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 24 min ago

Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens.

Sun, 21/02/2021 - 13:01
Related Articles Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens. Cardiovasc Drugs Ther. 2021 Feb 20;: Authors: Gallogly S, Fujisawa T, Hung JD, Brittan M, Skinner EM, Mitchell AJ, Medine C, Luque N, Zodda E, Cascante M, Hadoke PW, Mills NL, Tura-Ceide O Abstract PURPOSE: Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. METHODS: In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. RESULTS: CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. CONCLUSIONS: CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes. PMID: 33608862 [PubMed - as supplied by publisher]

The glycosyltransferase UGT76B1 modulates N-hydroxy-pipecolic acid homeostasis and plant immunity.

Sun, 21/02/2021 - 13:01
Related Articles The glycosyltransferase UGT76B1 modulates N-hydroxy-pipecolic acid homeostasis and plant immunity. Plant Cell. 2021 Jan 11;: Authors: Mohnike L, Rekhter D, Huang W, Feussner K, Tian H, Herrfurth C, Zhang Y, Feussner I Abstract The tradeoff between growth and defense is a critical aspect of plant immunity. Therefore, the plant immune response needs to be tightly regulated. Salicylic acid (SA) is an important plant hormone regulating defense against biotrophic pathogens. Recently, N-hydroxy-pipecolic acid (NHP) was identified as another regulator for plant innate immunity and systemic acquired resistance (SAR). Although the biosynthetic pathway leading to NHP formation is already been identified, how NHP is further metabolized is unclear. Here, we present UGT76B1 as a uridine diphosphate-dependent glycosyltransferase (UGT) that modifies NHP by catalyzing the formation of 1-O-glucosyl-pipecolic acid in Arabidopsis thaliana. Analysis of T-DNA and clustered regularly interspaced short palindromic repeats (CRISPR) knock-out mutant lines of UGT76B1 by targeted and nontargeted ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) underlined NHP and SA as endogenous substrates of this enzyme in response to Pseudomonas infection and UV treatment. ugt76b1 mutant plants have a dwarf phenotype and constitutive defense response which can be suppressed by loss of function of the NHP biosynthetic enzyme FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1). This suggests that elevated accumulation of NHP contributes to the enhanced disease resistance in ugt76b1. Externally applied NHP can move to distal tissue in ugt76b1 mutant plants. Although glycosylation is not required for the long-distance movement of NHP during SAR, it is crucial to balance growth and defense. PMID: 33608715 [PubMed - as supplied by publisher]

Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings.

Sun, 21/02/2021 - 13:01
Related Articles Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings. Heart. 2021 Feb 19;: Authors: Iliou A, Mikros E, Karaman I, Elliott F, Griffin JL, Tzoulaki I, Elliott P Abstract Metabolomics, the comprehensive measurement of low-molecular-weight molecules in biological fluids used for metabolic phenotyping, has emerged as a promising tool to better understand pathways underlying cardiovascular disease (CVD) and to improve cardiovascular risk stratification. Here, we present the main methodologies for metabolic phenotyping, the methodological steps to analyse these data in epidemiological settings and the associated challenges. We discuss evidence from epidemiological studies linking metabolites to coronary heart disease and stroke. These studies indicate the systemic nature of CVD and identify associated metabolic pathways such as gut microbial cometabolism, branched-chain amino acids, glycerophospholipid and cholesterol metabolism, as well as activation of inflammatory processes. Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation. The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established. As sample sizes with high-dimensional molecular data increase in epidemiological settings, integration of metabolomic data across studies and platforms with other molecular data will lead to new understanding of the metabolic processes underlying CVD and contribute to identification of potentially novel preventive and pharmacological targets. Metabolic phenotyping offers a powerful tool in the characterisation of the molecular signatures of CVD, paving the way to new mechanistic understanding and therapies, as well as improving risk prediction of CVD patients. However, there are still challenges to face in order to contribute to clinically important improvements in CVD. PMID: 33608305 [PubMed - as supplied by publisher]

CANTARE: finding and visualizing network-based multi-omic predictive models.

Sun, 21/02/2021 - 13:01
Related Articles CANTARE: finding and visualizing network-based multi-omic predictive models. BMC Bioinformatics. 2021 Feb 19;22(1):80 Authors: Siebert JC, Saint-Cyr M, Borengasser SJ, Wagner BD, Lozupone CA, Görg C Abstract BACKGROUND: One goal of multi-omic studies is to identify interpretable predictive models for outcomes of interest, with analytes drawn from multiple omes. Such findings could support refined biological insight and hypothesis generation. However, standard analytical approaches are not designed to be "ome aware." Thus, some researchers analyze data from one ome at a time, and then combine predictions across omes. Others resort to correlation studies, cataloging pairwise relationships, but lacking an obvious approach for cohesive and interpretable summaries of these catalogs. METHODS: We present a novel workflow for building predictive regression models from network neighborhoods in multi-omic networks. First, we generate pairwise regression models across all pairs of analytes from all omes, encoding the resulting "top table" of relationships in a network. Then, we build predictive logistic regression models using the analytes in network neighborhoods of interest. We call this method CANTARE (Consolidated Analysis of Network Topology And Regression Elements). RESULTS: We applied CANTARE to previously published data from healthy controls and patients with inflammatory bowel disease (IBD) consisting of three omes: gut microbiome, metabolomics, and microbial-derived enzymes. We identified 8 unique predictive models with AUC > 0.90. The number of predictors in these models ranged from 3 to 13. We compare the results of CANTARE to random forests and elastic-net penalized regressions, analyzing AUC, predictions, and predictors. CANTARE AUC values were competitive with those generated by random forests and  penalized regressions. The top 3 CANTARE models had a greater dynamic range of predicted probabilities than did random forests and penalized regressions (p-value = 1.35 × 10-5). CANTARE models were significantly more likely to prioritize predictors from multiple omes than were the alternatives (p-value = 0.005). We also showed that predictive models from a network based on pairwise models with an interaction term for IBD have higher AUC than predictive models built from a correlation network (p-value = 0.016). R scripts and a CANTARE User's Guide are available at https://sourceforge.net/projects/cytomelodics/files/CANTARE/ . CONCLUSION: CANTARE offers a flexible approach for building parsimonious, interpretable multi-omic models. These models yield quantitative and directional effect sizes for predictors and support the generation of hypotheses for follow-up investigation. PMID: 33607938 [PubMed - as supplied by publisher]

metabolomics; +21 new citations

Sat, 20/02/2021 - 15:45
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 2021/02/20PubMed 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

Sat, 20/02/2021 - 12:45
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 2021/02/20PubMed 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; +25 new citations

Fri, 19/02/2021 - 15:38
25 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 2021/02/19PubMed 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; +25 new citations

Thu, 18/02/2021 - 12:27
25 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 2021/02/18PubMed 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; +35 new citations

Wed, 17/02/2021 - 15:21
35 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 2021/02/17PubMed 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; +35 new citations

Wed, 17/02/2021 - 12:20
35 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 2021/02/17PubMed 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; +19 new citations

Tue, 16/02/2021 - 15:12
19 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 2021/02/16PubMed 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.

Acute-onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro-pollutants.

Tue, 16/02/2021 - 09:11
Related Articles Acute-onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro-pollutants. Eur J Neurol. 2021 Feb 14;: Authors: Schneider F, Agin A, Baldacini M, Maurer L, Schenck M, Alemann M, Solis M, Helms J, Villette C, Artzner T, Kremer S, Heintz D Abstract BACKGROUND: COVID-19 affects the brain in various ways, among which delirium is worrying. We assessed whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome-patients after life-saving re-oxygenation. METHODS: We studied ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury, and seven controls with non-COVID encephalopathy. The assessment took place when the intractable delirium started at weaning off ventilation support. We performed brain magnetic resonance imaging (MRI), followed by standard cerebrospinal fluid (CSF)-analyses and assessment of CSF-erythropoietin (EPO) concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF-metabolomics using LC-HR-Mass Spectrometry. RESULTS: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] versus 9 [4.5; 12.5] days, p=0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p=0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter hemorrhages only in COVID+. In the latter, CSF-EPO concentration was lower (1.73 [1.6; 2.06] versus 3.04 [2.9; 3.91] mUI/ml, p= 0.01), and CSF-metabolomics indicated: a) increased compounds such as foodborne molecules (sequiterpenes), molecules from industrialized beverages, and micro-pollutants (di-ethanolamine); b) decreased molecules as incomplete breakdown-products of protein catabolism, and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+. CONCLUSIONS: Some COVID+ patients are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants. PMID: 33583103 [PubMed - as supplied by publisher]

Transcription-associated metabolomic adjustments in maize occur during combined drought and cold stress.

Tue, 16/02/2021 - 09:11
Related Articles Transcription-associated metabolomic adjustments in maize occur during combined drought and cold stress. Plant Physiol. 2021 Feb 04;: Authors: Guo Q, Li X, Niu L, Jameson PE, Zhou W Abstract Although simultaneous drought and cold stress occurs, especially in northwestern and eastern regions of China, and is an important factor limiting agricultural productivity, there are few studies focusing on plant responses to a combination of drought and cold stress. Here, by partially overlapping drought and cold stresses, we characterized the acclimation of maize (Zea mays B73) to these two stresses using physiological measurements, as well as comparative transcriptomics combined with metabolomics and hormonal analyses during the stress treatments and recovery stages. The combined drought and cold stress and drought stress alone were accompanied by a decline in photosynthetic capacity and enhanced transcriptional response, and subsequent recovery of these following removal from stress, whereas cold stress alone was accompanied by irreversible damage to photosynthetic capacity and chloroplast structure. The stress combination induced transcription-associated metabolomic alterations, in which raffinose, trehalose-6-phosphate, and proline accumulated, and monosaccharide abundance increased. Concomitantly, the increased abscisic acid (ABA) content and upregulated ABA signaling pathway may have provided the transcriptional regulation for the metabolic changes. In a parallel experiment, ABA treatments prior to exposure of the plants to cold stress primed the plants to survive the cold stress, thus confirming a key role for the endogenous ABA activated by the drought pretreatment in acclimation of the plants to cold. We present a model showing that the plant response to the combined stress is multi-faceted and reveal an ABA-dependent maize acclimation mechanism to the stress combination. PMID: 33582802 [PubMed - as supplied by publisher]

Alginate coating modifies the biological effects of cerium oxide nanoparticles to the freshwater bivalve Dreissena polymorpha.

Tue, 16/02/2021 - 09:11
Related Articles Alginate coating modifies the biological effects of cerium oxide nanoparticles to the freshwater bivalve Dreissena polymorpha. Sci Total Environ. 2021 Feb 04;773:145612 Authors: Della Torre C, Maggioni D, Nigro L, Farè F, Hamza H, Protano G, Magni S, Fontana M, Riccardi N, Chiara M, Caruso D, Binelli A Abstract The adsorption of biomacromolecules is a fundamental process that can alter the behaviour and adverse effects of nanoparticles (NPs) in natural systems. While the interaction of NPs with natural molecules present in the environment has been described, their biological impacts are largely unknown. Therefore, this study aims to provide a first evidence of the influence of biomolecules sorption on the toxicity of cerium oxide nanoparticles (CeO2NPs) towards the freshwater bivalve Dreissena polymorpha. To this aim, we compared naked CeO2NPs and coated with alginate and chitosan, two polysaccharides abundant in aquatic environments. Mussels were exposed to the three CeO2NPs (naked, chitosan- and alginate-coated) up to 14 days at 100 μg L-1, which is a concentration higher than the environmental one predicted for this type of NP. A suite of biomarkers related to oxidative stress and energy metabolism was applied, and metabolomics was also carried out to identify metabolic pathways potentially targeted by CeO2NPs. Results showed that the coating with chitosan reduced NP aggregation and increased the stability in water. Nonetheless, the Ce accumulation in mussels was similar in all treatments. As for biological effects, all three types of CeO2NPs reduced significantly the level of reactive oxygen species and the activity of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. The effect was more pronounced in individuals exposed to CeO2NPs coated with alginate, which also significantly induced the activity of the electron transport system. Metabolomics analysis of amino acid metabolism showed modulation only in mussels treated with CeO2NPs coated with alginate. In this group, 25 metabolites belonging to nucleotides, lipids/sterols and organic osmolytes were also modulated, suggesting that the nanoparticles affect energetic metabolism and osmoregulation of mussels. This study highlights the key role of the interaction between nanoparticles and natural molecules as a driver of nanoparticle ecotoxicity. PMID: 33582348 [PubMed - as supplied by publisher]

Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver.

Tue, 16/02/2021 - 09:11
Related Articles Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver. Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Feb 11;:158905 Authors: Singh MK, Jayarajan R, Varshney S, Upadrasta S, Singh A, Yadav R, Scaria V, Sengupta S, Shanmugam D, Shalimar, Sivasubbu S, Gandotra S, Sachidanandan C Abstract Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship is unclear. In a transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation of triglycerides. Transcriptomics and proteomics analysis of the IL6-OE liver revealed a deregulation of glycolysis/gluconeogenesis pathway, especially a striking down regulation of the glycolytic enzyme aldolase b. Metabolomics analysis by mass spectrometry showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for fatty liver. This mechanism may be relevant for NAFLD in lean individuals, an emerging class of NAFLD prevalent more in Asian Indian populations. PMID: 33582286 [PubMed - as supplied by publisher]

Effect of fractionated whole-brain irradiation on brain and plasma in a rat model: Metabolic, volumetric and histopathological changes.

Tue, 16/02/2021 - 09:11
Related Articles Effect of fractionated whole-brain irradiation on brain and plasma in a rat model: Metabolic, volumetric and histopathological changes. Neurochem Int. 2021 Feb 11;:104985 Authors: Bálentová S, Hnilicová P, Kalenská D, Baranovičová E, Muríň P, Hajtmanová E, Adamkov M Abstract In the present study, we investigated the correlation between histopathological, metabolic, and volumetric changes in the brain and plasma under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 32 Gy delivered in 4 fractions (dose 8 Gy per fraction) once a week on the same day for 4 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS) and imaging were used to detect metabolic and volumetric changes in the brain and plasma. Histopathological changes in the brain were determined by image analysis of immunofluorescent stained sections. Metabolic changes in the brain measured by 1H MRS before, 48 hours, and 9 weeks after the end of fWBI showed a significant decrease in the ratio of total N-acetylaspartate to total creatine (tNAA/tCr) in the corpus striatum. We found a significant decrease in glutamine + glutamate/ tCr (Glx/tCr) and, conversely, an increase in gamma-aminobutyric acid to tCr (GABA/tCr) in olfactory bulb (OB). The ratio of astrocyte marker myoinositol/tCr (mIns/tCr) significantly increased in almost all evaluated areas. Magnetic resonance imaging (MRI)-based brain volumetry showed a significant increase in volume, and a concomitant increase in the T2 relaxation time of the hippocampus. Proton nuclear magnetic resonance (1H NMR) plasma metabolomics displayed a significant decrease in the level of glucose and glycolytic intermediates and an increase in ketone bodies. The histomorphological analysis showed a decrease to elimination of neuroblasts, increased astrocyte proliferation, and a mild microglia response. The results of the study clearly reflect early subacute changes 9 to 11 weeks after fWBI with strong manifestations of brain edema, astrogliosis, and ongoing ketosis. PMID: 33582163 [PubMed - as supplied by publisher]

metabolomics; +23 new citations

Sun, 14/02/2021 - 14:55
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 2021/02/14PubMed 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; +29 new citations

Sat, 13/02/2021 - 14:46
29 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 2021/02/13PubMed 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; +27 new citations

Fri, 12/02/2021 - 14:38
27 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 2021/02/12PubMed 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.

metabolomics; +27 new citations

Thu, 11/02/2021 - 14:28
27 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 2021/02/11PubMed 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.

Pages