The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronid...The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronidase,and tyrosinase in relation to its chemical composition.Ultra Performance Liquid Chromatography-Mass Spectrometry(UPLC-MS)identified 27 metabolites(15 flavonoids,8 phenolic acids and their derivatives,and 4 coumarins).ASE showed strong antioxidant capacity in DPPH(IC_(50)value of 26.05μg/mL)and FRAP(2433μM FeSO_(4)/g extract)assays.The extract inhibited MMP-1 and MMP-9 in a concentration-dependent manner and suppressed collagenase,elastase,hyaluronidase,and tyrosinase activities(IC_(50)=35.038,40.748,61.389,and 30.980μg/mL,respectively).A network pharmacology study was conducted to uncover the mechanisms responsible for skin anti-aging effects,and molecular docking further evaluated interactions of key metabolites with hub targets.Twenty-one bioactive metabolites,selected based on oral bioavailability and drug-likeness,highlighted cinnamic acid,acacetin,luteolin,kaempferol,and apigenin as key compounds.MMP-9,ESR1,PTGS-2,and EGFR were identified as main targets.Docking studies revealed that acacetin and apigenin have stronger binding affinities to MMP-9,PTGS-2,and EGFR than other constituents.These findings suggest that ASE may serve as a natural multi-target skin anti-aging remedy with potential cosmetic applications.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabo...Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.展开更多
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and di...A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.展开更多
Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal varia...Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.展开更多
Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysi...Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysis to evaluate the causal effects of 871 circulating metabolites on MDD,using the Genome-Wide Association Studies datasets of MDD(N=1035760)and metabolites(N=8299).Bayesian colocalisation and druggability analyses were employed to identify genetic variants contributing to both MDD and levels of metabolites in plasma and to pinpoint metabolites with therapeutic potential,respectively.Results MR analysis identified 11 metabolites associated with MDD(false discovery rate<0.05).Eight metabolites,including arachidonate(20:4n6)(odds ratio(OR):0.97),1-arachidonoyl-GPC(20:4n6)(OR:0.98),1-(1-enylpalmitoyl)-2-palmitoleoyl-GPC(P-16:0/16:1)(OR:0.97),succinoyltaurine(OR:0.98),3-methoxycatechol sulphate(1)(OR:0.98)and 11β-hydroxyandrosterone glucuronide(OR:0.97),showed protective effects against MDD.Three metabolites were associated with increased risk,namely,butyrylglycine(OR:1.03),3-carboxy-4-methyl-5-propyl-2-furanpropanoate(OR:1.02)and 1-(1-enyl-stearoyl)-2-oleoyl-GPE(P-18:0/18:1)(OR:1.02).Colocalisation analysis supported shared genetic signals between five lipid metabolites and MDD,particularly at loci harbouring FADS and ATP9A.Notably,a majority of metabolites associated with MDD are being explored as therapeutic targets for various psychiatric disorders.Conclusions Genetically predicted levels of certain circulating metabolites make a causal contribution to MDD.Further investigation of their roles may provide novel pathophysiological insights and give clues for targeted therapies.展开更多
To investigate the in vitro digestion and fermentation properties of soybean oligosaccharides(SBOS)extracted from defatted soybean meal,the changes in monosaccharide composition and molecular mass were analyzed.Subseq...To investigate the in vitro digestion and fermentation properties of soybean oligosaccharides(SBOS)extracted from defatted soybean meal,the changes in monosaccharide composition and molecular mass were analyzed.Subsequently,the effect of SBOS on microbial community structure and metabolites was studied by 16S rRNA gene sequencing and untargeted metabolomics based on liquid chromatography-mass spectrometry.Results showed that SBOS was not easily enzymolyzed during simulated digestion and could reach the large intestine through the digestive system.The significant decrease in the molecular mass of SBOS after in vitro fermentation indicated its utilization by the gut microbiota,which increased the contents of short-chain fatty acids and lactic acid,thereby reducing the pH of the fermentation broth.Moreover,the core community was found to consist of Blautia,Lactobacillaceae,and Pediococcus.SBOS up-regulated beneficial differential metabolites such as myo-inositol,lactose,and glucose,which were closely related to galactose,amino sugar,and nucleotide sugar metabolism.This study will provide a reference for exploring the relationship between the gut microbiota and the metabolites of SBOS,and provide a basis for the development and application of SBOS as an ingredient for functional products.展开更多
Background:The composition of the intestinal flora and the resulting metabolites af-fect patients'sleep after surgery.Methods:We intended to elucidate the mechanisms by which disordered intestinal flora modulate t...Background:The composition of the intestinal flora and the resulting metabolites af-fect patients'sleep after surgery.Methods:We intended to elucidate the mechanisms by which disordered intestinal flora modulate the pathophysiology of postoperative sleep disturbances in hosts.In this study,we explored the impacts of anesthesia,surgery,and postoperative sleep duration on the fecal microbiota and metabolites of individuals classified postpro-cedurally as poor sleepers(PS)and good sleepers(GS),as diagnosed by the bispec-tral index.We also performed fecal microbiota transplantation in pseudo-germ-free(PGF)rats and applied Western blotting,immunohistochemistry,and gut permeability analyses to identify the potential mechanism of its effect.Results:Research finding shows the PS group had significantly higher postopera-tive stool levels of the metabolites tryptophan and kynurenine than the GS group.PGF rats that received gut microbiota from PSs exhibited less rapid eye movement(REM)sleep than those that received GS microbiota(GS-PGF:11.4%±1.6%,PS-PGF:4.8%±2.0%,p<0.001).Measurement of 5-hydroxytryptophan(5-HTP)levels in the stool,serum,and prefrontal cortex(PFC)indicated that altered 5-HTP levels,includ-ing reduced levels in the PFC,caused sleep loss in PGF rats transplanted with PS gut flora.Through the brain-gut axis,the inactivity of tryptophan hydroxylase 1(TPH1)and TPH2 in the colon and PFC,respectively,caused a loss of REM sleep in PGF rats and decreased the 5-HTP level in the PFC.Conclusions:These findings indicate that postoperative gut dysbiosis and defective 5-HTP metabolism may cause postoperative sleep disturbances.Clinicians and sleep researchers may gain new insights from this study.展开更多
Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2...Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2))of ethiprole showed higher acute toxicity than ethiprole.Therefore,assessing the thyroid toxicity of its metabolites is crucial for safety assessment.In this study,the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico,in vitro,and in vivo assays,with the aim of conducting a comparative study on thyroid toxicity.Molecular docking analysis showed that ethiprole,M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3,5-triiodothyronine(T3).GH3 cell proliferation assays revealed that ethiprole,M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation.Using the zebrafish model,we further investigated that exposure to ethiprole,M1,and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid(HPT)axis-related genes.Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta,M1 mainly through binding with the corticotropin releasing factor receptor-1,and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity.M2 showed the highest developmental toxicity and thyroid disrupting effects,which significantly reducing hatching rates,increasing deformity rates,exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis.This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.展开更多
This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Baye...This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Bayesian kernel machine regression,and toxicogenomic analysis were key approaches.PM_(2.5)exposure was positively associated with the risk of developing depression,whereas phenylglyoxylic acid exposure was negatively associated with depression risk.We found a significant overall relationship between ambient air pollution and depression,particularly at the 55th and 60th percentiles.Although statistical significance was not reached at the 65th percentile,there was a noticeable upward trend,indicating a potential association.Interestingly,no significant connection was found between a combination of metabolites from ambient air pollution and depression.PM_(2.5)and phenylglyoxylic acid emerged as the most influential compounds in the models,respectively.PM_(2.5)exposure altered the expression of 42 specific targets associated with depression,especially POMC,SCL6A4,IL6,and SOD2.The study identified specific pathways related to insulin secretion,energy metabolism,blood circulation,tube diameter,and maintenance of blood vessel diameter,as well as key molecular mechanisms involving hsa-miR-124-3p,hsa-miR-155-5p,hsa-miR-16-5p,and SP1.These mechanisms were found to underlie the etiology of depression associated with PM_(2.5)exposure.In conclusions,PM_(2.5)and phenylglyoxylic acid were found to be associated with depression.Further work is needed to gain insight into the molecular mechanisms by which these chemicals affect depression,especially pathways related to insulin secretion and blood circulation.展开更多
A new alkaloid,diacedolinate(1),along with fourteen known compounds(2-15)was isolated from the sponge associated fungus Penicillium crustosum SCSIO 41442.The structures of these compounds were determined by spectrum a...A new alkaloid,diacedolinate(1),along with fourteen known compounds(2-15)was isolated from the sponge associated fungus Penicillium crustosum SCSIO 41442.The structures of these compounds were determined by spectrum analysis and ECD.All compounds were evaluated for their antioxidant and antimicrobial activities.The results showed that compound 1 exhibited weak antioxidant activity with an IC_(50)value of(71.00±0.14)μg·mL^(−1),while compound 2,in contrast,displayed broad antioxidant activity with an IC_(50)value of(1.25±0.10)μg·mL^(−1),compared with the positive control,vitamin C.In addition,compounds 9,10,11,and 15 demonstrated broad-spectrum antimicrobial activity against a variety of pathogens,including MRSA,Colletotrichum asianum HNM 408,Colletotrichum acutatum HNM RC178,and Alternaria alternate,with MIC values ranging from 2.5 to 160μg·mL^(−1).The bioactivities of these compounds are reported here for the first time.展开更多
Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the caus...Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.展开更多
This study was performed to investigate the changes in microbial communities and metabolites during the long-term fermentation of commercially manufactured anchovy sauce.Samples of commercial anchovy sauce were collec...This study was performed to investigate the changes in microbial communities and metabolites during the long-term fermentation of commercially manufactured anchovy sauce.Samples of commercial anchovy sauce were collected from large-scale fermentation tanks with fermentation periods of up to 7.87 years.The complex bacterial community was simplified to two genera,Tetragenococcus and Halanaerobium,after approximately 0.55 years of fermentation.Although genera,such as Saccharomyces,Cladosporium,Candida,and Aspergillus,were relatively dominant,no clear pattern was identified in fungal community analysis.The longitudinal metabolite profile demonstrated that approximately half(55.8%)of the metabolites present in anchovy sauce were produced within a year of fermentation due to rapid fermentation.Despite the static microbial community,the contents of several metabolites including amino acids and biogenic amines changed continuously during the long-term fermentation of anchovy sauce.This study provides novel insights into the changes in microbiota and metabolites in fish sauce produced without any starter inoculation.展开更多
Pyropia yezoensis(red algae)or commonly known as nori,is highly regarded for its nutritional benefits and distinct taste,leading to its widespread consumption.The bio-activity and sensory characteristics of P.yezoensi...Pyropia yezoensis(red algae)or commonly known as nori,is highly regarded for its nutritional benefits and distinct taste,leading to its widespread consumption.The bio-activity and sensory characteristics of P.yezoensis are attributed to the metabolites it contains.In this study,identification and quantification of the diverse range of metabolites of P.yezoensis and metabolomic analysis were conducted using gas chromatography-mass spectrometry(GC-MS).Furthermore,the impact of high temperature on its metabolites regulation was also investigated.Due to metabolomic analysis,a diverse range of metabolites were identified in P.yezoensis,including lipids,amino acids,carbohydrates,and secondary metabolites.Several known bioactive compounds,including alcohol and polyols,amines,amino acids-peptides-analogues,beta hydroxy acids and derivatives,carbohydrates and carbohydrate conjugates,cholestane steroids,dicarboxylic acid and derivatives,and fatty acids and conjugates were detected in abundance,highlighting the nutritional and functional properties of P.yezoensis.Additionally,the metabolites composition of P.yezoensis was significantly affected in high temperatures,which led to up-regulation of considerable primary metabolites and few were down-regulated,and suggested a potential response and adaptation mechanism of P.yezoensis to elevated temperature conditions.This research highlighted the metabolomics of P.yezoensis,provided insights into its metabolite composition and regulatory responses to high temperature conditions,enhanced our knowledge of the biochemical pathways and adaptive mechanisms of P.yezoensis,which can assist the improvement strategies of utilization and cultivation to promote this valuable alga in response to fluctuating environmental conditions.展开更多
Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promis...Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promising therapeutic strategies for various diseases.While BMSCs and ADSCs exhibit distinct functional profiles tailored to different therapeutic applications,emerging evidence suggests that ADSCs may be a more promising approach for treating ischemic pathologies,including myocardial infarction,ischemic stroke,and peripheral artery disease,in comparison with BMSCs.However,the precise molecular mechanisms by which ADSCs enhance the therapeutic outcomes in these diseases remain poorly understood.In this editorial,we comment on the article by Li et al,which systematically compares the therapeutic efficacy of ADSCs and BMSCs derived from the same elderly patients with coronary heart disease and explores the underlying mechanism from a metabolic perspective.This study proposes that the metabolite L-arginine in ADSCs isolated from elderly patients promotes angiogenesis and protects against apoptosis in a hypoxic and ischemic microenvironment,thereby enhancing myocardial repair following infarction.These findings not only highlight the metabolic plasticity of ADSCs but also position L-arginine as a pivotal therapeutic effector in coronary heart disease.Given the novel and crucial role of L-arginine in ischemic heart diseases,further exploration of L-arginine in ADSCs(particularly those derived from elderly individuals)is essential,including its roles in angiogenesis,cell death,and the potential therapeutic implications in other ischemic pathologies.Additionally,further investigation into additional metabolites in ADSCs is warranted to enhance the therapeutic potential of ADSCs in ischemic pathologies.展开更多
The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately...The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.展开更多
In the world of microorganisms,the genud Streptomyces is renowned as a"natural pharmacy".This genus of bacteria is the primary source of clinical antibiotics,with approximately two-thirds of antibiotics deri...In the world of microorganisms,the genud Streptomyces is renowned as a"natural pharmacy".This genus of bacteria is the primary source of clinical antibiotics,with approximately two-thirds of antibiotics derived from it.However,industrial production faces challenges such as low yields and complex regulation.This study introduces the Streptomyces multiplexed artificial control system(SMARTS):a novel"plug-and-play"dynamic regulatory framework integrating trigger,stabilizer,and multiplexer modules.This enables the cross-species,predictable,and scalable production of secondary metabolites.Evolutionary analysis of 521 quorum-sensing receptors revealed conserved DNA-binding domains,informing the design of a universal trigger.SMARTS efficiently and robustly produced baiweimycin in a 120 m3 industrial fermenter,a process validated through a closed-loop pipeline ranging from molecular mechanisms to field applications.Implementing orthogonal control and hierarchical optimization enhances the efficiency of metabolic engineering and sheds light on the evolution of Streptomyces quorum sensing.This breakthrough offers a scalable solution for industrial production and advances synthetic biology,with significant implications for agriculture,pharmaceuticals,and global health.展开更多
[Objectives]To investigate the mechanism of endophytic fungi mediating the plant growth and promoting the accumulation of secondary metabolites in Camellia oleifera.[Methods]Four strains of endophytic fungi isolated f...[Objectives]To investigate the mechanism of endophytic fungi mediating the plant growth and promoting the accumulation of secondary metabolites in Camellia oleifera.[Methods]Four strains of endophytic fungi isolated from the rhizomes of C.oleifera were co-cultured with C.oleifera seedlings individually in sterile soil for 49 d:Didymella sp.(DS),Fusarium sp.(FS),Penicillium sp.(PS),and Clonostachys rosea(CR).[Results]The biological activities of the four fungal strains differed,but all exhibited the ability to promote quercetin accumulation while simultaneously reducing quercetin glycosides after co-culture with C.oleifera seedlings.The DS,FS and PS treatments resulted in a significant increase in the leaf area of C.oleifera,with all of the experimental groups exhibiting a weight increase of over 50%compared to the control(CON)group.[Conclusions]Our findings demonstrate the potential utility of endophytic fungi in the production of C.oleifera,highlighting their capacity to enhance both productivity and the accumulation of plant metabolites.展开更多
BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patien...BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.展开更多
基金funded by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.(DGSSR-2023-01-02126).
文摘The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronidase,and tyrosinase in relation to its chemical composition.Ultra Performance Liquid Chromatography-Mass Spectrometry(UPLC-MS)identified 27 metabolites(15 flavonoids,8 phenolic acids and their derivatives,and 4 coumarins).ASE showed strong antioxidant capacity in DPPH(IC_(50)value of 26.05μg/mL)and FRAP(2433μM FeSO_(4)/g extract)assays.The extract inhibited MMP-1 and MMP-9 in a concentration-dependent manner and suppressed collagenase,elastase,hyaluronidase,and tyrosinase activities(IC_(50)=35.038,40.748,61.389,and 30.980μg/mL,respectively).A network pharmacology study was conducted to uncover the mechanisms responsible for skin anti-aging effects,and molecular docking further evaluated interactions of key metabolites with hub targets.Twenty-one bioactive metabolites,selected based on oral bioavailability and drug-likeness,highlighted cinnamic acid,acacetin,luteolin,kaempferol,and apigenin as key compounds.MMP-9,ESR1,PTGS-2,and EGFR were identified as main targets.Docking studies revealed that acacetin and apigenin have stronger binding affinities to MMP-9,PTGS-2,and EGFR than other constituents.These findings suggest that ASE may serve as a natural multi-target skin anti-aging remedy with potential cosmetic applications.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金supported by the National Science and Technology Major Program for Noncommunicable Chronic Diseases(2023ZD0503500)the National Natural Science Foundation of China(82030102,12126602,91857118)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSP-GG-2)。
文摘Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.
基金supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,China(Grant Nos.:CI2023E002 and CI2021A04513)the National Natural Science Foundation of China(Grant Nos.:82204619 and 82274094)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ15-YQ-067 and ZZ16-ND-10-26).
文摘A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
基金supported by grants from Singhealth Duke-NUS Academic Medicine Research grant(AM/SU035/2020)NMRC Clinician-Scientist Individual Research Grant New Investigator Grant(CNIG20nov-0003).
文摘Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.
文摘Background Metabolic dysregulation has been implicated in major depressive disorder(MDD).Aims We aimed to explore the potential role of plasma metabolites in MDD.Methods We conducted Mendelian randomisation(MR)analysis to evaluate the causal effects of 871 circulating metabolites on MDD,using the Genome-Wide Association Studies datasets of MDD(N=1035760)and metabolites(N=8299).Bayesian colocalisation and druggability analyses were employed to identify genetic variants contributing to both MDD and levels of metabolites in plasma and to pinpoint metabolites with therapeutic potential,respectively.Results MR analysis identified 11 metabolites associated with MDD(false discovery rate<0.05).Eight metabolites,including arachidonate(20:4n6)(odds ratio(OR):0.97),1-arachidonoyl-GPC(20:4n6)(OR:0.98),1-(1-enylpalmitoyl)-2-palmitoleoyl-GPC(P-16:0/16:1)(OR:0.97),succinoyltaurine(OR:0.98),3-methoxycatechol sulphate(1)(OR:0.98)and 11β-hydroxyandrosterone glucuronide(OR:0.97),showed protective effects against MDD.Three metabolites were associated with increased risk,namely,butyrylglycine(OR:1.03),3-carboxy-4-methyl-5-propyl-2-furanpropanoate(OR:1.02)and 1-(1-enyl-stearoyl)-2-oleoyl-GPE(P-18:0/18:1)(OR:1.02).Colocalisation analysis supported shared genetic signals between five lipid metabolites and MDD,particularly at loci harbouring FADS and ATP9A.Notably,a majority of metabolites associated with MDD are being explored as therapeutic targets for various psychiatric disorders.Conclusions Genetically predicted levels of certain circulating metabolites make a causal contribution to MDD.Further investigation of their roles may provide novel pathophysiological insights and give clues for targeted therapies.
文摘To investigate the in vitro digestion and fermentation properties of soybean oligosaccharides(SBOS)extracted from defatted soybean meal,the changes in monosaccharide composition and molecular mass were analyzed.Subsequently,the effect of SBOS on microbial community structure and metabolites was studied by 16S rRNA gene sequencing and untargeted metabolomics based on liquid chromatography-mass spectrometry.Results showed that SBOS was not easily enzymolyzed during simulated digestion and could reach the large intestine through the digestive system.The significant decrease in the molecular mass of SBOS after in vitro fermentation indicated its utilization by the gut microbiota,which increased the contents of short-chain fatty acids and lactic acid,thereby reducing the pH of the fermentation broth.Moreover,the core community was found to consist of Blautia,Lactobacillaceae,and Pediococcus.SBOS up-regulated beneficial differential metabolites such as myo-inositol,lactose,and glucose,which were closely related to galactose,amino sugar,and nucleotide sugar metabolism.This study will provide a reference for exploring the relationship between the gut microbiota and the metabolites of SBOS,and provide a basis for the development and application of SBOS as an ingredient for functional products.
基金supported by a grant from the National Natural Science Foundation of China(82171187).
文摘Background:The composition of the intestinal flora and the resulting metabolites af-fect patients'sleep after surgery.Methods:We intended to elucidate the mechanisms by which disordered intestinal flora modulate the pathophysiology of postoperative sleep disturbances in hosts.In this study,we explored the impacts of anesthesia,surgery,and postoperative sleep duration on the fecal microbiota and metabolites of individuals classified postpro-cedurally as poor sleepers(PS)and good sleepers(GS),as diagnosed by the bispec-tral index.We also performed fecal microbiota transplantation in pseudo-germ-free(PGF)rats and applied Western blotting,immunohistochemistry,and gut permeability analyses to identify the potential mechanism of its effect.Results:Research finding shows the PS group had significantly higher postopera-tive stool levels of the metabolites tryptophan and kynurenine than the GS group.PGF rats that received gut microbiota from PSs exhibited less rapid eye movement(REM)sleep than those that received GS microbiota(GS-PGF:11.4%±1.6%,PS-PGF:4.8%±2.0%,p<0.001).Measurement of 5-hydroxytryptophan(5-HTP)levels in the stool,serum,and prefrontal cortex(PFC)indicated that altered 5-HTP levels,includ-ing reduced levels in the PFC,caused sleep loss in PGF rats transplanted with PS gut flora.Through the brain-gut axis,the inactivity of tryptophan hydroxylase 1(TPH1)and TPH2 in the colon and PFC,respectively,caused a loss of REM sleep in PGF rats and decreased the 5-HTP level in the PFC.Conclusions:These findings indicate that postoperative gut dysbiosis and defective 5-HTP metabolism may cause postoperative sleep disturbances.Clinicians and sleep researchers may gain new insights from this study.
基金supported by the National Natural Science Foundation of China(Nos.42207320 and 22076214).
文摘Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2))of ethiprole showed higher acute toxicity than ethiprole.Therefore,assessing the thyroid toxicity of its metabolites is crucial for safety assessment.In this study,the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico,in vitro,and in vivo assays,with the aim of conducting a comparative study on thyroid toxicity.Molecular docking analysis showed that ethiprole,M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3,5-triiodothyronine(T3).GH3 cell proliferation assays revealed that ethiprole,M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation.Using the zebrafish model,we further investigated that exposure to ethiprole,M1,and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid(HPT)axis-related genes.Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta,M1 mainly through binding with the corticotropin releasing factor receptor-1,and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity.M2 showed the highest developmental toxicity and thyroid disrupting effects,which significantly reducing hatching rates,increasing deformity rates,exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis.This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.
文摘This study investigates the relationships between exposures to ambient air pollution—specifically particulate matter 2.5 (PM_(2.5)) and its metabolites—and the risk of depression.Nonlinear and linear regression,Bayesian kernel machine regression,and toxicogenomic analysis were key approaches.PM_(2.5)exposure was positively associated with the risk of developing depression,whereas phenylglyoxylic acid exposure was negatively associated with depression risk.We found a significant overall relationship between ambient air pollution and depression,particularly at the 55th and 60th percentiles.Although statistical significance was not reached at the 65th percentile,there was a noticeable upward trend,indicating a potential association.Interestingly,no significant connection was found between a combination of metabolites from ambient air pollution and depression.PM_(2.5)and phenylglyoxylic acid emerged as the most influential compounds in the models,respectively.PM_(2.5)exposure altered the expression of 42 specific targets associated with depression,especially POMC,SCL6A4,IL6,and SOD2.The study identified specific pathways related to insulin secretion,energy metabolism,blood circulation,tube diameter,and maintenance of blood vessel diameter,as well as key molecular mechanisms involving hsa-miR-124-3p,hsa-miR-155-5p,hsa-miR-16-5p,and SP1.These mechanisms were found to underlie the etiology of depression associated with PM_(2.5)exposure.In conclusions,PM_(2.5)and phenylglyoxylic acid were found to be associated with depression.Further work is needed to gain insight into the molecular mechanisms by which these chemicals affect depression,especially pathways related to insulin secretion and blood circulation.
文摘A new alkaloid,diacedolinate(1),along with fourteen known compounds(2-15)was isolated from the sponge associated fungus Penicillium crustosum SCSIO 41442.The structures of these compounds were determined by spectrum analysis and ECD.All compounds were evaluated for their antioxidant and antimicrobial activities.The results showed that compound 1 exhibited weak antioxidant activity with an IC_(50)value of(71.00±0.14)μg·mL^(−1),while compound 2,in contrast,displayed broad antioxidant activity with an IC_(50)value of(1.25±0.10)μg·mL^(−1),compared with the positive control,vitamin C.In addition,compounds 9,10,11,and 15 demonstrated broad-spectrum antimicrobial activity against a variety of pathogens,including MRSA,Colletotrichum asianum HNM 408,Colletotrichum acutatum HNM RC178,and Alternaria alternate,with MIC values ranging from 2.5 to 160μg·mL^(−1).The bioactivities of these compounds are reported here for the first time.
基金supported by the Natural Science Foundation of Hunan Province,China(2024JJ7627).
文摘Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.
基金supported by the National Research Foundation of Korea(NRF)(RS-2024-00333618 and RS-2023-00240999)a Korea University Grantthe Institute of Biomedical Science&Food Safety,CJ-Korea University Food Safety Hall at Korea University,Republic of Korea。
文摘This study was performed to investigate the changes in microbial communities and metabolites during the long-term fermentation of commercially manufactured anchovy sauce.Samples of commercial anchovy sauce were collected from large-scale fermentation tanks with fermentation periods of up to 7.87 years.The complex bacterial community was simplified to two genera,Tetragenococcus and Halanaerobium,after approximately 0.55 years of fermentation.Although genera,such as Saccharomyces,Cladosporium,Candida,and Aspergillus,were relatively dominant,no clear pattern was identified in fungal community analysis.The longitudinal metabolite profile demonstrated that approximately half(55.8%)of the metabolites present in anchovy sauce were produced within a year of fermentation due to rapid fermentation.Despite the static microbial community,the contents of several metabolites including amino acids and biogenic amines changed continuously during the long-term fermentation of anchovy sauce.This study provides novel insights into the changes in microbiota and metabolites in fish sauce produced without any starter inoculation.
基金Supported by the National Key R&D Program of China(No.2016 YFC 1402102)the National Natural Science Foundation of China(No.41976109)+1 种基金the Ministry of Natural Resources Key Laboratory of Eco-Environmental Science and Technology of China(No.MEEST-2020-2)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Pyropia yezoensis(red algae)or commonly known as nori,is highly regarded for its nutritional benefits and distinct taste,leading to its widespread consumption.The bio-activity and sensory characteristics of P.yezoensis are attributed to the metabolites it contains.In this study,identification and quantification of the diverse range of metabolites of P.yezoensis and metabolomic analysis were conducted using gas chromatography-mass spectrometry(GC-MS).Furthermore,the impact of high temperature on its metabolites regulation was also investigated.Due to metabolomic analysis,a diverse range of metabolites were identified in P.yezoensis,including lipids,amino acids,carbohydrates,and secondary metabolites.Several known bioactive compounds,including alcohol and polyols,amines,amino acids-peptides-analogues,beta hydroxy acids and derivatives,carbohydrates and carbohydrate conjugates,cholestane steroids,dicarboxylic acid and derivatives,and fatty acids and conjugates were detected in abundance,highlighting the nutritional and functional properties of P.yezoensis.Additionally,the metabolites composition of P.yezoensis was significantly affected in high temperatures,which led to up-regulation of considerable primary metabolites and few were down-regulated,and suggested a potential response and adaptation mechanism of P.yezoensis to elevated temperature conditions.This research highlighted the metabolomics of P.yezoensis,provided insights into its metabolite composition and regulatory responses to high temperature conditions,enhanced our knowledge of the biochemical pathways and adaptive mechanisms of P.yezoensis,which can assist the improvement strategies of utilization and cultivation to promote this valuable alga in response to fluctuating environmental conditions.
基金Supported by National Natural Science Foundation of China,No.82303047,No.82372507,No.82172196,and No.32401046atural Science Foundation of Hunan Province,No.2022JJ40801.
文摘Bone marrow-derived mesenchymal stem cells(BMSCs)and adipose tissuederived mesenchymal stem cells(ADSCs),two principal subtypes of mesenchymal stem cells with multilineage regenerative potential,have emerged as promising therapeutic strategies for various diseases.While BMSCs and ADSCs exhibit distinct functional profiles tailored to different therapeutic applications,emerging evidence suggests that ADSCs may be a more promising approach for treating ischemic pathologies,including myocardial infarction,ischemic stroke,and peripheral artery disease,in comparison with BMSCs.However,the precise molecular mechanisms by which ADSCs enhance the therapeutic outcomes in these diseases remain poorly understood.In this editorial,we comment on the article by Li et al,which systematically compares the therapeutic efficacy of ADSCs and BMSCs derived from the same elderly patients with coronary heart disease and explores the underlying mechanism from a metabolic perspective.This study proposes that the metabolite L-arginine in ADSCs isolated from elderly patients promotes angiogenesis and protects against apoptosis in a hypoxic and ischemic microenvironment,thereby enhancing myocardial repair following infarction.These findings not only highlight the metabolic plasticity of ADSCs but also position L-arginine as a pivotal therapeutic effector in coronary heart disease.Given the novel and crucial role of L-arginine in ischemic heart diseases,further exploration of L-arginine in ADSCs(particularly those derived from elderly individuals)is essential,including its roles in angiogenesis,cell death,and the potential therapeutic implications in other ischemic pathologies.Additionally,further investigation into additional metabolites in ADSCs is warranted to enhance the therapeutic potential of ADSCs in ischemic pathologies.
基金supported by grants from the Chinese Academy of Sciences(XDB39050800)the Major Project of Guangzhou National Laboratory(GZNL2024A03013)the National Natural Science Foundation of China(92357308 and 32321004)。
文摘The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.
基金the Program for the National Key R&D Program of China(2022YFD1700204)the National Natural Science Foundation(32272580).
文摘In the world of microorganisms,the genud Streptomyces is renowned as a"natural pharmacy".This genus of bacteria is the primary source of clinical antibiotics,with approximately two-thirds of antibiotics derived from it.However,industrial production faces challenges such as low yields and complex regulation.This study introduces the Streptomyces multiplexed artificial control system(SMARTS):a novel"plug-and-play"dynamic regulatory framework integrating trigger,stabilizer,and multiplexer modules.This enables the cross-species,predictable,and scalable production of secondary metabolites.Evolutionary analysis of 521 quorum-sensing receptors revealed conserved DNA-binding domains,informing the design of a universal trigger.SMARTS efficiently and robustly produced baiweimycin in a 120 m3 industrial fermenter,a process validated through a closed-loop pipeline ranging from molecular mechanisms to field applications.Implementing orthogonal control and hierarchical optimization enhances the efficiency of metabolic engineering and sheds light on the evolution of Streptomyces quorum sensing.This breakthrough offers a scalable solution for industrial production and advances synthetic biology,with significant implications for agriculture,pharmaceuticals,and global health.
基金Supported by the Key Field Project of Guizhou Provincial Education Department(KY[2021]044)Guizhou Forestry Science Research Project(QJH KY[2021]11)Guizhou Higher Education Characteristic Key Laboratory Construction Project(QJH KY[2021]002).
文摘[Objectives]To investigate the mechanism of endophytic fungi mediating the plant growth and promoting the accumulation of secondary metabolites in Camellia oleifera.[Methods]Four strains of endophytic fungi isolated from the rhizomes of C.oleifera were co-cultured with C.oleifera seedlings individually in sterile soil for 49 d:Didymella sp.(DS),Fusarium sp.(FS),Penicillium sp.(PS),and Clonostachys rosea(CR).[Results]The biological activities of the four fungal strains differed,but all exhibited the ability to promote quercetin accumulation while simultaneously reducing quercetin glycosides after co-culture with C.oleifera seedlings.The DS,FS and PS treatments resulted in a significant increase in the leaf area of C.oleifera,with all of the experimental groups exhibiting a weight increase of over 50%compared to the control(CON)group.[Conclusions]Our findings demonstrate the potential utility of endophytic fungi in the production of C.oleifera,highlighting their capacity to enhance both productivity and the accumulation of plant metabolites.
基金Supported by WBE Liver Foundation,No.WBE20220182022 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYY-YN-2022-092023 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYYYN2023-14.
文摘BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.
