Tanreqing(TRQ), a traditional Chinese medicine(TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-t...Tanreqing(TRQ), a traditional Chinese medicine(TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride(CCl_4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids(BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry(UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg^(-1) body weight, respectively. Moreover, our results suggested that taurocholic acid(TCA) and taurohyodesoxycholic acid(THDCA) were the most important biochemical markers, which were indicative of CCl_4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.展开更多
BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accept...BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accepted by patients because of its invasive nature,and atypical liver histology can confuse diagnosis.In view of the lack of effective diagnostic markers for PBC and AIH,combined with the increasingly mature metabolomics technologies,including full-contour metabolomics and target.AIM To determine non-invasive,reliable,and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS Serum samples from 54 patients with PBC,26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatographytandem mass spectrometry serum metabolomics.The metabolites and metabolic pathways were identified,and the metabolic changes,metabolic pathways and inter-group differences between PBC and AIH were analyzed.Fifteen kinds of target metabolites of bile acids(BAs)were quantitatively analyzed by SRM,and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS We found the changes in the levels of amino acids,BAs,organic acids,phospholipids,choline,sugar,and sugar alcohols in patients with PBC and AIH.Furthermore,the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid,lithocholic acid(LCA),taurolithocholic acid(TLCA),and LCA+TLCA in the PBC group compared with those in the AIH group.The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases.The levels of glycochenodeoxycholic acid,glycochenodeoxycholic sulfate,and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class,which was correlated with the severity of disease.CONCLUSION The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.展开更多
Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism ...Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.展开更多
AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients...AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylala-nine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.展开更多
The Asian rice gall midge（Orseolia oryzae WoodMason） is a serious pest of rice that causes huge loss in yield.While feeding inside the susceptible host,maggots secrete substances that facilitate the formation of a h...The Asian rice gall midge（Orseolia oryzae WoodMason） is a serious pest of rice that causes huge loss in yield.While feeding inside the susceptible host,maggots secrete substances that facilitate the formation of a hollow tube-like structure called gall and prevent panicle formation.The present investigation was carried out to get an account of biochemical changes occurring in the rice plant upon gall midge feeding.Metabolic profiling of host tissues from three rice varieties,namely,TN1,Kavya,and RP2068,exposed to gall midge biotype 1（GMB1）,was carried out using gas chromatography mass spectrometry（GC-MS）.TN1 and GMB1 represented compatible interaction,while Kavya and GMB1 as well as RP2068 and GMB1 represented incompatible interactions.The current study identified several metabolites that could be grouped as resistance,susceptibility,infestation,and host features based on their relative abundance.These may be regarded as biomarkers for insect-plant interaction in general and rice-gall midge interaction in particular.展开更多
Background： Antegrade selective cerebral perfusion （ASCP） is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest （DHCA）. How...Background： Antegrade selective cerebral perfusion （ASCP） is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest （DHCA）. However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods： To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with （DHCA＋ASCP [DA] group, n = 6） and without （ DHCA [D] group, n = 6） ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student＇s t-test was applied to test for statistical significance between the two groups. Results： Metabolic profiling of brain was distinctive significantly between the two groups （Q2y = 0.88 for partial least squares-DA model）. In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine （P = 0.0019）, 5-methoxyindole-3-acetic acid （P = 0.0499）, and 5-hydroxyindole-3-acetic acid （P = 0.0495） in tryptophan metabolism pathways were decreased, and citrulline （P - 0.0158） in urea cycle was increased in group DA comparing to group D. Conclusions： The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.展开更多
Colorectal cancer （CRC） is the third commonest malignancy cancer worldwide. Clear understandings of global metabolic profiling of the normal mucosa and cancer tissues are vitally important to aid optimizing the clin...Colorectal cancer （CRC） is the third commonest malignancy cancer worldwide. Clear understandings of global metabolic profiling of the normal mucosa and cancer tissues are vitally important to aid optimizing the clinical management strategy and understanding CRC biology. We studied metabolic characteristics of 20 CRC and 20 distant normal mucosa tissues extracts from 20 patients using high resolution ^1H NMR spectroscopy in conjunction with multivariate analyses, such as principal component analysis （PCA）. Compared with distant normal mucosa tissues, lactate, taurine, ornithine and polyamine were present at significantly higher levels in CRC tissue extracts whereas myo-inositol was present at significantly lower level. Two metabolites ratios such as myo-inositolltaurine and myo-inositol/（ornithine＋polyamine） appear to be the most valuable biomarkers for the differentiation CRC from normal mucosa tissues. Our data suggested that HR ~H NMR spectroscopy combined with multivariate analy- ses is a potentially useful technology for detecting malignant changes in the normal mucosa tissues, the technique may be further exploited for future CRC biomarker research or identification of targets for therapeutic manipulations.展开更多
Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fru...Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fruits,leaves,stem barks) P.thonningii were evaluated for their bioactive contents,enzyme inhibitory,antioxidant and antimicrobial activities.Antioxidant potentials were also displayed in various methods like phosphomolybdenum assay (0.79–5.94 mmol TE/g),radical scavenging assays (DPPH:20.39–471.28 mg TE/g;ABTS:42.43–654.14 mg TE/g);reducing assays (CUPRAC:102.98–1207.42 mg TE/g;FRAP:45.30–656.25 mg TE/g) and metal chelating activity (2.55–22.32 mg EDTAE/g).In particular,the methanolic and water extracts showed better antioxidant potential.Except for a few,the extracts were also found to act as inhibitors of enzymes such as acetylcholinesterase (2.35–5.35 mg GALAE/g),butyrylcholinesterase (0.83–13.80 mg GALAE/g),tyrosinase (4.03–143.86 mg KAE/g),amylase (0.21–1.39 mmol ACAE/g) and glucosidase (3.52–7.13 mmol ACAE/g).Additionally,all the tested extracts possessed significant antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration:0.11–0.61 mg/ml) and antifungal (MIC and minimum fungicidal concentration:0.04–0.61 mg/ml) effects.Indeed,the data garnered from the present study provides a bright scope for the advanced investigation on this particular plant possessing pharmacologically active traits.展开更多
BACKGROUND Major depressive disorder(MDD)is characterized by persistent depressed mood and cognitive symptoms.This study aimed to discover biomarkers for MDD,explore its pathological mechanisms,and examine the associa...BACKGROUND Major depressive disorder(MDD)is characterized by persistent depressed mood and cognitive symptoms.This study aimed to discover biomarkers for MDD,explore its pathological mechanisms,and examine the associations of the identified biomarkers with clinical and psychological variables.AIM To discover candidate biomarkers for MDD identification and provide insight into the pathological mechanism of MDD.METHODS The current study adopted a single-center cross-sectional case-control design.Serum samples were obtained from 100 individuals diagnosed with MDD and 97 healthy controls(HCs)aged between 18 to 60 years.Metabolomics was performed on an Ultimate 3000 UHPLC system coupled with Q-Exactive MS(Thermo Scien-tific).The online software Metaboanalyst 6.0 was used to process and analyze the acquired raw data of peak intensities from the instrument.RESULTS The study included 100 MDD patients and 97 HCs.Metabolomic profiling identified 35 significantly different metabolites(e.g.,cortisol,sebacic acid,and L-glutamic acid).Receiver operating characteristic curve analysis highlighted 8-HETE,10-HDoHE,cortisol,12-HHTrE,and 10-hydroxydecanoic acid as top diagnostic biomarkers for MDD.Significant correlations were found between metabolites(e.g.,some lipids,steroids,and amino acids)and clinical and psychological variables.CONCLUSION Our study reported metabolites(some lipids,steroids,amino acids,carnitines,and alkaloids)responsible for discriminating MDD patients and HCs.This metabolite profile may enable the development of a laboratory-based diagnostic test for MDD.The mechanisms underlying the association between psychological or clinical variables and differential metabolites deserve further exploration.展开更多
Objective:Lanqin oral liquid(LOL),as a traditional Chinese medicine prescription,has obvious clinical efficacy in the treatment of pharyngeal inflammation.Exploring the distribution of LOL prototype components and met...Objective:Lanqin oral liquid(LOL),as a traditional Chinese medicine prescription,has obvious clinical efficacy in the treatment of pharyngeal inflammation.Exploring the distribution of LOL prototype components and metabolites in plasma is of great significance for understanding potentially effective compounds.The aim of this study is to elucidate the metabolites and main metabolic pathways of LQL in vivo.Methods:In this study,a reliable approach integrated background subtraction and mass defect filtering(MDF),based on quadrupole time-of-flight mass spectrometry(QTOF-MS)technology,was performed to systematically scan the metabolites of LOL in rat plasma.In addition,according to the prototype mass spectrometry fragmentation pattern and combined with metabolic pathway analysis,a biotransformation oriented analysis strategy was established and applied to the identification of metabolites in LOL in vivo.Results:As a result,159 compounds(58 prototypes and 101 metabolites)were identified or tentatively characterized in drug-containing plasma,including 74 flavonoids,30 alkaloids,34 terpenoids,five phenylpropanoids,six phenolic acids,five fatty acids,and five other type components.The main metabolic pathways include methylation,demethylation,hydroxylation,hydrogenation,glucuronidation,and sulfation.Conclusions:This study provides an overall characterization of the metabolites of LOL in vivo for the first time,providing a solid material basis for exploring the therapeutic effects and pharmacological mechanisms of LOL.展开更多
A freshwater green microalgae Chlorella sp., UMACC344 was shown to produce high lipid content and has the potential to be used as feedstock for biofuel production. In this study, photosynthetic effciency, biochemical ...A freshwater green microalgae Chlorella sp., UMACC344 was shown to produce high lipid content and has the potential to be used as feedstock for biofuel production. In this study, photosynthetic effciency, biochemical pro?les and non-targeted metabolic pro?ling were studied to compare between the nitrogen-replete and deplete conditions. Slowed growth, change in photosynthetic pigments and lowered photosynthetic effciency were observed in response to nitrogen deprivation. Biochemical pro?les of the cultures showed an increased level of carbohydrate, lipids and total fatty acids, while the total soluble protein content was lowered. A trend of fatty acid saturation was observed in the nitrogen-deplete culture with an increase in the level of saturated fatty acids especially C16:0 and C18:0, accompanied by a decrease in proportions of monounsaturated and polyunsaturated fatty acids. Fifty-nine metabolites, including amino acids, lipids, phytochemical compounds, vitamins and cofactors were signi?cantly dysregulated and annotated in this study. Pathway mapping analysis revealed a rewiring of metabolic pathways in the cells, particularly purine, carotenoid, nicotinate and nicotinamide, and amino acid metabolisms. Within the treatment period of nitrogen deprivation, the key processes involved were reshu ? ing of nitrogen from proteins and photosynthetic machinery, together with carbon repartitioning in carbohydrates and lipids.展开更多
Danshen, the dried root of Salvia miltiorrhiza Bunge（Lamiaceae）, is one of the traditional Chinese medicines（TCMs） most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, litt...Danshen, the dried root of Salvia miltiorrhiza Bunge（Lamiaceae）, is one of the traditional Chinese medicines（TCMs） most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, little is known about the chemical and metabolic profiles of danshen in vitro or in vivo. In particular, more information is needed in relation to the 50% ethanol extracts usually used in danshen formulations such as Fufang Xueshuantong Capsules and Fufang Danshen tablets. High-performance liquid chromatography coupled with a linear ion trapOrbitrap mass spectrometer（HPLC-LTQ-Orbitrap） provides a sensitive and accurate method for analyzing the composition of samples. This method was used to determine the in vitro and in vivo chemical and metabolic profiles of danshen. Sixty-nine components of danshen extract and 118 components of danshen in rat plasma, urine, feces, and bile were unambiguously or tentatively identified. These results not only revealed the material composition of danshen, but also provided a comprehensive research approach for the identification of multi-constituents in TCMs.展开更多
Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this...Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this study,a UPLC-Q-Exactive Orbitrap/MS-based untargeted metabolomics method was used to evaluate the metabolites in leaf tips of 32 sweet potato varieties.Three varieties with distinct overall metabolic profiles(A01,A02,and A03),two varieties with distinct profiles of phenolic acids(A20 and A18),and three varieties with distinct profiles of flavonoids(A05,A12,and A16)were identified.In addition,a total of 163 and 29 differentially expressed metabolites correlated with the color and leaf shape of sweet potato leaf tips,respectively,were identified through morphological characterization.Group comparison analysis of the phenotypic traits and a metabolite-phenotypic trait correlation analysis indicated that the color differences of sweet potato leaf tips were markedly associated with flavonoids.Also,the level of polyphenols was correlated with the leaf shape of sweet potato leaf tips,with lobed leaf types having higher levels of polyphenols than the entire leaf types.The findings on the metabolic profiles and differentially expressed metabolites associated with the morphology of sweet potato leaf tips can provide useful information for breeding sweet potato varieties with higher nutritional value.展开更多
Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QY...Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry(UPLC-QTOF-MS^(E))was developed to identify QYSLD-related xenobiotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one prototype and five metabolites underwent the process of“appearing-disappearing-reappearing”in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.展开更多
Chemical exposure can indirectly affect leaf microbiota communities,but the mechanism driving this phenomenon remains largely unknown.Results revealed that the co-exposure of glyphosate and multi-carbon nanotubes(CNTs...Chemical exposure can indirectly affect leaf microbiota communities,but the mechanism driving this phenomenon remains largely unknown.Results revealed that the co-exposure of glyphosate and multi-carbon nanotubes(CNTs)caused a synergistic inhibitory effect on the growth and metabolism of Arabidopsis thaliana shoots.However,only a slight inhibitory effect was induced by nanotubes or glyphosate alone at the tested concentrations.Several intermediate metabolites of nitrogen metabolism and fatty acid synthesis pathways were upregulated under the combined treatment,which increased the amount of energy required to alleviate the disruption caused by the combined treatment.Additionally,compared with the two individual treatments,the glyphosate/nanotube combination treatment induced greater fluctuations in the phyllosphere bacterial community members with low abundance(relative abundance(RA)<1%)at both the family and genus levels,and among these bacteria some plant growth promotion and nutrient supplement related bacteria were markable increased.Strikingly,strong correlations between phyllosphere bacterial diversity and metabolites suggested a potential role of leaf metabolism,particularly nitrogen and carbohydrate metabolism,in restricting the range of leaf microbial taxa.These correlations between phyllosphere bacterial diversity and leaf metabolism will improve our understanding of plant-microbe interactions and the extent of their drivers of variation and the underlying causes of variability in bacterial community composition.展开更多
Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adv...Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.展开更多
Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is u...Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39%of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.展开更多
Background： Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, ...Background： Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, there is little metabolic profile data available about Korean Hanwoo cows. Therefore, this study aimed to determine the reference intervals of metabolic profile for Korean Hanwoo cows. Methods： Healthy animals （2,205） were selected and divided into early （day 1 to 95）, middle （day 96 to 190） and late （day 191 to 285） period according to their gestating period. Metabolic profile including total protein （TP）, albumin （AIb）, urea （UREA）, glucose （Glu）, total cholesterol （T-Cho）, long-chain fatty acid （LCFA）, aspartate aminotransferase （AST）, gamma-glutamyl transpeptidase （GGT）, creatinine （Crea）, calcium （Ca）, inorganic phosphorous （iP） and magnesium （Mg） were analyzed using a TBA-4OFR automatic biochemical analyzer. The data of Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows. Results： Most of the data of the Korean Hanwoo cows were relatively higher than those of Japanese Wagyu cows, with the exception of Glu and GGT. This may indicate that the nutritional level of feed for the Korean Hanwoo cows was higher than that of the Japanese Wagyu cows because of the different feeding system. In particular, relatively higher levels of UREA and LCFA were observed in the Korean Hanwoo cows, and this may also contribute to the low reproduction efficiency. Conclusions： These findings may provide some theoretical basis for understanding the reproductive and feeding situation of Korean Hanwoo cows.展开更多
Metabolic-associated fatty liver disease(MAFLD)refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide.Although metabolis...Metabolic-associated fatty liver disease(MAFLD)refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide.Although metabolism is highly influenced by the effects of sex hormones,studies of sex differences in the incidence and progression of MAFLD are scarce.Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms.First,metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time.Second,metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers.Some studies demonstrate associations between circulating metabolites and early and established MAFLD,but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management.In this review,we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD,the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers,and how this evidence may help in the future management of the disease.展开更多
Background: The diversified and high value-added utilization of cotton by products can promote the sustainable development of modern agriculture. Di erences in potential nutrients among varieties can be explained by v...Background: The diversified and high value-added utilization of cotton by products can promote the sustainable development of modern agriculture. Di erences in potential nutrients among varieties can be explained by variations in the composition and abundance of fatty acids, polyphenols, carbohydrates, amino acids, and organic acids. Therefore, the analysis of metabolite species and relationships in cottonseed is meaningful for the development of cotton byproducts.Results: In this study, the metabolomes of three representative cotton cultivars of di erent species were compared using untargeted GC-TOF/MS analysis. A total of 263 metabolites were identified from 705 peaks, and their levels were compared across cultivars. Principal component analysis and OPLS-DA clearly distinguish these samples based on metabolites. There were significant di erences in the contents of amino acids, carbohydrates, organic acids, flavonoids, and lipids in G. hirsutum TM-1 compared with G. arboreum Shixiya1 and G. barbadense Hai7124. Notably, the bioactive nutrient compound catechin obtained from the di erential metabolites significantly accumulated in TM-1. Furthermore, a comprehensive analysis using catechin and oil-related traits was conducted in core collections of Gossypium hirsutum. The results revealed the reliability of the GC-TOF/MS analysis, as well as that catechin content has a negative association with myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and total fatty acids.Conclusion: These findings suggest that untargeted GC-TOF/MS analysis could provide a new method for investigating the underlying plant biochemistry of nutrient variation in cottonseed, and that catechin content has a negative association with oil-related traits in cottonseed. This study may pave the way to exploit the value of cotton byproducts.展开更多
基金supported by the National Natural Science Foundation of China(No.81403089)the China Postdoctoral Science Foundation(No.2012M520920)
文摘Tanreqing(TRQ), a traditional Chinese medicine(TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride(CCl_4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids(BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry(UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg^(-1) body weight, respectively. Moreover, our results suggested that taurocholic acid(TCA) and taurohyodesoxycholic acid(THDCA) were the most important biochemical markers, which were indicative of CCl_4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
基金Supported by Health and Family Planning Commission Project of Jilin Province,No.2016Q043Health and Hygiene Committee Project of Jilin Province,No.2021LC082。
文摘BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accepted by patients because of its invasive nature,and atypical liver histology can confuse diagnosis.In view of the lack of effective diagnostic markers for PBC and AIH,combined with the increasingly mature metabolomics technologies,including full-contour metabolomics and target.AIM To determine non-invasive,reliable,and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS Serum samples from 54 patients with PBC,26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatographytandem mass spectrometry serum metabolomics.The metabolites and metabolic pathways were identified,and the metabolic changes,metabolic pathways and inter-group differences between PBC and AIH were analyzed.Fifteen kinds of target metabolites of bile acids(BAs)were quantitatively analyzed by SRM,and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS We found the changes in the levels of amino acids,BAs,organic acids,phospholipids,choline,sugar,and sugar alcohols in patients with PBC and AIH.Furthermore,the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid,lithocholic acid(LCA),taurolithocholic acid(TLCA),and LCA+TLCA in the PBC group compared with those in the AIH group.The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases.The levels of glycochenodeoxycholic acid,glycochenodeoxycholic sulfate,and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class,which was correlated with the severity of disease.CONCLUSION The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.
基金the UGC,New Delhi awarding Maulana Azad National Fellowship to Ms.Gaganjot[Grant No.F1-17.1/2015-16/MANF-2015-17-PUN-53869]The authors would like to extend their sincere appreciation to the Researchers Supporting Project No.(RSP-2021/19),King Saud University,Riyadh,Saudi Arabia.
文摘Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.
文摘AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylala-nine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.
基金Research on rice gall midge and gall midge-rice interaction in SN's laboratory is partially supported by coregrants from ICGEBextramural funding from the Department of Biotechnology(DBT)+1 种基金Indian Council of Agricultural Research(ICAR),Government of Indiathe University Grants Commission(UGC),Government of India,for a Junior Research Fellowship
文摘The Asian rice gall midge（Orseolia oryzae WoodMason） is a serious pest of rice that causes huge loss in yield.While feeding inside the susceptible host,maggots secrete substances that facilitate the formation of a hollow tube-like structure called gall and prevent panicle formation.The present investigation was carried out to get an account of biochemical changes occurring in the rice plant upon gall midge feeding.Metabolic profiling of host tissues from three rice varieties,namely,TN1,Kavya,and RP2068,exposed to gall midge biotype 1（GMB1）,was carried out using gas chromatography mass spectrometry（GC-MS）.TN1 and GMB1 represented compatible interaction,while Kavya and GMB1 as well as RP2068 and GMB1 represented incompatible interactions.The current study identified several metabolites that could be grouped as resistance,susceptibility,infestation,and host features based on their relative abundance.These may be regarded as biomarkers for insect-plant interaction in general and rice-gall midge interaction in particular.
基金the grants from National Natural Science Foundation of China
文摘Background： Antegrade selective cerebral perfusion （ASCP） is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest （DHCA）. However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods： To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with （DHCA＋ASCP [DA] group, n = 6） and without （ DHCA [D] group, n = 6） ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student＇s t-test was applied to test for statistical significance between the two groups. Results： Metabolic profiling of brain was distinctive significantly between the two groups （Q2y = 0.88 for partial least squares-DA model）. In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine （P = 0.0019）, 5-methoxyindole-3-acetic acid （P = 0.0499）, and 5-hydroxyindole-3-acetic acid （P = 0.0495） in tryptophan metabolism pathways were decreased, and citrulline （P - 0.0158） in urea cycle was increased in group DA comparing to group D. Conclusions： The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.
基金Project supported by the National Natural Science Foundation of China （No. 20872018）, the Science ＆ Technology Commission of Shanghai Municipality （No. 08411961800）, the China Postdoctoral Science Foundation （No. 20090450065） and the State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics （No. T152805）.
文摘Colorectal cancer （CRC） is the third commonest malignancy cancer worldwide. Clear understandings of global metabolic profiling of the normal mucosa and cancer tissues are vitally important to aid optimizing the clinical management strategy and understanding CRC biology. We studied metabolic characteristics of 20 CRC and 20 distant normal mucosa tissues extracts from 20 patients using high resolution ^1H NMR spectroscopy in conjunction with multivariate analyses, such as principal component analysis （PCA）. Compared with distant normal mucosa tissues, lactate, taurine, ornithine and polyamine were present at significantly higher levels in CRC tissue extracts whereas myo-inositol was present at significantly lower level. Two metabolites ratios such as myo-inositolltaurine and myo-inositol/（ornithine＋polyamine） appear to be the most valuable biomarkers for the differentiation CRC from normal mucosa tissues. Our data suggested that HR ~H NMR spectroscopy combined with multivariate analy- ses is a potentially useful technology for detecting malignant changes in the normal mucosa tissues, the technique may be further exploited for future CRC biomarker research or identification of targets for therapeutic manipulations.
文摘Piliostigma thonningii (Fabaceae) is a versatile medicinal plant used as a traditional remedy,especially in African countries.In the present study,ethyl acetate,methanolic and water extracts of different parts of (fruits,leaves,stem barks) P.thonningii were evaluated for their bioactive contents,enzyme inhibitory,antioxidant and antimicrobial activities.Antioxidant potentials were also displayed in various methods like phosphomolybdenum assay (0.79–5.94 mmol TE/g),radical scavenging assays (DPPH:20.39–471.28 mg TE/g;ABTS:42.43–654.14 mg TE/g);reducing assays (CUPRAC:102.98–1207.42 mg TE/g;FRAP:45.30–656.25 mg TE/g) and metal chelating activity (2.55–22.32 mg EDTAE/g).In particular,the methanolic and water extracts showed better antioxidant potential.Except for a few,the extracts were also found to act as inhibitors of enzymes such as acetylcholinesterase (2.35–5.35 mg GALAE/g),butyrylcholinesterase (0.83–13.80 mg GALAE/g),tyrosinase (4.03–143.86 mg KAE/g),amylase (0.21–1.39 mmol ACAE/g) and glucosidase (3.52–7.13 mmol ACAE/g).Additionally,all the tested extracts possessed significant antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration:0.11–0.61 mg/ml) and antifungal (MIC and minimum fungicidal concentration:0.04–0.61 mg/ml) effects.Indeed,the data garnered from the present study provides a bright scope for the advanced investigation on this particular plant possessing pharmacologically active traits.
基金Supported by National Natural Science Foundation of China,No.32300926Youth Project of Science and Technology Research Program of Chongqing Education Commission of China,No.KJQN202402810Science and Health Joint Medical Research Project of Chongqing Nanan District,No.2020-12.
文摘BACKGROUND Major depressive disorder(MDD)is characterized by persistent depressed mood and cognitive symptoms.This study aimed to discover biomarkers for MDD,explore its pathological mechanisms,and examine the associations of the identified biomarkers with clinical and psychological variables.AIM To discover candidate biomarkers for MDD identification and provide insight into the pathological mechanism of MDD.METHODS The current study adopted a single-center cross-sectional case-control design.Serum samples were obtained from 100 individuals diagnosed with MDD and 97 healthy controls(HCs)aged between 18 to 60 years.Metabolomics was performed on an Ultimate 3000 UHPLC system coupled with Q-Exactive MS(Thermo Scien-tific).The online software Metaboanalyst 6.0 was used to process and analyze the acquired raw data of peak intensities from the instrument.RESULTS The study included 100 MDD patients and 97 HCs.Metabolomic profiling identified 35 significantly different metabolites(e.g.,cortisol,sebacic acid,and L-glutamic acid).Receiver operating characteristic curve analysis highlighted 8-HETE,10-HDoHE,cortisol,12-HHTrE,and 10-hydroxydecanoic acid as top diagnostic biomarkers for MDD.Significant correlations were found between metabolites(e.g.,some lipids,steroids,and amino acids)and clinical and psychological variables.CONCLUSION Our study reported metabolites(some lipids,steroids,amino acids,carnitines,and alkaloids)responsible for discriminating MDD patients and HCs.This metabolite profile may enable the development of a laboratory-based diagnostic test for MDD.The mechanisms underlying the association between psychological or clinical variables and differential metabolites deserve further exploration.
文摘Objective:Lanqin oral liquid(LOL),as a traditional Chinese medicine prescription,has obvious clinical efficacy in the treatment of pharyngeal inflammation.Exploring the distribution of LOL prototype components and metabolites in plasma is of great significance for understanding potentially effective compounds.The aim of this study is to elucidate the metabolites and main metabolic pathways of LQL in vivo.Methods:In this study,a reliable approach integrated background subtraction and mass defect filtering(MDF),based on quadrupole time-of-flight mass spectrometry(QTOF-MS)technology,was performed to systematically scan the metabolites of LOL in rat plasma.In addition,according to the prototype mass spectrometry fragmentation pattern and combined with metabolic pathway analysis,a biotransformation oriented analysis strategy was established and applied to the identification of metabolites in LOL in vivo.Results:As a result,159 compounds(58 prototypes and 101 metabolites)were identified or tentatively characterized in drug-containing plasma,including 74 flavonoids,30 alkaloids,34 terpenoids,five phenylpropanoids,six phenolic acids,five fatty acids,and five other type components.The main metabolic pathways include methylation,demethylation,hydroxylation,hydrogenation,glucuronidation,and sulfation.Conclusions:This study provides an overall characterization of the metabolites of LOL in vivo for the first time,providing a solid material basis for exploring the therapeutic effects and pharmacological mechanisms of LOL.
基金Supported by the Aerospace Malaysia Innovation Centre&Airbus Group Innovation(No.PV001-2013)the Ministry of Higher Education Malaysia HICoE grant(No.IOES-2014H)+1 种基金the Fundamental Research Grant Scheme(No.FP048-2016)the University of Malaya UMCoE RU Grant(No.RU009H-2015)
文摘A freshwater green microalgae Chlorella sp., UMACC344 was shown to produce high lipid content and has the potential to be used as feedstock for biofuel production. In this study, photosynthetic effciency, biochemical pro?les and non-targeted metabolic pro?ling were studied to compare between the nitrogen-replete and deplete conditions. Slowed growth, change in photosynthetic pigments and lowered photosynthetic effciency were observed in response to nitrogen deprivation. Biochemical pro?les of the cultures showed an increased level of carbohydrate, lipids and total fatty acids, while the total soluble protein content was lowered. A trend of fatty acid saturation was observed in the nitrogen-deplete culture with an increase in the level of saturated fatty acids especially C16:0 and C18:0, accompanied by a decrease in proportions of monounsaturated and polyunsaturated fatty acids. Fifty-nine metabolites, including amino acids, lipids, phytochemical compounds, vitamins and cofactors were signi?cantly dysregulated and annotated in this study. Pathway mapping analysis revealed a rewiring of metabolic pathways in the cells, particularly purine, carotenoid, nicotinate and nicotinamide, and amino acid metabolisms. Within the treatment period of nitrogen deprivation, the key processes involved were reshu ? ing of nitrogen from proteins and photosynthetic machinery, together with carbon repartitioning in carbohydrates and lipids.
基金Project supported by the Ministry of Science and Technology of China(No.2011ZX09201-201-22)
文摘Danshen, the dried root of Salvia miltiorrhiza Bunge（Lamiaceae）, is one of the traditional Chinese medicines（TCMs） most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, little is known about the chemical and metabolic profiles of danshen in vitro or in vivo. In particular, more information is needed in relation to the 50% ethanol extracts usually used in danshen formulations such as Fufang Xueshuantong Capsules and Fufang Danshen tablets. High-performance liquid chromatography coupled with a linear ion trapOrbitrap mass spectrometer（HPLC-LTQ-Orbitrap） provides a sensitive and accurate method for analyzing the composition of samples. This method was used to determine the in vitro and in vivo chemical and metabolic profiles of danshen. Sixty-nine components of danshen extract and 118 components of danshen in rat plasma, urine, feces, and bile were unambiguously or tentatively identified. These results not only revealed the material composition of danshen, but also provided a comprehensive research approach for the identification of multi-constituents in TCMs.
基金This work was supported by grants from the construction and operation of the Food Nutrition and Health Research Center of Guangdong Academy of Agricultural Sciences,China(XTXM 202205)the earmarked fund for CARS-10Sweetpotato,and the Guangdong Modern Agro-industry Technology Research System,China(2022KJ111).
文摘Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this study,a UPLC-Q-Exactive Orbitrap/MS-based untargeted metabolomics method was used to evaluate the metabolites in leaf tips of 32 sweet potato varieties.Three varieties with distinct overall metabolic profiles(A01,A02,and A03),two varieties with distinct profiles of phenolic acids(A20 and A18),and three varieties with distinct profiles of flavonoids(A05,A12,and A16)were identified.In addition,a total of 163 and 29 differentially expressed metabolites correlated with the color and leaf shape of sweet potato leaf tips,respectively,were identified through morphological characterization.Group comparison analysis of the phenotypic traits and a metabolite-phenotypic trait correlation analysis indicated that the color differences of sweet potato leaf tips were markedly associated with flavonoids.Also,the level of polyphenols was correlated with the leaf shape of sweet potato leaf tips,with lobed leaf types having higher levels of polyphenols than the entire leaf types.The findings on the metabolic profiles and differentially expressed metabolites associated with the morphology of sweet potato leaf tips can provide useful information for breeding sweet potato varieties with higher nutritional value.
基金supported by grants from the National Natural Science Foundation of China(Grant No.:81903765)the Open Fund Project of Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Major Pulmonary Diseases of the Anhui Provincial Department of Education(Grant No.:JYTKF2020-5)the Graduate Science and Technology Innovation Fund project of Anhui University of Chinese Medicine(Grant No.:2020YB06).
文摘Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry(UPLC-QTOF-MS^(E))was developed to identify QYSLD-related xenobiotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one prototype and five metabolites underwent the process of“appearing-disappearing-reappearing”in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.
基金supported by the National Natural Science Foundation of China(Nos.21777144,21976161,41907210)the Changjiang Scholars and Innovative Research Team in University(No.IRT_17R97)。
文摘Chemical exposure can indirectly affect leaf microbiota communities,but the mechanism driving this phenomenon remains largely unknown.Results revealed that the co-exposure of glyphosate and multi-carbon nanotubes(CNTs)caused a synergistic inhibitory effect on the growth and metabolism of Arabidopsis thaliana shoots.However,only a slight inhibitory effect was induced by nanotubes or glyphosate alone at the tested concentrations.Several intermediate metabolites of nitrogen metabolism and fatty acid synthesis pathways were upregulated under the combined treatment,which increased the amount of energy required to alleviate the disruption caused by the combined treatment.Additionally,compared with the two individual treatments,the glyphosate/nanotube combination treatment induced greater fluctuations in the phyllosphere bacterial community members with low abundance(relative abundance(RA)<1%)at both the family and genus levels,and among these bacteria some plant growth promotion and nutrient supplement related bacteria were markable increased.Strikingly,strong correlations between phyllosphere bacterial diversity and metabolites suggested a potential role of leaf metabolism,particularly nitrogen and carbohydrate metabolism,in restricting the range of leaf microbial taxa.These correlations between phyllosphere bacterial diversity and leaf metabolism will improve our understanding of plant-microbe interactions and the extent of their drivers of variation and the underlying causes of variability in bacterial community composition.
基金supported by the National Key Research and Development Program of China(No.2017YFC1600500)。
文摘Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.
基金supported by the National Natural Science Foundation of China (Grant Nos.: 81530095 and 81673591)Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.: XDA12020348)+1 种基金National Standardization of Traditional Chinese Medicine Project (Grant No.: ZYBZH-K-LN-01)Science and Technology Commission Foundation of Shanghai (Grant No.: 15DZ0502800)
文摘Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable significance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39%of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.
基金supported by Bioindustry Technology Development Program (313020041SB010) for Ministry of Agriculture, Food and Rural Affairs, Republic of Korea and Concentrated Research Professor Program for Konkuk University, Seoul, Republic of Korea
文摘Background： Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, there is little metabolic profile data available about Korean Hanwoo cows. Therefore, this study aimed to determine the reference intervals of metabolic profile for Korean Hanwoo cows. Methods： Healthy animals （2,205） were selected and divided into early （day 1 to 95）, middle （day 96 to 190） and late （day 191 to 285） period according to their gestating period. Metabolic profile including total protein （TP）, albumin （AIb）, urea （UREA）, glucose （Glu）, total cholesterol （T-Cho）, long-chain fatty acid （LCFA）, aspartate aminotransferase （AST）, gamma-glutamyl transpeptidase （GGT）, creatinine （Crea）, calcium （Ca）, inorganic phosphorous （iP） and magnesium （Mg） were analyzed using a TBA-4OFR automatic biochemical analyzer. The data of Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows. Results： Most of the data of the Korean Hanwoo cows were relatively higher than those of Japanese Wagyu cows, with the exception of Glu and GGT. This may indicate that the nutritional level of feed for the Korean Hanwoo cows was higher than that of the Japanese Wagyu cows because of the different feeding system. In particular, relatively higher levels of UREA and LCFA were observed in the Korean Hanwoo cows, and this may also contribute to the low reproduction efficiency. Conclusions： These findings may provide some theoretical basis for understanding the reproductive and feeding situation of Korean Hanwoo cows.
文摘Metabolic-associated fatty liver disease(MAFLD)refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide.Although metabolism is highly influenced by the effects of sex hormones,studies of sex differences in the incidence and progression of MAFLD are scarce.Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms.First,metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time.Second,metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers.Some studies demonstrate associations between circulating metabolites and early and established MAFLD,but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management.In this review,we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD,the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers,and how this evidence may help in the future management of the disease.
基金supported by China Agriculture Research System(CARS-15-27)Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences.
文摘Background: The diversified and high value-added utilization of cotton by products can promote the sustainable development of modern agriculture. Di erences in potential nutrients among varieties can be explained by variations in the composition and abundance of fatty acids, polyphenols, carbohydrates, amino acids, and organic acids. Therefore, the analysis of metabolite species and relationships in cottonseed is meaningful for the development of cotton byproducts.Results: In this study, the metabolomes of three representative cotton cultivars of di erent species were compared using untargeted GC-TOF/MS analysis. A total of 263 metabolites were identified from 705 peaks, and their levels were compared across cultivars. Principal component analysis and OPLS-DA clearly distinguish these samples based on metabolites. There were significant di erences in the contents of amino acids, carbohydrates, organic acids, flavonoids, and lipids in G. hirsutum TM-1 compared with G. arboreum Shixiya1 and G. barbadense Hai7124. Notably, the bioactive nutrient compound catechin obtained from the di erential metabolites significantly accumulated in TM-1. Furthermore, a comprehensive analysis using catechin and oil-related traits was conducted in core collections of Gossypium hirsutum. The results revealed the reliability of the GC-TOF/MS analysis, as well as that catechin content has a negative association with myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and total fatty acids.Conclusion: These findings suggest that untargeted GC-TOF/MS analysis could provide a new method for investigating the underlying plant biochemistry of nutrient variation in cottonseed, and that catechin content has a negative association with oil-related traits in cottonseed. This study may pave the way to exploit the value of cotton byproducts.
