PubMed

Metabolomics Differential Analysis Reveals Clinostat Rotation Affects Metabolite Transportation and Increases Organic Acid Production of Aspergillus carbonarius. Appl Environ Microbiol. 2019 Jul 12;: Authors: Jiang C, Guo D, Li Z, Lei S, Shi J, Shao D Abstract Contamination by fungi may pose a threat to the long-term operation of the space station because fungi produce organic acids that corrode equipment and mycotoxins that harm human health. Microgravity is an unavoidable and special condition in the space station. However, the influence of microgravity on fungal metabolism has not been well studied. Clinostat rotation is widely used to simulate the microgravity condition in studies carried out on Earth. Here, we used metabolomics differential analysis to study the influence of clinostat rotation on the accumulation of organic acids and related biosynthetic pathways in ochratoxin A (OTA)-producing Aspergillus carbonarius As results, clinostat rotation did not affect fungal cell growth or colony appearance, but significantly increased the accumulation of organic acids and OTA both inside cells and in the medium, particularly isocitric acid, citric acid, oxalic acid, as well as a much higher accumulation of some products inside than outside cells, indicating that transport of these metabolites from the cell to the medium was inhibited. This finding corresponded with the change in fatty acid composition of cell membranes and reduced thickness of the cell walls and cell membranes. Amino acid and energy metabolic pathways, particularly the TCA cycle was influenced the most during clinostat rotation compared to normal gravity.IMPORTANCEFungi are ubiquitous in nature and have the ability to corrode various materials by producing metabolites. Research on how the space station environment, especially microgravity, affects fungal metabolism is helpful to understand the role of fungi in space station. This work provides insights on the mechanisms involved in metabolism of corrosive fungus Aspergillus carbonarius under simulated microgravity condition. Our findings have significance not only for preventing material corrosion, but also for ensuring food safety, especially in the space environment. PMID: 31300399 [PubMed - as supplied by publisher]

23 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 2019/07/13PubMed 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.

17 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 2019/07/12PubMed 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.

Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study. Mol Nutr Food Res. 2019 Jul 10;:e1900140 Authors: Hernández-Alonso P, Papandreou C, Bulló M, Ruiz-Canela M, Dennis C, Deik A, Wang DD, Guasch-Ferré M, Yu E, Toledo E, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Serra-Majem L, Liang L, Clish CB, Martínez-González MA, Hu FB, Salas-Salvadó J Abstract SCOPE: The relationship between red wine (RW) consumption and metabolism is poorly understood. We aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS: Cross-sectional analysis of 1,157 participants. Subjects were divided as non-RW consumers versus RW consumers (> 1 glass/day RW (100 mL/day)). Plasma metabolomics analysis was performed using LC-MS. Associations between 386 identified metabolites and RW consumption were assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) was performed and receiver operating characteristic curves were constructed in each of the validation datasets based on weighted models. A subset of 13 metabolites was consistently selected and discriminated RW consumers versus non-consumers. Based on the multi-metabolite model weighted with the regression coefficients of metabolites, the area under the curve was 0.83 (95% CI: 0.80-0.86). These metabolites mainly consisted of lipid species (e.g. triglycerides and phosphatidylcholines), some organic acids and alkaloids. CONCLUSIONS: A multi-metabolite model identified in a Mediterranean population appeared useful to discriminate between frequent RW consumers and non-consumers. Further studies are needed to assess the contribution of these metabolites in health and disease. This article is protected by copyright. All rights reserved. PMID: 31291050 [PubMed - as supplied by publisher]

Deep Metabolomics of a High-Grade Serous Ovarian Cancer Triple-Knockout Mouse Model. J Proteome Res. 2019 Jul 10;: Authors: Huang D, Gaul DA, Nan H, Kim J, Fernández FM Abstract High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer (OC) type, accounting for 70-80% of OC deaths. This high mortality is largely due to late diagnosis. Early detection is thus crucial to reduce mortality, yet the tumor pathogenesis of HGSC remains poorly understood, making early detection exceedingly difficult. Faithfully and reliably representing the clinical nature of human HGSC, a recently developed triple-knockout (TKO) mouse model offers a unique opportunity to examine the entire disease spectrum of HGSC. Metabolic alterations were investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to serum samples collected from these mice at premalignant, early, and advanced stages of HGSC. This comprehensive analysis revealed a panel of 29 serum metabolites that distinguished mice with HGSC from controls and mice with uterine tumors with over 95% accuracy. Meanwhile, our panel could further distinguish early-stage HGSC from controls with 100% accuracy and from advanced-stage HGSC with over 90% accuracy. Important identified metabolites included phospholipids, sphingomyelins, sterols, N-acyltaurine, oligopeptides, bilirubin, 2(3)-hydroxysebacic acids, uridine, N-acetylneuraminic acid, and pyrazine derivatives. Overall, our study provides insights into dysregulated metabolism associated with HGSC development and progression, and serves as a useful guide toward early detection. PMID: 31290664 [PubMed - as supplied by publisher]

A large-scale analysis of targeted metabolomics data from heterogeneous biological samples provides insights into metabolite dynamics. Metabolomics. 2019 Jul 09;15(7):103 Authors: Lee HJ, Kremer DM, Sajjakulnukit P, Zhang L, Lyssiotis CA Abstract INTRODUCTION: We previously developed a tandem mass spectrometry-based label-free targeted metabolomics analysis framework coupled to two distinct chromatographic methods, reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), with dynamic multiple reaction monitoring (dMRM) for simultaneous detection of over 200 metabolites to study core metabolic pathways. OBJECTIVES: We aim to analyze a large-scale heterogeneous data compendium generated from our LC-MS/MS platform with both RPLC and HILIC methods to systematically assess measurement quality in biological replicate groups and to investigate metabolite abundance changes and patterns across different biological conditions. METHODS: Our metabolomics framework was applied in a wide range of experimental systems including cancer cell lines, tumors, extracellular media, primary cells, immune cells, organoids, organs (e.g. pancreata), tissues, and sera from human and mice. We also developed computational and statistical analysis pipelines, which include hierarchical clustering, replicate-group CV analysis, correlation analysis, and case-control paired analysis. RESULTS: We generated a compendium of 42 heterogeneous deidentified datasets with 635 samples using both RPLC and HILIC methods. There exist metabolite signatures that correspond to various phenotypes of the heterogeneous datasets, involved in several metabolic pathways. The RPLC method shows overall better reproducibility than the HILIC method for most metabolites including polar amino acids. Correlation analysis reveals high confidence metabolites irrespective of experimental systems such as methionine, phenylalanine, and taurine. We also identify homocystine, reduced glutathione, and phosphoenolpyruvic acid as highly dynamic metabolites across all case-control paired samples. CONCLUSIONS: Our study is expected to serve as a resource and a reference point for a systematic analysis of label-free LC-MS/MS targeted metabolomics data in both RPLC and HILIC methods with dMRM. PMID: 31289941 [PubMed - in process]

Insights into Allosteric Control of Human Blood Group A and B Glycosyltransferases from Dynamic NMR. ChemistryOpen. 2019 Jun;8(6):760-769 Authors: Flügge F, Peters T Abstract Human blood group A and B glycosyltransferases (GTA, GTB) are retaining glycosyltransferases, requiring a catalytic mechanism that conserves the anomeric configuration of the hexopyranose moiety of the donor substrate (UDP-GalNAc, UDP-Gal). Previous studies have shown that GTA and GTB cycle through structurally distinct states during catalysis. Here, we link binding and release of substrates, substrate-analogs, and products to transitions between open, semi-closed, and closed states of the enzymes. Methyl TROSY based titration experiments in combination with zz-exchange experiments uncover dramatic changes of binding kinetics associated with allosteric interactions between donor-type and acceptor-type ligands. Taken together, this highlights how allosteric control of on- and off-rates correlates with conformational changes, driving catalysis to completion. PMID: 31289712 [PubMed]

Global serum metabolomics profiling of colorectal cancer. Mol Clin Oncol. 2019 Jul;11(1):3-14 Authors: Hashim NAA, Ab-Rahim S, Suddin LS, Saman MSA, Mazlan M Abstract Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC. PMID: 31289671 [PubMed]

Ectopic defense gene expression is associated with growth defects in Medicago truncatula lignin pathway mutants. Plant Physiol. 2019 Jul 09;: Authors: Ha CM, Fine D, Bhatia A, Rao X, Martin M, Engle N, Wherritt DJ, Tschaplinski T, Sumner L, Dixon RA Abstract Lignin provides essential mechanical support for plant cell walls but decreases the digestibility of forage crops and increases the recalcitrance of biofuel crops. Attempts to modify lignin content and/or composition by genetic modification often result in negative growth effects. Although several studies have attempted to address the basis for such effects in individual transgenic lines, no common mechanism linking lignin modification with perturbations in plant growth and development has yet been identified. To address whether a common mechanism exists, we have analyzed transposon insertion mutants resulting in independent loss of function of five enzymes of the monolignol pathway, as well as one double mutant, in the model legume Medicago truncatula. These plants exhibit growth phenotypes from essentially wild-type to severely retarded. Extensive phenotypic, transcriptomic, and metabolomics analyses, including structural characterization of differentially expressed compounds, revealed diverse phenotypic consequences of lignin pathway perturbation that were perceived early in plant development, but were not predicted by lignin content or composition alone. Notable phenotypes among the mutants with severe growth impairment were increased trichome numbers, accumulation of a variety of triterpene saponins, and extensive but differential ectopic expression of defense response genes. No currently proposed model explains the observed phenotypes across all lines. We propose that re-allocation of resources into defense pathways is linked to the severity of the final growth phenotype in monolignol pathway mutants of Medicago, although it remains unclear as to whether this is a cause or an effect of the growth impairment. PMID: 31289215 [PubMed - as supplied by publisher]

Novel pyrrolo[3,2-d]pyrimidine compounds target mitochondrial and cytosolic one-carbon metabolism with broad-spectrum antitumor efficacy. Mol Cancer Ther. 2019 Jul 09;: Authors: Dekhne AS, Shah K, Ducker GS, Katinas JM, Wong-Roushar J, Nayeen MJ, Doshi A, Ning C, Bao X, Frühauf J, Liu J, Wallace-Povirk A, O'Connor C, Dzinic SH, White K, Kushner J, Kim S, Hüttemann M, Polin L, Rabinowitz JD, Li J, Hou Z, Dann CE, Gangjee A, Matherly LH Abstract Folate-dependent one-carbon (C1) metabolism is compartmentalized into the mitochondria and cytosol and supports cell growth through nucleotide and amino acid biosynthesis. Mitochondrial C1 metabolism, including serine hydroxymethyltransferase (SHMT) 2, provides glycine, NAD(P)H, ATP, and C1 units for cytosolic biosynthetic reactions, and is implicated in the oncogenic phenotype across a wide range of cancers. Whereas multi-targeted inhibitors of cytosolic C1 metabolism such as pemetrexed are used clinically, there are currently no anticancer drugs that specifically target mitochondrial C1 metabolism. We used molecular modeling to design novel small-molecule pyrrolo[3,2-d]pyrimidine inhibitors targeting mitochondrial C1 metabolism at SHMT2. In vitro antitumor efficacy was established with the lead compounds (AGF291, AGF320, AGF347) toward lung, colon, and pancreatic cancer cells. Intracellular targets were identified by metabolic rescue with glycine and nucleosides, and by targeted metabolomics using a stable isotope tracer, with confirmation by in vitro assays with purified enzymes. In addition to targeting SHMT2, inhibition of the cytosolic purine biosynthetic enzymes, β-glycinamide ribonucleotide formyltransferase and/or 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase, and SHMT1 was also established. AGF347 generated significant in vivo antitumor efficacy with potential for complete responses against both early stage and upstage MIA PaCa-2 pancreatic tumor xenografts, providing compelling proof-of-concept for therapeutic targeting of SHMT2 and cytosolic C1 enzymes by this series. Our results establish structure-activity relationships and identify exciting new drug prototypes for further development as multi-targeted antitumor agents. PMID: 31289137 [PubMed - as supplied by publisher]

Comparison and Discrimination of Artemisia argyi and Artemisia lavandulifolia by Gas Chromatography-Mass Spectrometry-Based Metabolomic Approach. J AOAC Int. 2019 Jul 09;: Authors: Guo L, Zhang D, Wang L, Xue Z, Guo M, Duan L, Zheng Y Abstract Background: Artemisia argyi and A. lavandulifolia are two morphologically similar herbal medicines derived from the Artemisia genus. Although the two Artemisia herbs have been used as herbal medicines for a long time, studies on their phytochemicals and bioactive compositions are still limited, and no research has been devoted to compare the volatile compounds in A. argyi and A. lavandulifolia. Objective: To compare the volatile constituents in A. argyi and A. lavandulifolia and to explore chemical markers for discrimination and quality evaluation of the two Artemisia herbal medicines. Methods: A GC-MS-based metabolomic approach was employed to compare and discriminate A. argyi and A. lavandulifolia from the aspect of volatile compounds. Multivariate statistical methods, including principal component analysis and orthogonal partial least-squares discriminate analysis, were applied to explore chemical markers for discrimination of the two Artemisia herbal medicines. Results: Thirty volatile compounds were identified, and the chemical profiles of volatile compounds in A. argyi and A. lavandulifolia were quite similar. Principal component analysis and orthogonal partial least-squares discrimination analysis results indicated that the two Artemisia herbal medicines could be distinguished effectively from each other. Ten volatile compounds were selected as potential chemical markers for discrimination of the two Artemisia herbal medicines. Conclusions: The GC-MS-based metabolomics could be an acceptable strategy for comparison and discrimination of A. argyi and A. lavandulifolia as well as authentication of herbal medicines derived from other closely related species. Highlights: GC-MS based metabolomic approach was firstly applied to compare and discriminate Artemisia argyi and Artemisia lavandulifolia. PMID: 31288892 [PubMed - as supplied by publisher]

Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity. Metabolites. 2019 Jul 08;9(7): Authors: Saoi M, Li A, McGlory C, Stokes T, von Allmen MT, Phillips SM, Britz-McKibbin P Abstract Sarcopenia is the age-related loss of skeletal muscle mass, strength and function, which may be accelerated during periods of physical inactivity. Declines in skeletal muscle and functionality not only impacts mobility but also increases chronic disease risk, such as type 2 diabetes. The aim of this study was to measure adaptive metabolic responses to acute changes in habitual activity in a cohort of overweight, pre-diabetic older adults (age = 69 ± 4 years; BMI = 27 ± 4 kg/m2, n = 17) when using non-targeted metabolite profiling by multisegment injection-capillary electrophoresis-mass spectrometry. Participants completed two weeks of step reduction (<1000 steps/day) followed by a two week recovery period, where fasting plasma samples were collected at three time intervals at baseline, after step reduction and following recovery. Two weeks of step reduction elicited increases in circulatory metabolites associated with a decline in muscle energy metabolism and protein degradation, including glutamine, carnitine and creatine (q < 0.05; effect size > 0.30), as well as methionine and deoxycarnitine (p < 0.05; effect size ≈ 0.20) as compared to baseline. Similarly, decreases in uremic toxins in plasma that promote muscle inflammation, indoxyl sulfate and hippuric acid, as well as oxoproline, a precursor used for intramuscular glutathione recycling, were also associated with physical inactivity (p < 0.05; effect size > 0.20). Our results indicate that older persons are susceptible to metabolic perturbations due to short-term step reduction that were not fully reversible with resumption of normal ambulatory activity over the same time period. These plasma biomarkers may enable early detection of inactivity-induced metabolic dysregulation in older persons at risk for sarcopenia not readily measured by current imaging techniques or muscle function tests, which is required for the design of therapeutic interventions to counter these deleterious changes in support of healthy ageing. PMID: 31288431 [PubMed]

Related Articles Deletion of TSPO Resulted in Change of Metabolomic Profile in Retinal Pigment Epithelial Cells. Int J Mol Sci. 2019 Mar 19;20(6): Authors: Alamri A, Biswas L, Watson DG, Shu X Abstract Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD. PMID: 30893912 [PubMed - indexed for MEDLINE]

Related Articles The biology of ageing and the omics revolution. Biogerontology. 2018 12;19(6):435-436 Authors: Harries L, Goljanek-Whysall K Abstract PMID: 30288632 [PubMed - indexed for MEDLINE]

Related Articles Transcription factor repertoire in Ashwagandha (Withania somnifera) through analytics of transcriptomic resources: Insights into regulation of development and withanolide metabolism. Sci Rep. 2017 11 30;7(1):16649 Authors: Tripathi S, Sangwan RS, Narnoliya LK, Srivastava Y, Mishra B, Sangwan NS Abstract Transcription factors (TFs) are important regulators of cellular and metabolic functions including secondary metabolism. Deep and intensive RNA-seq analysis of Withania somnifera using transcriptomic databases provided 3532 annotated transcripts of transcription factors in leaf and root tissues, belonging to 90 different families with major abundance for WD-repeat (174 and 165 transcripts) and WRKY (93 and 80 transcripts) in root and leaf tissues respectively, followed by that of MYB, BHLH and AP2-ERF. Their detailed comparative analysis with Arabidopsis thaliana, Capsicum annum, Nicotiana tabacum and Solanum lycopersicum counterparts together gave interesting patterns. However, no homologs for WsWDR representatives, LWD1 and WUSCHEL, were observed in other Solanaceae species. The data extracted from the sequence read archives (SRA) in public domain databases were subjected to re-annotation, re-mining, re-analysis and validation for dominant occurrence of WRKY and WD-repeat (WDR) gene families. Expression of recombinant LWD1 and WUSCHEL proteins in homologous system led to enhancements in withanolide content indicating their regulatory role in planta in the biosynthesis. Contrasting expression profiles of WsLWD1 and WsWUSCHEL provided tissue-specific insights for their participation in the regulation of developmental processes. The in-depth analysis provided first full-spectrum and comparative characteristics of TF-transcripts across plant species, in the perspective of integrated tissue-specific regulation of metabolic processes including specialized metabolism. PMID: 29192149 [PubMed - indexed for MEDLINE]

46 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 2019/07/10PubMed 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.

Related Articles Metabolomic Status of The Oral Cavity in Chronic Periodontitis. In Vivo. 2019 Jul-Aug;33(4):1165-1174 Authors: Gawron K, Wojtowicz W, Łazarz-Bartyzel K, Łamasz A, Qasem B, Mydel P, Chomyszyn-Gajewska M, Potempa J, Mlynarz P Abstract Chronic periodontitis is an inflammatory disease of tooth-supporting tissues associated with Porphyromonas gingivalis. Expansion and invasion of this bacterium into the periodontium is associated with changes in the metabolome of the oral cavity. MATERIALS AND METHODS: Metabolomics analysis of mouth washout and tongue swab samples based on proton nuclear magnetic resonance (1H-NMR) method was employed to determine metabolic status of the oral cavity in chronic periodontal disease. RESULTS: Mouth washout extracts contained a total of 23 metabolites and tongue swab extracts contained 17. Identified metabolites partially overlap with the content of saliva and gingival crevicular fluid. The colonization of the oral cavity of patients with periodontitis by bacteria was manifested in the change in levels of eight metabolites. CONCLUSION: NMR-based metabolomics analysis is a potentially useful methodological approach for monitoring the pathological processes observed in the oral cavity in the course of periodontitis. PMID: 31280206 [PubMed - in process]

Related Articles Untargeted liquid chromatography coupled with mass spectrometry reveals metabolic changes in nitrogen-deficient Isatis indigotica Fortune. Phytochemistry. 2019 Jul 04;166:112058 Authors: Cao YW, Qu RJ, Miao YJ, Tang XQ, Zhou Y, Wang L, Geng L Abstract Isatis indigotica Fortune is a popular herb in traditional Chinese medicine, and various types of metabolites are the basis for its pharmacological efficacy. The biosynthesis and accumulation of these metabolites are closely linked to nitrogen availability; the benefits of low nitrogen application on the environment and herb quality are increasingly prominent. To analyze metabolic changes in the leaves and roots of I.indigotica in nitrogen deficiency conditions, and to identify the pathways and metabolites induced by low nitrogen availability, we used untargeted liquid chromatography coupled with mass spectrometry (UHPLC-TripleTOF) to obtain metabolomics profiling of I.indigotica under two N-deficiency treatments (0 kg/hm2; 337.5 kg/hm2) and normal nitrogen treatment (675 kg/hm2). A total of 447 metabolites were annotated. Principal component analysis separated the three nitrogen treatments. A greater diversity of metabolites was observed in roots than in leaves under N-deficiency treatments, suggesting that roots have a more important function in low N tolerance. Differential metabolites were mainly enriched in purine metabolism, phenylpropanoid biosynthesis, the shikimate pathway, tryptophan metabolism, and flavonoid biosynthesis that notably induced only in leaves in low nitrogen stress. Moderate N-deficiency benefits carbohydrate accumulation, whereas accumulation of most amino acids decreases. Uniquely, L-tryptophan was maintained at a high concentration in N-deficiency conditions. Low nitrogen stress induced the accumulation of some specialized metabolites (matairesinol, dictamnine, 5-hydroxyindoleacetate (serotonin) in roots and vitexin, xanthohumol, sinapyl alcohol in leaves). N-deficiency also increased the accumulation of adenosine and quality indicators of I.indigotica (indirubin-indigo, epigoitrin and anthranilic acid) in a certain degree. Our findings showed that nitrogen deficiency modified roots and leaves conditions of I.indigotica, affecting both the primary and secondary metabolism. Moderate nitrogen reduction was beneficial to the accumulation of active ingredients. Our methods and analysis are expected to provide an insight regarding the diversity of metabolites and regulation of their synthesis in low nitrogen application, and better investigate the nitrogen deficiency effect on I.indigotica. PMID: 31280093 [PubMed - as supplied by publisher]

Related Articles Application of metabolomics for unveiling the therapeutic role of traditional Chinese medicine in metabolic diseases. J Ethnopharmacol. 2019 Jul 04;:112057 Authors: Wu G, Zhang W, Li H Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine has been practiced for thousands of years in China and some Asian countries. Traditional Chinese Medicine (TCM) is characterized as multi-component and multiple targets in disease therapy, and it is a great challenge for elucidating the mechanisms of TCM. AIM OF THE REVIEW: Comprehensively summarize the application of metabolomics in biomarker discovery, stratification of TCM syndromes, and mechanism underlying TCM therapy on metabolic diseases. METHODS: This review systemically searched the publications with key words such as metabolomics, traditional Chinese medicine, metabolic diseases, obesity, cardiovascular disease, diabetes mellitus in "Title OR Abstract" in major databases including PubMed, the Web of Science, Google Scholar, Science Direct, CNKI from 2010 to 2019. RESULTS: A total of 135 papers was searched and included in this review. An overview of articles indicated that metabolic characteristics may be a hallmark of different syndromes/models of metabolic diseases, which provides a new perspective for disease diagnosis and therapeutic optimization. Moreover, TCM treatment has significantly altered the metabolic perturbations associated with metabolic diseases, which may be an important mechanism for the therapeutic effect of TCM. CONCLUSIONS: Until now, many metabolites and differential biomarkers related to the pathogenesis of metabolic diseases and TCM therapy have been discovered through metabolomics research. Unfortunately, the biological role and mechanism of disease-related metabolites were largely unclarified so far, which warrants further investigation. PMID: 31279867 [PubMed - as supplied by publisher]

Related Articles A 1H-NMR based study of hemolymph metabonomics in different resistant silkworms, Bombyx mori (Lepidotera), after BmNPV inoculation. J Insect Physiol. 2019 Jul 04;:103911 Authors: Wang XY, Shao ZM, Zhang YJ, Vu TT, Wu YC, Xu JP, Deng MJ Abstract Bombyx mori nucleopolyhedrovirus (BmNPV) is a primary silkworm pathogen, and the molecular mechanism of silkworm defense to BmNPV infection is still unclear. Herein, comparative metabolomics was adopted to analyze the variations in the hemolymph metabolites of different resistant silkworm strains following BmNPV inoculation using a 1H-NMR method. Trehalose, as an instant source of energy, plays a crucial role in the response to pathogen infections in insects. The level of trehalose was persistently upregulated in the hemolymph of the resistant silkworm strain YeA following infection with BmNPV, compared to that of the susceptible strain YeB, indicating that trehalose metabolism plays a vital role in the response to BmNPV infection. The significant upregulation of TCA cycle relevant metabolites, including malate, fumarate, citrate, succinate, and α-ketoglutarate, was identified at 0 h, 12 h, 48 h, and 96 h post-infection in YeA hemolymph, whereas a significant upregulation in YeB hemolymph was only detected at an early stage of infection (0 h-24 h). The expression level of selected key metabolic enzymes, determined using RT-qPCR, validated the differences in trehalose and TCA cycle relevant metabolite levels. The variations in branched-chain amino acid (BCAA) pathway relevant metabolites in resistant silkworm strains following BmNPV infection showed a regular undulation at different times after infection. A significant accumulation of phenylalanine and tyrosine was observed in YeA following BmNPV infection compared to YeB. The glycolysis and gluconeogenesis pathways showed a relatively low activity in YeA following BmNPV infection. Moreover, the levels of other metabolites related to fat metabolism, transamination, energy metabolism, and glycometabolism, such as glycine, threonine, glutamine, and glutamate, were unstable in the two silkworm strains following BmNPV infection. Thus, our study provides an overview of the metabolic response of the silkworm in response to BmNPV infection, which lays the foundation for clarifying the mechanism of silkworm resistance to BmNPV infection. PMID: 31279633 [PubMed - as supplied by publisher]