Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumo...Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and metastasis.In this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and metastasis.The results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor tissues.Furthermore,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.展开更多
Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments invo...Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector machine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.展开更多
Colon cancer is one of the malignant tumors with high morbidity and mortality worldwide[1],and its early diagnosis is crucial for improving patient survival.However,due to the lack of obvious early symptoms of colon c...Colon cancer is one of the malignant tumors with high morbidity and mortality worldwide[1],and its early diagnosis is crucial for improving patient survival.However,due to the lack of obvious early symptoms of colon cancer,many patients are in the middle to late stage when diagnosed and miss the best time for treatment.Therefore,developing an efficient and accurate diagnostic method for colon cancer is of great clinical significance and scientific value.Currently,the current colon cancer biomarkers carcinoembryonic antigen and carbohydrate antigen 19-9[2]have low sensitivity and specificity,the emerging markers circulating tumor DNA(ctDNA)and miRNA face high cost and standardization challenges,and the existing methods lack spatial resolution,prompting the incorporation of spatial metabolomics technologies to enhance diagnostic capabilities.展开更多
Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.Howeve...Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.展开更多
Global crop productivity faces a significant threat from climate change-induced drought stress(DS),which is vital for sustainable agriculture and global food security.Uncovering DS adaptation and tolerance mechanisms ...Global crop productivity faces a significant threat from climate change-induced drought stress(DS),which is vital for sustainable agriculture and global food security.Uncovering DS adaptation and tolerance mechanisms in crops is necessary to alleviate climate challenges.Innovative plant breeding demands revolutionary approaches to develop stress-smart plants.Metabolomics,a promising field in plant breeding,offers a predictive tool to identify metabolic markers associated with plant performance under DS,enabling accelerated crop improvement.Central to DS adaptation is metabolomics-driven metabolic regulation,which is critical for maintaining cell osmotic potential in crops.Recent innovations allow rapid mapping of specific metabolites to their genetic pathways,providing a valuable resource for plant scientists.Metabolomics-driven molecular breeding,integrating techniques such as mQTL and mGWAS,enhances our ability to discover key genetic elements linked to stress-responsive metabolites.This integration offers a beneficial platform for plant scientists,yielding significant insights into the complex metabolic networks underlying DS tolerance.Therefore,this review discusses(1)insights into metabolic regulation for DS adaptation,(2)the multifaceted role of metabolites in DS tolerance and nutritional/yield trait improvement,(3)the potential of single-cell metabolomics and imaging,(4)metabolomics-driven molecular breeding,and(5)the application of metabolic and genetic engineering for DS-tolerant crops.We finally propose that the metabolomics-driven approach positions drought-smart crops as key contributors to future food production,supporting the vital goal of achieving“zero hunger”.展开更多
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:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mou...Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.展开更多
Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants h...Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants have some differences in efficacy,but the flower buds are easily confused for similar traits.In addition,large-scale cultivation of ornamental rose flowers may lead to a decrease in the effective components of medicinal roses.Therefore,it is necessary to study the chemical composition and make quality evaluation of Rosae Chinensis Flos(Yueji)and Rosae Rugosae Flos(Meigui).Methods:In this study,40 batches of samples including Meigui and Yueji from different regions in China were collected to establish high-performance liquid chromatography fingerprints.Then,the fingerprints data was analyzed using principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis analysis chemometrics to obtain information on intergroup differences,and non-targeted metabolomic techniques were applied to identify and compare chemical compositions of samples which were chosen from groups with large differences.Differential compounds were screened by orthogonal partial least-squares discriminant analysis and S-plot,and finally multi-component quantification was performed to comprehensively evaluate the quality of Yueji and Meigui.Results:The similarity between the fingerprints of 40 batches roses and the reference print R was 0.73 to 0.93,indicating that there were similarities and differences between the samples.Through principal component analysis and hierarchical cluster analysis of fingerprints data,the samples from different origins and varieties were intuitively divided into four groups.Partial least-squares discriminant analysis analysis showed that Meigui and Yueji cluster into two categories and the model was reliable.A total of 89 compounds were identified by high resolution mass spectrometry,mainly were flavonoids and flavonoid glycosides,as well as phenolic acids.Eight differential components were screened out by orthogonal partial least-squares discriminant analysis and S-plot analysis.Quantitative analyses of the eight compounds,including gallic acid,ellagic acid,hyperoside,isoquercitrin,etc.,showed that Yueji was generally richer in phenolic acids and flavonoids than Meigui,and the quality of Yueji from Shandong and Hebei was better.It is worth noting that Xinjiang rose is rich in various components,which is worth focusing on more in-depth research.Conclusion:In this study,the fingerprints of Meigui and Yueji were established.The chemical components information of roses was further improved based on non-targeted metabolomics and mass spectrometry technology.At the same time,eight differential components of Meigui and Yueji were screened out and quantitatively analyzed.The research results provided a scientific basis for the quality control and rational development and utilization of Rosae Chinensis Flos and Rosae Rugosae Flos,and also laid a foundation for the study of their pharmacodynamic material basis.展开更多
The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,...The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.展开更多
Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely li...Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.展开更多
Atlantic salmon(Salmo salar)represents the primary species in aquaculture.The gut microbiota plays a crucial role in nutrient processing and protection against pathogenic bacteria.Nonetheless,the composition and funct...Atlantic salmon(Salmo salar)represents the primary species in aquaculture.The gut microbiota plays a crucial role in nutrient processing and protection against pathogenic bacteria.Nonetheless,the composition and functionality of the gut microbiota in Salmo salar at different growth stages remain largely unexplored.This study investigated the alterations within the gut microbial communities and their associated metabolites across different growth stages of Salmo salar,specifically when the body weights were 1.0 kg(S1 group),2.0 kg(S2 group),4.0 kg(S3 group),and 6.0 kg(S4 group),using microbiome sequencing and liquid chromatographymass spectrometry(LC-MS)technology.Results indicated significant changes in the gut microbiota and metabolite profiles concurrent with fish growth.Notably,the abundance of Firmicutes decreased,and Proteobacteria increased,resulting in a decreased Firmicutes/Bacteroidetes(F/B)ratio.Concurrently,the abundance of potential pathogenic bacteria such as Stenotrophomonas,Vibrio,Aeromonas,Staphylococcaceae,Enterobacteriaceae,Enterococcaceae,and Haemophilus increased,whereas beneficial bacteria like Lactobacillus and Bacilli decreased.The gut microbiota in the S1 group exhibited an increase in the abundance of beneficial bacteria.Conversely,in the S2,S3,and S4 groups,the prevalence of pathogenic bacteria increased.Metabolic profiling revealed significant upregulation of arachidonic acid(ARA)and taurine in the S2 and S3 groups,while citric acid,riboflavin,and pantothenic acid notably increased in the S4 group.Particularly,several amino acids such as threonine,lysine,and serine in the gut microbiota metabolites were significantly reduced in the S2,S3,and S4 groups,correlating positively with the respective essential amino acid concentrations in muscle tissue.The S1 group exhibited a more active gut microbiota associated with amino acid metabolism,resulting in higher muscle amino acid content.This study identified gut microbiota and its metabolic products at different growth stages of Salmo salar,providing a scientific basis for proactive intervention of gut microbiota and improve the quality of aquatic products.展开更多
Nuclear magnetic resonance(NMR)spectroscopy is an excellent tool for simultaneous identification and quantification of metabolites(metabolomics).NMR quantification of human lipoprotein subfractions and their component...Nuclear magnetic resonance(NMR)spectroscopy is an excellent tool for simultaneous identification and quantification of metabolites(metabolomics).NMR quantification of human lipoprotein subfractions and their components has proven to be a powerful approach to reveal pathophysiological insights in numerous diseases[1,2].This method has now been standardized with excellent inter-laboratory reproducibility within 10 days for simultaneous quantification of 105 lipoprotein components and 24 low-molecular weight(LMW)metabolites[3];close clustering was also shown for 12 quality-control(QC)samples measured in 3 months although without statistical details[2].However,these reports[[1],[2],[3]]did not cover many vital parameters for lipoprotein components(e.g.,cholesterol-esters and total-lipids),fatty acids,and N-acetyl-glycoproteins(NAGs).展开更多
Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in So...Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in Soybean presents certain challenges.Therefore,we introduced the spectrum-effect relationship-ingredient knockout identification technique to identify a series of antioxidant active ingredients in soybean.By combining untargeted metabolomics with network pharmacology,we predicted the antioxidant active ingredients and their target sites.We successfully identified 4 antioxidant active compounds(daidzein,genistein,daidzein,and glycitin)and 10 corresponding antioxidant targets(epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),steroid receptor coactivator(SRC),tumor necrosis factor(TNF),kinase insert domain receptor(KDR),AKT serine/threonine kinase 1(AKT1),growth factor receptor bound protein 2(GRB2),signal transducer and activator of transcription1(STAT1),mitogen-activated protein kinase 8(MAPK8),B-cell lymphoma-2(BCL2))by our analysis.The validation results from cell experiments revealed that glycitin exhibited the best antioxidant activity and significantly influenced the expression of EGFR and the proteins associated with nuclear factor erythroid 2-related factor 2/NAD(P)H quinone dehydrogenase 1(NRF2/NQO1)signaling pathways.These findings were consistent with the predicted outcomes and were further confirmed in a zebrafish model.It suggests that glycitin may exert antioxidant effects by regulating the expression of EGFR,NRF2,and NQO1 proteins.The results demonstrate that a rapid analytical method for determining antioxidant activity was established.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
Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic p...Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.展开更多
Aging is one of the causes of cognitive dysfunction,which seriously affects people's quality of life.Unsaponifiable matter(USM)has antioxidant potential,but the molecular mechanisms that ameliorate aging and cogni...Aging is one of the causes of cognitive dysfunction,which seriously affects people's quality of life.Unsaponifiable matter(USM)has antioxidant potential,but the molecular mechanisms that ameliorate aging and cognitive dysfunction are unknown.In this study,we used a galactose-induced brain aging mouse model and systematically analyzed the mechanism of USM in delaying aging in mice by detecting changes in serum and brain by metabolomics and transcriptomics.USM was compared with the model group,and non-targeted metabolomics identified 68(15 up-regulated,53 down-regulated)differentially metabolites,and transcriptomics identified 303 differentially expressed genes(228 up-regulated,75 down-regulated).Combined multi-omics analyses showed that USM maintains normal brain function by regulating glycolytic processes,the tricarboxylic acid cycle(TCA),tryptophan metabolism,pyrimidine metabolism,the alanine,aspartate,and glutamate metabolism,and p38 mitogen-activated protein kinase(p38 MAPK)pathway.Meanwhile,USM increased neurotransmitter release from GABAergic synapses and cholinergic synapses by regulating synaptic vesicle cycling.In summary,USM increased energy metabolism and enhanced brain nerve signaling in the mouse brain,thereby delaying brain aging.This investigation offers novel perspectives into the molecular mechanism of USM to mitigate brain aging.展开更多
OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(...OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.展开更多
Metabolomics can be used to identify the changes and metabolic pathways of nutrients and flavor substances in foods at specific processing or fermentation stages.This study revealed the accumulation and degradation of...Metabolomics can be used to identify the changes and metabolic pathways of nutrients and flavor substances in foods at specific processing or fermentation stages.This study revealed the accumulation and degradation of phytochemicals during the fermentation of kiwifruit juice(KJ)by lactic acid bacteria(LAB)through widely targeted metabolomics and explored the impact of different fermentation strategies on the nutritional quality and functional characteristics of KJ.LAB utilized the original sugars,acids,amino acids,and nucleotides of the matrix to produce numerous bioactive compounds,including phenols,organic acids,free fatty acids,and vitamins,while achieving bacterial proliferation and reduced anti-nutritional factors such as alkaloids,thus improving the nutritional and functional properties of KJ.Moreover,compared with monoculture fermentation,mixed fermentation promoted the production of more biologically active phenols and alkaloids,among which vanillic acid and luteolin-8-C-arabinoside were the characteristic metabolites of mixed and mono-fermentation.Subsequently,the metabolic pathways of key metabolites were predicted,including the glycolytic Embden-Meyerhof-Parnas pathway,pentose phosphoketolase pathway,organic acid metabolic and arginine deiminase pathways for improving the acid resistance of LAB,and the phenolic-acid based phenylalanine and tyrosine metabolic pathway.展开更多
Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows pro...Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.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
基金financial support from the National Key R&D Program of China(No.2022YFC3401003)the National Natural Science Foundation of China(Nos.21927808,82073817,22104160)。
文摘Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and metastasis.In this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and metastasis.The results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor tissues.Furthermore,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.
基金supported by the National Key R&D Program of China(Grant No.:2022YFC3501805)the National Natural Science Foundation of China(Grant No.:82374030)+2 种基金the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030)the Tianjin Outstanding Youth Fund,China(Grant No.:23JCJQJC00030)the China Postdoctoral Science Foundation-Tianjin Joint Support Program(Grant No.:2023T030TJ).
文摘Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector machine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.
文摘Colon cancer is one of the malignant tumors with high morbidity and mortality worldwide[1],and its early diagnosis is crucial for improving patient survival.However,due to the lack of obvious early symptoms of colon cancer,many patients are in the middle to late stage when diagnosed and miss the best time for treatment.Therefore,developing an efficient and accurate diagnostic method for colon cancer is of great clinical significance and scientific value.Currently,the current colon cancer biomarkers carcinoembryonic antigen and carbohydrate antigen 19-9[2]have low sensitivity and specificity,the emerging markers circulating tumor DNA(ctDNA)and miRNA face high cost and standardization challenges,and the existing methods lack spatial resolution,prompting the incorporation of spatial metabolomics technologies to enhance diagnostic capabilities.
基金supported by the National Natural Science Foundation of China (No.82274223)。
文摘Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.
基金supported by Chinese National Key R&DProject for Synthetic Biology(2018YFA0902500)National Natural Science Foundation of China(32273118)+3 种基金The Guangdong Key R&D Project(2022B1111070005)Shenzhen Special Fund for Sustainable Development(KCXFZ20211020164013021)Shenzhen University 2035 Program for Excellent Research(2022B010)supported by a startup grant from the Food Futures Institute of Murdoch University,Australia.
文摘Global crop productivity faces a significant threat from climate change-induced drought stress(DS),which is vital for sustainable agriculture and global food security.Uncovering DS adaptation and tolerance mechanisms in crops is necessary to alleviate climate challenges.Innovative plant breeding demands revolutionary approaches to develop stress-smart plants.Metabolomics,a promising field in plant breeding,offers a predictive tool to identify metabolic markers associated with plant performance under DS,enabling accelerated crop improvement.Central to DS adaptation is metabolomics-driven metabolic regulation,which is critical for maintaining cell osmotic potential in crops.Recent innovations allow rapid mapping of specific metabolites to their genetic pathways,providing a valuable resource for plant scientists.Metabolomics-driven molecular breeding,integrating techniques such as mQTL and mGWAS,enhances our ability to discover key genetic elements linked to stress-responsive metabolites.This integration offers a beneficial platform for plant scientists,yielding significant insights into the complex metabolic networks underlying DS tolerance.Therefore,this review discusses(1)insights into metabolic regulation for DS adaptation,(2)the multifaceted role of metabolites in DS tolerance and nutritional/yield trait improvement,(3)the potential of single-cell metabolomics and imaging,(4)metabolomics-driven molecular breeding,and(5)the application of metabolic and genetic engineering for DS-tolerant crops.We finally propose that the metabolomics-driven approach positions drought-smart crops as key contributors to future food production,supporting the vital goal of achieving“zero hunger”.
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.
基金Science Foundation of Hunan Province(2021JJ40510)General Guidance Project of Hunan Health Commission(202203074169)+1 种基金Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK51901)and Key Guiding Projects of Hunan Health Commission(20201918)for supporting this study.
文摘Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.
基金supported by the key project at the central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(Grant number 2060302)the National Natural Science Foundation of China(Grant number 82373982,82173929).
文摘Background:Rosa chinensis Jacq.and Rosa rugosa Thunb.are not only of ornamental value,but also edible flowers and the flower buds have been listed in the Chinese Pharmacopoeia as traditional medicines.The two plants have some differences in efficacy,but the flower buds are easily confused for similar traits.In addition,large-scale cultivation of ornamental rose flowers may lead to a decrease in the effective components of medicinal roses.Therefore,it is necessary to study the chemical composition and make quality evaluation of Rosae Chinensis Flos(Yueji)and Rosae Rugosae Flos(Meigui).Methods:In this study,40 batches of samples including Meigui and Yueji from different regions in China were collected to establish high-performance liquid chromatography fingerprints.Then,the fingerprints data was analyzed using principal component analysis,hierarchical cluster analysis,and partial least squares discriminant analysis analysis chemometrics to obtain information on intergroup differences,and non-targeted metabolomic techniques were applied to identify and compare chemical compositions of samples which were chosen from groups with large differences.Differential compounds were screened by orthogonal partial least-squares discriminant analysis and S-plot,and finally multi-component quantification was performed to comprehensively evaluate the quality of Yueji and Meigui.Results:The similarity between the fingerprints of 40 batches roses and the reference print R was 0.73 to 0.93,indicating that there were similarities and differences between the samples.Through principal component analysis and hierarchical cluster analysis of fingerprints data,the samples from different origins and varieties were intuitively divided into four groups.Partial least-squares discriminant analysis analysis showed that Meigui and Yueji cluster into two categories and the model was reliable.A total of 89 compounds were identified by high resolution mass spectrometry,mainly were flavonoids and flavonoid glycosides,as well as phenolic acids.Eight differential components were screened out by orthogonal partial least-squares discriminant analysis and S-plot analysis.Quantitative analyses of the eight compounds,including gallic acid,ellagic acid,hyperoside,isoquercitrin,etc.,showed that Yueji was generally richer in phenolic acids and flavonoids than Meigui,and the quality of Yueji from Shandong and Hebei was better.It is worth noting that Xinjiang rose is rich in various components,which is worth focusing on more in-depth research.Conclusion:In this study,the fingerprints of Meigui and Yueji were established.The chemical components information of roses was further improved based on non-targeted metabolomics and mass spectrometry technology.At the same time,eight differential components of Meigui and Yueji were screened out and quantitatively analyzed.The research results provided a scientific basis for the quality control and rational development and utilization of Rosae Chinensis Flos and Rosae Rugosae Flos,and also laid a foundation for the study of their pharmacodynamic material basis.
文摘The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.
基金supported by the National Natural Science Foundation of China(No.82360897)Natural Science Foundation of Jiangxi Province of China(No.20212BAB216007)Administration of Traditional Chinese Medicine of Jiangxi Province of China(No.2022A328).
文摘Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.
基金supported by the Key R&D Program of Shandong Province(No.2021LZGC027)the Shandong Provincial Natural Science Foundation(No.ZR202102250235)+1 种基金the Major Agricultural Application Technology Innovation Projects in Shandong Province(No.SD2019YY 006)the‘First Class Fishery Discipline’Program in Shandong Province,China。
文摘Atlantic salmon(Salmo salar)represents the primary species in aquaculture.The gut microbiota plays a crucial role in nutrient processing and protection against pathogenic bacteria.Nonetheless,the composition and functionality of the gut microbiota in Salmo salar at different growth stages remain largely unexplored.This study investigated the alterations within the gut microbial communities and their associated metabolites across different growth stages of Salmo salar,specifically when the body weights were 1.0 kg(S1 group),2.0 kg(S2 group),4.0 kg(S3 group),and 6.0 kg(S4 group),using microbiome sequencing and liquid chromatographymass spectrometry(LC-MS)technology.Results indicated significant changes in the gut microbiota and metabolite profiles concurrent with fish growth.Notably,the abundance of Firmicutes decreased,and Proteobacteria increased,resulting in a decreased Firmicutes/Bacteroidetes(F/B)ratio.Concurrently,the abundance of potential pathogenic bacteria such as Stenotrophomonas,Vibrio,Aeromonas,Staphylococcaceae,Enterobacteriaceae,Enterococcaceae,and Haemophilus increased,whereas beneficial bacteria like Lactobacillus and Bacilli decreased.The gut microbiota in the S1 group exhibited an increase in the abundance of beneficial bacteria.Conversely,in the S2,S3,and S4 groups,the prevalence of pathogenic bacteria increased.Metabolic profiling revealed significant upregulation of arachidonic acid(ARA)and taurine in the S2 and S3 groups,while citric acid,riboflavin,and pantothenic acid notably increased in the S4 group.Particularly,several amino acids such as threonine,lysine,and serine in the gut microbiota metabolites were significantly reduced in the S2,S3,and S4 groups,correlating positively with the respective essential amino acid concentrations in muscle tissue.The S1 group exhibited a more active gut microbiota associated with amino acid metabolism,resulting in higher muscle amino acid content.This study identified gut microbiota and its metabolic products at different growth stages of Salmo salar,providing a scientific basis for proactive intervention of gut microbiota and improve the quality of aquatic products.
基金financial supports from the National Key R&D Program of China(Grant Nos.:2022YFC3400700 and 2022YFA0806400)the Shanghai Municipal Science and Technology Major Project,China(Grant No.:2017SHZDZX01)the National Natural Science Foundation of China(Grant No.:31821002).
文摘Nuclear magnetic resonance(NMR)spectroscopy is an excellent tool for simultaneous identification and quantification of metabolites(metabolomics).NMR quantification of human lipoprotein subfractions and their components has proven to be a powerful approach to reveal pathophysiological insights in numerous diseases[1,2].This method has now been standardized with excellent inter-laboratory reproducibility within 10 days for simultaneous quantification of 105 lipoprotein components and 24 low-molecular weight(LMW)metabolites[3];close clustering was also shown for 12 quality-control(QC)samples measured in 3 months although without statistical details[2].However,these reports[[1],[2],[3]]did not cover many vital parameters for lipoprotein components(e.g.,cholesterol-esters and total-lipids),fatty acids,and N-acetyl-glycoproteins(NAGs).
基金supported by National Key R&D Program of China(2022YFF1100300)Joint Fund of Henan Province Science and Technology R&D Program(235200810051)+1 种基金Key Project in Science and Technology Agency of Henan Province(242102310561)key research projects of higher education institutions in Henan Province(24B350002).
文摘Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in Soybean presents certain challenges.Therefore,we introduced the spectrum-effect relationship-ingredient knockout identification technique to identify a series of antioxidant active ingredients in soybean.By combining untargeted metabolomics with network pharmacology,we predicted the antioxidant active ingredients and their target sites.We successfully identified 4 antioxidant active compounds(daidzein,genistein,daidzein,and glycitin)and 10 corresponding antioxidant targets(epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),steroid receptor coactivator(SRC),tumor necrosis factor(TNF),kinase insert domain receptor(KDR),AKT serine/threonine kinase 1(AKT1),growth factor receptor bound protein 2(GRB2),signal transducer and activator of transcription1(STAT1),mitogen-activated protein kinase 8(MAPK8),B-cell lymphoma-2(BCL2))by our analysis.The validation results from cell experiments revealed that glycitin exhibited the best antioxidant activity and significantly influenced the expression of EGFR and the proteins associated with nuclear factor erythroid 2-related factor 2/NAD(P)H quinone dehydrogenase 1(NRF2/NQO1)signaling pathways.These findings were consistent with the predicted outcomes and were further confirmed in a zebrafish model.It suggests that glycitin may exert antioxidant effects by regulating the expression of EGFR,NRF2,and NQO1 proteins.The results demonstrate that a rapid analytical method for determining antioxidant activity was established.
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 Research and Development Program of China(No.2018YFE0207300)Beijing Natural Science Foundation(No.M23008)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-124)the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-057)。
文摘Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.
基金supported by the National Key Research and Development Program(2022YFD1600402).
文摘Aging is one of the causes of cognitive dysfunction,which seriously affects people's quality of life.Unsaponifiable matter(USM)has antioxidant potential,but the molecular mechanisms that ameliorate aging and cognitive dysfunction are unknown.In this study,we used a galactose-induced brain aging mouse model and systematically analyzed the mechanism of USM in delaying aging in mice by detecting changes in serum and brain by metabolomics and transcriptomics.USM was compared with the model group,and non-targeted metabolomics identified 68(15 up-regulated,53 down-regulated)differentially metabolites,and transcriptomics identified 303 differentially expressed genes(228 up-regulated,75 down-regulated).Combined multi-omics analyses showed that USM maintains normal brain function by regulating glycolytic processes,the tricarboxylic acid cycle(TCA),tryptophan metabolism,pyrimidine metabolism,the alanine,aspartate,and glutamate metabolism,and p38 mitogen-activated protein kinase(p38 MAPK)pathway.Meanwhile,USM increased neurotransmitter release from GABAergic synapses and cholinergic synapses by regulating synaptic vesicle cycling.In summary,USM increased energy metabolism and enhanced brain nerve signaling in the mouse brain,thereby delaying brain aging.This investigation offers novel perspectives into the molecular mechanism of USM to mitigate brain aging.
基金Supported by Traditional Chinese Medicine Science and Technology Development Plan of Jiangsu Province (No. MS2021013, ZD202215):Exploring the Efficacy and Mechanism of Professor Cao Shihong's Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomicsa Real-World Cohort Study on Traditional Chinese Medicine for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary DiseaseIntra-hospital Fund of Jiangsu Provincial Hospital of Traditional Chinese Medicine Development (No. Y2021ZR11):Investigating the Mechanism of Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomics
文摘OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.
基金funded by the National Nature Science Foundation Project(32372261)the Innovation Capacity Support Plan of Shaanxi Province(2024NC-BSLD-01,2024NC-ZDCYL-04-22,2024NC-LSTD-001,2024QCY-KXJ-083).
文摘Metabolomics can be used to identify the changes and metabolic pathways of nutrients and flavor substances in foods at specific processing or fermentation stages.This study revealed the accumulation and degradation of phytochemicals during the fermentation of kiwifruit juice(KJ)by lactic acid bacteria(LAB)through widely targeted metabolomics and explored the impact of different fermentation strategies on the nutritional quality and functional characteristics of KJ.LAB utilized the original sugars,acids,amino acids,and nucleotides of the matrix to produce numerous bioactive compounds,including phenols,organic acids,free fatty acids,and vitamins,while achieving bacterial proliferation and reduced anti-nutritional factors such as alkaloids,thus improving the nutritional and functional properties of KJ.Moreover,compared with monoculture fermentation,mixed fermentation promoted the production of more biologically active phenols and alkaloids,among which vanillic acid and luteolin-8-C-arabinoside were the characteristic metabolites of mixed and mono-fermentation.Subsequently,the metabolic pathways of key metabolites were predicted,including the glycolytic Embden-Meyerhof-Parnas pathway,pentose phosphoketolase pathway,organic acid metabolic and arginine deiminase pathways for improving the acid resistance of LAB,and the phenolic-acid based phenylalanine and tyrosine metabolic pathway.
基金supported by Pudong New Area Science and Technology Development Fund Special Research Project on the Livelihood of Institutions(No.PKJ2023-Y03)Pudong New Area Chinese Medicine Senior Teacher Training Program(No.PDZY-2023-0801)Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine(No.JY2024-08).
文摘Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.
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.
