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
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
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
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
[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
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
Angelica L.has attracted global interest for its traditional medicinal uses and commercial values.However,few studies have focused on the metabolomic differences among the Angelica species.In this study,widely targete...Angelica L.has attracted global interest for its traditional medicinal uses and commercial values.However,few studies have focused on the metabolomic differences among the Angelica species.In this study,widely targeted metabolomics based on gas chromatography-tandem mass spectrometry was employed to analyze the metabolomes of four Angelica species(Angelicasinensis(Oliv.)Diels(A.sinensis),Angelica biserrata(R.H.Shan &Yuan)C.Q.Yuan & R.H.Shan(A.biserrata),Angelica dahurica(Hoffm.)Benth.& Hook.f.ex Franch.& Sav.(A.dahurica)and Angelica keiskei Koidz.(A.keiskei)).A total of 698 volatile metabolites were identified and classified into fifteen different categories.The metabo-lomic analysis indicated that 7-hydroxycoumarin and Z-ligustilide accumulated at significantly higher levels in A.sinensis,whereas bornyl acetate showed the opposite pattern.Furthermore,a high correspondence between the dendrogram of metabolite contents and phylogenetic positions of the four species.This study provides a comprehensive biochemical map for the exploitation,application and development of the Angelica species as medicinal plants or health-related dietary supplements.展开更多
Inflammatory bowel disease(IBD)is a chronic gastrointestinal disease with a high incidence.Treatment for IBD includes medications and diet,and common anti-inflammatory medications have limitations like drug resistance...Inflammatory bowel disease(IBD)is a chronic gastrointestinal disease with a high incidence.Treatment for IBD includes medications and diet,and common anti-inflammatory medications have limitations like drug resistance and serious adverse effects.Accumulating evidence has demonstrated that dietary flavonoids exhibit an alleviative effect on IBD by influencing gut microbiota.The microbiota-derived metabolites also regulate IBD and maintain intestinal homeostasis.In this review,we investigate the therapeutic effect of gut microbiota and metabolites on IBD by intestinal immune and intestinal barrier function.We demonstrate the underlying mechanism of dietary flavonoids as an anti-inflammatory molecule alleviating IBD by regulating gut microbiota,short chain fatty acid(SCFA),bile acid(BA),tryptophan(Trp)metabolism and lipopolysaccharides(LPS)-toll-like receptor 4(TLR4)signaling pathway.Based on structural differences of flavonoids,we summarize the recent research progress on the role of different dietary flavonoids in alleviating IBD by gut microbiota and metabolites in animal and clinical trials.This review indicates that dietary flavonoids targeting gut microbiota and metabolites provide a promising strategy for the treatment of inflammation and novel insights into the management of IBD.展开更多
The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty ...The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.展开更多
Background:Fructose may induce non-alcoholic fatty acids(NAFLD)due to the gut-liver axis interactions.The mechanism of fructose impairing colon barrier is unrevealed.Methods:Normal and dextran sulfate sodium(DSS)-indu...Background:Fructose may induce non-alcoholic fatty acids(NAFLD)due to the gut-liver axis interactions.The mechanism of fructose impairing colon barrier is unrevealed.Methods:Normal and dextran sulfate sodium(DSS)-induced Sprague-Dawley rats fed by 35%fructose diets were used to evaluate colon barrier functions.Microbiome and metabolome were applied to screen potential biomarker bacteria and metabolites induced by fructose.HT-29 cells were applied to validate metabolite biomarker indoleacrylic acid(IAA)and indole-3-carboxaldehyde(I3A)function in colon barrier which impaired by fructose.Results:Fructose induced colon barrier dysfunction,aggravated colon impairment in DSS-induced rats.With fructose intake,the colon length shortened,goblet numbers declined,inflammation infiltration induced,inflammatory cytokines increased,and apoptosis signals upregulated in colon tissue.Moreover,fructose induced dysbiosis of microbiota and their metabolites.Adlercreutzia and Holdemania were screened out as potential bacteria biomarkers,IAA and I3A as tryptophan metabolites were selected as metabolite biomarkers inhibited by fructose.IAA and I3A treatment alleviated the impairment induced by fructose by increasing trans epithelial electric resistance value,tight junction proteins,and Aryl hydrocarbon receptor(Ah R)activity in HT-29 cell.Conclusion:Fructose stimulated inflammation,apoptosis,gut bacteria alteration,and induced the reduction of IAA and I3A.Since fructose inhibited production of IAA and I3A,Ah R remained inactivated and consequently induced colon barrier dysfunction.展开更多
The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects ...The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.展开更多
Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were inve...Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were investigated by methylglyoxal(MGO)trapping and radical scavenging ability assays,docking studies and nano LC-orbitrap-MS/MS technology.Results indicated that the inhibition of urolithins on HSA glycation was highly positive correlated with the number of phenolic hydroxy groups.Addition of UroD and EA could effectively enhance the content of free amino group,suppress dicarbonyl compounds and advanced glycation end-products(AGEs)formation,alleviated tryptophan and protein oxidation,inhibited HSA amyloid-like aggregation.They could also trap MGO and scavenge 1,1-diphenyl-2-picrylhydrazyl free radical(DPPH·)and2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical(ABTS^(+)·).Molecular docking indicated that EA and UroA-UroD interact with HSA mainly through hydrogen bound and hydrophobic interaction,among which 2 or 3 hydrogen bonds were formed.The number of glycation sites were reduced from 11 to10,10,7,and 10,respectively,when 90μmol/L of EA,UroA,UroC and UroD were added.However,weak inhibition was observed on UroA and UroB.These findings can provide scientific evidence for the application of ellagitannins-rich foods in alleviating diabetic complications.展开更多
BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers a...BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.展开更多
Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed...Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.展开更多
Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary me...Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary metabolites in different organs of P.sarmentosum were identified and their relative abundances were characterized.The metabolic profiles of leaves,roots,stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry(LC-HR-MS)and the data subsequently analyzed using multivariate statistical methods.Manual interpretation of the tandem mass spectrometric(MS/MS)fragmentation patterns revealed the presence of 154 tentatively identified metabolites,mostly represented by alkaloids and flavonoids.Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids,lignans and phenyl propanoids in leaves,aporphines in stems,piperamides in fruits and lignan-amides in roots.Overall,this study provides extensive data on the metabolite composition of P.sarmentosum,supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs.This can be used to optimize production and harvesting as well as to maximize the plant’s economic value as herbal medicine or in food applications.展开更多
Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic ac...Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.展开更多
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.
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 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.
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 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.
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 Science Foundation of China,Grant 32470245.
文摘Angelica L.has attracted global interest for its traditional medicinal uses and commercial values.However,few studies have focused on the metabolomic differences among the Angelica species.In this study,widely targeted metabolomics based on gas chromatography-tandem mass spectrometry was employed to analyze the metabolomes of four Angelica species(Angelicasinensis(Oliv.)Diels(A.sinensis),Angelica biserrata(R.H.Shan &Yuan)C.Q.Yuan & R.H.Shan(A.biserrata),Angelica dahurica(Hoffm.)Benth.& Hook.f.ex Franch.& Sav.(A.dahurica)and Angelica keiskei Koidz.(A.keiskei)).A total of 698 volatile metabolites were identified and classified into fifteen different categories.The metabo-lomic analysis indicated that 7-hydroxycoumarin and Z-ligustilide accumulated at significantly higher levels in A.sinensis,whereas bornyl acetate showed the opposite pattern.Furthermore,a high correspondence between the dendrogram of metabolite contents and phylogenetic positions of the four species.This study provides a comprehensive biochemical map for the exploitation,application and development of the Angelica species as medicinal plants or health-related dietary supplements.
基金supported by grants from the National Natural Science Foundation of China(31560459)Jiangxi Provincial Natural Science Foundation(20224ACB205014)The Double Thousands Talents Plan of Jiangxi(jxsq2018102075,jxsq2018102076)。
文摘Inflammatory bowel disease(IBD)is a chronic gastrointestinal disease with a high incidence.Treatment for IBD includes medications and diet,and common anti-inflammatory medications have limitations like drug resistance and serious adverse effects.Accumulating evidence has demonstrated that dietary flavonoids exhibit an alleviative effect on IBD by influencing gut microbiota.The microbiota-derived metabolites also regulate IBD and maintain intestinal homeostasis.In this review,we investigate the therapeutic effect of gut microbiota and metabolites on IBD by intestinal immune and intestinal barrier function.We demonstrate the underlying mechanism of dietary flavonoids as an anti-inflammatory molecule alleviating IBD by regulating gut microbiota,short chain fatty acid(SCFA),bile acid(BA),tryptophan(Trp)metabolism and lipopolysaccharides(LPS)-toll-like receptor 4(TLR4)signaling pathway.Based on structural differences of flavonoids,we summarize the recent research progress on the role of different dietary flavonoids in alleviating IBD by gut microbiota and metabolites in animal and clinical trials.This review indicates that dietary flavonoids targeting gut microbiota and metabolites provide a promising strategy for the treatment of inflammation and novel insights into the management of IBD.
文摘The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.
基金supported by the Special Funds of Basic Research of Central Public Welfare Institute(JY2010 and ZX2410)。
文摘Background:Fructose may induce non-alcoholic fatty acids(NAFLD)due to the gut-liver axis interactions.The mechanism of fructose impairing colon barrier is unrevealed.Methods:Normal and dextran sulfate sodium(DSS)-induced Sprague-Dawley rats fed by 35%fructose diets were used to evaluate colon barrier functions.Microbiome and metabolome were applied to screen potential biomarker bacteria and metabolites induced by fructose.HT-29 cells were applied to validate metabolite biomarker indoleacrylic acid(IAA)and indole-3-carboxaldehyde(I3A)function in colon barrier which impaired by fructose.Results:Fructose induced colon barrier dysfunction,aggravated colon impairment in DSS-induced rats.With fructose intake,the colon length shortened,goblet numbers declined,inflammation infiltration induced,inflammatory cytokines increased,and apoptosis signals upregulated in colon tissue.Moreover,fructose induced dysbiosis of microbiota and their metabolites.Adlercreutzia and Holdemania were screened out as potential bacteria biomarkers,IAA and I3A as tryptophan metabolites were selected as metabolite biomarkers inhibited by fructose.IAA and I3A treatment alleviated the impairment induced by fructose by increasing trans epithelial electric resistance value,tight junction proteins,and Aryl hydrocarbon receptor(Ah R)activity in HT-29 cell.Conclusion:Fructose stimulated inflammation,apoptosis,gut bacteria alteration,and induced the reduction of IAA and I3A.Since fructose inhibited production of IAA and I3A,Ah R remained inactivated and consequently induced colon barrier dysfunction.
文摘The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.
基金supported by the Natural Science Foundation of Jiangxi Province(20212BAB205017,20192ACB21011)National Science and Technology Award Reserve Cultivation Program Project of Jiangxi(20212AEI91001)。
文摘Effect of ellagitannins gut microbiota metabolites ellagic acid(EA)and urolithin A-urolithin D(UroA-UroD)on human serum albumin(HSA)glycation were firstly evaluated in this research.The inhibition mechanisms were investigated by methylglyoxal(MGO)trapping and radical scavenging ability assays,docking studies and nano LC-orbitrap-MS/MS technology.Results indicated that the inhibition of urolithins on HSA glycation was highly positive correlated with the number of phenolic hydroxy groups.Addition of UroD and EA could effectively enhance the content of free amino group,suppress dicarbonyl compounds and advanced glycation end-products(AGEs)formation,alleviated tryptophan and protein oxidation,inhibited HSA amyloid-like aggregation.They could also trap MGO and scavenge 1,1-diphenyl-2-picrylhydrazyl free radical(DPPH·)and2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical(ABTS^(+)·).Molecular docking indicated that EA and UroA-UroD interact with HSA mainly through hydrogen bound and hydrophobic interaction,among which 2 or 3 hydrogen bonds were formed.The number of glycation sites were reduced from 11 to10,10,7,and 10,respectively,when 90μmol/L of EA,UroA,UroC and UroD were added.However,weak inhibition was observed on UroA and UroB.These findings can provide scientific evidence for the application of ellagitannins-rich foods in alleviating diabetic complications.
基金Supported by Medical Education Association Foundation of China,No.2020KTY001National Natural Science Foundation of China,No.81673806National Natural Science Foundation Youth Fund,No.82104702.
文摘BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.
基金partly funded by the Department of Science and Technology Fund for Improvement of S&T Infrastructure (Grant No. SR/FST/LS-I/2018/125)。
文摘Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.
基金supported by the German Academic Exchange Service(DAAD)as a grant scholarship and part of the Ph.D.thesis of IW.Funding program/-ID:Research Grants-Doctoral Programs in Germany,2017/18(57299294),ST34.
文摘Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary metabolites in different organs of P.sarmentosum were identified and their relative abundances were characterized.The metabolic profiles of leaves,roots,stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry(LC-HR-MS)and the data subsequently analyzed using multivariate statistical methods.Manual interpretation of the tandem mass spectrometric(MS/MS)fragmentation patterns revealed the presence of 154 tentatively identified metabolites,mostly represented by alkaloids and flavonoids.Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids,lignans and phenyl propanoids in leaves,aporphines in stems,piperamides in fruits and lignan-amides in roots.Overall,this study provides extensive data on the metabolite composition of P.sarmentosum,supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs.This can be used to optimize production and harvesting as well as to maximize the plant’s economic value as herbal medicine or in food applications.
基金supported by the project of the National Natural Science Foundation of China(32272331)the project of Fundamental Research Funds for the Central Universities(2662019PY034)。
文摘Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.
