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
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
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
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
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
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
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
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
A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing po...A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.展开更多
Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed dur...Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed during the thermal processing of seafood.The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming.In addition,it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms,thereby,they could influence the bioavailability of metal ion.While there have been numerous studies on the toxic effects of cadmium or CDs,none have explored the combined toxicity of food-borne CDs from clams(CCDs)and Cd^(2+).In this study,we investigated the single or co-exposure(combined exposure)of Cd^(2+)and CCDs on PC12 cells to investigate the combined toxicity of them.Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd^(2+).More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd^(2+)and CCDs led to significant metabolic disorders,causing an antagonistic effect on energy metabolism,and a synergistic effect on amino acids and lipids metabolism.The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure.These findings provide new evidence that support the enhanced cytotoxicity of Cd^(2+)by the CCDs derived from the thermal processing of clams.This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.展开更多
The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metab...The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metabolomics,and soil properties.Thus,in this study,the long-term impact of coke combustion on soil microbial community structure,enzyme activities,and metabolic pathways within a former coking plant site was investigated.Soil samples were collected from both the coking production area(CA group)and office area(OLA group),approximately 0 to 20 cm in depth.Compared with OLA group,elevated levels of 16 PAHs in the list of US EPA were detected by gas chromatography-mass spectrometry in the CA group.Several dominant microorganisms,such as Altererythrobacter,Lysobacter,and Sulfurifustis,were identified by 16 s ribosomal DNA sequencing in the CA group.The fatty acid biosynthesis pathway exhibited specific inhibition,while the phenylalanine metabolic pathwaywas promoted in response to PAH stress.Long-term PAH exposure led to the inhibition of soil urease activity.The co-occurrence network ofmicroorganisms revealed intricate patterns of co-metabolism and co-adaptation within complex bacterial communities,facilitating their adaptation to and decomposition of soil-borne PAHs.This research could provide valuable insights into the community characteristics andmetabolic mechanisms of microorganisms inhabiting PAH-polluted soil within coking plant sites.The findings enhance our understanding of the indigenous soil microbiome and its intricate network dynamics under the persistent stress of PAHs,contributing to a more comprehensive knowledge of soil ecosystems in such environments.展开更多
Objective:In traditional medicine,Asari Radix et Rhizoma(Xi Xin)is used to effectively treat respiratory diseases.However,the therapeutic portion of Xi Xin contains trace quantities of aristolochic acid I(AAI),which r...Objective:In traditional medicine,Asari Radix et Rhizoma(Xi Xin)is used to effectively treat respiratory diseases.However,the therapeutic portion of Xi Xin contains trace quantities of aristolochic acid I(AAI),which raises safety concerns.Furthermore,no compelling laboratory evidence confirms its safety.AAI-induced extensive renal tubular necrosis and inflammatory cell infiltration occurred primarily in the cortex and outer medulla.Accordingly,we examined the changes in metabolites within the aforementioned areas and thoroughly investigated the interactions between these differential metabolites and immune cells.Methods:We mapped the spatial distribution of the differential metabolites L-glutamic acid and glutamine in mouse kidneys and explored the underlying mechanisms using transcriptomics and flow cytometry,further validating these findings through co-culture experiments in vitro.Results:Administering 1 mg/kg AAI daily for 7 days(approximately 200 times the pharmacopeial Xi Xin dose)did not induce detectable levels of carcinogenic 7-(deoxyadenosin-N6-yl)-aristolactam I(dA-ALI)in mouse kidneys.However,dA-ALI was detected on the day after the administration of 10 mg/kg AAI.Mice with lipopolysaccharide-induced pneumonia exhibit increased tolerance to AAI-mediated nephrotoxicity.Based on integrated spatial metabolomics and renal transcriptomic analyses,increased tolerance to AAI-mediated nephrotoxicity may be related to glutamine-mediated oxidative stress regulation mechanisms.During pneumonia,mouse kidneys exhibit both immune and metabolic stress responses.Ly6C^(+)macrophages convert L-glutamic acid into glutamine,thereby reducing reactive oxygen species(ROS)levels in the extracellular matrix.This process,which is regulated by the ITGA5 receptor in renal tubular epithelial cells,modulates the pAkt/pNrf2/NQO1 pathway and reduces AAI-induced kidney damage.Conclusions:Collectively,our findings indicate that Xi Xin is safe at conventional clinical dosages,and its targeted use can further minimize potential risks.展开更多
Bacillus subtilis JZXJ-7 isolated from shrimp paste can significantly degrade histamine under salt stress but the mechanism is unclear.This study aims to evaluate the effect of 170 and 340 mmol/L Na Cl on B.subtilis J...Bacillus subtilis JZXJ-7 isolated from shrimp paste can significantly degrade histamine under salt stress but the mechanism is unclear.This study aims to evaluate the effect of 170 and 340 mmol/L Na Cl on B.subtilis JZXJ-7 growth,histamine degradation,antioxidant enzymes(catalase(CAT),superoxide dismutase(SOD)and glutathione S-transferase(GST))activities and Na^(+)/K^(+)-ATPase activity.Furthermore,comparative metabolomics was used to investigate histamine biodegradation mechanism by B.subtilis JZXJ-7 subjected to salt stress.Both 170 and 340 mmol/L Na Cl promoted B.subtilis JZXJ-7 growth in late stages of reproduction(32-48 h),increased h istamine degradation rate by 64.85%and 79.87%(P<0.05),Na^(+)/K^(+)-ATPase activity to 6.28(P<0.05)and 11.63 U/mg(P<0.01)respectively.N a Cl treatment significantly increased the activities of CAT,GST and SOD(P<0.05),a mino acids and its metabolites(33.39%),benzene and substituted derivatives(12.05%),heterocyclic compounds(10.62%),organic acids and derivatives(9.75%),aldehydes,ketones,esters(5.59%)and nucleotides and its metabolites(4.58%).Metabolite set enrichment analysis revealed Na Cl induced differential metabolic pathways of D-glutamine,D-glutamate,L-arginine,L-proline,histidine and glycerophospholipids,L-lysine degradation,and aminoacyl-t RNA biosynthesis.Exposure to 340 mmol/L Na Cl up-regulated carbohydrate,glutathione and glycerophospholipid metabolism.The new insights into the mechanism of salt stress to promote B.subtilis JZJX-7 growth,energy metabolic pathways and to degrade histamine provide the theoretical basis for application of B.subtilis JZXJ-7 in food fermentation industry.展开更多
BACKGROUND Fruits of Gardenia jasminoides(G.jasminoides)have extremely high medicinal value.However,the quality and traits of the plants vary significantly based on their provenances.In addition,the behaviour of the k...BACKGROUND Fruits of Gardenia jasminoides(G.jasminoides)have extremely high medicinal value.However,the quality and traits of the plants vary significantly based on their provenances.In addition,the behaviour of the known bioactive components,such as geniposide and crocin,has been the primary focus of the research on G.jasminoides.However,the identification of unknown bioactive components and their metabolomics remains underexplored.Therefore,analysing the metabolic differences between gardenias from different sources is essential to provide a comprehensive theoretical basis for the evaluation of G.jasminoides and germplasm resource identification.AIM To systematically evaluate the morphology,secondary metabolites,typical active ingredients,and antioxidant activity of wild G.jasminoides fruits.METHODS Gardenia fruits were collected from different provenances.Metabolites were identified via ultra-high-performance liquid chromatography–tandem mass spectrometry(UPLC-MS/MS).The metabolic differences were compared using hierarchical cluster analysis(HCA).The antioxidant capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays and ferric reducing antioxidant power assays,and its correlation with typical active ingredients was analysed.RESULTS A total of 444 and 240 metabolites were identified using UPLC-MS/MS in positive and negative ion modes,respectively.The HCA results of the flavonoids indicated that the higher content of flavonoids was in the fruits from Lukou.The differential analysis of metabolites in fruits from Shaoyang,Miluo and Lukou showed that the fruit from Miluo had the highest upregulated differential metabolites.CONCLUSION The metabolic characteristics of the Ningxiang and Xiangxi extracts were similar,while those of Lukou,Miluo and Shaoyang extracts differed significantly.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 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 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.
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.
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 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.
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 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 the National Natural Science Foundation of China(No.82374158)National Science and Technology Major Project(No.2018ZX09711001-002-004)+1 种基金the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(No.CXTD22007)the Medical and Health Technology Innovation Project(No.2022-I2M-1-020).
文摘A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.
基金supported by the National Key Research and Development Project of China(2017YFC1600702)the Central Funds Guiding the Local Science and Technology Development of China(2020JH6/10500002).
文摘Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed during the thermal processing of seafood.The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming.In addition,it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms,thereby,they could influence the bioavailability of metal ion.While there have been numerous studies on the toxic effects of cadmium or CDs,none have explored the combined toxicity of food-borne CDs from clams(CCDs)and Cd^(2+).In this study,we investigated the single or co-exposure(combined exposure)of Cd^(2+)and CCDs on PC12 cells to investigate the combined toxicity of them.Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd^(2+).More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd^(2+)and CCDs led to significant metabolic disorders,causing an antagonistic effect on energy metabolism,and a synergistic effect on amino acids and lipids metabolism.The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure.These findings provide new evidence that support the enhanced cytotoxicity of Cd^(2+)by the CCDs derived from the thermal processing of clams.This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.
基金supported by the National Key Research and Development Program of China(Nos.2018YFA0901100 and 2018YFC1801103)the National Natural Science Foundation of China(Nos.22206202 and 22076216)。
文摘The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metabolomics,and soil properties.Thus,in this study,the long-term impact of coke combustion on soil microbial community structure,enzyme activities,and metabolic pathways within a former coking plant site was investigated.Soil samples were collected from both the coking production area(CA group)and office area(OLA group),approximately 0 to 20 cm in depth.Compared with OLA group,elevated levels of 16 PAHs in the list of US EPA were detected by gas chromatography-mass spectrometry in the CA group.Several dominant microorganisms,such as Altererythrobacter,Lysobacter,and Sulfurifustis,were identified by 16 s ribosomal DNA sequencing in the CA group.The fatty acid biosynthesis pathway exhibited specific inhibition,while the phenylalanine metabolic pathwaywas promoted in response to PAH stress.Long-term PAH exposure led to the inhibition of soil urease activity.The co-occurrence network ofmicroorganisms revealed intricate patterns of co-metabolism and co-adaptation within complex bacterial communities,facilitating their adaptation to and decomposition of soil-borne PAHs.This research could provide valuable insights into the community characteristics andmetabolic mechanisms of microorganisms inhabiting PAH-polluted soil within coking plant sites.The findings enhance our understanding of the indigenous soil microbiome and its intricate network dynamics under the persistent stress of PAHs,contributing to a more comprehensive knowledge of soil ecosystems in such environments.
基金supported by the Consulting Project Funds of the Chinese Academy of Engineering(2023-XZ-88,China)Key Program of the National Natural Science Foundation of China(81721002 and 82230118,China)Key Program of the National Natural Science Foundation of China Regional Union Fund(U23A20519,China).
文摘Objective:In traditional medicine,Asari Radix et Rhizoma(Xi Xin)is used to effectively treat respiratory diseases.However,the therapeutic portion of Xi Xin contains trace quantities of aristolochic acid I(AAI),which raises safety concerns.Furthermore,no compelling laboratory evidence confirms its safety.AAI-induced extensive renal tubular necrosis and inflammatory cell infiltration occurred primarily in the cortex and outer medulla.Accordingly,we examined the changes in metabolites within the aforementioned areas and thoroughly investigated the interactions between these differential metabolites and immune cells.Methods:We mapped the spatial distribution of the differential metabolites L-glutamic acid and glutamine in mouse kidneys and explored the underlying mechanisms using transcriptomics and flow cytometry,further validating these findings through co-culture experiments in vitro.Results:Administering 1 mg/kg AAI daily for 7 days(approximately 200 times the pharmacopeial Xi Xin dose)did not induce detectable levels of carcinogenic 7-(deoxyadenosin-N6-yl)-aristolactam I(dA-ALI)in mouse kidneys.However,dA-ALI was detected on the day after the administration of 10 mg/kg AAI.Mice with lipopolysaccharide-induced pneumonia exhibit increased tolerance to AAI-mediated nephrotoxicity.Based on integrated spatial metabolomics and renal transcriptomic analyses,increased tolerance to AAI-mediated nephrotoxicity may be related to glutamine-mediated oxidative stress regulation mechanisms.During pneumonia,mouse kidneys exhibit both immune and metabolic stress responses.Ly6C^(+)macrophages convert L-glutamic acid into glutamine,thereby reducing reactive oxygen species(ROS)levels in the extracellular matrix.This process,which is regulated by the ITGA5 receptor in renal tubular epithelial cells,modulates the pAkt/pNrf2/NQO1 pathway and reduces AAI-induced kidney damage.Conclusions:Collectively,our findings indicate that Xi Xin is safe at conventional clinical dosages,and its targeted use can further minimize potential risks.
基金supported by the National Key R&D Program of China(2019YFD0901702)National Natural Science Foundation of China(32201929,32202134)+3 种基金2025 Guangdong Basic and Applied Basic Research Foundation of Natural Science Foundation Project(2025A1515011748)High-level Talent Project of Lingnan Normal University(ZL2415)China Postdoctoral Science Foundation(2022M712625)2021 and 2022 Chongqing Postdoctoral Special Funding Project。
文摘Bacillus subtilis JZXJ-7 isolated from shrimp paste can significantly degrade histamine under salt stress but the mechanism is unclear.This study aims to evaluate the effect of 170 and 340 mmol/L Na Cl on B.subtilis JZXJ-7 growth,histamine degradation,antioxidant enzymes(catalase(CAT),superoxide dismutase(SOD)and glutathione S-transferase(GST))activities and Na^(+)/K^(+)-ATPase activity.Furthermore,comparative metabolomics was used to investigate histamine biodegradation mechanism by B.subtilis JZXJ-7 subjected to salt stress.Both 170 and 340 mmol/L Na Cl promoted B.subtilis JZXJ-7 growth in late stages of reproduction(32-48 h),increased h istamine degradation rate by 64.85%and 79.87%(P<0.05),Na^(+)/K^(+)-ATPase activity to 6.28(P<0.05)and 11.63 U/mg(P<0.01)respectively.N a Cl treatment significantly increased the activities of CAT,GST and SOD(P<0.05),a mino acids and its metabolites(33.39%),benzene and substituted derivatives(12.05%),heterocyclic compounds(10.62%),organic acids and derivatives(9.75%),aldehydes,ketones,esters(5.59%)and nucleotides and its metabolites(4.58%).Metabolite set enrichment analysis revealed Na Cl induced differential metabolic pathways of D-glutamine,D-glutamate,L-arginine,L-proline,histidine and glycerophospholipids,L-lysine degradation,and aminoacyl-t RNA biosynthesis.Exposure to 340 mmol/L Na Cl up-regulated carbohydrate,glutathione and glycerophospholipid metabolism.The new insights into the mechanism of salt stress to promote B.subtilis JZJX-7 growth,energy metabolic pathways and to degrade histamine provide the theoretical basis for application of B.subtilis JZXJ-7 in food fermentation industry.
基金Supported by The Forestry Science and Technology Innovation Funded Project of Hunan Forestry Bureau,No.XLKY202221。
文摘BACKGROUND Fruits of Gardenia jasminoides(G.jasminoides)have extremely high medicinal value.However,the quality and traits of the plants vary significantly based on their provenances.In addition,the behaviour of the known bioactive components,such as geniposide and crocin,has been the primary focus of the research on G.jasminoides.However,the identification of unknown bioactive components and their metabolomics remains underexplored.Therefore,analysing the metabolic differences between gardenias from different sources is essential to provide a comprehensive theoretical basis for the evaluation of G.jasminoides and germplasm resource identification.AIM To systematically evaluate the morphology,secondary metabolites,typical active ingredients,and antioxidant activity of wild G.jasminoides fruits.METHODS Gardenia fruits were collected from different provenances.Metabolites were identified via ultra-high-performance liquid chromatography–tandem mass spectrometry(UPLC-MS/MS).The metabolic differences were compared using hierarchical cluster analysis(HCA).The antioxidant capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays and ferric reducing antioxidant power assays,and its correlation with typical active ingredients was analysed.RESULTS A total of 444 and 240 metabolites were identified using UPLC-MS/MS in positive and negative ion modes,respectively.The HCA results of the flavonoids indicated that the higher content of flavonoids was in the fruits from Lukou.The differential analysis of metabolites in fruits from Shaoyang,Miluo and Lukou showed that the fruit from Miluo had the highest upregulated differential metabolites.CONCLUSION The metabolic characteristics of the Ningxiang and Xiangxi extracts were similar,while those of Lukou,Miluo and Shaoyang extracts differed significantly.
