Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and li...Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.展开更多
BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the dif...BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.展开更多
BACKGROUND Gastrointestinal cancers are among the most commonly diagnosed cancers globally.Traditional Chinese medicine(TCM)offers distinct advantages in preventing and treating these cancers.AIM To investigate the me...BACKGROUND Gastrointestinal cancers are among the most commonly diagnosed cancers globally.Traditional Chinese medicine(TCM)offers distinct advantages in preventing and treating these cancers.AIM To investigate the metabolic basis of a common TCM syndrome in gastrointestinal cancers,exploring underlying metabolic mechanisms and identifying potential METHODS Thirty healthy controls(normal group),30 patients with gastric cancer(GC),and 30 patients with colorectal cancer(CRC)were enrolled in 2023.Plasma metabolic profiles were detected using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry,and pathway enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes.RESULTS Metabolic profiling revealed distinct alterations in gastrointestinal cancers.CRC samples exhibited 455 differentially expressed metabolites(234 upregulated and 221 downregulated).Similarly,GC samples exhibited 459 differentially expressed metabolites(251 upregulated and 208 downregulated).Additionally,352 shared metabolites were identified among gastrointestinal cancers.Enrichment analysis highlighted the involvement of these shared metabolites in 10 metabolic pathways.CONCLUSION To some extent,this study revealed the metabolomic characteristics of spleen deficiency and blood stasis toxin(PXYD)syndrome in gastrointestinal cancers.It provides the rationale for the"same treatment for different diseases"approach in PXYD syndrome of gastrointestinal cancers,and for identifying potential metabolomicsbased biomarkers.展开更多
Cor a 14 is one of the most vital allergens in hazelnuts.However,the features of intestinal metabolites and microbiota associated with Cor a 14-induced allergy remain unclear.In this study,we established a hazelnut Co...Cor a 14 is one of the most vital allergens in hazelnuts.However,the features of intestinal metabolites and microbiota associated with Cor a 14-induced allergy remain unclear.In this study,we established a hazelnut Cor a 14-allergic BALB/c mice model,which was distinguished by the dropped temperature and enhanced allergic inflammatory factor levels in serum.Faeces were collected to detect characteristics of the intestinal metabolites by untargeted metabolomics and the gut microbiota by 16S rRNA sequencing.Theα-andβ-diversity of gut microbiota in Cor a 14-allergic mice differed from the controls with elevated relative abundance of Lactobacillus and reduced relative abundances of Odoribacter,Chloroplast,Alistipes and Lachnospiraceae_NK4A136_group.Untargeted metabolomics results revealed that 238 significantly differential metabolites(111 up-regulated,127 down-regulated)were identified,of which,L-tryptophan,histamine and N-acetylhistamine were remarkably accumulated and primarily enriched in the enhanced L-tryptophan and histidine metabolism pathways.Spearman correlation analysis suggested that L-tryptophan was positively correlated with allergic indicators and screened as the potential biomarker for Cor a 14 allergy.Collectively,our findings uncovered the characteristics of intestinal metabolites and gut microbiota during Cor a 14 anaphylaxis and provided new potential insights for diagnosis of hazelnut allergy.展开更多
BACKGROUND Metabolomics sequencing technology was used to investigate the changes of intestinal flora and metabolites in gastric cancer patients in plateau areas.AIM To investigate changes in gut microbiota and their ...BACKGROUND Metabolomics sequencing technology was used to investigate the changes of intestinal flora and metabolites in gastric cancer patients in plateau areas.AIM To investigate changes in gut microbiota and their metabolites in patients with gastric cancer from plateau regions using untargeted metabolomic sequencing.METHODS Fresh morning fecal samples were collected from 30 gastric cancer patients diagnosed at a tertiary hospital in Qinghai Province and 30 healthy individuals(controls).Liquid chromatography-tandem mass spectrometry based untargeted metabolomic sequencing was used to analyze metabolite changes and predict metabolic function.RESULTS Metabolomic analysis identified 281 metabolites in samples from both groups.These metabolites were categorized into eight major classes,listed in descending order of abundance:Lipids and lipid-like molecules(35.443%);organic acids and derivatives(29.114%);organic oxygen compounds(15.19%);nucleosides,nucleotides,and analogs(13.924%);organoheterocyclic compounds(2.532%),amino acids and peptides(1.266%);benzenoids(1.266%);and fatty acids(1.266%).Compared with the control group,the top 10 metabolites elevated in the gastric cancer group included:Dethiobiotin,glycylproline,glycine,hydroxyisocaproic acid,tyramine,methionine sulfoxide,5-aminopentanoic acid,citrulline,betonicine,and formiminoglutamic acid and the top 10 decreased were:Cytidine,5'-methylthioadenosine,trehalose,melibiose,lotaustralin,adenosine,inosine,ribothymidine,raffinose,and galactinol.Functional prediction analysis revealed that these differential metabolites were primarily enriched in 12 metabolic pathways,including purine metabolism,cysteine and methionine metabolism,galactose metabolism,lysine degradation,glycine,serine,and threonine metabolism,biotin metabolism,pyrimidine metabolism,arginine and proline metabolism,histidine metabolism,primary bile acid biosynthesis,starch and sucrose metabolism,and tyrosine metabolism.CONCLUSION Significant differences in intestinal microbial metabolites and associated metabolic pathways were observed between gastric cancer patients and healthy controls residing in plateau regions.展开更多
Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce th...Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.展开更多
Bigeye tuna is a protein-rich fish that is susceptible to spoilage during cold storage,however,there is limited information on untargeted metabolomic profiling of bigeye tuna concerning spoilage-associated enzymes and...Bigeye tuna is a protein-rich fish that is susceptible to spoilage during cold storage,however,there is limited information on untargeted metabolomic profiling of bigeye tuna concerning spoilage-associated enzymes and metabolites.This study aimed to investigate how cold storage affects enzyme activities,nutrient composition,tissue microstructures and spoilage metabolites of bigeye tuna.The activities of cathepsins B,H,L increased,while Na^(+)/K^(+)-ATPase and Mg^(2+)-ATPase decreased,α-glucosidase,lipase and lipoxygenase first increased and then decreased during cold storage,suggesting that proteins undergo degradation and ATP metabolism occurs at a faster rate during cold storage.Nutrient composition(moisture and lipid content),total amino acids decreased,suggesting that the nutritional value of bigeye tuna was reduced.Besides,a logistic regression equation has been established as a food analysis tool and assesses the dynamics and correlation of the enzyme of bigeye tuna during cold storage.Based on untargeted metabolomic profiling analysis,a total of 524 metabolites were identified in the bigeye tuna contained several spoilage metabolites involved in lipid metabolism(glycerophosphocholine and choline phosphate),amino acid metabolism(L-histidine,5-deoxy-5′-(methylthio)adenosine,5-methylthioadenosine),carbohydrate metabolism(D-gluconic acid,α-D-fructose 1,6-bisphosphate,D-glyceraldehyde 3-phosphate).The results of tissue microstructures of tuna showed a looser network and visible deterioration of tissue fiber during cold storage.Therefore,metabolomic analysis and tissue microstructures provide insight into the spoilage mechanism investigations on bigeye tuna during cold storage.展开更多
Metabolomics utilizes advanced analytical profiling techniques to comprehensively measure small molecules in cells,tissues,and biological fluids.Nutritional metabolomics studies in pigs have reported changes in hundre...Metabolomics utilizes advanced analytical profiling techniques to comprehensively measure small molecules in cells,tissues,and biological fluids.Nutritional metabolomics studies in pigs have reported changes in hundreds of metabolites across various sample types,including plasma,serum,urine,digesta,and feces,following dietary interventions.These findings can help identify biomarkers of gastrointestinal functionality and beyond,as well as investigate mechanistic interactions between diet,host,microbiome,and metabolites.This review aims to summarize the current literature on nutritional metabolomics in pigs and its use to investigate how different dietary approaches impact the gut health of pigs.Here,we critically assessed and categorized the impact of the main macronutrients-carbohydrates,proteins,and fats—along with feed additives such as amino acids,bile acids,and probiotics,as well as feeding strategies like creep feeding,milk replacer introduction,and time-restricted feeding,on the pig metabolome.Additionally,we discuss the potential modes of action of the key affected metabolites on pig gut health.展开更多
Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and a...Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and are closely related to grain quality.However,it remains unclear about the changes in lipids profling under different AWD regimes.This study set up three irrigation regimes including conventional irrigation(CI),alternate wetting and moderate soil drying irrigation(AWMD),and alternate wetting and severe soil drying irrigation(AWSD).It explored lipidome changes in milled rice of Yangdao 6(YD6)using the untargeted lipidomics approach and analyzed rice cooking and eating quality.The results identifed seven lipid classes,55 lipid subclasses,and 1,086 lipid molecular species.Compared with the CI regime,the AWMD regime mainly altered lipid subclasses consisting of triglyceride(TG),ceramide(Cer),diglyceride(DG),bis-methyl lysophosphatidic acid(BisMePA),phosphocholine(PC),phosphoethanolamine(PE),monogalactosyldiacylglycerol(MGDG),and digalactosyl diglyceride(DGDG)in milled rice and improved cooking and eating quality of rice;in contrast,the AWSD regime distinctly changed lipid subclasses like TG,Cer,DG,PC,PE,hexosylceramide(Hex1Cer),DGDG,and BisMePA and degraded cooking and eating quality of rice.Specifcally,AWMD most signifcantly altered the expressions of lipid molecules,including DGDG(18:0_18:2),DGDG(16:0_14:0),PC(33:1),Cer(t17:0_26:0),and Cer(t17:0_16:0);AWSD most obviously influenced the expressions of TG(6:0_14:0_18:3),PC(41:1),TG(19:1_18:4_18:4),Hex1Cer(d18:2_24:0+O),and Hex1Cer(d18:2_24:1).These 10 altered lipid molecules in milled rice can be preferentially used for investigating their relationships with grain quality in rice.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become one of the most common chronic liver diseases in the world.In our early clinical data and questionnaire analysis of NAFLD,it was found that the body mass in...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become one of the most common chronic liver diseases in the world.In our early clinical data and questionnaire analysis of NAFLD,it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity.The consumption of high-temperature-processed foods such as fried food,hot pot and barbecue is closely related to the occurrence of nonobese NAFLD.Reducing the intake of this kind of food can reduce disease severity and improve prognosis.AIM To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperatureprocessed feed.METHODS Fifty-four male Sprague-Dawley rats were divided into three groups:The control group received a standard diet;the nonfried soybeans(NDFS)group received 60%NDFS and 40%basic feed and the dry-fried soybeans(DFS)group received 60%DFS and 40%basic feed.Six rats were sacrificed at week 4,8,and 12 in each group.The food intake,body weight,Lee’s index,liver index,serological index and hepatic histopathology were assessed.Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12.Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed.We selected some of the metabolites,both within the pathway and outside of the pathway,to explain preliminarily the difference in liver pathology in the three groups of rats.RESULTS There were no statistically significant differences in the food intake,body weight,Lee's index or serological index between the DFS group and the control group(P>0.05).At week 8 and week 12,the steatosis scores in the DFS group were significantly higher than those in the other two groups(P<0.05).At week 12,the liver index of the DFS group was the lowest(NDFS group vs DFS group,P<0.05).The fibrosis score in the DFS group was significantly higher than those in the other two groups(P<0.05).The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances:Five positively correlated substances and five negatively correlated substances.The positively correlated substances included taurochenodeoxycholate-3-sulfate,acetylcarnitine,20a,22bdihydroxycholesterol,13E-tetranor-16-carboxy-LTE4 and taurocholic acid.The negatively correlated substances included choline,cholesterane-3,7,12,25-tetrol-3-glucuronide,nicotinamide adenine dinucleotide phosphate,lysoPC[16:1(9Z)]and glycerol 3-phosphate.The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances:Four positively correlated substances and 9 negatively correlated substances.The positively correlated substances included 4-hydroxy-6-eicosanone,3-phosphoglyceric acid,13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate.The negatively correlated substances included lysoPC[16:1(9Z)],S-(9-hydroxy-PGA1)-glutathione,lysoPC[20:5(5Z,8Z,11Z,14Z,17Z)],SM(d18:1/14:0),nicotinamide adenine dinucleotide phosphate,5,10-methylene-THF,folinic acid,N-lactoylglycine and 6-hydroxy-5-methoxyindole glucuronide.CONCLUSION We successfully induced liver damage in rats by using a specially prepared hightemperature-processed feed and explored the untargeted metabolomics characteristics.展开更多
Quality control of ginseng currently is mainly based on ginsenoside analysis,but rarely focuses on the volatile organic components.In the current work,an untargeted metabolomics approach,by headspace solid-phase micro...Quality control of ginseng currently is mainly based on ginsenoside analysis,but rarely focuses on the volatile organic components.In the current work,an untargeted metabolomics approach,by headspace solid-phase micro-extraction gas chromatography/mass spectrometry(HS-SPME-GC/MS),was elaborated and further employed to holistically compare the compositional difference of the volatile components simultaneously from 12 Panax herbal medicines,which included P.ginseng(PG),P.quinquefolius(PQ),P.notoginseng(PN),red ginseng(PGR),P.ginseng leaf(PGL),P.quinquefolius leaf(PQL),P.notoginseng leaf(PNL),P.ginseng flower(PGF),P.quinquefolius flower(PQF),P.notoginseng flower(PNF),P.japonicus(PJ),and P.japonicus var.major(PJvm).Chromatographic separation was performed on an HP-5MS elastic quartz capillary column using helium as the carrier gas,enabling good resolution within 1 h.We were able to characterize totally 259 volatile compounds,including 82 terpenes(T),46 alcohols(Alc),29 ketones(K),25 aldehydes(Ald),21 esters(E),and the others.By analyzing 90 batches of ginseng samples based on the untargeted metabolomics workflows,236 differential ions were unveiled,and accordingly 36 differential volatile components were discovered.It is the first report that simultaneously compares the compositional difference of volatile components among 12 Panax herbal medicines,and useful information is provided for the quality control of ginseng aside from the well-known ginsenosides.展开更多
Abdominal aortic aneurysm(AAA)and atherosclerosis(AS)have considerable similarities in clinical risk factors and molecular pathogenesis.The aim of our study was to investigate the differences between AAA and AS from t...Abdominal aortic aneurysm(AAA)and atherosclerosis(AS)have considerable similarities in clinical risk factors and molecular pathogenesis.The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics,and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics.Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry(LC-MS).A total of 18 remarkably different metabolites were identified,and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS,with an area under the curve(AUC)of0.93.Subsequently,we analyzed both the metabolomics and transcriptomics data and found that seven metabolites,especially 2’-deoxy-D-ribose(2 d DR),were significantly correlated with differentially expressed genes.In conclusion,our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients,and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.展开更多
Objective:As an important part of metabolomics analysis,untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric dat...Objective:As an important part of metabolomics analysis,untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric data which also poses great challenges to data analysis,from the extraction of raw data to the identification of differential metabolites.To date,a large number of analytical tools and processes have been developed and constructed to serve untargeted metabolomics research.The different selection of analytical tools and parameter settings lead to varied results of untargeted metabolomics data.Our goal is to establish an easily operated platform and obtain a repeatable analysis result.Methods:We used the R language basic environment to construct the preprocessing system of the original data and the LAMP(Linux+Apache+MySQL+PHP)architecture to build a cloud mass spectrum data analysis system.Results:An open-source analysis software for untargeted metabolomics data(openNAU)was constructed.It includes the extraction of raw mass data and quality control for the identification of differential metabolic ion peaks.A reference metabolomics database based on public databases was also constructed.Conclusions:A complete analysis system platform for untargeted metabolomics was established.This platform provides a complete template interface for the addition and updating of the analysis process,so we can finish complex analyses of untargeted metabolomics with simple human-computer interactions.The source code can be downloaded from https://github.com/zjuRong/openNAU.展开更多
BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human ...BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.展开更多
OBJECTIVE: To investigate the effect of baijinpingchuan(白金平喘, BJPC) on the asthma rat model and identify differential metabolites and disturbed metabolic pathways. METHODS: The rats were categorized into six group...OBJECTIVE: To investigate the effect of baijinpingchuan(白金平喘, BJPC) on the asthma rat model and identify differential metabolites and disturbed metabolic pathways. METHODS: The rats were categorized into six groups: control, dexamethasone(DEX), ovalbumin(OVA), and low-, median-, and high-dose BJPC. The rats, except for the control group, were initially treated with OVA to develop the asthma model, which was then activated using DEX, OVA, and low-, median-, and high-dose BJPC. Enzyme-linked immunosorbent assay kit was used to detect the expression of interleukin(IL)-33, IL-25, thymic stromal lymphopoietin(TSLP), and transforming growth factor-beta 1(TGF-β1). Hematoxylin and eosin staining were performed to observe the pathological condition of the lung. Untargeted serum metabonomic analysis was conducted to identify differential metabolites and disturbed metabolic pathways. RESULTS: High-dose BJPC significantly inhibited the expression of IL-33, IL-25, TSLP, and TGF-β1(P < 0.0001). Further, high-dose BJPC improved inflammatory cell infiltration, which plays a similar role in asthma as DEX. OVA-induced and BJPC-treated rats were identified through 17 differential metabolites, especially cholic acid. Furthermore, primary bile acid biosynthesis was a significantly differential pathway in the mechanism of BJPC for treating asthma. CONCLUSIONS: BJPC plays an anti-inflammation role in asthma, which might be a promising therapy through mediating primary bile acid biosynthesis.展开更多
Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymi...Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymine T3*,adenines A2*and A4*so that between them hydrogen bonds are formed.Canonical adenine and cytosine can be incorporated opposite canonical thymine only.Canonical thymine and guanine can be incorporated opposite canonical adenine only.If in the synthesis of DNA containing rare tautomeric forms of thymine T3*,adenines A2*and A4*,involved DNA polymerases with relatively high fidelity of synthesis,mutations not appear.However,if further DNA synthesis will involve DNA polymerases having a low fidelity of synthesis,there may be base substitution mutations.It was shown that the conclusion made in the Tomasetti and Vogelstein cancer risk model that the formation of about 67%of all mutations was not caused by exposure to any mutagens is erroneous.展开更多
Objective To investigate the changes of metabolites in urine of automobile manufacturing workers with muscle fatigue using metabolomics technology,and to explore potential biomarkers and disrupted metabolic pathways.M...Objective To investigate the changes of metabolites in urine of automobile manufacturing workers with muscle fatigue using metabolomics technology,and to explore potential biomarkers and disrupted metabolic pathways.Methods In July 2022,urine samples were collected from35maleworkers in a certain automobile manufacturing industry before and after muscle fatigue,and metabolite analysis was conducted.Subsequently,multivariate statistical analysis was uused fordata processing to screen differential metabolites.Metabolic pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes(KEGG)database(http://www.kegg.jp),and potential biomarkers were screened through the receiver operating characteristic(ROC)curve.Results Metabolomics analysis revealed that compared to pre-fatigue samples,a total of 363 differential metabolites were identified in the post-fatigue urine samples of the subjects.Among these,201 metabolites(55.4%)showed increased relative expression,while 162 metabolites(44.6%)showed decreased relative expression.The metabolic pathways involved mainly included histidine metabolism,tryptophan metabolism,valine,leucine and isoleucine biosynthesis,caffeine metabolism,niacin and nicotinamide metabolism,and oxidative phosphorylation.The ROC curve analysis results showed that the areas under the ROC curves for 1-methylnicotinamide,2-piperidinone,kojic acid and diferuloyl Putrescine were 0.992,0.959,0.937 and 0.902,respectively.Conclusion Muscle fatigue could cause changes in urine metabolite profiles of automobile manufacturing workers.The metabolites represented by 1-methylnicotinamide in urine can be used as potential biomarkers。展开更多
Metabolic genome-wide association studies （mGWAS）, whereupon metabolite levels are regarded as traits, can help unravel the genetic basis of metabolic networks. A total of 309Arabidopsis accessions were grown under ...Metabolic genome-wide association studies （mGWAS）, whereupon metabolite levels are regarded as traits, can help unravel the genetic basis of metabolic networks. A total of 309Arabidopsis accessions were grown under two independent environmental conditions （control and stress） and subjected to untargeted LC-MS- based metabolomic profiling; levels of the obtained hydrophilic metabolites were used in GWAS. Our two- condition-based GWAS for more than 3000 semi-polar metabolites resulted in the detection of 123 highly resolved metabolite quantitative trait loci （p ≤ 1.0E-08）, 24.39% of which were environment-specific. Interestingly, differently from natural variation in Arabidopsis primary metabolites, which tends to be controlled by a large number of small-effect loci, we found several major large-effect loci alongside a vast number of small-effect loci controlling variation of secondary metabolites. The two-condition-based GWAS was fol- lowed by integration with network-derived metabolite-transcript correlations using a time-course stress experiment. Through this integrative approach, we selected 70 key candidate associations between struc- tural genes and metabolites, and experimentally validated eight novel associations, two of them showing differential genetic regulation in the two environments studied. We demonstrate the power of combining large-scale untargeted metabolomics-based GWAS with time-course-derived networks both performed under different ablotic environments for identifying metabollte-gene associations, providing novel global insights into the metabolic landscape of Arabidopsis.展开更多
In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3 B2,H226, Ovcar3 and N87 were extracted and digested with γLys C and trypsin. The resulting peptide lysate were pre-fractionate...In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3 B2,H226, Ovcar3 and N87 were extracted and digested with γLys C and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the Max Quant and the protein abundances were estimated using total peak area(TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption,metabolism, disposition and elimination(ADME) proteins including UDP-glucuronosyltransferase,cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3 B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.展开更多
Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolom...Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolomics.The emerging role of IM-MS in untargeted metabolomics enables the separation of metabolite isomers and generation of multidimension data to support the identification of metabolites.In this review,we first introduced the basic principles of IM-MS instruments commonly used for untargeted metabolomics.Then,we demonstrated the application of IM-MS for metabolite separation and identification of both known and unknown metabolites.Finally,we discussed the future developments of IM-MS technology to improve untargeted metabolomics.展开更多
基金supported by the National Natural Science Foundation of China(82274424).
文摘Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.
文摘BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.
基金Supported by the National Key R and D Program of China,No.2022YFC3500200,No.2022YFC3500202 and No.2022YFC3500204Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202208+4 种基金NATCM’s Project of High-Level Construction of Key TCM Disciplines,No.[2023]85Qing Lan Project of Jiangsu Higher Education Institutions,No.[2023]27Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.SJCX22_0706General Project of Universities’Philosophy and Social Science in Jiangsu Province,No.2024SJYB0564Jiangsu Provincial Leading Talents Program in Traditional Chinese Medicine,No.SLJ0314.
文摘BACKGROUND Gastrointestinal cancers are among the most commonly diagnosed cancers globally.Traditional Chinese medicine(TCM)offers distinct advantages in preventing and treating these cancers.AIM To investigate the metabolic basis of a common TCM syndrome in gastrointestinal cancers,exploring underlying metabolic mechanisms and identifying potential METHODS Thirty healthy controls(normal group),30 patients with gastric cancer(GC),and 30 patients with colorectal cancer(CRC)were enrolled in 2023.Plasma metabolic profiles were detected using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry,and pathway enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes.RESULTS Metabolic profiling revealed distinct alterations in gastrointestinal cancers.CRC samples exhibited 455 differentially expressed metabolites(234 upregulated and 221 downregulated).Similarly,GC samples exhibited 459 differentially expressed metabolites(251 upregulated and 208 downregulated).Additionally,352 shared metabolites were identified among gastrointestinal cancers.Enrichment analysis highlighted the involvement of these shared metabolites in 10 metabolic pathways.CONCLUSION To some extent,this study revealed the metabolomic characteristics of spleen deficiency and blood stasis toxin(PXYD)syndrome in gastrointestinal cancers.It provides the rationale for the"same treatment for different diseases"approach in PXYD syndrome of gastrointestinal cancers,and for identifying potential metabolomicsbased biomarkers.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)。
文摘Cor a 14 is one of the most vital allergens in hazelnuts.However,the features of intestinal metabolites and microbiota associated with Cor a 14-induced allergy remain unclear.In this study,we established a hazelnut Cor a 14-allergic BALB/c mice model,which was distinguished by the dropped temperature and enhanced allergic inflammatory factor levels in serum.Faeces were collected to detect characteristics of the intestinal metabolites by untargeted metabolomics and the gut microbiota by 16S rRNA sequencing.Theα-andβ-diversity of gut microbiota in Cor a 14-allergic mice differed from the controls with elevated relative abundance of Lactobacillus and reduced relative abundances of Odoribacter,Chloroplast,Alistipes and Lachnospiraceae_NK4A136_group.Untargeted metabolomics results revealed that 238 significantly differential metabolites(111 up-regulated,127 down-regulated)were identified,of which,L-tryptophan,histamine and N-acetylhistamine were remarkably accumulated and primarily enriched in the enhanced L-tryptophan and histidine metabolism pathways.Spearman correlation analysis suggested that L-tryptophan was positively correlated with allergic indicators and screened as the potential biomarker for Cor a 14 allergy.Collectively,our findings uncovered the characteristics of intestinal metabolites and gut microbiota during Cor a 14 anaphylaxis and provided new potential insights for diagnosis of hazelnut allergy.
基金Supported by Gansu Provincial Natural Science Foundation Project,No.23JRRA725Postgraduate Research Innovation Project of Northwest Minzu University in 2025,No.31920250001-382024 Qinghai Province's"Kunlun Talent High-end Innovative and Entrepreneurial Talent Project"Cultivates Top Talents Project,No.QHKLYC-GDCXCY-2024-155.
文摘BACKGROUND Metabolomics sequencing technology was used to investigate the changes of intestinal flora and metabolites in gastric cancer patients in plateau areas.AIM To investigate changes in gut microbiota and their metabolites in patients with gastric cancer from plateau regions using untargeted metabolomic sequencing.METHODS Fresh morning fecal samples were collected from 30 gastric cancer patients diagnosed at a tertiary hospital in Qinghai Province and 30 healthy individuals(controls).Liquid chromatography-tandem mass spectrometry based untargeted metabolomic sequencing was used to analyze metabolite changes and predict metabolic function.RESULTS Metabolomic analysis identified 281 metabolites in samples from both groups.These metabolites were categorized into eight major classes,listed in descending order of abundance:Lipids and lipid-like molecules(35.443%);organic acids and derivatives(29.114%);organic oxygen compounds(15.19%);nucleosides,nucleotides,and analogs(13.924%);organoheterocyclic compounds(2.532%),amino acids and peptides(1.266%);benzenoids(1.266%);and fatty acids(1.266%).Compared with the control group,the top 10 metabolites elevated in the gastric cancer group included:Dethiobiotin,glycylproline,glycine,hydroxyisocaproic acid,tyramine,methionine sulfoxide,5-aminopentanoic acid,citrulline,betonicine,and formiminoglutamic acid and the top 10 decreased were:Cytidine,5'-methylthioadenosine,trehalose,melibiose,lotaustralin,adenosine,inosine,ribothymidine,raffinose,and galactinol.Functional prediction analysis revealed that these differential metabolites were primarily enriched in 12 metabolic pathways,including purine metabolism,cysteine and methionine metabolism,galactose metabolism,lysine degradation,glycine,serine,and threonine metabolism,biotin metabolism,pyrimidine metabolism,arginine and proline metabolism,histidine metabolism,primary bile acid biosynthesis,starch and sucrose metabolism,and tyrosine metabolism.CONCLUSION Significant differences in intestinal microbial metabolites and associated metabolic pathways were observed between gastric cancer patients and healthy controls residing in plateau regions.
基金supported by the Qi-Huang Chief Scientist Program of the National Administration of Traditional Chinese Medicine(2020)the National Key Research and Development Program of China(No.2022YFC3501705)+1 种基金Shanghai Sailing Program(No.23YF1447500)the China Postdoctoral Science Foundation(No.2023M732335).
文摘Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.
基金supported by the Shanghai Sailing Program(22YF1416300)Youth Fund Project of National Natural Science Foundation of China(32202117)+1 种基金National Key Research and Development Program of China(2022YFD2100104)the China Agriculture Research System(CARS-47).
文摘Bigeye tuna is a protein-rich fish that is susceptible to spoilage during cold storage,however,there is limited information on untargeted metabolomic profiling of bigeye tuna concerning spoilage-associated enzymes and metabolites.This study aimed to investigate how cold storage affects enzyme activities,nutrient composition,tissue microstructures and spoilage metabolites of bigeye tuna.The activities of cathepsins B,H,L increased,while Na^(+)/K^(+)-ATPase and Mg^(2+)-ATPase decreased,α-glucosidase,lipase and lipoxygenase first increased and then decreased during cold storage,suggesting that proteins undergo degradation and ATP metabolism occurs at a faster rate during cold storage.Nutrient composition(moisture and lipid content),total amino acids decreased,suggesting that the nutritional value of bigeye tuna was reduced.Besides,a logistic regression equation has been established as a food analysis tool and assesses the dynamics and correlation of the enzyme of bigeye tuna during cold storage.Based on untargeted metabolomic profiling analysis,a total of 524 metabolites were identified in the bigeye tuna contained several spoilage metabolites involved in lipid metabolism(glycerophosphocholine and choline phosphate),amino acid metabolism(L-histidine,5-deoxy-5′-(methylthio)adenosine,5-methylthioadenosine),carbohydrate metabolism(D-gluconic acid,α-D-fructose 1,6-bisphosphate,D-glyceraldehyde 3-phosphate).The results of tissue microstructures of tuna showed a looser network and visible deterioration of tissue fiber during cold storage.Therefore,metabolomic analysis and tissue microstructures provide insight into the spoilage mechanism investigations on bigeye tuna during cold storage.
基金the PIG-PARADIGM project,funded by the Novo Nordisk Foundation(Grant No.NNFSA210073688).
文摘Metabolomics utilizes advanced analytical profiling techniques to comprehensively measure small molecules in cells,tissues,and biological fluids.Nutritional metabolomics studies in pigs have reported changes in hundreds of metabolites across various sample types,including plasma,serum,urine,digesta,and feces,following dietary interventions.These findings can help identify biomarkers of gastrointestinal functionality and beyond,as well as investigate mechanistic interactions between diet,host,microbiome,and metabolites.This review aims to summarize the current literature on nutritional metabolomics in pigs and its use to investigate how different dietary approaches impact the gut health of pigs.Here,we critically assessed and categorized the impact of the main macronutrients-carbohydrates,proteins,and fats—along with feed additives such as amino acids,bile acids,and probiotics,as well as feeding strategies like creep feeding,milk replacer introduction,and time-restricted feeding,on the pig metabolome.Additionally,we discuss the potential modes of action of the key affected metabolites on pig gut health.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20241931 and BK20221371)the National Natural Science Foundation of China(32071943 and 32372214)the National Key Research and Development Program of China(2022YFD2300304)。
文摘Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and are closely related to grain quality.However,it remains unclear about the changes in lipids profling under different AWD regimes.This study set up three irrigation regimes including conventional irrigation(CI),alternate wetting and moderate soil drying irrigation(AWMD),and alternate wetting and severe soil drying irrigation(AWSD).It explored lipidome changes in milled rice of Yangdao 6(YD6)using the untargeted lipidomics approach and analyzed rice cooking and eating quality.The results identifed seven lipid classes,55 lipid subclasses,and 1,086 lipid molecular species.Compared with the CI regime,the AWMD regime mainly altered lipid subclasses consisting of triglyceride(TG),ceramide(Cer),diglyceride(DG),bis-methyl lysophosphatidic acid(BisMePA),phosphocholine(PC),phosphoethanolamine(PE),monogalactosyldiacylglycerol(MGDG),and digalactosyl diglyceride(DGDG)in milled rice and improved cooking and eating quality of rice;in contrast,the AWSD regime distinctly changed lipid subclasses like TG,Cer,DG,PC,PE,hexosylceramide(Hex1Cer),DGDG,and BisMePA and degraded cooking and eating quality of rice.Specifcally,AWMD most signifcantly altered the expressions of lipid molecules,including DGDG(18:0_18:2),DGDG(16:0_14:0),PC(33:1),Cer(t17:0_26:0),and Cer(t17:0_16:0);AWSD most obviously influenced the expressions of TG(6:0_14:0_18:3),PC(41:1),TG(19:1_18:4_18:4),Hex1Cer(d18:2_24:0+O),and Hex1Cer(d18:2_24:1).These 10 altered lipid molecules in milled rice can be preferentially used for investigating their relationships with grain quality in rice.
基金Science and Technology Project Task Book of Beijing,No.Z171100001717008.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become one of the most common chronic liver diseases in the world.In our early clinical data and questionnaire analysis of NAFLD,it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity.The consumption of high-temperature-processed foods such as fried food,hot pot and barbecue is closely related to the occurrence of nonobese NAFLD.Reducing the intake of this kind of food can reduce disease severity and improve prognosis.AIM To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperatureprocessed feed.METHODS Fifty-four male Sprague-Dawley rats were divided into three groups:The control group received a standard diet;the nonfried soybeans(NDFS)group received 60%NDFS and 40%basic feed and the dry-fried soybeans(DFS)group received 60%DFS and 40%basic feed.Six rats were sacrificed at week 4,8,and 12 in each group.The food intake,body weight,Lee’s index,liver index,serological index and hepatic histopathology were assessed.Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12.Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed.We selected some of the metabolites,both within the pathway and outside of the pathway,to explain preliminarily the difference in liver pathology in the three groups of rats.RESULTS There were no statistically significant differences in the food intake,body weight,Lee's index or serological index between the DFS group and the control group(P>0.05).At week 8 and week 12,the steatosis scores in the DFS group were significantly higher than those in the other two groups(P<0.05).At week 12,the liver index of the DFS group was the lowest(NDFS group vs DFS group,P<0.05).The fibrosis score in the DFS group was significantly higher than those in the other two groups(P<0.05).The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances:Five positively correlated substances and five negatively correlated substances.The positively correlated substances included taurochenodeoxycholate-3-sulfate,acetylcarnitine,20a,22bdihydroxycholesterol,13E-tetranor-16-carboxy-LTE4 and taurocholic acid.The negatively correlated substances included choline,cholesterane-3,7,12,25-tetrol-3-glucuronide,nicotinamide adenine dinucleotide phosphate,lysoPC[16:1(9Z)]and glycerol 3-phosphate.The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances:Four positively correlated substances and 9 negatively correlated substances.The positively correlated substances included 4-hydroxy-6-eicosanone,3-phosphoglyceric acid,13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate.The negatively correlated substances included lysoPC[16:1(9Z)],S-(9-hydroxy-PGA1)-glutathione,lysoPC[20:5(5Z,8Z,11Z,14Z,17Z)],SM(d18:1/14:0),nicotinamide adenine dinucleotide phosphate,5,10-methylene-THF,folinic acid,N-lactoylglycine and 6-hydroxy-5-methoxyindole glucuronide.CONCLUSION We successfully induced liver damage in rats by using a specially prepared hightemperature-processed feed and explored the untargeted metabolomics characteristics.
基金National Natural Science Foundation of China(Grant No.81872996)Natural Science Foundation of Tianjin of China(Grant No.20JCYBJC00060).
文摘Quality control of ginseng currently is mainly based on ginsenoside analysis,but rarely focuses on the volatile organic components.In the current work,an untargeted metabolomics approach,by headspace solid-phase micro-extraction gas chromatography/mass spectrometry(HS-SPME-GC/MS),was elaborated and further employed to holistically compare the compositional difference of the volatile components simultaneously from 12 Panax herbal medicines,which included P.ginseng(PG),P.quinquefolius(PQ),P.notoginseng(PN),red ginseng(PGR),P.ginseng leaf(PGL),P.quinquefolius leaf(PQL),P.notoginseng leaf(PNL),P.ginseng flower(PGF),P.quinquefolius flower(PQF),P.notoginseng flower(PNF),P.japonicus(PJ),and P.japonicus var.major(PJvm).Chromatographic separation was performed on an HP-5MS elastic quartz capillary column using helium as the carrier gas,enabling good resolution within 1 h.We were able to characterize totally 259 volatile compounds,including 82 terpenes(T),46 alcohols(Alc),29 ketones(K),25 aldehydes(Ald),21 esters(E),and the others.By analyzing 90 batches of ginseng samples based on the untargeted metabolomics workflows,236 differential ions were unveiled,and accordingly 36 differential volatile components were discovered.It is the first report that simultaneously compares the compositional difference of volatile components among 12 Panax herbal medicines,and useful information is provided for the quality control of ginseng aside from the well-known ginsenosides.
基金supported by the National Natural Science Foundation of China(Nos.51890894,81770481,and 82070492)the Chinese Academy of Medical SciencesInnovation Fund for Medical Sciences(CIFMS 2017-I2M-1-008)。
文摘Abdominal aortic aneurysm(AAA)and atherosclerosis(AS)have considerable similarities in clinical risk factors and molecular pathogenesis.The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics,and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics.Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry(LC-MS).A total of 18 remarkably different metabolites were identified,and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS,with an area under the curve(AUC)of0.93.Subsequently,we analyzed both the metabolomics and transcriptomics data and found that seven metabolites,especially 2’-deoxy-D-ribose(2 d DR),were significantly correlated with differentially expressed genes.In conclusion,our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients,and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.
文摘Objective:As an important part of metabolomics analysis,untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric data which also poses great challenges to data analysis,from the extraction of raw data to the identification of differential metabolites.To date,a large number of analytical tools and processes have been developed and constructed to serve untargeted metabolomics research.The different selection of analytical tools and parameter settings lead to varied results of untargeted metabolomics data.Our goal is to establish an easily operated platform and obtain a repeatable analysis result.Methods:We used the R language basic environment to construct the preprocessing system of the original data and the LAMP(Linux+Apache+MySQL+PHP)architecture to build a cloud mass spectrum data analysis system.Results:An open-source analysis software for untargeted metabolomics data(openNAU)was constructed.It includes the extraction of raw mass data and quality control for the identification of differential metabolic ion peaks.A reference metabolomics database based on public databases was also constructed.Conclusions:A complete analysis system platform for untargeted metabolomics was established.This platform provides a complete template interface for the addition and updating of the analysis process,so we can finish complex analyses of untargeted metabolomics with simple human-computer interactions.The source code can be downloaded from https://github.com/zjuRong/openNAU.
基金Supported by the University Scientific Research Projects of Anhui,No. KJ2020A0401 and 2022AH050491the open fund of the Ministry of Education Key Laboratory of Glucolipid Metabolic Disorder,No. GYDKFXM01+5 种基金the Anhui University Collaborative Innovation Project,No. GXXT-2020-025the National Natural Science Foundation of China,No. 82174153the National Key Research and Development Program,No. 2018YFC1704202the Anhui Provincial Quality Engineering Project of Universities,No. 2021jyxm0834the Major and Difficult Diseases Project of Anhui Province,No. 2021zdynjb06the Clinical Research Project of Anhui University of Traditional Chinese Medicine,No. 2021yfylc01
文摘BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.
基金Science and Technology Development Plan Project of Jilin Provincial:Research on the Development of Baijin Pingchuan Granules as an In-hospital Preparation for the Treatment of Pediatric Asthma (Heat-type Asthma)(No. 20200404043YY)Traditional Chinese Medicine Science and Technology Project of Jilin Provincial:Exploring the Mechanism of Baijin Pingchuan Granules in Alleviating Airway Inflammation in Asthma based on the “Three-Stage Differentiation and Treatment” Theory of National Medical Masters (2020090)。
文摘OBJECTIVE: To investigate the effect of baijinpingchuan(白金平喘, BJPC) on the asthma rat model and identify differential metabolites and disturbed metabolic pathways. METHODS: The rats were categorized into six groups: control, dexamethasone(DEX), ovalbumin(OVA), and low-, median-, and high-dose BJPC. The rats, except for the control group, were initially treated with OVA to develop the asthma model, which was then activated using DEX, OVA, and low-, median-, and high-dose BJPC. Enzyme-linked immunosorbent assay kit was used to detect the expression of interleukin(IL)-33, IL-25, thymic stromal lymphopoietin(TSLP), and transforming growth factor-beta 1(TGF-β1). Hematoxylin and eosin staining were performed to observe the pathological condition of the lung. Untargeted serum metabonomic analysis was conducted to identify differential metabolites and disturbed metabolic pathways. RESULTS: High-dose BJPC significantly inhibited the expression of IL-33, IL-25, TSLP, and TGF-β1(P < 0.0001). Further, high-dose BJPC improved inflammatory cell infiltration, which plays a similar role in asthma as DEX. OVA-induced and BJPC-treated rats were identified through 17 differential metabolites, especially cholic acid. Furthermore, primary bile acid biosynthesis was a significantly differential pathway in the mechanism of BJPC for treating asthma. CONCLUSIONS: BJPC plays an anti-inflammation role in asthma, which might be a promising therapy through mediating primary bile acid biosynthesis.
文摘Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymine T3*,adenines A2*and A4*so that between them hydrogen bonds are formed.Canonical adenine and cytosine can be incorporated opposite canonical thymine only.Canonical thymine and guanine can be incorporated opposite canonical adenine only.If in the synthesis of DNA containing rare tautomeric forms of thymine T3*,adenines A2*and A4*,involved DNA polymerases with relatively high fidelity of synthesis,mutations not appear.However,if further DNA synthesis will involve DNA polymerases having a low fidelity of synthesis,there may be base substitution mutations.It was shown that the conclusion made in the Tomasetti and Vogelstein cancer risk model that the formation of about 67%of all mutations was not caused by exposure to any mutagens is erroneous.
文摘Objective To investigate the changes of metabolites in urine of automobile manufacturing workers with muscle fatigue using metabolomics technology,and to explore potential biomarkers and disrupted metabolic pathways.Methods In July 2022,urine samples were collected from35maleworkers in a certain automobile manufacturing industry before and after muscle fatigue,and metabolite analysis was conducted.Subsequently,multivariate statistical analysis was uused fordata processing to screen differential metabolites.Metabolic pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes(KEGG)database(http://www.kegg.jp),and potential biomarkers were screened through the receiver operating characteristic(ROC)curve.Results Metabolomics analysis revealed that compared to pre-fatigue samples,a total of 363 differential metabolites were identified in the post-fatigue urine samples of the subjects.Among these,201 metabolites(55.4%)showed increased relative expression,while 162 metabolites(44.6%)showed decreased relative expression.The metabolic pathways involved mainly included histidine metabolism,tryptophan metabolism,valine,leucine and isoleucine biosynthesis,caffeine metabolism,niacin and nicotinamide metabolism,and oxidative phosphorylation.The ROC curve analysis results showed that the areas under the ROC curves for 1-methylnicotinamide,2-piperidinone,kojic acid and diferuloyl Putrescine were 0.992,0.959,0.937 and 0.902,respectively.Conclusion Muscle fatigue could cause changes in urine metabolite profiles of automobile manufacturing workers.The metabolites represented by 1-methylnicotinamide in urine can be used as potential biomarkers。
文摘Metabolic genome-wide association studies （mGWAS）, whereupon metabolite levels are regarded as traits, can help unravel the genetic basis of metabolic networks. A total of 309Arabidopsis accessions were grown under two independent environmental conditions （control and stress） and subjected to untargeted LC-MS- based metabolomic profiling; levels of the obtained hydrophilic metabolites were used in GWAS. Our two- condition-based GWAS for more than 3000 semi-polar metabolites resulted in the detection of 123 highly resolved metabolite quantitative trait loci （p ≤ 1.0E-08）, 24.39% of which were environment-specific. Interestingly, differently from natural variation in Arabidopsis primary metabolites, which tends to be controlled by a large number of small-effect loci, we found several major large-effect loci alongside a vast number of small-effect loci controlling variation of secondary metabolites. The two-condition-based GWAS was fol- lowed by integration with network-derived metabolite-transcript correlations using a time-course stress experiment. Through this integrative approach, we selected 70 key candidate associations between struc- tural genes and metabolites, and experimentally validated eight novel associations, two of them showing differential genetic regulation in the two environments studied. We demonstrate the power of combining large-scale untargeted metabolomics-based GWAS with time-course-derived networks both performed under different ablotic environments for identifying metabollte-gene associations, providing novel global insights into the metabolic landscape of Arabidopsis.
文摘In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3 B2,H226, Ovcar3 and N87 were extracted and digested with γLys C and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the Max Quant and the protein abundances were estimated using total peak area(TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption,metabolism, disposition and elimination(ADME) proteins including UDP-glucuronosyltransferase,cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3 B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.
基金The work was supported by National Natural Science Foundation of China(Grant No.31971356)Shang-hai Municipal Science and Technology Major Project(Grant No.2019SHZDZX02)。
文摘Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolomics.The emerging role of IM-MS in untargeted metabolomics enables the separation of metabolite isomers and generation of multidimension data to support the identification of metabolites.In this review,we first introduced the basic principles of IM-MS instruments commonly used for untargeted metabolomics.Then,we demonstrated the application of IM-MS for metabolite separation and identification of both known and unknown metabolites.Finally,we discussed the future developments of IM-MS technology to improve untargeted metabolomics.
