Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabolomics analyses to characterize metabolic alterations in Korean native calves by oral vitamin A supplementation.

Mon, 18/05/2020 - 00:41
Related Articles Metabolomics analyses to characterize metabolic alterations in Korean native calves by oral vitamin A supplementation. Sci Rep. 2020 May 15;10(1):8092 Authors: Peng DQ, Kim SJ, Lee HG Abstract Previous studies have reported that vitamin A administration in the birth stage of calves could promote preadipocyte and muscle development. However, the metabolic change after vitamin A administration remains unknown. Thus, the objective of this study was to perform metabonomics analyses to investigate the effect of vitamin A in Korean native calves. Ten newborn calves (initial average body weight: 30.4 kg [SD 2.20]) were randomly divided into two groups treated with or without vitamin A supplementation (0 IU vs. 25,000 IU vitamin A/day) for two months until weaning. Metabolic changes in the serum and longissimus dorsi muscle of calves were investigated using GC-TOF-MS and multivariate statistical analysis. As a result, ten metabolic parameters in the serum and seven metabolic parameters in the longissimus dorsi muscle were down-regulated in the vitamin A treatment group compared to those in the control group (VIP value > 1.0, p < 0.05). Both serum and longissimus dorsi muscle showed lower levels of cholesterol and myo-inositol in the vitamin A treatment group than in the control group (p < 0.05). These results indicate that vitamin A supplementation in the early growth period of calf could maintain the preadipocyte status, which can contribute to future adipogenesis in the intramuscular fat production of Korean native cattle. PMID: 32415141 [PubMed - as supplied by publisher]

Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal.

Mon, 18/05/2020 - 00:41
Related Articles Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal. Nat Commun. 2020 May 15;11(1):2420 Authors: Lau KX, Mason EA, Kie J, De Souza DP, Kloehn J, Tull D, McConville MJ, Keniry A, Beck T, Blewitt ME, Ritchie ME, Naik SH, Zalcenstein D, Korn O, Su S, Romero IG, Spruce C, Baker CL, McGarr TC, Wells CA, Pera MF Abstract Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells. PMID: 32415101 [PubMed - as supplied by publisher]

Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR -21-Peli1-c-Rel Pathway Prevents Autoimmunity.

Mon, 18/05/2020 - 00:41
Related Articles Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR -21-Peli1-c-Rel Pathway Prevents Autoimmunity. J Immunol. 2020 May 15;: Authors: Qiu R, Yu X, Wang L, Han Z, Yao C, Cui Y, Hou G, Dai D, Jin W, Shen N Abstract It is well known that some pathogenic cells have enhanced glycolysis; the regulatory network leading to increased glycolysis are not well characterized. In this study, we show that CNS-infiltrated pathogenic TH17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal TH17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic TH17 cells are highly glycolytic compared with nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo that show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-κB binding sites. Mechanistic studies reveal that miR-21 targets the E3 ubiquitin ligase Peli1-c-Rel pathway to promote glucose metabolism of pathogenic TH17 cells. Therapeutic targeting c-Rel-mediated glycolysis in pathogenic TH17 cells represses autoimmune diseases. These findings extend our understanding of the regulation TH17 cell glycolysis in vivo and provide insights for future therapeutic intervention to TH17 cell-mediated autoimmune diseases. PMID: 32414810 [PubMed - as supplied by publisher]

Untargeted metabolomics predicts the functional outcome of ischemic stroke.

Mon, 18/05/2020 - 00:41
Related Articles Untargeted metabolomics predicts the functional outcome of ischemic stroke. J Formos Med Assoc. 2020 May 13;: Authors: Chi NF, Chang TH, Lee CY, Wu YW, Shen TA, Chan L, Chen YR, Chiou HY, Hsu CY, Hu CJ Abstract BACKGROUND/PURPOSE: Metabolites in blood have been found associated with the occurrence of vascular diseases, but its role in the functional recovery of stroke is unclear. The aim of this study is to investigate whether the untargeted metabolomics at the acute stage of ischemic stroke is able to predict functional recovery. METHODS: One hundred and fifty patients with acute ischemic stroke were recruited and followed up for 3 months. Fasting blood samples within 7 days of stroke were obtained, liquid chromatography and mass spectrometry were applied to identify outcome-associated metabolites. The patients' clinical characteristics and identified metabolites were included for constructing the outcome prediction model using machine learning approaches. RESULTS: By using multivariate analysis, 220 differentially expressed metabolites (DEMs) were discovered between patients with favorable outcomes (modified Rankin Scale, mRS ≤ 2 at 3 months, n = 77) and unfavorable outcomes (mRS ≥ 3 at 3 months, n = 73). After feature selection, 63 DEMs were chosen for constructing the outcome prediction model. The predictive accuracy was below 0.65 when including patients' clinical characteristics, and could reach 0.80 when including patients' clinical characteristics and 63 selected DEMs. The functional enrichment analysis identified platelet activating factor (PAF) as the strongest outcome-associated metabolite, which involved in proinflammatory mediators release, arachidonic acid metabolism, eosinophil degranulation, and production of reactive oxygen species. CONCLUSION: Metabolomics is a potential method to explore the blood biomarkers of acute ischemic stroke. The patients with unfavorable outcomes had a lower PAF level compared to those with favorable outcomes. PMID: 32414667 [PubMed - as supplied by publisher]

PlantaSyst: Teaming up for Systems Biology and Biotechnology.

Mon, 18/05/2020 - 00:41
Related Articles PlantaSyst: Teaming up for Systems Biology and Biotechnology. Trends Plant Sci. 2020 May 12;: Authors: Gechev T, Georgiev MI, Fernie AR Abstract We describe the principles of PlantaSYST as an example for the novel European Teaming projects, funded under the 'Spreading Excellence and Widening Participation' Horizon 2020 program. The goal of the Teaming projects is to bridge the gap between research centers with low and high participation in the EU framework program. PMID: 32414602 [PubMed - as supplied by publisher]

A Metabolomic Approach for Predicting Diurnal Changes in Cortisol.

Mon, 18/05/2020 - 00:41
Related Articles A Metabolomic Approach for Predicting Diurnal Changes in Cortisol. Metabolites. 2020 May 13;10(5): Authors: Eshima J, Davis TJ, Bean HD, Fricks J, Smith BS Abstract Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods: We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results: The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion: This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time. PMID: 32414047 [PubMed - as supplied by publisher]

Role of the Mitochondrial Citrate-malate Shuttle in Hras12V-Induced Hepatocarcinogenesis: A Metabolomics-Based Analysis.

Mon, 18/05/2020 - 00:41
Related Articles Role of the Mitochondrial Citrate-malate Shuttle in Hras12V-Induced Hepatocarcinogenesis: A Metabolomics-Based Analysis. Metabolites. 2020 May 13;10(5): Authors: Lei C, Chen J, Li H, Fan T, Zheng X, Wang H, Zhang N, Liu Y, Luo X, Wang J, Wang A Abstract The activation of the Ras signaling pathway is a crucial process in hepatocarcinogenesis. Till now, no reports have scrutinized the role of dynamic metabolic changes in Ras oncogene-induced transition of the normal and precancerous liver cells to hepatocellular carcinoma in vivo. In the current study, we attempted a comprehensive investigation of Hras12V transgenic mice (Ras-Tg) by concatenating nontargeted metabolomics, transcriptomics analysis, and targeted-metabolomics incorporating [U-13C] glucose. A total of 631 peaks were detected, out of which 555 metabolites were screened. Besides, a total of 122 differently expressed metabolites (DEMs) were identified, and they were categorized and subtyped with the help of variation tendency analysis of the normal (W), precancerous (P), and hepatocellular carcinoma (T) liver tissues. Thus, the positive or negative association between metabolites and the hepatocellular carcinoma and Ras oncogene were identified. The bioinformatics analysis elucidated the hepatocarcinogenesis-associated significant metabolic pathways: glycolysis, mitochondrial citrate-malate shuttle, lipid biosynthesis, pentose phosphate pathway (PPP), cholesterol and bile acid biosynthesis, and glutathione metabolism. The key metabolites and enzymes identified in this analysis were further validated. Moreover, we confirmed the PPP, glycolysis, and conversion of pyruvate to cytosol acetyl-CoA by mitochondrial citrate-malate shuttle, in vivo, by incorporating [U-13C] glucose. In summary, the current study presented the comprehensive bioinformatics analysis, depicting the Ras oncogene-induced dynamic metabolite variations in hepatocarcinogenesis. A significant finding of our study was that the mitochondrial citrate-malate shuttle plays a crucial role in detoxification of lactic acid, maintenance of mitochondrial integrity, and enhancement of lipid biosynthesis, which, in turn, promotes hepatocarcinogenesis. PMID: 32414018 [PubMed - as supplied by publisher]

Metabolomics Analysis Reveals Global Metabolic Changes in the Evolved E. coli Strain with Improved Growth and 1-Butanol Production in Minimal Medium.

Mon, 18/05/2020 - 00:41
Related Articles Metabolomics Analysis Reveals Global Metabolic Changes in the Evolved E. coli Strain with Improved Growth and 1-Butanol Production in Minimal Medium. Metabolites. 2020 May 13;10(5): Authors: Laviña WA, Sakurai SSM, Pontrelli S, Putri SP, Fukusaki E Abstract Production of 1-butanol from microorganisms has garnered significant interest due to its prospect as a drop-in biofuel and precursor for a variety of commercially relevant chemicals. Previously, high 1-butanol titer has been reported in Escherichia coli strain JCL166, which contains a modified clostridial 1-butanol pathway. Although conventional and metabolomics-based strain improvement strategies of E. coli strain JCL166 have been successful in improving production in rich medium, 1-butanol titer was severely limited in minimal medium. To further improve growth and consequently 1-butanol production in minimal medium, adaptive laboratory evolution (ALE) using mutD5 mutator plasmid was done on JCL166. Comparative metabolomics analysis of JCL166 and BP1 revealed global perturbations in the evolved strain BP1 compared to JCL166 (44 out of 64 metabolites), encompassing major metabolic pathways such as glycolysis, nucleotide biosynthesis, and CoA-related processes. Collectively, these metabolic changes in BP1 result in improved growth and, consequently, 1-butanol production in minimal medium. Furthermore, we found that the mutation in ihfB caused by ALE had a significant effect on the metabolome profile of the evolved strain. This study demonstrates how metabolomics was utilized for characterization of ALE-developed strains to understand the overall effect of mutations acquired through evolution. PMID: 32414016 [PubMed - as supplied by publisher]

metabolomics; +24 new citations

Sat, 16/05/2020 - 15:13
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +24 new citations

Sat, 16/05/2020 - 12:12
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +24 new citations

Fri, 15/05/2020 - 14:56
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +20 new citations

Thu, 14/05/2020 - 17:42
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +20 new citations

Thu, 14/05/2020 - 14:41
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Wed, 13/05/2020 - 14:30
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +28 new citations

Tue, 12/05/2020 - 14:23
28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Evaluation of Quenching Methods for Metabolite Recovery in Photoautotrophic Synechococcus sp. PCC 7002.

Mon, 11/05/2020 - 14:18
Evaluation of Quenching Methods for Metabolite Recovery in Photoautotrophic Synechococcus sp. PCC 7002. Biotechnol Prog. 2020 May 10;:e3015 Authors: Sake CL, Newman DM, Boyle NR Abstract The first step of many metabolomics studies is quenching, a technique vital for rapidly halting metabolism and ensuring that the metabolite profile remains unchanging during sample processing. The most widely used approach is to plunge the sample into pre-chilled cold methanol, however, this led to significant metabolite loss in Synecheococcus sp. PCC 7002. Here we describe our analysis of the impacts of cold methanol quenching on the model marine cyanobacterium Synechococcus sp. PCC 7002, as well as our brief investigation of alternative quenching methods. We tested several methods including cold methanol, cold saline, and two filtration approaches. Targeted central metabolites were extracted and metabolomic profiles were generated using liquid chromatography mass spectrometry (LC-MS/MS). The results indicate that cold methanol quenching induces dramatic metabolite leakage in Synechococcus, resulting in a majority of central metabolites being lost prior to extraction. Alternatively, usage of a chilled saline quenching solution mitigates metabolite leakage and improves sample recovery without sacrificing rapid quenching of cellular metabolism. Finally, we illustrate that metabolite leakage can be assessed, and subsequently accounted for, in order to determine absolute metabolite pool sizes; however, our results show that metabolite leakage is inconsistent across various metabolite pools and therefore must be determined for each individually measured metabolite. PMID: 32388924 [PubMed - as supplied by publisher]

Higher dimensional metabolomics using stable isotope labeling for identifying the missing specialized metabolism in plants.

Mon, 11/05/2020 - 14:18
Higher dimensional metabolomics using stable isotope labeling for identifying the missing specialized metabolism in plants. Curr Opin Plant Biol. 2020 May 06;55:84-92 Authors: Nakabayashi R, Saito K Abstract The exact mechanics of specialized metabolism and its importance throughout plant evolution remain mysterious. Specialized metabolites and their corresponding biosynthetic genes are crucial to understand the reason for the prevalence of certain metabolism. Even though mass spectrometry-based metabolomics has enabled us to acquire data about the structural properties of unknown specialized metabolites as well as known metabolites and their corresponding isomers/analogs, extensive analytical approaches are still required. Herein, we review the most advanced analytical approaches using stable isotope labeling that can be used to identify the unknown specialized metabolites. PMID: 32388402 [PubMed - as supplied by publisher]

Green tea polyphenols boost gut-microbiota-dependent mitochondrial TCA and urea cycles in Sprague-Dawley rats.

Mon, 11/05/2020 - 14:18
Green tea polyphenols boost gut-microbiota-dependent mitochondrial TCA and urea cycles in Sprague-Dawley rats. J Nutr Biochem. 2020 Apr 08;81:108395 Authors: Zhou J, Tang L, Shen CL, Wang JS Abstract Green tea polyphenols (GTPs) were found to boost mammal energy conversion by modulating gut-microbial community structure, gene orthologs and metabolic pathways. Here we examined the metabolites present in the gut-microbiota-dependent mitochondrial tricarboxylic acid (TCA) cycle and urea cycle using hydrophilic interaction liquid chromatography (HILIC)-heated electrospray ionization (HESI)-tandem liquid chromatogram mass spectrometry (LC-MS). Six groups (n=12) of Sprague-Dawley rats (6-mo, ~250 g) were administered with water containing 0%, 0.5%, and 1.5% GTPs (wt/vol or g/dL). Gut-content samples were collected at 3- and 6-mo. Untargeted metabolomics detected 2177 features, with 91 features demonstrating significant dose- and time-dependencies on the GTPs treatment. Targeted metabolomics analysis revealed remarkable changes of 39 metabolites in the mitochondrial TCA cycle and urea cycle, including argininosuccunic acid (0.9-fold vs control), dihydrouracil (1.14-fold vs control), fumaric acid (1.19-fold vs control), malic acid (2.17-fold vs control), citrulline (1.86-fold vs control), and succinic acid (0.4-fold vs control). The untargeted metabolomics data were mined using bioinformatics approaches, such as analysis of variance-simultaneous component analysis (ASCA), enrichment pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping analysis. The results of 16S rRNA survey, metagenomics analysis, and metabolomics analysis were extrapolated and integrated using databases of Integrated Microbial Genomes and Microbiomes (IMG/M) and KEGG. Our analysis demonstrates that GTPs enhance energy conversion by boosting mitochondrial TCA cycle and urea cycle of gut-microbiota in rats. This metabolic modulation is achieved by enriching many gene orthologs, following the increase of beneficial microbials in families C. Ruminococcaceae, C. Lachnospiraceae and B. Bacteroidaceae. PMID: 32388254 [PubMed - as supplied by publisher]

Age-dependent characterization of volatile organic compounds and age discrimination in Chinese rice wine using an untargeted GC/MS-based metabolomic approach.

Mon, 11/05/2020 - 14:18
Age-dependent characterization of volatile organic compounds and age discrimination in Chinese rice wine using an untargeted GC/MS-based metabolomic approach. Food Chem. 2020 Apr 23;325:126900 Authors: Wang N, Chen S, Zhou Z Abstract An untargeted gas chromatography/mass spectrometry (GC/MS)-based metabolomics by XCMS-Online software combined with partial least squares regression (PLSR) was applied to characterize volatile organic compounds (VOCs) during Chinese rice wine aging and discriminate ages for the first time. Finally, seven different ages between 0 and 15 years were well discriminated by PLSR. Total 104 feature groups were isolated from all optimized candidate peaks, and 94 VOCs (including unknowns) were preliminarily identified as aging markers. Therein, alcohols, sulfides, phenols and their derivatives, small esters and acids exhibited significantly better discrimination of short-aged rice wines. Correspondingly, furans, aromatics, aldehydes, ketones, most esters and acids, discriminated the long-aged samples better. Meanwhile, the potential origins of certain VOCs were also proposed for further research. Overall, this untargeted GC/MS-based metabolomics coupled with PLSR was a feasible tool for a rapidly and globally age-dependent characterization of volatile metabolomic signals in Chinese rice wine and thus for age discrimination. PMID: 32387958 [PubMed - as supplied by publisher]

Antidepressant metabolomics study of Danzhi Xiaoyao powder on Rat Model of Chronic Unpredictable Mild Stress(CUMS).

Mon, 11/05/2020 - 14:18
Antidepressant metabolomics study of Danzhi Xiaoyao powder on Rat Model of Chronic Unpredictable Mild Stress(CUMS). J Ethnopharmacol. 2020 May 06;:112832 Authors: Zhu YL, Li SL, Zhu CY, Wang W, Zuo WF, Qiu XJ Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi Xiaoyao powder (DZXY) was a classical prescription, which has been extensively used in traditional Chinese medicine (TMC) to treat depression for many years. However, its concrete active compounds and its mechanism on depression are unclear. AIM OF THE STUDY: The aim was to investigate the mechanism of DZXY's antidepressant effect on Rat Model of Chronic Unpredictable Mild Stress(CUMS). MATERIALS AND METHODS: Forty male SD rats with similar Open Field Test (OFT) results were randomly divided into control group (n = 10) and experimental group (n = 30). Depression model was established on the experimental group using CUMS method. After the CUMS model was established successfully, rats were randomly divided into depression model group and DZXY group. DZXY group was fed with DZXY, while depression model group and control group were given an equal amount of 0.5% sodium carboxymethyl cellulose suspension. Intragastric administration was performed once daily for 14 consecutive days. The weight, sugar preference test, open field test and forced swimming test were used to evaluate the modeling effect and the antidepressant effect of DZXY. After the experiment, the plasma of rats was collected and the changes of plasma metabolites were detected by UPLC/Q-TOF-MS, and the dates of UPLC/Q-TOF-MS spectra have been analyzed by pattern recognition analysis to find out the changed endogenous metabolites in the rat's plasma samples. RESULTS: The results of behavioral investigation showed that the rat model of depression was successfully replicated, and DZXY had antidepressant effect. Using LC-MS/MS metabolomics platform, partial least squares (PLS) and orthogonal partial least squares (OPLS) metabolic profiling models (R2, Q2 ≥ 0.5) of rat plasma were successfully constructed. The model can distinguish the control group, the depression model group and the DZXY group. Finally, 38 differential metabolites were screened from plasma. According to the KEGG pathway analysis, the pathways of amino acid metabolism, lipid metabolism, purine metabolism, prolactin signaling pathway and bile secretion in plasma metabolism have a large weight, which is the main metabolic pathway. CONCLUSIONS: This study successfully established a rat CUMS depression model. A total of 38 differential metabolites associated with depression were identified in the plasma of rats, 24 of which were able to be modulated by DZXY. It is suggested that DZXY can improve the excitability and play an antidepressant role by regulating phenylalanine metabolism, arachidonic acid metabolism, porphyrin metabolism, D-arginine and D-ornithine metabolism, steroid hormone biosynthesis, unsaturated fatty acid biosynthesis and steroid biosynthesis. PMID: 32387465 [PubMed - as supplied by publisher]

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