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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 16 min ago

Metabolic changes induced by oral glucose tests in horses and their diagnostic use.

Sun, 06/12/2020 - 14:30
Related Articles Metabolic changes induced by oral glucose tests in horses and their diagnostic use. J Vet Intern Med. 2020 Dec 05;: Authors: Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T Abstract BACKGROUND: Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. OBJECTIVES: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. ANIMALS: Twelve Icelandic horses in various metabolic states. METHODS: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis tandem mass spectrometry metabolomic assay. Insulin concentrations were measured using an ELISA. Analysis was performed using linear models and partial least-squares regression. RESULTS: The kynurenine : tryptophan ratio increased over time during the OGT (adjusted P-value = .001). A high insulin response was associated with lower arginine (adjusted P-value = .02) and carnitine (adjusted P-value = .03) concentrations. A predictive model using only baseline samples performed well with as few as 7 distinct metabolites (sensitivity, 86%; 95% confidence interval [CI], 81%-90%; specificity, 88%; 95% CI, 84%-92%). CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest induction of low-grade inflammation during the OGT. Plasma arginine and carnitine concentrations were lower in horses with high insulin response and could constitute potential therapeutic targets. Development of screening tools to identify insulin-dysregulated horses using only baseline blood sample appears promising. PMID: 33277752 [PubMed - as supplied by publisher]

Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture.

Sun, 06/12/2020 - 14:30
Related Articles Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture. Sci Rep. 2020 Dec 04;10(1):21244 Authors: Acevedo-Acevedo S, Millar DC, Simmons AD, Favreau P, Cobra PF, Skala M, Palecek SP Abstract Breast cancer metastasis occurs via blood and lymphatic vessels. Breast cancer cells 'educate' lymphatic endothelial cells (LECs) to support tumor vascularization and growth. However, despite known metabolic alterations in breast cancer, it remains unclear how lymphatic endothelial cell metabolism is altered in the tumor microenvironment and its effect in lymphangiogenic signaling in LECs. We analyzed metabolites inside LECs in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using [Formula: see text] nuclear magnetic resonance (NMR) metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk. LECs co-cultured with breast cancer cells exhibited cell-line dependent altered metabolic profiles, including significant changes in lactate concentration in breast cancer co-culture. Cell metabolic phenotype analysis using Seahorse showed LECs in co-culture exhibited reduced mitochondrial respiration, increased reliance on glycolysis and reduced metabolic flexibility. Optical redox ratio measurements revealed reduced NAD(P)H levels in LECs potentially due to increased NAD(P)H utilization to maintain redox homeostasis. [Formula: see text]-labeled glucose experiments did not reveal lactate shuttling into LECs from breast cancer cells, yet showed other [Formula: see text] signals in LECs suggesting internalized metabolites and metabolic exchange between the two cell types. We also determined that breast cancer co-culture stimulated lymphangiogenic signaling in LECs, yet activation was not stimulated by lactate alone. Increased lymphangiogenic signaling suggests paracrine signaling between LECs and breast cancer cells which could have a pro-metastatic role. PMID: 33277521 [PubMed - as supplied by publisher]

Alterations in One-Carbon Metabolism in Celiac Disease.

Sun, 06/12/2020 - 14:30
Related Articles Alterations in One-Carbon Metabolism in Celiac Disease. Nutrients. 2020 Dec 02;12(12): Authors: Martín-Masot R, Mota-Martorell N, Jové M, Maldonado J, Pamplona R, Nestares T Abstract Celiac disease (CD) is an autoimmune enteropathy associated with alterations of metabolism. Metabolomics studies, although limited, showed changes in choline, choline-derived lipids, and methionine concentrations, which could be ascribed to alterations in one-carbon metabolism. To date, no targeted metabolomics analysis investigating differences in the plasma choline/methionine metabolome of CD subjects are reported. This work is a targeted metabolomic study that analyzes 37 metabolites of the one-carbon metabolism in 17 children with CD, treated with a gluten-free diet and 17 healthy control siblings, in order to establish the potential defects in this metabolic network. Our results demonstrate the persistence of defects in the transsulfuration pathway of CD subjects, despite dietary treatment, while choline metabolism, methionine cycle, and folate cycle seem to be reversed and preserved to healthy levels. These findings describe for the first time, a metabolic defect in one-carbon metabolism which could have profound implications in the physiopathology and treatment of CD. PMID: 33276620 [PubMed - as supplied by publisher]

Single-Step Extraction Coupled with Targeted HILIC-MS/MS Approach for Comprehensive Analysis of Human Plasma Lipidome and Polar Metabolome.

Sun, 06/12/2020 - 14:30
Related Articles Single-Step Extraction Coupled with Targeted HILIC-MS/MS Approach for Comprehensive Analysis of Human Plasma Lipidome and Polar Metabolome. Metabolites. 2020 Dec 02;10(12): Authors: Medina J, van der Velpen V, Teav T, Guitton Y, Gallart-Ayala H, Ivanisevic J Abstract Expanding metabolome coverage to include complex lipids and polar metabolites is essential in the generation of well-founded hypotheses in biological assays. Traditionally, lipid extraction is performed by liquid-liquid extraction using either methyl-tert-butyl ether (MTBE) or chloroform, and polar metabolite extraction using methanol. Here, we evaluated the performance of single-step sample preparation methods for simultaneous extraction of the complex lipidome and polar metabolome from human plasma. The method performance was evaluated using high-coverage Hydrophilic Interaction Liquid Chromatography-ESI coupled to tandem mass spectrometry (HILIC-ESI-MS/MS) methodology targeting a panel of 1159 lipids and 374 polar metabolites. The criteria used for method evaluation comprised protein precipitation efficiency, and relative MS signal abundance and repeatability of detectable lipid and polar metabolites in human plasma. Among the tested methods, the isopropanol (IPA) and 1-butanol:methanol (BUME) mixtures were selected as the best compromises for the simultaneous extraction of complex lipids and polar metabolites, allowing for the detection of 584 lipid species and 116 polar metabolites. The extraction with IPA showed the greatest reproducibility with the highest number of lipid species detected with the coefficient of variation (CV) < 30%. Besides this difference, both IPA and BUME allowed for the high-throughput extraction and reproducible measurement of a large panel of complex lipids and polar metabolites, thus warranting their application in large-scale human population studies. PMID: 33276464 [PubMed - as supplied by publisher]

metabolomics; +17 new citations

Sat, 05/12/2020 - 14:21
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 2020/12/05PubMed 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; +21 new citations

Fri, 04/12/2020 - 14:14
21 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 2020/12/04PubMed 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; +17 new citations

Thu, 03/12/2020 - 14:06
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 2020/12/03PubMed 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; +41 new citations

Wed, 02/12/2020 - 17:02
41 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 2020/12/02PubMed 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; +23 new citations

Tue, 01/12/2020 - 13:58
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 2020/12/01PubMed 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.

Catechin-Rich Green Tea Extract and the Loss-of-TLR4 Signaling Differentially Alter the Hepatic Metabolome in Mice with Nonalcoholic Steatohepatitis.

Mon, 30/11/2020 - 13:53
Related Articles Catechin-Rich Green Tea Extract and the Loss-of-TLR4 Signaling Differentially Alter the Hepatic Metabolome in Mice with Nonalcoholic Steatohepatitis. Mol Nutr Food Res. 2020 Nov 28;:e2000998 Authors: Sasaki GY, Li J, Cichon MJ, Kopec RE, Bruno RS Abstract SCOPE: Catechin-rich green tea extract (GTE) limits inflammation in nonalcoholic steatohepatitis (NASH) consistent with a Toll-like receptor 4 (TLR4)-dependent mechanism. Our hypothesis was that GTE supplementation during NASH would shift the hepatic metabolome similar to that attributed to the loss-of-TLR4 signaling. METHODS AND RESULTS: Wild-type (WT) and loss-of-function TLR4-mutant (TLR4mut ) mice were fed a high-fat diet containing 0% or 2% GTE for 8 weeks prior to performing untargeted mass spectrometry-based metabolomics on liver tissue. The loss-of-TLR4 signaling and GTE shifted the hepatic metabolome away from that of WT mice. However, relatively few metabolites were altered by GTE in WT mice to the same extent as the loss-of-TLR4 signaling in TLR4mut mice. GTE increased acetyl-CoA precursors and spermidine to a greater extent than the loss-of-TLR4 signaling. Select metabolites associated with thiol metabolism were similarly affected by GTE and the loss-of-TLR4 signaling. Glycerophospholipid catabolites were decreased by GTE, but were unaffected in TLR4mut mice. Conversely, the loss-of-TLR4 signaling but not GTE increased several bile acid metabolites. CONCLUSION: GTE limitedly alters the hepatic metabolome consistent with a TLR4-dependent mechanism. This suggests that the anti-inflammatory activities of GTE and loss-of-TLR4 signaling that regulate hepatic metabolism to abrogate NASH are likely due to distinct mechanisms. This article is protected by copyright. All rights reserved. PMID: 33249742 [PubMed - as supplied by publisher]

A shift in abscisic acid/gibberellin balance underlies retention of dormancy induced by seed development temperature.

Mon, 30/11/2020 - 13:53
Related Articles A shift in abscisic acid/gibberellin balance underlies retention of dormancy induced by seed development temperature. Plant Cell Environ. 2020 Nov 28;: Authors: Tuan PA, Nguyen TN, Jordan MC, Ayele BT Abstract Through a combination of physiological, pharmacological, molecular and targeted metabolomics approaches, we showed that retention of wheat (Triticum aestivum L.) seed dormancy levels induced by low and high seed development temperature during post-desiccation phases is associated with modulation of GA level and seed responsiveness to ABA and GA via expression of TaABI5 and TaGAMYB, respectively. Dormancy retention during imbibition, however, is associated with modulations of both ABA level and responsiveness via expression of specific ABA metabolism (TaNCED2 and TaCYP707A1) and signaling (TaPYL2, TaSnRK2, TaABI3, TaABI4 and TaABI5) genes, and alterations in GA levels and responsiveness through expression of specific GA biosynthesis (TaGA20ox1, TaGA20ox2 and TaGA3ox2) and signaling (TaGID1 and TaGID2) genes, respectively. Expression patterns of GA signaling genes, TaRHT1 and TaGAMYB, lacked positive correlation with that of GA regulated genes and dormancy level observed in seeds developed at the two temperatures, implying their regulation at posttranscriptional level. Our results overall implicate that a shift in ABA/GA balance underlies retention of dormancy levels induced by seed development temperature during post-desiccation and imbibition phases. Consistently, genes regulated by ABA and GA during imbibition overlapped with those differentially expressed between imbibed seeds developed at the two temperatures and mediate different biological functions. This article is protected by copyright. All rights reserved. PMID: 33249604 [PubMed - as supplied by publisher]

Mapping choline metabolites in normal and transformed cells.

Mon, 30/11/2020 - 13:53
Related Articles Mapping choline metabolites in normal and transformed cells. Metabolomics. 2020 Nov 29;16(12):125 Authors: Roci I, Watrous JD, Lagerborg KA, Jain M, Nilsson R Abstract INTRODUCTION: Choline is an essential human nutrient that is particular important for proliferating cells, and altered choline metabolism has been associated with cancer transformation. Yet, the various metabolic fates of choline in proliferating cells have not been investigated systematically. OBJECTIVES: This study aims to map the metabolic products of choline in normal and cancerous proliferating cells. METHODS: We performed 13C-choline tracing followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis of metabolic products in normal and in vitro-transformed (tumor-forming) epithelial cells, and also in tumor-derived cancer cell lines. Selected metabolites were quantified by internal standards. RESULTS: Untargeted analysis revealed 121 LCMS peaks that were 13C-labeled from choline, including various phospholipid species, but also previously unknown products such as monomethyl- and dimethyl-ethanolamines. Interestingly, we observed formation of betaine from choline specifically in tumor-derived cells. Expression of choline dehydrogenase (CHDH), which catalyzes the first step of betaine synthesis, correlated with betaine synthesis across the cell lines studied. RNAi silencing of CHDH did not affect cell proliferation, although we observed an increased fraction of G2M phase cells with some RNAi sequences, suggesting that CHDH and its product betaine may play a role in cell cycle progression. Betaine cell concentration was around 10 µM, arguing against an osmotic function, and was not used as a methyl donor. The function of betaine in these tumor-derived cells is presently unknown. CONCLUSION: This study identifies novel metabolites of choline in cancer and normal cell lines, and reveals altered choline metabolism in cancer cells. PMID: 33249526 [PubMed - as supplied by publisher]

Longan (Dimocarpus longan Lour.) Aril ameliorates cognitive impairment in AD mice induced by combination of D-gal/AlCl3 and an irregular diet via RAS/MEK/ERK signaling pathway.

Mon, 30/11/2020 - 13:53
Related Articles Longan (Dimocarpus longan Lour.) Aril ameliorates cognitive impairment in AD mice induced by combination of D-gal/AlCl3 and an irregular diet via RAS/MEK/ERK signaling pathway. J Ethnopharmacol. 2020 Nov 26;:113612 Authors: Li H, Lei T, Zhang J, Yan Y, Wang N, Song C, Li C, Sun M, Li J, Guo Y, Yang J, Kang T Abstract ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as "forgetfulness" or "dementia", and it can be caused by spleen deficiency. Longan Aril (the aril of Dimocarpus longan Lour., LA) is a kind of Chinese medicine, and it can improve intelligence attributed to entering the spleen-meridian. This study aimed to explore the therapeutic effects of LA on AD mice with spleen deficiency, and to understand anti-AD mechanism of LA. MATERIAL AND METHODS: A mouse model of AD with spleen deficiency was established by D-gal (140 mg/kg, intraperitoneal injection) and AlCl3 (20 mg/kg, intragastrical administration) in combination with an irregular diet for 60 days, in which mice in LA group were daily given LA (0.5, 1.0 or 2.0 g/kg). The anti-AD effects of LA were evaluated by the Morris water maze, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E), Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The anti-AD mechanism of LA was studied by using metabolomics, and the expressions of RAS/MEK/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins were detected by Western blotting. RESULTS: LA improved learning and memory abilities, superoxide dismutase (SOD) level, and form and number of Nissl bodies, while reduced the levels of Aβ42, phosphorylated-tau (p-tau), reactive oxygen species (ROS), malondialdehyde (MDA), monoamine oxidase-B (MAO-B), histological injury, and apoptosis rate in AD group (P < 0.05, P < 0.01 or P < 0.001). The anti-AD mechanism of LA may be related to RAS/MEK/ERK and other signaling pathways, in which the expressions of RAS/MEK/ERK signaling pathway-related proteins significantly reduced (P < 0.05 or P < 0.01). CONCLUSIONS: LA could improve the cognitive ability and reduce the pathologic impairment in AD mice, which might be partly mediated via inhibition of RAS/MEK/ERK singling pathway. PMID: 33249246 [PubMed - as supplied by publisher]

Metabolomics in posttraumatic stress disorder: Untargeted metabolomic analysis of plasma samples from Croatian war veterans.

Mon, 30/11/2020 - 13:53
Related Articles Metabolomics in posttraumatic stress disorder: Untargeted metabolomic analysis of plasma samples from Croatian war veterans. Free Radic Biol Med. 2020 Nov 26;: Authors: Konjevod M, Erjavec GN, Perkovic MN, Sáiz J, Tudor L, Uzun S, Kozumplik O, Strac DS, Zarkovic N, Pivac N Abstract Posttraumatic stress disorder (PTSD) is a severe, multifactorial and debilitating neuropsychiatric disorder, which can develop in a subset of individuals as a result of the exposure to severe stress or trauma. Such traumatic experiences have a major impact on molecular, biochemical and cellular systems, causing psychological and somatic alterations that affect the whole organism. Although the etiology of PTSD is still unclear, it seems to involve complex interaction between various biological genetic and environmental factors. Metabolomics, as one of the rapidly developing "omics" techniques, might be a useful tool for determining altered metabolic pathways and stress-related metabolites as new potential biomarkers of PTSD. The aim of our study was to identify metabolites whose altered levels allow us to differentiate between patients with PTSD and healthy control individuals. The study included two cohorts. The first, exploratory, group included 50 Croatian veterans with PTSD and 50 healthy control subjects, whereas a validation group consisted of 52 veterans with PTSD and 52 control subjects. The metabolomic analysis of plasma samples was conducted using liquid chromatography coupled with mass spectrometry (LC-MS), as well as gas chromatography coupled with mass spectrometry (GC-MS). The LC-MS analysis determined significantly different levels of two glycerophospholipids, PE(18:1/0:0) and PC(18:1/0:0), between control subjects and PTSD patients in both cohorts. The altered metabolites might play a role in multiple cellular processes, including inflammation, mitochondrial dysfunction, membrane breakdown, oxidative stress and neurotoxicity, which could be associated with PTSD pathogenesis. PMID: 33249139 [PubMed - as supplied by publisher]

An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease.

Mon, 30/11/2020 - 13:53
Related Articles An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease. Neurobiol Dis. 2020 Nov 26;:105199 Authors: Kong G, Ellul S, Narayana VK, Kanojia K, Ha HTT, Li S, Renoir T, Cao KL, Hannan AJ Abstract BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the gut-brain-axis bidirectional communication via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12 weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n = 9 per group) at 12 weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile. RESULTS: Modelled time profiles of each species, KEGG Orthologs and bacterial genes, revealed heightened volatility in the R6/1 mice, indicating potential early effects of HD mutation in the gut. In addition to gut dysbiosis in R6/1 mice at 12 weeks of age, gut microbiome function was perturbed. In particular, the butanoate metabolism pathway was elevated, suggesting increased production of the protective SCFA, butyrate, in the gut. No significant alterations were found in the plasma butyrate and propionate levels in the R6/1 mice at 12 weeks of age. The statistical integration of the metagenomics and metabolomics unraveled several Bacteroides species that were negatively correlated with ATP and pipecolic acid in the plasma. CONCLUSIONS: The present study revealed the instability of the HD gut microbiome during the pre-motor symptomatic stage of the disease which may have dire consequences on the host's health. Perturbation of the HD gut microbiome function prior to significant cognitive and motor dysfunction suggest the potential role of the gut in modulating the pathogenesis of HD, potentially via specific altered plasma metabolites which mediate gut-brain signaling. PMID: 33249136 [PubMed - as supplied by publisher]

Effect of neonicotinoid dinotefuran on root exudates of Brassica rapa var. chinensis.

Mon, 30/11/2020 - 13:53
Related Articles Effect of neonicotinoid dinotefuran on root exudates of Brassica rapa var. chinensis. Chemosphere. 2020 Nov 19;:129020 Authors: Li X, Zhang M, Li Y, Yu X, Nie J Abstract Root exudates are released by plant roots and are important carrier substances for material exchange and information transmission among plants and the rhizosphere. In the present study, the effect of dinotefuran on root exudates of Chinese cabbage (Brassica rapa var. chinensis) was investigated. The physiological activities revealed that dinotefuran uptake caused oxidative stress in vegetable tissues even at low dinotefuran exposure levels. The metabolic profile of plant root exudates acquired by LC-QTOF/MS was clearly changed by dinotefuran, where the numbers of both up- and down-regulated MS peaks increased with increasing dinotefuran concentration. Under dinotefuran stress, some osmotic adjustment substances (proline and betaine) and defence-related metabolites (spermidine, phenylalanine and some phenolic acids) were significantly upregulated, which may help plants adapt to adverse environmental conditions. Specifically, the contents of some phenylalanine-derived secondary metabolites increased with increasing dinotefuran concentration, which may increase the external detoxification ability of plants. Moreover, respiration metabolism was significantly affected, where some intermediates in the TCA cycle (succinic acid and malic acid) were upregulated with low-level dinotefuran exposure; however, anaerobic respiration products (lactic acid and 3-phenyllactic acid) were accumulated at high exposure levels. In addition, the release of glucosinolates was significantly inhibited in both dinotefuran treatment groups. PMID: 33248730 [PubMed - as supplied by publisher]

Multi-omics integration in biomedical research - A metabolomics-centric review.

Mon, 30/11/2020 - 13:53
Related Articles Multi-omics integration in biomedical research - A metabolomics-centric review. Anal Chim Acta. 2021 Jan 02;1141:144-162 Authors: Wörheide MA, Krumsiek J, Kastenmüller G, Arnold M Abstract Recent advances in high-throughput technologies have enabled the profiling of multiple layers of a biological system, including DNA sequence data (genomics), RNA expression levels (transcriptomics), and metabolite levels (metabolomics). This has led to the generation of vast amounts of biological data that can be integrated in so-called multi-omics studies to examine the complex molecular underpinnings of health and disease. Integrative analysis of such datasets is not straightforward and is particularly complicated by the high dimensionality and heterogeneity of the data and by the lack of universal analysis protocols. Previous reviews have discussed various strategies to address the challenges of data integration, elaborating on specific aspects, such as network inference or feature selection techniques. Thereby, the main focus has been on the integration of two omics layers in their relation to a phenotype of interest. In this review we provide an overview over a typical multi-omics workflow, focusing on integration methods that have the potential to combine metabolomics data with two or more omics. We discuss multiple integration concepts including data-driven, knowledge-based, simultaneous and step-wise approaches. We highlight the application of these methods in recent multi-omics studies, including large-scale integration efforts aiming at a global depiction of the complex relationships within and between different biological layers without focusing on a particular phenotype. PMID: 33248648 [PubMed - as supplied by publisher]

Effects of different stocking densities on tracheal barrier function and its metabolic changes in finishing broilers.

Mon, 30/11/2020 - 13:53
Related Articles Effects of different stocking densities on tracheal barrier function and its metabolic changes in finishing broilers. Poult Sci. 2020 Dec;99(12):6307-6316 Authors: Wang Y, Wang D, Wang J, Li K, Heng C, Jiang L, Cai C, Zhan X Abstract In the present study, we evaluated the effects of various stocking densities on the tracheal barrier and plasma metabolic profiles of finishing broilers. We randomly assigned 1,440 Lingnan Yellow feathered broilers (age 22 d) to 5 different stocking density groups (8 m-2, 10 m-2, 12 m-2, 14 m-2, and 16 m-2). Each of these consisted of 3 replicates. The interleukin (IL)-1β and IL-10 concentrations were substantially higher in the 16 m-2 treatment group than they were in the 8 m-2 and 10 m-2 treatment groups (P < 0.05). Nevertheless, IL-4 did not significantly differ among the 5 treatments (P > 0.05). The tracheal mucosae of the birds in the 16 m-2 group (high stocking density, HSD) were considerably thicker than those for the birds in the 10 m-2 group (control, CSD). Relative to CSD, the claudin1 expression level was lower, and the muc2 and caspase3 expression levels were higher for HSD. Compared with CSD, 10 metabolites were significantly upregulated (P < 0.05), and 7 were significantly downregulated (P < 0.05) in HSD. Most of these putative diagnostic biomarkers were implicated in matter biosynthesis and energy metabolism. A metabolic pathway analysis revealed that the most relevant and critical biomarkers were pentose and glucuronate interconversions and the pentose phosphate pathway. Activation of the aforementioned pathways may partially counteract the adverse effects of the stress induced by high stocking density. This work helped improve our understanding of the harmful effects of high stocking density on the tracheal barrier and identified 2 metabolic pathways that might be associated with high stocking density-induced metabolic disorders in broilers. PMID: 33248546 [PubMed - as supplied by publisher]

High-throughput metabolomics discovers metabolite biomarkers and insights the protective mechanism of schisandrin B on myocardial injury rats.

Sun, 29/11/2020 - 13:47
Related Articles High-throughput metabolomics discovers metabolite biomarkers and insights the protective mechanism of schisandrin B on myocardial injury rats. J Sep Sci. 2020 Nov 28;: Authors: Zhao LK, Zhao YB, Zhang PX Abstract Schisandrin B has been proved to possess anti-inflammatory and anti-endoplasmic effects, could improve cardiac function, inhibit apoptosis, and reduce inflammation after ischemic injury. However, the detailed metabolic mechanism and potential pathways of Schisandrin B effects on myocardial injury are unclear. Metabolomics could yield in-depth mechanistic insights and explore the potential therapeutic effect of natural products. In this study, the preparation of doxorubicin-induced myocardial injury rat model for evaluation of Schisandrin B on viral myocarditis sequelae related pathological changes and its mechanism. The metabolite profiling of myocardial injury rats was performed through ultra-high performance liquid chromatography combined with mass spectrometry combined with pattern recognition approaches and pathway analysis. A total of 15 metabolites (9 in positive ion mode and 6 in negative ion mode) were considered as potential biomarkers of myocardial injury, and these metabolites may correlate with the regulation of Schisandrin B treatment. A total of 6 metabolic pathways are closely related to Schisandrin B treatment, including glycerophospholipid metabolism, sphingolipid metabolism, purine metabolism, etc. This study revealed the potential biomarkers and metabolic network pathways of myocardial injury, and illuminated the protective mechanism of Schisandrin B on myocardial injury. This article is protected by copyright. All rights reserved. PMID: 33247873 [PubMed - as supplied by publisher]

Changes of embryonic development, locomotor activity, and metabolomics in zebrafish co-exposed to chlorpyrifos and deltamethrin.

Sun, 29/11/2020 - 13:47
Related Articles Changes of embryonic development, locomotor activity, and metabolomics in zebrafish co-exposed to chlorpyrifos and deltamethrin. J Appl Toxicol. 2020 Nov 28;: Authors: Hu Y, Hu J, Li W, Gao Y, Tian Y Abstract Organophosphates (OPs) and pyrethroids (PYRs) are extensively used pesticides and often occur in the form of mixture, whereas little was known about their joint toxicities. We aim to investigate the individual and joint effects of OPs and PYRs exposure on zebrafish embryo by employing chlorpyrifos (CPF) and deltamethrin (DM) as representatives. Zebrafish embryos at 2 hours post fertilization (hpf) were exposed to CPF (4.80, 39.06, and 78.13 μg/L), DM exposure (0.06, 1.60, and 3.19 μg/L), and CPF + DM (4.80 + 0.06, 39.06 + 1.60, and 78.13 + 3.19 μg/L) until 144 hpf. Embryonic development, locomotor activity, and metabolomic changes were recorded and examined. Results displayed that individual exposure to CPF and DM significantly increased the mortality and malformation rate of zebrafish embryos, but decreased hatching rate was only found in CPF + DM co-exposure groups (p < .05). Meanwhile, individual CPF exposure had no detrimental effect on locomotor activity, high dose of individual CPF exposure decreased the swimming speed but had adaptability to the conversion from dark to light, whereas high dose of CPF + DM co-exposure exhibited not only significant decline in swimming speed but also no adaptability to the repeated stimulations, suggesting deficit in learning and memory function. In metabolomic analysis, individual CPF exposure mainly influenced the metabolism of glycerophospholipids and amino acids, individual DM exposure mainly influenced glycerophospholipids, and CPF + DM co-exposure mainly influenced glycerophospholipids and amino acids. Taken together, our findings suggested the embryonic toxicities and neurobehavioral changes caused by CPF and/or DM exposure. The disorder metabolomics of glycerophospholipids and amino acids might be involved in the underlying mechanism of those toxicities. PMID: 33247449 [PubMed - as supplied by publisher]

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