In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results ...In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.展开更多
Inoculation of starter culture is a viable method to improve the quality of fermented foods,but its effect on the flavor metabolite profiles and the underlying mechanisms are still unclear.This study aimed to elucidat...Inoculation of starter culture is a viable method to improve the quality of fermented foods,but its effect on the flavor metabolite profiles and the underlying mechanisms are still unclear.This study aimed to elucidate the effects of starters(Lactiplantibacillus plantarum(LP)and Staphylococcus simulans(SS)individually or in combination(LS))on the flavor metabolite profiles of fermented sausages via metabolomics and genomics.L.plantarum markedly modified the composition of bacterial communities and made Lactobacillus spp.dominant in sausages(98.29%and 85.03%in LP and LS groups,respectively).Additionally,inoculation with a single starter,L.plantarum,and a mixed starter yielded similar non-volatile flavor metabolites,which were mainly characterized at the amino acid and peptide levels(relative intensities of 349.65 and 348.62 for the LP and LS groups,respectively).Meanwhile,the mixed starter group had the most volatile flavor metabolites(relative intensity of 34728.67),some of which were contributed by L.plantarum,such as ethyl acetate(relative intensities of 583.33 and 588.33 for the LP and LS groups,respectively)and benzaldehyde(relative intensities of 786.67 and 909.00 for the LP and LS groups,respectively),and several of which were generated by S.simulans,such as ethyl propionate(relative intensities of 214.67 and 136.67 for the SS and LS groups,respectively)and benzyl alcohol(relative intensities of 720.00 and 656.00 for the SS and LS groups,respectively).Furthermore,L.plantarum was found to possess more genes encoding peptidases(48)and carbohydrate-active enzymes(124),while S.simulans had more genes related to lipid hydrolysis(12).In conclusion,differences in the properties and combinations of indigenous strains play a crucial role in the generation of flavor metabolites in sausages.展开更多
Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on ...Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.展开更多
Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cel...Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy.However,systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited.In this study,we reviewed articles on ischemic stroke metabolites from 2005 to 2024,identified metabolites showing significant changes,and constructed a metabolite database based on the findings from 128 studies.The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model,246 detected in an middle cerebral artery occlusion rat model,and 764 identified in ischemic stroke patient samples.Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses.Based on this analysis,three positive metabolites and two negative metabolites were identified.Glutamic acid,glycerol,and 1-octadecanoyl-sn-glycero-3-phosphocholine(LysoPC(18:0))were further recognized as potential biomarkers.Imbalances in metabolic pathways such as alanine,aspartate,and glutamate metabolism as well as the citrate cycle(tricarboxylic acid cycle)were analyzed.These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity,oxidative stress,inflammation,and energy metabolism.The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction,diagnosis,and prognostic assessment of ischemic stroke.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary ob...Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.展开更多
1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrie...1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].展开更多
Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathwa...Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathways in mice, and providing a scientific basis for clinical treatment. Methods: An acute colitis model in mice was established by administering dextran sodium sulfate (DSS) in drinking water continuously for 7 days. After successful modeling, the mice were randomly divided into an ulcerative colitis model group, a mesalazine group, and low-, medium-, and high-dose Dahuang Mudan Decoction groups. The intervention was administered via continuous gavage for 7 days. Body weight changes and colon length were recorded, and the disease activity index (DAI) and fecal occult blood status were monitored. Colon length was measured, and colon tissue was subjected to HE staining and pathological scoring to assess inflammatory damage. Intestinal tissue samples were collected for metabolomic analysis to screen for differential metabolites and perform pathway enrichment analysis. Results: The experimental results indicated that, compared with the model group, intervention with Dahuang Mudan Decoction significantly improved the colitis phenotype induced by DSS, as evidenced by alleviated weight loss, reduced DAI scores, decreased colon shortening, and mitigated histopathological damage, along with improved inflammatory cell infiltration and crypt structure destruction. Metabolomic analysis revealed a clear separation in metabolic profiles between the model and normal groups. Conclusion: Dahuang Mudan Decoction induced a holistic shift in the metabolic phenotype of the model mice, partially reverting/remodeling it toward the normal state.展开更多
OBJECTIVE:To identify the antitumor effects of Gualou Beimu Yin(瓜蒌贝母饮,GLBMY)in triple-negative breast cancer(TNBC)and to explore the underlying mechanisms.METHODS:A mouse model of breast cancer was established an...OBJECTIVE:To identify the antitumor effects of Gualou Beimu Yin(瓜蒌贝母饮,GLBMY)in triple-negative breast cancer(TNBC)and to explore the underlying mechanisms.METHODS:A mouse model of breast cancer was established and treated with GLBMY.Freeze-dried GLBMY powder was used to treat MDA-MB-231 and BT549 cells to assess the therapeutic efficacy of GLBMY against TNBC.Network pharmacology,transcriptomics and metabolomics were employed to identify the potential mechanism of GLBMY in TNBC treatment.Finally,the main regulating genes and proteins in the enriched pathways were validated by Quantitative real-time polymerase chain reaction(q PCR)and Western blotting analysis to confirm its mechanism.RESULTS:GLBMY can inhibit the growth of TNBC through apoptosis and necroptosis pathways and inhibit TNBC lung metastasis by inhibiting epithelialmesenchymal transition(EMT).Network pharmacology has elucidated the most important active ingredients(tubeimoside I,emodin,cucurbitacin,and ursolic acid)and the most critical targets[interleukin-6(IL6),signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase 3(MAPK3)]of GLBMY in treating TNBC.RNA-seq revealed that GLBMY affected the nuclear factor kappa-light-chain-enhancer of activated B cells,rat sarcoma virus,and MAPK signalling pathways.Metabolomics revealed that the metabolites mainly affected by GLBMY were L-(+)-lactic acid,isocitric acid,benzoic acid and indoxyl sulfate.Subsequent experiments demonstrated that GLBMY can inhibit EMT in TNBC through the MAPK/ERK pathway and inhibit the proliferation and progression of TNBC through the IL6-STAT signalling pathway.CONCLUSIONS:We confirmed that GLBMY inhibits the development and metastasis of TNBC through the MAPK/Erk and IL6-STAT signalling pathways.GLBMY shows promise as a long-term supplementary or alternative therapy for TNBC,offering new insights for TNBC treatment.展开更多
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
Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underl...Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.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
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
Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of...Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain.This study analyzed widely targeted metabolomic data of expressed prostatic secretions(EPS)and plasma to reveal the underlying pathological mechanisms of CP/CPPS.A total of 24 CP/CPPS patients from The Second Nanning People’s Hospital(Nanning,China),and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University(Nanning,China)were enrolled.The indicators related to CP/CPPS and psychiatric symptoms were recorded.Differential analysis,coexpression network analysis,and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS.The crucial links between EPS and plasma were further investigated.The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals.Pathway analysis revealed dysregulation of amino acid metabolism,lipid metabolism,and the citrate cycle in EPS.The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes.Moreover,the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS.Overall,metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage,energy metabolism abnormalities,neurological impairment,and immune dysregulation.These alterations may be associated with chronic pain,voiding symptoms,reduced fertility,and depression in CP/CPPS.This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.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: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
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
文摘In this study,thyme essential oil(TEO)nanoemulsion(tPTNs)was constructed with transglutaminase(TGase)-modified potato protein,and its antibacterial activity and mechanism of action were evaluated and explored.Results indicated that tPTNs exhibited great antibacterial activity against both Staphylococcus aureus and Escherichia coli,with minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of 2.5 and 5.0 mg/mL,respectively.Also,the antibacterial effects of tPTNs were concentration-dependent.We observed a significant decrease in the absolute value of the zeta potential,and significant increases in particle size,cell membrane hydrophobicity,conductivity,the release of metal ions,and the leakage of nucleic acid as the concentration of tPTNs increased from 0 mg/mL to MBC.Furthermore,sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)demonstrated that protein synthesis was inhibited or even disrupted.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that treatment with tPTNs caused significant changes in bacterial metabolites,1117 and 692 differential metabolites being found for S.aureus and E.coli,respectively.The differential metabolites were involved in nucleotide metabolism,amino acid metabolism,tricarboxylic acid cycle and other metabolic pathways.These findings provide valuable insights for the application of thyme essential oil as an efficient antibacterial agent and for the understanding of its mechanism of action.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institution(PAPD).
文摘Inoculation of starter culture is a viable method to improve the quality of fermented foods,but its effect on the flavor metabolite profiles and the underlying mechanisms are still unclear.This study aimed to elucidate the effects of starters(Lactiplantibacillus plantarum(LP)and Staphylococcus simulans(SS)individually or in combination(LS))on the flavor metabolite profiles of fermented sausages via metabolomics and genomics.L.plantarum markedly modified the composition of bacterial communities and made Lactobacillus spp.dominant in sausages(98.29%and 85.03%in LP and LS groups,respectively).Additionally,inoculation with a single starter,L.plantarum,and a mixed starter yielded similar non-volatile flavor metabolites,which were mainly characterized at the amino acid and peptide levels(relative intensities of 349.65 and 348.62 for the LP and LS groups,respectively).Meanwhile,the mixed starter group had the most volatile flavor metabolites(relative intensity of 34728.67),some of which were contributed by L.plantarum,such as ethyl acetate(relative intensities of 583.33 and 588.33 for the LP and LS groups,respectively)and benzaldehyde(relative intensities of 786.67 and 909.00 for the LP and LS groups,respectively),and several of which were generated by S.simulans,such as ethyl propionate(relative intensities of 214.67 and 136.67 for the SS and LS groups,respectively)and benzyl alcohol(relative intensities of 720.00 and 656.00 for the SS and LS groups,respectively).Furthermore,L.plantarum was found to possess more genes encoding peptidases(48)and carbohydrate-active enzymes(124),while S.simulans had more genes related to lipid hydrolysis(12).In conclusion,differences in the properties and combinations of indigenous strains play a crucial role in the generation of flavor metabolites in sausages.
基金funded by the Project of National Key Research and Development Program of China(2022YFD2101001)the Project of National Natural Science Foundation of China(32172226)+4 种基金China Agriculture Research System(CARS-40-K25CARS-40-S11)the Special Fund for Anhui Agriculture Research System(AHCYJSTX-NCPJG)-15the Project of Key Laboratory for Animal Food Green Manufacturing and Resource Ming of Anhui Province(PA2023GDSK0125)the Cooperative Project of Hefei University of Technology-Anhui Rongda Food Co.,Ltd.(W2020JSKF0489).
文摘Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.
基金supported by the National Natural Science Foundation of China,No.82104144(to LZ)The Fifth Affiliated Hospital of Sun Yat-sen University of Outstanding Young Talents Cultivation Program,No.3320104100322(to WC)+1 种基金“Five Five”Young Talents Program,No.220904094231(to LZ)the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province,No.2023LSYS001(to WC).
文摘Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy.However,systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited.In this study,we reviewed articles on ischemic stroke metabolites from 2005 to 2024,identified metabolites showing significant changes,and constructed a metabolite database based on the findings from 128 studies.The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model,246 detected in an middle cerebral artery occlusion rat model,and 764 identified in ischemic stroke patient samples.Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses.Based on this analysis,three positive metabolites and two negative metabolites were identified.Glutamic acid,glycerol,and 1-octadecanoyl-sn-glycero-3-phosphocholine(LysoPC(18:0))were further recognized as potential biomarkers.Imbalances in metabolic pathways such as alanine,aspartate,and glutamate metabolism as well as the citrate cycle(tricarboxylic acid cycle)were analyzed.These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity,oxidative stress,inflammation,and energy metabolism.The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction,diagnosis,and prognostic assessment of ischemic stroke.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
文摘Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.
文摘1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].
文摘Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathways in mice, and providing a scientific basis for clinical treatment. Methods: An acute colitis model in mice was established by administering dextran sodium sulfate (DSS) in drinking water continuously for 7 days. After successful modeling, the mice were randomly divided into an ulcerative colitis model group, a mesalazine group, and low-, medium-, and high-dose Dahuang Mudan Decoction groups. The intervention was administered via continuous gavage for 7 days. Body weight changes and colon length were recorded, and the disease activity index (DAI) and fecal occult blood status were monitored. Colon length was measured, and colon tissue was subjected to HE staining and pathological scoring to assess inflammatory damage. Intestinal tissue samples were collected for metabolomic analysis to screen for differential metabolites and perform pathway enrichment analysis. Results: The experimental results indicated that, compared with the model group, intervention with Dahuang Mudan Decoction significantly improved the colitis phenotype induced by DSS, as evidenced by alleviated weight loss, reduced DAI scores, decreased colon shortening, and mitigated histopathological damage, along with improved inflammatory cell infiltration and crypt structure destruction. Metabolomic analysis revealed a clear separation in metabolic profiles between the model and normal groups. Conclusion: Dahuang Mudan Decoction induced a holistic shift in the metabolic phenotype of the model mice, partially reverting/remodeling it toward the normal state.
基金Supported by the National Natural Science Foundation of China:Study on Mechanism of Transdifferentiation of Hepatocellular Carcinoma Cells Induced by Huoxue Ruanjian Traditional Chinese Medicine (No. 82174103)。
文摘OBJECTIVE:To identify the antitumor effects of Gualou Beimu Yin(瓜蒌贝母饮,GLBMY)in triple-negative breast cancer(TNBC)and to explore the underlying mechanisms.METHODS:A mouse model of breast cancer was established and treated with GLBMY.Freeze-dried GLBMY powder was used to treat MDA-MB-231 and BT549 cells to assess the therapeutic efficacy of GLBMY against TNBC.Network pharmacology,transcriptomics and metabolomics were employed to identify the potential mechanism of GLBMY in TNBC treatment.Finally,the main regulating genes and proteins in the enriched pathways were validated by Quantitative real-time polymerase chain reaction(q PCR)and Western blotting analysis to confirm its mechanism.RESULTS:GLBMY can inhibit the growth of TNBC through apoptosis and necroptosis pathways and inhibit TNBC lung metastasis by inhibiting epithelialmesenchymal transition(EMT).Network pharmacology has elucidated the most important active ingredients(tubeimoside I,emodin,cucurbitacin,and ursolic acid)and the most critical targets[interleukin-6(IL6),signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase 3(MAPK3)]of GLBMY in treating TNBC.RNA-seq revealed that GLBMY affected the nuclear factor kappa-light-chain-enhancer of activated B cells,rat sarcoma virus,and MAPK signalling pathways.Metabolomics revealed that the metabolites mainly affected by GLBMY were L-(+)-lactic acid,isocitric acid,benzoic acid and indoxyl sulfate.Subsequent experiments demonstrated that GLBMY can inhibit EMT in TNBC through the MAPK/ERK pathway and inhibit the proliferation and progression of TNBC through the IL6-STAT signalling pathway.CONCLUSIONS:We confirmed that GLBMY inhibits the development and metastasis of TNBC through the MAPK/Erk and IL6-STAT signalling pathways.GLBMY shows promise as a long-term supplementary or alternative therapy for TNBC,offering new insights for TNBC treatment.
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supported by grants from the Core Program grants of Guizhou Province,China(Grant No.QKHZDZXZ[2024]28)the Guizhou Provincial Science and Technology Projects of China(Grant No.YQK[2023]008)the Guizhou Provincial Scientific and Technological Program(Grant No.QKHFQ[2024]004-1).
文摘Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.
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 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 the National Natural Science Foundation of China(No.81770759 and No.82270806)Innovation Project of Guangxi Graduate Education(No.YCBZ2022094).
文摘Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a complex disease that is often accompanied by mental health disorders.However,the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain.This study analyzed widely targeted metabolomic data of expressed prostatic secretions(EPS)and plasma to reveal the underlying pathological mechanisms of CP/CPPS.A total of 24 CP/CPPS patients from The Second Nanning People’s Hospital(Nanning,China),and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University(Nanning,China)were enrolled.The indicators related to CP/CPPS and psychiatric symptoms were recorded.Differential analysis,coexpression network analysis,and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS.The crucial links between EPS and plasma were further investigated.The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals.Pathway analysis revealed dysregulation of amino acid metabolism,lipid metabolism,and the citrate cycle in EPS.The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes.Moreover,the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS.Overall,metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage,energy metabolism abnormalities,neurological impairment,and immune dysregulation.These alterations may be associated with chronic pain,voiding symptoms,reduced fertility,and depression in CP/CPPS.This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
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.
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.
