Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of H...Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.展开更多
BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model w...BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.展开更多
Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics lev...Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.展开更多
A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids(EFAs and NEFAs) in plasma.Merely 10μL of plasma was required.The pretreatment...A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids(EFAs and NEFAs) in plasma.Merely 10μL of plasma was required.The pretreatment of the sample was simple without disposing the protein.After simple extraction and derivation,15 FAs in plasma were precisely quantified.Gas chromatography tandem mass spectrometry(GC-MS) was used in the study and the quantities of the analytes,which varied in abundance over three orders of magnitude.The established method showed good accuracy.The curve correlation coefficients were all above 0.997.The RSDs of precision for all compounds were below 15%and recoveries were all between 80 and 110%.PLS-DA modal was used in the data management.展开更多
Metabonomics, a novel systemic approach, was applied to studies of Traditional Chinese Medicine scutellarin in rat urine. The liquid chromatography coupled with ion trap mass spectrometry combined with PCA was used in...Metabonomics, a novel systemic approach, was applied to studies of Traditional Chinese Medicine scutellarin in rat urine. The liquid chromatography coupled with ion trap mass spectrometry combined with PCA was used in this paper. With this methodology, two potential metabolites of scutellarin were detected and the nine ions responsible for the gender variation and one ion for the dosage variation were found.展开更多
OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation...OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma.METHODS According to clinical pathogeny,three kinds of syndrome models were established to simulate the disease of chest impediment.Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes,respectively.RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups.Furthermore,three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified.In the QSBS group,the potential biomarkers could include 2-keto-glutaramic acid,L-methionine,L-homocysteic acid,octadecanamide,stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9 Z)),indoxyl sulfate and cholic acid.In the COQS group,they could be aminoadipic acid,palmitic amide,oleamide,lysoPC(P-16:0),lysoPC(P-18:0),lysoPC(20:2(11 Z,14 Z)),9-HETE and tauroursodeoxycholic acid.Moreover,4-pyridoxic acid,L-palmi.toylcarnitine,lysoPC(20:0),lysoPC(22:5(4 Z,7 Z,10 Z,13 Z,16 Z)),3-hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group.CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome.Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism,fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.展开更多
Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and...Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.展开更多
This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 wee...This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.展开更多
Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic ac...Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.展开更多
为了解平菇生长发育过程中子实体形成的代谢物基础,采用超高效液相色谱-电喷雾串联四级杆质谱(UPLC-ESI-MS/MS)技术结合多变量统计分析方法对发菌完成期(MM)、原基期(MP)及子实体分化期(MF)的平菇菌丝体进行代谢组学分析。结果表明,主成...为了解平菇生长发育过程中子实体形成的代谢物基础,采用超高效液相色谱-电喷雾串联四级杆质谱(UPLC-ESI-MS/MS)技术结合多变量统计分析方法对发菌完成期(MM)、原基期(MP)及子实体分化期(MF)的平菇菌丝体进行代谢组学分析。结果表明,主成分(PCA)模型分析结果显示3个时期平菇菌丝体中的代谢产物具有明显差异。通过正交偏最小二乘判别分析(OPLS‐DA),以VIP(varible importance in the projection)>1和差异倍数值(fold change)≥2或≤0.5为条件对MM vs MP、MM vs MF和MP vs MF中的差异代谢物进行比较分析,分别获得139个、147个和67个差异代谢物,变化倍数最大的物质包括氨基酸及其衍生物、脂质、生物碱、有机酸等,说明这些差异代谢物对平菇子实体发育具有重要影响。KEGG分析表明,苯丙氨酸代谢、色氨酸代谢、嘌呤代谢等20条代谢通路表现活跃。在子实体发育过程中,脂质、有机酸、核苷酸及其衍生物、氨基酸及其衍生物之间明显相关。以上研究结果为平菇子实体发育机制和标准化栽培提供了理论依据。展开更多
Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,inf...Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,influenza,etc.At the same time,its allergic reactions have also emerged,which limits clinical applications.However,few scholars pay attention to the mechanism of allergic reactions.In this present study,metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction;we and analyzed the metabolites,metabolic pathway,and the mechanism which were closely related to the allergic reactions.The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed.Based on the UPLC-Q-TOF/MS metabonomics,we carried out the pattern recognition analysis,selected potential biomarkers associated with allergic reactions,and explored the pathological mechanism for SHLI induced allergic reaction,which laid the foundation for the safety research of SHLI.Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction;we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved,such as metabolism of linolenic acid,phenylalanine,amino acid,2-oxo acid,and purine and other metabolic pathways.展开更多
Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated hea...Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated heart failure(ADHF)patients were enrolled,and their CM syndromes before and after UF were collected.In addition,their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis.Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples.Partial least-squares to latent structure-discriminant analyses were used for data analysis.Results:An obvious difference was observed preand post-treatment.A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine,1-methylhistidine,phytosphingosine,O-decanoyl-R-carnitine,etc.were screened out,showing a significant change after UF.The major adjusted m etabolic pathways were purine metabolism,histidine metabolism,leucine and isoleucine metabolism,arginine and proline metabolism,carnitine shuttle,sphingolipid metabolism and phospholipid metabolism.Conclusions:Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.展开更多
Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The...Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with selfreported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes).Conclusions:The YODI provides population-based data with a high response rate(89.7%)on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China.Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases.The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.展开更多
Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprot...Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.展开更多
Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete rando...Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete random design,including control,model,aspirin(ASP,0.14 g/kg body weight),JLZ(14 g/kg body weight),Corydalis yanhusuo(YHS,14 g/kg body weight),and Toosendan Fructus(TF,14 g/kg body weight)groups,6 mice in each group.The mice in the control and model groups were given the same volume of saline,daily for 2 consecutive weeks.At 30,60,90,and 120 min after the last administration,the pain threshold of mice in each group was measured,and the improvement rate of pain threshold was calculated.Serum endogenous metabolites were analyzed by gas chromatography–mass spectrometry(GC–MS).Results:There was no statistical difference in pain threshold among groups before administration(P>0.05).After 2 weeks of administration,compared with the model group,the pain threshold in JLZ,YHS,TF and ASP groups were increased to varying degrees(P<0.05).JLZ had the best analgesic effect and was superior to YHS and TF groups.A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs.These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism,glycine,serine and threonine metabolism,valine,leucine and isoleucine biosynthesis,aminoacyl-t RNA biosynthesis and inositol phosphate metabolism.Conclusions:The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor,producing post-synaptic potential,reducing the excitability of neurons,and weakening the afferent effect of painful information.展开更多
基金supported by the National Natural Science Foundation of China(No.82073617)Joint Research Fund for Beijing Natural Science Foundation and Haidian Original Innovation(No.L202007)+1 种基金Fundamental Research Funds for the Central Universities and Peking University Health Science Center(No.BMU2021YJ041)Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation(No.BMU2021PY005).
文摘Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.
基金supported by the grants from Zhejiang Provincial Natural Science Foundation(LGF19H150004)Zhejiang Provincial Medical Science and Technology project(2022RC258)。
文摘BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.
基金National Natural Science Foundation of China(8160338581673631+4 种基金8150100381601149)Science Foundation of Shaanxi Province(2017JM8006)China Postdoctoral Science Foundation(2015M5804652017JQ8038)
文摘Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.
基金offered by China-Japan Friendship Hospital(Beijing,China)supported by grantfrom the National Basic Research Development Program of China(973 Program,No.2005CB523503)the National Natural Science Foundations of China(Nos.90709045 and 20805026)
文摘A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids(EFAs and NEFAs) in plasma.Merely 10μL of plasma was required.The pretreatment of the sample was simple without disposing the protein.After simple extraction and derivation,15 FAs in plasma were precisely quantified.Gas chromatography tandem mass spectrometry(GC-MS) was used in the study and the quantities of the analytes,which varied in abundance over three orders of magnitude.The established method showed good accuracy.The curve correlation coefficients were all above 0.997.The RSDs of precision for all compounds were below 15%and recoveries were all between 80 and 110%.PLS-DA modal was used in the data management.
文摘Metabonomics, a novel systemic approach, was applied to studies of Traditional Chinese Medicine scutellarin in rat urine. The liquid chromatography coupled with ion trap mass spectrometry combined with PCA was used in this paper. With this methodology, two potential metabolites of scutellarin were detected and the nine ions responsible for the gender variation and one ion for the dosage variation were found.
基金supported by National Natural Science Foundation of China(8147357981273654+2 种基金81102879) Beijing Natural Science Foundation(7173267) National Science and Technology Major Projects for ＂Major New Drugs Innovation and Development＂(2013ZX09103002-022)
文摘OBJECTIVE To have a systematic pathomechanism view of three chest impediment.syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn.drome(QSBS),Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma.METHODS According to clinical pathogeny,three kinds of syndrome models were established to simulate the disease of chest impediment.Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes,respectively.RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups.Furthermore,three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified.In the QSBS group,the potential biomarkers could include 2-keto-glutaramic acid,L-methionine,L-homocysteic acid,octadecanamide,stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9 Z)),indoxyl sulfate and cholic acid.In the COQS group,they could be aminoadipic acid,palmitic amide,oleamide,lysoPC(P-16:0),lysoPC(P-18:0),lysoPC(20:2(11 Z,14 Z)),9-HETE and tauroursodeoxycholic acid.Moreover,4-pyridoxic acid,L-palmi.toylcarnitine,lysoPC(20:0),lysoPC(22:5(4 Z,7 Z,10 Z,13 Z,16 Z)),3-hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group.CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome.Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism,fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.
基金supported by the Key R&D Plan of Hubei Province for local special support in the field of general health(No.2022BCE066).
文摘Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.
基金supported by Shandong Taishan industry leading talent project(LJNY202101)the National Key R&D of China(2018YFC0311201)。
文摘This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.
基金supported by the project of the National Natural Science Foundation of China(32272331)the project of Fundamental Research Funds for the Central Universities(2662019PY034)。
文摘Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.
文摘为了解平菇生长发育过程中子实体形成的代谢物基础,采用超高效液相色谱-电喷雾串联四级杆质谱(UPLC-ESI-MS/MS)技术结合多变量统计分析方法对发菌完成期(MM)、原基期(MP)及子实体分化期(MF)的平菇菌丝体进行代谢组学分析。结果表明,主成分(PCA)模型分析结果显示3个时期平菇菌丝体中的代谢产物具有明显差异。通过正交偏最小二乘判别分析(OPLS‐DA),以VIP(varible importance in the projection)>1和差异倍数值(fold change)≥2或≤0.5为条件对MM vs MP、MM vs MF和MP vs MF中的差异代谢物进行比较分析,分别获得139个、147个和67个差异代谢物,变化倍数最大的物质包括氨基酸及其衍生物、脂质、生物碱、有机酸等,说明这些差异代谢物对平菇子实体发育具有重要影响。KEGG分析表明,苯丙氨酸代谢、色氨酸代谢、嘌呤代谢等20条代谢通路表现活跃。在子实体发育过程中,脂质、有机酸、核苷酸及其衍生物、氨基酸及其衍生物之间明显相关。以上研究结果为平菇子实体发育机制和标准化栽培提供了理论依据。
基金supported by the Research and Development Projects of Application of Technology of Heilongjiang Province in China(No.GC13C109)Major Projects of Science and Technology "Significant Drug Discovery"-Transformation of SHL Powder for Injection,(China)(No.2011ZX09201-201-15)Science and Technology Projects on Heilongjiang Province of traditional Chinese Medicine(China)(No.ZHY16-099)
文摘Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,influenza,etc.At the same time,its allergic reactions have also emerged,which limits clinical applications.However,few scholars pay attention to the mechanism of allergic reactions.In this present study,metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction;we and analyzed the metabolites,metabolic pathway,and the mechanism which were closely related to the allergic reactions.The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed.Based on the UPLC-Q-TOF/MS metabonomics,we carried out the pattern recognition analysis,selected potential biomarkers associated with allergic reactions,and explored the pathological mechanism for SHLI induced allergic reaction,which laid the foundation for the safety research of SHLI.Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction;we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved,such as metabolism of linolenic acid,phenylalanine,amino acid,2-oxo acid,and purine and other metabolic pathways.
基金Supported by the National Natural Science Foundation of China(No.81273932)。
文摘Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated heart failure(ADHF)patients were enrolled,and their CM syndromes before and after UF were collected.In addition,their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis.Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples.Partial least-squares to latent structure-discriminant analyses were used for data analysis.Results:An obvious difference was observed preand post-treatment.A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine,1-methylhistidine,phytosphingosine,O-decanoyl-R-carnitine,etc.were screened out,showing a significant change after UF.The major adjusted m etabolic pathways were purine metabolism,histidine metabolism,leucine and isoleucine metabolism,arginine and proline metabolism,carnitine shuttle,sphingolipid metabolism and phospholipid metabolism.Conclusions:Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.
基金This study was supported by Yueqing Eye Health Project:Benefiting the People with Technology and Science,Grant 2014H01007 from the Science&Technology Department of the Zhejiang Province,China.
文摘Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with selfreported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes).Conclusions:The YODI provides population-based data with a high response rate(89.7%)on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China.Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases.The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.
基金This work was supported by the National Natural Science Foundation of China(Nos.81403066 and 81473417).
文摘Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.
文摘Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete random design,including control,model,aspirin(ASP,0.14 g/kg body weight),JLZ(14 g/kg body weight),Corydalis yanhusuo(YHS,14 g/kg body weight),and Toosendan Fructus(TF,14 g/kg body weight)groups,6 mice in each group.The mice in the control and model groups were given the same volume of saline,daily for 2 consecutive weeks.At 30,60,90,and 120 min after the last administration,the pain threshold of mice in each group was measured,and the improvement rate of pain threshold was calculated.Serum endogenous metabolites were analyzed by gas chromatography–mass spectrometry(GC–MS).Results:There was no statistical difference in pain threshold among groups before administration(P>0.05).After 2 weeks of administration,compared with the model group,the pain threshold in JLZ,YHS,TF and ASP groups were increased to varying degrees(P<0.05).JLZ had the best analgesic effect and was superior to YHS and TF groups.A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs.These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism,glycine,serine and threonine metabolism,valine,leucine and isoleucine biosynthesis,aminoacyl-t RNA biosynthesis and inositol phosphate metabolism.Conclusions:The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor,producing post-synaptic potential,reducing the excitability of neurons,and weakening the afferent effect of painful information.
