRNA expressions involved in lipolysis(CPT1 and HSL)(P<0.05).Furthermore,dietary BET increased serum SAM concentration and the SAM/SAH ratio in pigs fed low-NE diets(P<0.05),thereby providing sufficient methyl groups through regulating the activities of enzymes participated in BET metabolism.Mechanistically,BET increased m^(6)A modification level and regulated mRNA and protein expressions of m^(6)A modified proteins including METTL3,METTL14,WTAP,YTHDF1,and ALKBH5.Correlation analysis showed a significant association between m^(6)A RNA methylation and hepatic lipid metabolism,suggesting that m^(6)A RNA methylation may play a critical role in mediating hepatic lipid metabolism.Conclusions Dietary BET supplementation in low-NE diets alleviated hepatic lipid metabolism disorders by regulating m^(6)A RNA methylation,ultimately reducing hepatic lipid accumulation in finishing pigs.
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 the National Research Foundation of Korea grant funded by the Korean government(Grant no.:RS-2022-NR070862).
文摘Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.
基金supported by the National Natural Science Foundation of China(no.32372838,U22A20506)the National Key Research and Development Program of China(no.2024YFD1300104)+1 种基金the scientific and technological development program of Jilin province(YDZJ202203CGZH037)the earmarked fund for JLARS-2025-070203。
文摘Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.
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 Vetenskapsrådet 2022-00799 and the Ulla and Ingemar Dahlberg Foundation(to PAW).
文摘The majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in the brain.This interpretation has the benefit of providing a level of constancy to what we experience as vision but also limits our ability to perceive subtle decline in our own vision.
