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
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 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
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
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
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
The objective of this experiment was to evaluate the effect of supplementing rumen-protected Lys based on a Lys-deficient diet on liver metabolism in growing Holstein heifers.The experiment was conducted for 3 months ...The objective of this experiment was to evaluate the effect of supplementing rumen-protected Lys based on a Lys-deficient diet on liver metabolism in growing Holstein heifers.The experiment was conducted for 3 months with 36 Holstein heifers(initial body weight:200±9.0 kg;7-month-old).Heifers were randomly assigned to 2 diets based on corn,soybean meal,alfalfa hay,and wheat bran:control,Lysdeficient diet(LD;0.66%Lys in diet),and Lys-adequate diet(LA;1.00%Lys in diet).The results showed no difference in growth performance between the 2 groups(P>0.05).However,there was a clear trend of increasing feed conversion rate with Lys supplementation(0.05<P<0.01).The serum urea nitrogen concentration was significantly decreased,and the aspartate aminotransferase-to-alanine aminotransferase ratio was significantly decreased by Lys supplementation(P<0.05).Moreover,growing heifers fed a Lys-adequate diet had lower levels of urine nitrogen excretion and higher levels of the biological value of nitrogen(P<0.05).Metabolomic analysis revealed that 5 types of phosphatidylcholine and 3 types of ceramide were significantly increased and enriched in sphingolipid metabolism and glycero phospholipid metabolism(P<0.05).His,Leu,and Asp levels were significantly decreased in the liver following Lys supplementation(P<0.05).In conclusion,Lys supplementation may promote the synthesis of body tissue proteins,as evidenced by significantly decreased amino acids in the liver and urine N excretion,it also improves hepatic lipid metabolism by providing lipoprotein precursors.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
BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
Quality deterioration induced by microbial community in Litopenaeus vannamei during superchilling storage were demonstrated in this study.In this study,6 microorganisms were identified as the biomarkers by 16S rDNA se...Quality deterioration induced by microbial community in Litopenaeus vannamei during superchilling storage were demonstrated in this study.In this study,6 microorganisms were identified as the biomarkers by 16S rDNA sequencing and 71 differential metabolites were identified by untargeted metabolomics.The correlation analysis between microorganisms and differential metabolites revealed that Oceanicaulis,Aliihoeflea,Prauserella,Chelativorans and Pseudoalteromonas had the potential to be the important microorganisms of deterioration of superchilled shrimp.Moreover,the spearman correlation analysis revealed that lightness value had highly significant correlation with Shewanella(P<0.01),and thiobarbituric acid content,total viable count value,total sulfhydryl content,trichloroacetic acid-soluble peptide and Ca2+-ATPase activity showed significantly correlation with Oceanicaulis,Prauserella,Chelativorans,Aliihoefl ea and Pseudoalteromonas(P<0.05).This study offers a better understanding for mechanisms behind quality degradation induced by microorganisms,which may help the quality maintaining of Pacific white shrimp during superchilling storage.展开更多
Antibiotics are widely used to treat various diseases.However,growing evidence indicates that antibiotic therapy in human life increases the incidence of inflammatory bowel disease(IBD).Therefore,we need appropriate m...Antibiotics are widely used to treat various diseases.However,growing evidence indicates that antibiotic therapy in human life increases the incidence of inflammatory bowel disease(IBD).Therefore,we need appropriate methods to reduce the incidence or symptoms of IBD.In this study,we used lincomycin hydrochloride to construct a gut micro-bial dysbiosis model in mice,and then,constructed an ulcerative colitis(UC)model.Meanwhile,we used Lactobacillus plantarum A3 from equine to treat UC in mice with gut microbial dysbiosis.The results showed that lincomycin hydro-chloride had little effect on the small gut microbiota in mice,but had a more destructive effect on the large intestin.Lactobaillus plantarum A3 alleviated the symptoms of UC in mice,which was reflected in its significantly reduced spleen index and disease activity index(DAl)(p<0.05),inhibited the shortening of colon and alleviated the invasion of inflammatory cells in the colon.Moreover,we found that it played a mitigatory role by inhibiting oxidative stress and regulating inflammatory cytokines in mice.At the same time,it restored the diversity and composition of the colonic microbiota and significantly increased the abundance of beneficial bacteria such as Blautia and Akkermansia(p<0.05);Notably,it significantly increased the concentrations of arachidonoyl ethanolamide phosphate(AEA-P)and cortisone(p<0.05)which have analgesic and anti-inflammatory effects.In conclusion,our study found that Lactobacillus plan-tarum A3 has the potential to regulate UC in mice with gut microbial dysbiosis.展开更多
Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growt...Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growth,physiological,and metabolic responses of the widely promoted Tartary buckwheat variety Chuan Qiao No.1 to polyethylene glycol(PEG)-mediated drought stress.Drought significantly decreased shoot length,shoot biomass and relative water content.Root length,malondialdehyde content,electrolyte leakage,activities of superoxide dismutase,peroxidase,catalase and amylase,and contents of soluble sugar,soluble protein and proline were increased by PEG-mediated drought.Untargeted metabolomics analysis identified 32 core metabolites in seedlings subjected to PEG-mediated drought,16 of which increased—including quercetin,isovitexin,cyanidin 3-O-beta-D-glucoside,L-arginine,and glycerophosphocholine,while the other 16 decreased—including 3-methoxytyramine,2,6-diaminopimelic acid,citric acid,UDP-alpha-D-glucose,adenosine,keto-D-fructose.The 32 core metabolites were enriched in 29 metabolic pathways,including lysine biosynthesis,citrate(TCA)cycle,anthocyanin biosynthesis,and aminoacyl-tRNA biosynthesis.Among them,taurine and hypotaurine metabolism,flavor and flavor biosynthesis,indole alkaline biosynthesis,and alanine,aspartate and glutamate metabolism were the four main metabolic pathways affected by drought.Our findings provide new insights into the physiological and metabolic response mechanisms of Tartary buckwheat to drought stress.展开更多
BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut m...BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially,HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4,myeloid differentiation factor 88,p-nuclear factor kappa-B(NF-κB)/NF-κB,and p-inhibitorαof NF-κB(p-IκBα)/IκBαexpression levels in the lung,and raised the pulmonary vascular endothelial-cadherin,zonula occludens-1(ZO-1),and occludin levels and ileal ZO-1,claudin-1,and occludin expression levels.HUC-MSCs improved gut and BALF microbial homeostases.The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUCMSCs.Concurrently,the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased.In addition,Lactobacillus,Bacteroides,and unidentified_Rikenellaceae genera appeared in both feces and BALF.Moreover,this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS+MSC group compared to the LPS group,which were related to the purine metabolism and the taste transduction signaling pathways.Therefore,an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.展开更多
Background:The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development(EGD)than white crossbred gilts during the ovary-independent period(before 60 d of age).Then,the EGD continues under the ...Background:The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development(EGD)than white crossbred gilts during the ovary-independent period(before 60 d of age).Then,the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota(after 60 d of age).However,whether Meishan gilts’superiority in EGD lasting to the ovary-dependent period(after 60 d of age)and the role of gut microbiota in this period both remain unclear.Methods:Meishan gilts and Landrace x Yorkshire(LxY)gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota.Meanwhile,we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD.We sampled plasma every 3 weeks and collected the uterus,ovary,liver,and rectal feces after the sacrifice.We then determined the hormone concentrations and expressions of the EGD-related genes.We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics.Finally,the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.Results:Meishan gilts have larger endometrial gland area(P<0.001),longer uterine horn length(P<0.01)but lighter uterine horn weight(P<0.05),a distinctive gut microbiota compared with L×Y gilts.Fecal microbiota transplantation(FMT)increased endometrial gland area(P<0.01).FMT markedly shifted the metabolite profiles of both liver and plasma,and these differential metabolites enriched in steroid hormone biosynthesis pathway.FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically.FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene,epithelial cadherin,and forkhead box protein A2.There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.Conclusion:Sexually matured Meishan gilts achieved a superior EGD than LxY gilts.Meanwhile,gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.展开更多
Countless studies have been devoted to the scientific evaluation of the safety and/or efficacy of botanical natural products.Investigators involved in such studies face a unique set of challenges.Natural products diff...Countless studies have been devoted to the scientific evaluation of the safety and/or efficacy of botanical natural products.Investigators involved in such studies face a unique set of challenges.Natural products differ from their pharmaceutical counterparts in that they are typically complex mixtures,for which the identities and quantities of components present are not known.To further complicate matters,the composition of these mixtures will vary depending on source material and method of preparation.Investigators conducting clinical trials with complex botanical natural products must choose from a myriad of potential preparations,which may vary greatly in composition.In making such decisions,it is extremely useful to know which components of the mixture are most likely to be responsible for its purported biological activity(the"active constituents").The gold standard approach for identifying active constituents of botanical natural products is bioassay-guided fractionation,in which the mixture is subjected to successive rounds of purification and bioassays until an active compound is identified.Bioassay guided fractionation has historically played a critical role in drug discovery,but is,nonetheless,fraught with challenges.The process is biased towards the most abundant and easily isolatable mixture components,which may not be the most biologically active.Furthermore,if multiple compounds contribute either additively,antagonistically,or synergistically to the observed biological activity of the mixture,activity may be lost upon isolation.As a complementary strategy to bioassay-guided fractionation,our research group has developed untargeted metabolomics strategies to aid in the identification of bioactive mixture components.These strategies involve profiling botanical mixtures using ultraperformance chromatography coupled to high resolving power mass spectrometry.The resulting chemical data is then integrated with biological assay data using biochemometric data analysis strategies.Several case studies will be presented illustrating how this approach can be applied,including for the identification of compounds from the botanical green(Camellia sinensis)that inhibit drug metabolizing enzymes.Such studies are being conducted as part of the Center for Excellence in Natural Product Drug Interaction Studies(Na PDI),which is supported by a cooperative agreement with the National Center for Complementary and Integrative Health,a component of the National Institutes of Health.展开更多
Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products.Among these genera,Allokutzneria and Kibdelosporangium are two phylogenetically closely relat...Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products.Among these genera,Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites.However,there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera.In this study,we first investi-gated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters(BGCs).The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques.The findings unveiled that the majority(95.4%)of the gene cluster families(GCFs)encoded by Allokutzneria and Kibdelosporangium were genus-specific,including NRPS GCFs encoding siderophores.The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity,with the culture medium having a big impact on the metabolic profiles.Besides,an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917,with two of them,including a novel one(N-deoxy arthrobactin A),being experimentally validated.The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.展开更多
The production and reactivation of viable but nonculturable(VBNC)bacteria by chlorine disinfection leads to an overestimation of the disinfection effect and brings health risks.Therefore,this study is to evaluate the ...The production and reactivation of viable but nonculturable(VBNC)bacteria by chlorine disinfection leads to an overestimation of the disinfection effect and brings health risks.Therefore,this study is to evaluate the disinfection efficiency of combined ultrasound(US)and chlorine in inhibiting the production and reactivation of VBNC bacteria and to clarify the mechanisms.The number of culturable cells was effectively reduced by 99.97%after US/chlorine treatments.The number of VBNC bacteria introduced by US treatment and chlorine treatment was 10^(3.6)CFU/mL and 10^(5.2)CFU/mL,respectively.However,US/chlorine disinfection produces fewer VBNC bacteria(101.3 CFU/mL),and the dark reactivation of the VBNC bacteria was effectively inhibited.Ultrasound and chlorine have synergistic effects in disinfection-ultrasound further enhancing bacterial membrane permeability and chlorine-induced oxidative stress,causing the bacterial antioxidant system to collapse.In addition,single cell Raman spectroscopy and gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis revealed that US/chlorine treatment inhibits more strongly or even destroys the metabolism of bacteria.The significantly perturbed metabolic pathways mainly involved the amino acid,carbohydrate and lipid metabolisms.Thus,the combined US/chlorine treatment is a promising cleaner and a more efficient disinfection technology to remove VBNC bacteria in the field of water purification.展开更多
Dairy goats experience metabolic stress during the peripartal period,and their ability to navigate this stage of lactation is related to the occurrence and development of metabolic diseases.Unlike dairy cows,there is ...Dairy goats experience metabolic stress during the peripartal period,and their ability to navigate this stage of lactation is related to the occurrence and development of metabolic diseases.Unlike dairy cows,there is a lack of comprehensive analysis of changes in the plasma profiles of peripartal dairy goats,particularly using high-throughput techniques.A subset of 9 clinically-healthy dairy goats were used from a cohort of 96 primiparous Guanzhong dairy goats(BCS,2.75±0.15).Blood samples were collected at seven time points around parturition(d 21,14,7 before parturition,the day of kidding,and d 7,14,21 postpartum),were analyzed using untargeted metabolomics and targeted lipidomics.The orthogonal partial least squares discriminant analysis model revealed a total of 31 differential metabolites including p-cresol sulfate,pyruvic acid,cholic acid,and oxoglutaric acid.The pathway enrichment analysis identified phenylalanine metabolism,aminoacyl-tRNA biosynthesis,and citrate cycle as the top three significantly-altered pathways.The Limma package identified a total of 123 differentially expressed lipids.Phosphatidylserine(PS),free fatty acids(FFA),and acylcarnitines(ACs)were significantly increased on the day of kidding,while diacylglycerols(DAG)and triacylglycerols(TAG)decreased.Ceramides(Cer)and lyso-phosphatidylinositols(LPI)were significantly increased during postpartum period,while PS,FFA,and ACs decreased postpartum and gradually returned to antepartum levels.Individual species of FFA and phosphatidylcholines(PC)were segregated based on the differences in the saturation and length of the carbon chain.Overall,this work generated the largest repository of the plasma lipidome and metabolome in dairy goats across the peripartal period,which contributed to our understanding of the multifaceted adaptations of transition dairy goats.展开更多
Metabolites,especially secondary metabolites,are very important in the adaption of tea plants and the quality of tea products.Here,we focus on the seasonal variation in metabolites of fresh tea shoots and their regula...Metabolites,especially secondary metabolites,are very important in the adaption of tea plants and the quality of tea products.Here,we focus on the seasonal variation in metabolites of fresh tea shoots and their regulatory mechanism at the transcriptional level.The metabolic profiles of fresh tea shoots of 10 tea accessions collected in spring,summer,and autumn were analyzed using ultra-performance liquid chromatography coupled with quadrupole-obitrap mass spectrometry.We focused on the metabolites and key genes in the phenylpropanoid/flavonoid pathway integrated with transcriptome analysis.Multivariate statistical analysis indicates that metabolites were distinctly different with seasonal alternation.Flavonoids,amino acids,organic acids and alkaloids were the predominant metabolites.Levels of most key genes and downstream compounds in the flavonoid pathway were lowest in spring but the catechin quality index was highest in spring.The regulatory pathway was explored by constructing a metabolite correlation network and a weighted gene co-expression network.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.
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.
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.
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.
基金supported,in part,by the Key Research and Development Program of Hebei Province(19226621D)Earmarked Fund for Beijing Dairy Industry Innovation Consortium of Agriculture Research System,Chinese Academy of Agricultural Science and Technology Innovation Project(CAAS-XTCX-2016011-01)+2 种基金Fundamental Research Funds for Central Non-profit Scientific Institution(Y2019CG08)Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2017-FRI-04)Science and Technology Open Cooperation Project of Henan Province(182106000035)Study on the Pattern of Diet Amino Acid for Different Physiological Stages of Heifers。
文摘The objective of this experiment was to evaluate the effect of supplementing rumen-protected Lys based on a Lys-deficient diet on liver metabolism in growing Holstein heifers.The experiment was conducted for 3 months with 36 Holstein heifers(initial body weight:200±9.0 kg;7-month-old).Heifers were randomly assigned to 2 diets based on corn,soybean meal,alfalfa hay,and wheat bran:control,Lysdeficient diet(LD;0.66%Lys in diet),and Lys-adequate diet(LA;1.00%Lys in diet).The results showed no difference in growth performance between the 2 groups(P>0.05).However,there was a clear trend of increasing feed conversion rate with Lys supplementation(0.05<P<0.01).The serum urea nitrogen concentration was significantly decreased,and the aspartate aminotransferase-to-alanine aminotransferase ratio was significantly decreased by Lys supplementation(P<0.05).Moreover,growing heifers fed a Lys-adequate diet had lower levels of urine nitrogen excretion and higher levels of the biological value of nitrogen(P<0.05).Metabolomic analysis revealed that 5 types of phosphatidylcholine and 3 types of ceramide were significantly increased and enriched in sphingolipid metabolism and glycero phospholipid metabolism(P<0.05).His,Leu,and Asp levels were significantly decreased in the liver following Lys supplementation(P<0.05).In conclusion,Lys supplementation may promote the synthesis of body tissue proteins,as evidenced by significantly decreased amino acids in the liver and urine N excretion,it also improves hepatic lipid metabolism by providing lipoprotein precursors.
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Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2020A1515110360)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(320LH037)+3 种基金Hainan Provincial Natural Sciences Foundation of China(322QN434)Guangzhou Basic and Applied Basic Research Foundation(202102021062)Research and Development Projects in Key Areas of Guangdong Province,China(2021B0202060002)Postgraduate Education Innovation Project of Guangdong Ocean University(202242).
文摘Quality deterioration induced by microbial community in Litopenaeus vannamei during superchilling storage were demonstrated in this study.In this study,6 microorganisms were identified as the biomarkers by 16S rDNA sequencing and 71 differential metabolites were identified by untargeted metabolomics.The correlation analysis between microorganisms and differential metabolites revealed that Oceanicaulis,Aliihoeflea,Prauserella,Chelativorans and Pseudoalteromonas had the potential to be the important microorganisms of deterioration of superchilled shrimp.Moreover,the spearman correlation analysis revealed that lightness value had highly significant correlation with Shewanella(P<0.01),and thiobarbituric acid content,total viable count value,total sulfhydryl content,trichloroacetic acid-soluble peptide and Ca2+-ATPase activity showed significantly correlation with Oceanicaulis,Prauserella,Chelativorans,Aliihoefl ea and Pseudoalteromonas(P<0.05).This study offers a better understanding for mechanisms behind quality degradation induced by microorganisms,which may help the quality maintaining of Pacific white shrimp during superchilling storage.
文摘Antibiotics are widely used to treat various diseases.However,growing evidence indicates that antibiotic therapy in human life increases the incidence of inflammatory bowel disease(IBD).Therefore,we need appropriate methods to reduce the incidence or symptoms of IBD.In this study,we used lincomycin hydrochloride to construct a gut micro-bial dysbiosis model in mice,and then,constructed an ulcerative colitis(UC)model.Meanwhile,we used Lactobacillus plantarum A3 from equine to treat UC in mice with gut microbial dysbiosis.The results showed that lincomycin hydro-chloride had little effect on the small gut microbiota in mice,but had a more destructive effect on the large intestin.Lactobaillus plantarum A3 alleviated the symptoms of UC in mice,which was reflected in its significantly reduced spleen index and disease activity index(DAl)(p<0.05),inhibited the shortening of colon and alleviated the invasion of inflammatory cells in the colon.Moreover,we found that it played a mitigatory role by inhibiting oxidative stress and regulating inflammatory cytokines in mice.At the same time,it restored the diversity and composition of the colonic microbiota and significantly increased the abundance of beneficial bacteria such as Blautia and Akkermansia(p<0.05);Notably,it significantly increased the concentrations of arachidonoyl ethanolamide phosphate(AEA-P)and cortisone(p<0.05)which have analgesic and anti-inflammatory effects.In conclusion,our study found that Lactobacillus plan-tarum A3 has the potential to regulate UC in mice with gut microbial dysbiosis.
基金We acknowledge the Project of National Key Research and Development Program of China(2020YFD1001403)China Agriculture Research System(CARS-07-B-1)+3 种基金Science&Technology Department of Sichuan Province(2022YFQ0041)the National Natural Science Foundation of China(31601260,32160428)Innovative Training Program for College Students(S202111079058)Special Research Fund from Key Laboratory of Coarse Cereal Processing,Ministry of Agriculture and Rural Affairs(2020CC012)to facilitate the research.
文摘Tartary buckwheat(Fagopyrum tataricum)is an important pseudocereal feed crop with medicinal and nutritional value.Drought is one of the main causes of reduced growth and yield in these plants.We investigated the growth,physiological,and metabolic responses of the widely promoted Tartary buckwheat variety Chuan Qiao No.1 to polyethylene glycol(PEG)-mediated drought stress.Drought significantly decreased shoot length,shoot biomass and relative water content.Root length,malondialdehyde content,electrolyte leakage,activities of superoxide dismutase,peroxidase,catalase and amylase,and contents of soluble sugar,soluble protein and proline were increased by PEG-mediated drought.Untargeted metabolomics analysis identified 32 core metabolites in seedlings subjected to PEG-mediated drought,16 of which increased—including quercetin,isovitexin,cyanidin 3-O-beta-D-glucoside,L-arginine,and glycerophosphocholine,while the other 16 decreased—including 3-methoxytyramine,2,6-diaminopimelic acid,citric acid,UDP-alpha-D-glucose,adenosine,keto-D-fructose.The 32 core metabolites were enriched in 29 metabolic pathways,including lysine biosynthesis,citrate(TCA)cycle,anthocyanin biosynthesis,and aminoacyl-tRNA biosynthesis.Among them,taurine and hypotaurine metabolism,flavor and flavor biosynthesis,indole alkaline biosynthesis,and alanine,aspartate and glutamate metabolism were the four main metabolic pathways affected by drought.Our findings provide new insights into the physiological and metabolic response mechanisms of Tartary buckwheat to drought stress.
基金the Key Research and Development Project of Science and Technology Department of Zhejiang Province,No.2019C03041.
文摘BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially,HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4,myeloid differentiation factor 88,p-nuclear factor kappa-B(NF-κB)/NF-κB,and p-inhibitorαof NF-κB(p-IκBα)/IκBαexpression levels in the lung,and raised the pulmonary vascular endothelial-cadherin,zonula occludens-1(ZO-1),and occludin levels and ileal ZO-1,claudin-1,and occludin expression levels.HUC-MSCs improved gut and BALF microbial homeostases.The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUCMSCs.Concurrently,the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased.In addition,Lactobacillus,Bacteroides,and unidentified_Rikenellaceae genera appeared in both feces and BALF.Moreover,this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS+MSC group compared to the LPS group,which were related to the purine metabolism and the taste transduction signaling pathways.Therefore,an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.
基金supported by the Natural Science Foundation of China(31730090 and 31925037)Hubei Provincial Natural Science Foundation of China(2018CFA020).
文摘Background:The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development(EGD)than white crossbred gilts during the ovary-independent period(before 60 d of age).Then,the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota(after 60 d of age).However,whether Meishan gilts’superiority in EGD lasting to the ovary-dependent period(after 60 d of age)and the role of gut microbiota in this period both remain unclear.Methods:Meishan gilts and Landrace x Yorkshire(LxY)gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota.Meanwhile,we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD.We sampled plasma every 3 weeks and collected the uterus,ovary,liver,and rectal feces after the sacrifice.We then determined the hormone concentrations and expressions of the EGD-related genes.We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics.Finally,the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.Results:Meishan gilts have larger endometrial gland area(P<0.001),longer uterine horn length(P<0.01)but lighter uterine horn weight(P<0.05),a distinctive gut microbiota compared with L×Y gilts.Fecal microbiota transplantation(FMT)increased endometrial gland area(P<0.01).FMT markedly shifted the metabolite profiles of both liver and plasma,and these differential metabolites enriched in steroid hormone biosynthesis pathway.FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically.FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene,epithelial cadherin,and forkhead box protein A2.There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.Conclusion:Sexually matured Meishan gilts achieved a superior EGD than LxY gilts.Meanwhile,gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.
文摘Countless studies have been devoted to the scientific evaluation of the safety and/or efficacy of botanical natural products.Investigators involved in such studies face a unique set of challenges.Natural products differ from their pharmaceutical counterparts in that they are typically complex mixtures,for which the identities and quantities of components present are not known.To further complicate matters,the composition of these mixtures will vary depending on source material and method of preparation.Investigators conducting clinical trials with complex botanical natural products must choose from a myriad of potential preparations,which may vary greatly in composition.In making such decisions,it is extremely useful to know which components of the mixture are most likely to be responsible for its purported biological activity(the"active constituents").The gold standard approach for identifying active constituents of botanical natural products is bioassay-guided fractionation,in which the mixture is subjected to successive rounds of purification and bioassays until an active compound is identified.Bioassay guided fractionation has historically played a critical role in drug discovery,but is,nonetheless,fraught with challenges.The process is biased towards the most abundant and easily isolatable mixture components,which may not be the most biologically active.Furthermore,if multiple compounds contribute either additively,antagonistically,or synergistically to the observed biological activity of the mixture,activity may be lost upon isolation.As a complementary strategy to bioassay-guided fractionation,our research group has developed untargeted metabolomics strategies to aid in the identification of bioactive mixture components.These strategies involve profiling botanical mixtures using ultraperformance chromatography coupled to high resolving power mass spectrometry.The resulting chemical data is then integrated with biological assay data using biochemometric data analysis strategies.Several case studies will be presented illustrating how this approach can be applied,including for the identification of compounds from the botanical green(Camellia sinensis)that inhibit drug metabolizing enzymes.Such studies are being conducted as part of the Center for Excellence in Natural Product Drug Interaction Studies(Na PDI),which is supported by a cooperative agreement with the National Center for Complementary and Integrative Health,a component of the National Institutes of Health.
基金supported by the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.RF-A2022013)the program of the National Natural Science Foundation of China(No.42276137)the National Key Research and Development Programs(Nos.2022YFC2804104,and 2022YFC2804700).
文摘Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products.Among these genera,Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites.However,there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera.In this study,we first investi-gated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters(BGCs).The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques.The findings unveiled that the majority(95.4%)of the gene cluster families(GCFs)encoded by Allokutzneria and Kibdelosporangium were genus-specific,including NRPS GCFs encoding siderophores.The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity,with the culture medium having a big impact on the metabolic profiles.Besides,an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917,with two of them,including a novel one(N-deoxy arthrobactin A),being experimentally validated.The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.
基金supported by the National Natural Science Foundation of China(No.42077391)the Guangdong Foundation for Program of Science and Technology Research,China(No.2020B1212060053).
文摘The production and reactivation of viable but nonculturable(VBNC)bacteria by chlorine disinfection leads to an overestimation of the disinfection effect and brings health risks.Therefore,this study is to evaluate the disinfection efficiency of combined ultrasound(US)and chlorine in inhibiting the production and reactivation of VBNC bacteria and to clarify the mechanisms.The number of culturable cells was effectively reduced by 99.97%after US/chlorine treatments.The number of VBNC bacteria introduced by US treatment and chlorine treatment was 10^(3.6)CFU/mL and 10^(5.2)CFU/mL,respectively.However,US/chlorine disinfection produces fewer VBNC bacteria(101.3 CFU/mL),and the dark reactivation of the VBNC bacteria was effectively inhibited.Ultrasound and chlorine have synergistic effects in disinfection-ultrasound further enhancing bacterial membrane permeability and chlorine-induced oxidative stress,causing the bacterial antioxidant system to collapse.In addition,single cell Raman spectroscopy and gas chromatography-tandem mass spectrometry(GC-MS/MS)analysis revealed that US/chlorine treatment inhibits more strongly or even destroys the metabolism of bacteria.The significantly perturbed metabolic pathways mainly involved the amino acid,carbohydrate and lipid metabolisms.Thus,the combined US/chlorine treatment is a promising cleaner and a more efficient disinfection technology to remove VBNC bacteria in the field of water purification.
基金supported by the National Natural Science Foundation of China(grant numbers 32273085,32102742).
文摘Dairy goats experience metabolic stress during the peripartal period,and their ability to navigate this stage of lactation is related to the occurrence and development of metabolic diseases.Unlike dairy cows,there is a lack of comprehensive analysis of changes in the plasma profiles of peripartal dairy goats,particularly using high-throughput techniques.A subset of 9 clinically-healthy dairy goats were used from a cohort of 96 primiparous Guanzhong dairy goats(BCS,2.75±0.15).Blood samples were collected at seven time points around parturition(d 21,14,7 before parturition,the day of kidding,and d 7,14,21 postpartum),were analyzed using untargeted metabolomics and targeted lipidomics.The orthogonal partial least squares discriminant analysis model revealed a total of 31 differential metabolites including p-cresol sulfate,pyruvic acid,cholic acid,and oxoglutaric acid.The pathway enrichment analysis identified phenylalanine metabolism,aminoacyl-tRNA biosynthesis,and citrate cycle as the top three significantly-altered pathways.The Limma package identified a total of 123 differentially expressed lipids.Phosphatidylserine(PS),free fatty acids(FFA),and acylcarnitines(ACs)were significantly increased on the day of kidding,while diacylglycerols(DAG)and triacylglycerols(TAG)decreased.Ceramides(Cer)and lyso-phosphatidylinositols(LPI)were significantly increased during postpartum period,while PS,FFA,and ACs decreased postpartum and gradually returned to antepartum levels.Individual species of FFA and phosphatidylcholines(PC)were segregated based on the differences in the saturation and length of the carbon chain.Overall,this work generated the largest repository of the plasma lipidome and metabolome in dairy goats across the peripartal period,which contributed to our understanding of the multifaceted adaptations of transition dairy goats.
基金the National Natural Science Foundation of China(U19A2030,32072631,31500568)the Earmarked Fund for China Agricultural Research System(CARS-019)the Chinese Academy of Agricultural Sciences through the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2017-TRICAAS).We sincerely thank Dr.Pietro Altermatt for his constructive language editing.
文摘Metabolites,especially secondary metabolites,are very important in the adaption of tea plants and the quality of tea products.Here,we focus on the seasonal variation in metabolites of fresh tea shoots and their regulatory mechanism at the transcriptional level.The metabolic profiles of fresh tea shoots of 10 tea accessions collected in spring,summer,and autumn were analyzed using ultra-performance liquid chromatography coupled with quadrupole-obitrap mass spectrometry.We focused on the metabolites and key genes in the phenylpropanoid/flavonoid pathway integrated with transcriptome analysis.Multivariate statistical analysis indicates that metabolites were distinctly different with seasonal alternation.Flavonoids,amino acids,organic acids and alkaloids were the predominant metabolites.Levels of most key genes and downstream compounds in the flavonoid pathway were lowest in spring but the catechin quality index was highest in spring.The regulatory pathway was explored by constructing a metabolite correlation network and a weighted gene co-expression network.
