The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic...The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.展开更多
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
Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains...Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains very high levels of Vc. However, the Vc content of R. roxburghii varies considerably during plant development and ripening. To better understand the molecular mechanisms that underlie fluctuations in Vc content of R. roxburghii fruit at different developmental stages, we performed transcriptomic and metabolomic analyses and identified two significant gene networks/modules and 168 transcription factors directly involved in Vc synthesis. Promoter analysis of two core genes involved in Vc synthesis, RrGGP and RrGalUR, revealed the presence of a retroviral long terminal repeat(LTR) insert in the RrGalUR promoter. Using yeast one-hybrid and dual-luciferase assays, we demonstrated that the transcription factors RrHY5H and RrZIP9 bind to the promoter of RrGGP to promote its expression. RrZIP6 and RrWRKY4 bind to the LTR in the RrGalUR promoter to promote its expression. Our results reveal a molecular mechanism that controls Vc synthesis and accumulation in R. roxburghii fruit.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
As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the i...As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.展开更多
Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats wer...Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.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
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
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: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
A supramolecular system of active pharmaceutical ingredients(APIs)can modify the physicochemical properties and enhance the synergistic efficacy of their components;however,the relevant underlying mechanisms in vivo r...A supramolecular system of active pharmaceutical ingredients(APIs)can modify the physicochemical properties and enhance the synergistic efficacy of their components;however,the relevant underlying mechanisms in vivo remain unclear.This study employed a metabolomics-driven approach,combined with biological validation,to investigate the synergistic mechanisms of API-based supramolecular systems.Metabolic dysfunction exacerbates insulin resistance and obesity,contributing to hepatic steatosis and cardiac hypertrophy.A novel sodium-dependent glucose transporter 2(SGLT-2)/peroxisome proliferator-activated receptor-γ(PPAR-γ)dual receptor(dapagliflozin-pioglitazone(DAP-PIO))supramolecular system was selected as the model to explore the synergistic mechanism involved in the treatment of metabolic dysfunctions,diabetes and obesity.First,metabolomics analyses were performed to compare the effects of a simple physical mixture(PM)of DAP and PIO with the DAP-PIO supramolecular system after absorption into the bloodstream.The results demonstrated significant differences,with the supramolecular system activating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and adenosine monophosphate-activated protein kinase(AMPK)signaling pathways.Ceramide(Cer),a key metabolite in sphingolipid metabolism,emerged as a critical mediator.Subsequently,the mechanisms underlying the DAP-PIO supramolecular system’s hypoglycemic effects and its ability to ameliorate hepatic steatosis and myocardial hypertrophy by reducing insulin resistance were evaluated and confirmed.These findings provide an innovative strategy for developing SGLT-2/PPAR-γdual-receptor supramolecular systems to enhance the therapeutic outcomes for diabetes and obesity.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
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
Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.Howev...Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.展开更多
This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rat...This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rats through ovariectomy(OVX),followed by oral administration of either high or low doses of AR,as well as estradiol valerate,over a 14-week period.Micro-computed tomography(Micro-CT)was employed to examine the femur tissue morphology,while enzyme-linked immunosorbent assay(ELISA)was adopted to measure serum levels of PINP and CTX-I to evaluate AR’s efficacy in treating OP.Additionally,metabolomic profiling of femur tissues was conducted using gas chromatography-mass spectrometry(GC-MS).The bioactive components of AR,along with its therapeutic targets for OP,were identified through UPLC-MS/MS and online database searches,and metabolic networks were established by integrating differential metabolites and potential targets.Furthermore,Western blotting analysis confirmed key molecular targets.The findings revealed that AR treatment significantly mitigated OVX-induced OP in rats.Metabolomic analysis indicated that AR exerted its effects by modulating the levels of 10 key metabolites(such as linoleic acid and inositol)and influencing five crucial metabolic pathways,including linoleic acid metabolism and the phosphoinositide signaling system.Among these,the linoleic acid metabolic pathway emerged as a pivotal focus for further investigation based on the constructed interaction network of differential metabolites and targets.Western blotting analysis demonstrated that AR reversed the up-regulation of CYP1A2 and CYP2C9,two targets associated with the linoleic acid metabolic pathwa y,in OP rats.In conclusion,AR appeared to ameliorate OP by modulating metabolite levels in OVX rats,with its mechanism of action likely centered on regulating the linoleic acid metabolic pathway.展开更多
Background:Northern residents predominantly rely on coal-fired heating during winter,leading to severe air pollution.Polycyclic aromatic hydrocarbons(PAHs)adsorbed on atmospheric particulate matter pose significant he...Background:Northern residents predominantly rely on coal-fired heating during winter,leading to severe air pollution.Polycyclic aromatic hydrocarbons(PAHs)adsorbed on atmospheric particulate matter pose significant health risks.Among PAHs,dibenz[a,h]anthracene(DahA),though present at lower environmental concentrations compared to other PAHs,exhibits a carcinogenic potency that is 10 or more times greater than benzo[a]pyrene(BaP),underscoring its potential harm.Despite reports on DahA's multiple toxic effects,its impact on metabolic networks remains poorly understood.Methods:Based on the respiratory volume of adult rats and the concentration of PM2.5-bound DahA in heavily polluted cities of northern China,adult Sprague-Dawley rats were treated with DahA(0.07μg/kg and 0.2μg/kg)twice weekly for four weeks via intratracheal instillation.Metabolomic profiling of serum was performed using rapid resolution liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(RRLC/Q-TOF-MS)to elucidate metabolic disruptions caused by DahA exposure.Results:DahA exposure induced significant oxidative stress and inflammatory responses in rats,accompanied by notable alterations in the serum metabolome.A total of 11 metabolites were found to be decreased,and 2 metabolites were increased,with disruptions observed in folate biosynthesis,glycerophospholipid metabolism,and nitrogen metabolism pathways.Additionally,metabolic dysregulation may interfere with the tricarboxylic acid cycle and compromise nucleotide homeostasis.Conclusion:These findings enhance our understanding of the toxicological effects of DahA exposure and its role in lung damage.The results suggest that metabolic disturbances caused by DahA may contribute to the exacerbation of respiratory diseases associated with particulate matter-bound PAH pollution during the heating season in cold regions.展开更多
BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabo...BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.展开更多
基金financial support from the National Natural Science Foundation of China (Nos.82473887 and 21927808)the Scientific and Technological Innovation Program of Shanghai (No.23DZ2202500)the CAMS Innovation Fund for Medical Sciences (No.2021-1-I2M-026)。
文摘The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.
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.
基金supported in part by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the State Key Laboratory of Crop Genetics and Germplasm Enhancement (Grant No. ZW201813)supported by the high-performance computing platform at the Bioinformatics Center of Nanjing Agricultural University。
文摘Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains very high levels of Vc. However, the Vc content of R. roxburghii varies considerably during plant development and ripening. To better understand the molecular mechanisms that underlie fluctuations in Vc content of R. roxburghii fruit at different developmental stages, we performed transcriptomic and metabolomic analyses and identified two significant gene networks/modules and 168 transcription factors directly involved in Vc synthesis. Promoter analysis of two core genes involved in Vc synthesis, RrGGP and RrGalUR, revealed the presence of a retroviral long terminal repeat(LTR) insert in the RrGalUR promoter. Using yeast one-hybrid and dual-luciferase assays, we demonstrated that the transcription factors RrHY5H and RrZIP9 bind to the promoter of RrGGP to promote its expression. RrZIP6 and RrWRKY4 bind to the LTR in the RrGalUR promoter to promote its expression. Our results reveal a molecular mechanism that controls Vc synthesis and accumulation in R. roxburghii fruit.
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financially supported by the National Key Research and Development Program of China(2023YFD2000701)the Natural Science Foundation of Heilongjiang Province,China(YQ2023C011)+1 种基金the Key Research and Development Program of Heilongjiang Province,China(Grant no.2022ZX01A24)the Key Laboratory of Low-carbon Green Agriculture in Northeastern China,Ministry of Agriculture and Rural Affairs of China(LCGANE14)。
文摘As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.
基金sponsored by Shandong Provincial Key Research and Development Program(Major Technological Innovation Project)([2021]CXGC010508)Guizhou Province Youth Science and Technology Talent Plan(YQK[2023]038)+1 种基金Science and Technology Department of Zunyi City of Guizhou province of China([2020]7)Key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302).
文摘Background:The study aimed to investigate the protective effect and mechanism of total flavonoids of Scutellaria baicalensis(TFSB)on acute myocardial ischemia(AMI)rats by using functional metabonomics.Methods:Rats were divided into the Control,Model,AMI positive control(Propranolol hydrochloride,30 mg/kg),low dose TFSB(50 mg/kg),and high dose TFSB(100 mg/kg)groups.Rats received the corresponding treatment by intragastric administration once daily for 10 consecutive days.Electrocardiogram,myocardial enzyme,triphenyltetrazolium chloride staining,hematoxylin-eosin,and enzyme-linked immunosorbent assay were performed to evaluate the protective effect of TFSB on AMI rats.Then,the UHPLC-Q-Orbitrap MS method based on serum metabolomics was utilised to search for metabolic biomarkers and metabolic pathways.Subsequently,Western blot and RT-PCR techniques were employed to identify the respective genes and proteins.Results:Pharmacodynamics revealed that TFSB could ameliorate AMI in rats.The results of the metabolomics analysis indicated that the alterations in metabolic profile observed in rats with AMI were partially improved by treatment with TFSB.Moreover,the mRNA expression levels of 5-lipoxygenase(5-LOX)and 15-lipoxygenase(15-LOX)and the protein expression levels of 5-LOX,15-LOX,interleukin-1β(IL-1β),and NF-κB p65 were reduced following treatment with TFSB.Conclusion:The potential treatment of TFSB in AMI may be ascribed to its ability to regulate arachidonic acid metabolism.
基金supported by the National Natural Science Foundation of China(82274424).
文摘Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.
文摘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 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(Grant No.:22301060)the Central Guidance on Local Science and Technology Development Fund of Hebei Province(Grant No.:246Z2601G)+1 种基金Post-graduate’s Innovation Fund Project of Hebei Province(Grant No.:CXZZBS2024118)the Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(Project No.:2022391).
文摘A supramolecular system of active pharmaceutical ingredients(APIs)can modify the physicochemical properties and enhance the synergistic efficacy of their components;however,the relevant underlying mechanisms in vivo remain unclear.This study employed a metabolomics-driven approach,combined with biological validation,to investigate the synergistic mechanisms of API-based supramolecular systems.Metabolic dysfunction exacerbates insulin resistance and obesity,contributing to hepatic steatosis and cardiac hypertrophy.A novel sodium-dependent glucose transporter 2(SGLT-2)/peroxisome proliferator-activated receptor-γ(PPAR-γ)dual receptor(dapagliflozin-pioglitazone(DAP-PIO))supramolecular system was selected as the model to explore the synergistic mechanism involved in the treatment of metabolic dysfunctions,diabetes and obesity.First,metabolomics analyses were performed to compare the effects of a simple physical mixture(PM)of DAP and PIO with the DAP-PIO supramolecular system after absorption into the bloodstream.The results demonstrated significant differences,with the supramolecular system activating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and adenosine monophosphate-activated protein kinase(AMPK)signaling pathways.Ceramide(Cer),a key metabolite in sphingolipid metabolism,emerged as a critical mediator.Subsequently,the mechanisms underlying the DAP-PIO supramolecular system’s hypoglycemic effects and its ability to ameliorate hepatic steatosis and myocardial hypertrophy by reducing insulin resistance were evaluated and confirmed.These findings provide an innovative strategy for developing SGLT-2/PPAR-γdual-receptor supramolecular systems to enhance the therapeutic outcomes for diabetes and obesity.
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 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 China Agriculture Research System(CARS-02-20)the Henan Province Agro-ecosystem Field Observation and Research Station,China(30602535)。
文摘Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.
基金Foundation items:Wuhan Health Research Fund(Grant No.WZ21A06)National Natural Science Foundation of China(Grant No.81903815)。
文摘This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rats through ovariectomy(OVX),followed by oral administration of either high or low doses of AR,as well as estradiol valerate,over a 14-week period.Micro-computed tomography(Micro-CT)was employed to examine the femur tissue morphology,while enzyme-linked immunosorbent assay(ELISA)was adopted to measure serum levels of PINP and CTX-I to evaluate AR’s efficacy in treating OP.Additionally,metabolomic profiling of femur tissues was conducted using gas chromatography-mass spectrometry(GC-MS).The bioactive components of AR,along with its therapeutic targets for OP,were identified through UPLC-MS/MS and online database searches,and metabolic networks were established by integrating differential metabolites and potential targets.Furthermore,Western blotting analysis confirmed key molecular targets.The findings revealed that AR treatment significantly mitigated OVX-induced OP in rats.Metabolomic analysis indicated that AR exerted its effects by modulating the levels of 10 key metabolites(such as linoleic acid and inositol)and influencing five crucial metabolic pathways,including linoleic acid metabolism and the phosphoinositide signaling system.Among these,the linoleic acid metabolic pathway emerged as a pivotal focus for further investigation based on the constructed interaction network of differential metabolites and targets.Western blotting analysis demonstrated that AR reversed the up-regulation of CYP1A2 and CYP2C9,two targets associated with the linoleic acid metabolic pathwa y,in OP rats.In conclusion,AR appeared to ameliorate OP by modulating metabolite levels in OVX rats,with its mechanism of action likely centered on regulating the linoleic acid metabolic pathway.
基金supported partly by the Research Foundation of Health and family planning commission in Heilongjiang(2016-272)the Natural Science Foundation of Heilongjiang Province(LH2021H010).
文摘Background:Northern residents predominantly rely on coal-fired heating during winter,leading to severe air pollution.Polycyclic aromatic hydrocarbons(PAHs)adsorbed on atmospheric particulate matter pose significant health risks.Among PAHs,dibenz[a,h]anthracene(DahA),though present at lower environmental concentrations compared to other PAHs,exhibits a carcinogenic potency that is 10 or more times greater than benzo[a]pyrene(BaP),underscoring its potential harm.Despite reports on DahA's multiple toxic effects,its impact on metabolic networks remains poorly understood.Methods:Based on the respiratory volume of adult rats and the concentration of PM2.5-bound DahA in heavily polluted cities of northern China,adult Sprague-Dawley rats were treated with DahA(0.07μg/kg and 0.2μg/kg)twice weekly for four weeks via intratracheal instillation.Metabolomic profiling of serum was performed using rapid resolution liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(RRLC/Q-TOF-MS)to elucidate metabolic disruptions caused by DahA exposure.Results:DahA exposure induced significant oxidative stress and inflammatory responses in rats,accompanied by notable alterations in the serum metabolome.A total of 11 metabolites were found to be decreased,and 2 metabolites were increased,with disruptions observed in folate biosynthesis,glycerophospholipid metabolism,and nitrogen metabolism pathways.Additionally,metabolic dysregulation may interfere with the tricarboxylic acid cycle and compromise nucleotide homeostasis.Conclusion:These findings enhance our understanding of the toxicological effects of DahA exposure and its role in lung damage.The results suggest that metabolic disturbances caused by DahA may contribute to the exacerbation of respiratory diseases associated with particulate matter-bound PAH pollution during the heating season in cold regions.
基金supported by the National Key Research and Development Program of China(2021YFC2501800,2023YFC0872500 and 2024YFC3044600)the National Natural Science Foundation of China(82072214,82272198,82202373)+1 种基金the Science and Technology of Shanghai Committee(21MC1930400,22Y11900100 and 23Y31900100)the Shanghai Municipal Health Commission(2023ZDFC0101)。
文摘BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.
