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: 1 hour 40 min ago

Metabolomics analysis of microbiota-gut-brain axis in neurodegenerative and psychiatric diseases.

Mon, 07/12/2020 - 14:39
Related Articles Metabolomics analysis of microbiota-gut-brain axis in neurodegenerative and psychiatric diseases. J Pharm Biomed Anal. 2020 Nov 21;:113681 Authors: Konjevod M, Nikolac Perkovic M, Sáiz J, Svob Strac D, Barbas C, Rojo D Abstract Gut microbiota represents a complex physiological ecosystem that influences the host health. Alterations in the microbiome metabolism affect the body homeostasis and they have been associated with the development of different human neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease, autism spectrum disorder, bipolar disorder, depression, Huntington's disease, Parkinson's disease, posttraumatic stress disorder and schizophrenia. The development of these complex diseases is influenced by various factors, including genetic predisposition and environmental triggers. Gut microbiota has recently emerged as an important actor in their physiopathology that has been shown to play a role in inflammation, oxidative stress, and gut permeability. Therefore, targeting the metabolites that are produced by or associated with the gut microbiota may help us understand how imbalance in the gut-brain axis affects human health. This review offers a comprehensive overview of the literature on this matter, offering the readers an insight in the state-of-art metabolic measurements of the gut-brain axis in various brain-related diseases. PMID: 33279302 [PubMed - as supplied by publisher]

Development of mass spectrometry-based relatively quantitative targeted method for amino acids and neurotransmitters: Applications in the diagnosis of major depression.

Mon, 07/12/2020 - 14:39
Related Articles Development of mass spectrometry-based relatively quantitative targeted method for amino acids and neurotransmitters: Applications in the diagnosis of major depression. J Pharm Biomed Anal. 2020 Nov 20;:113773 Authors: Chen H, Xie H, Huang S, Xiao T, Wang Z, Ni X, Deng S, Lu H, Hu J, Li L, Wen Y, Shang D Abstract Targeted metabolomics analysis based on triple quadrupole (QQQ) MS coupled with multiple reaction monitoring mode (MRM) is the gold standard for metabolite quantification and it is widely applied in metabolomics. However, standard compounds for each metabolite and the corresponding analogs are necessary for quantitative measurements. To identify the differentially present metabolites in various groups, determining the relative concentration of metabolites would be more efficient than accurate quantification. In this study, a relatively quantitative targeted method was established for metabonomics research, on the basis of hydrophilic interaction liquid chromatography (HILIC)/QQQ MS operated in MRM mode. The quality control-base random forest signal correction algorithm (QC-RFSC algorithm) was applied for quality control instead of the internal standard method. High quality relative quantification was achieved without internal standards, and integrated peak areas were successfully used for statistical and pathway analyses. Amino acids and neurotransmitters (dopamine, kynurenic acid, urocanic acid, tryptophan, kynurenine, tyrosine, valine, threonine, serine, alanine, glycine, glutamine, citrulline, GABA, glutamate, aspartate, arginine, ornithine and histidine) in serum samples were simultaneously determined with the newly developed method. To demonstrate the applicability of this method in large-scale analyses, we analyzed the above metabolites in serum from patients with major depression. The serum levels of glutamate, aspartate, threonine, glycine and alanine were significantly higher, and those of citrulline, kynurenic acid and urocanic acid were significantly lower, in patients with major depression than in controls. This is the first report of the difference in urocanic acid, a compound reported to improve glutamate biosynthesis and release in the central nervous system, between healthy controls and patients with major depression. PMID: 33279298 [PubMed - as supplied by publisher]

Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status.

Sun, 06/12/2020 - 14:30
Related Articles Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status. Bone. 2020 Dec 02;:115780 Authors: Mangano KM, Noel SE, Lai CQ, Christensen JJ, Ordovas JM, Dawson-Hughes B, Tucker KL, Parnell LD Abstract BACKGROUND: The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown. OBJECTIVE: Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach. DESIGN: Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46-79 yr). METHODS: Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites. RESULTS: High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. CONCLUSIONS: These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links. PMID: 33278656 [PubMed - as supplied by publisher]

Systems biology approaches to study lipidomes in health and disease.

Sun, 06/12/2020 - 14:30
Related Articles Systems biology approaches to study lipidomes in health and disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Dec 02;:158857 Authors: Alves MA, Lamichhane S, Dickens A, McGlinchey A, Ribeiro HC, Sen P, Wei F, Hyötyläinen T, Orešič M Abstract Lipids have many important biological roles, such as energy storage sources, structural components of plasma membranes and as intermediates in metabolic and signaling pathways. Lipid metabolism is under tight homeostatic control, exhibiting spatial and dynamic complexity at multiple levels. Consequently, lipid-related disturbances play important roles in the pathogenesis of most of the common diseases. Lipidomics, defined as the study of lipidomes in biological systems, has emerged as a rapidly-growing field. Due to the chemical and functional diversity of lipids, the application of a systems biology approach is essential if one is to address lipid functionality at different physiological levels. In parallel with analytical advances to measure lipids in biological matrices, the field of computational lipidomics has been rapidly advancing, enabling modeling of lipidomes in their pathway, spatial and dynamic contexts. This review focuses on recent progress in systems biology approaches to study lipids in health and disease, with specific emphasis on methodological advances and biomedical applications. PMID: 33278596 [PubMed - as supplied by publisher]

Metabolic markers for diagnosis and risk-prediction of multiple myeloma.

Sun, 06/12/2020 - 14:30
Related Articles Metabolic markers for diagnosis and risk-prediction of multiple myeloma. Life Sci. 2020 Dec 02;:118852 Authors: Fei F, Ma T, Zhou X, Zheng M, Cao B, Li J Abstract AIMS: To discriminate metabolic biomarkers for diagnosis and risk prediction of multiple myeloma (MM) on a basis of metabolic characteristics in systemic circulation and local pathogenic niche. MAIN METHODS: A gas chromatography mass spectrometry-based untargeted metabolomics analysis was performed within the bone marrow (BM) supernatants and peripheral plasma from healthy donors and patients with MM. KEY FINDINGS: Distinct metabolic features between MM patients and healthy volunteers were profiled in both BM and plasma. Metabolic profiles of subgroups in which MM patients undergo high/medium/low risk displayed risk-dependent metabolic shift especially in BM. In MM patients, up-regulated glutamate level and down-regulated glutamine level in BM indicated enhanced glutamate metabolism which provided NH4+ for ammonia utilization. This resulted in increased level of urea and creatinine produced from urea cycle, arginine and proline metabolism in both BM and plasma collected from MM patients. The disorders of tricarboxylic acid cycle and carnitine synthesis were unique in BM of MM patients. Receiver operating characteristic curve analysis indicated that aspartate was a candidate plasma biomarker for diagnosis with the highest sensitivity and specificity in both BM and plasma. Threonine was identified as a preferential plasma biomarker for risk prediction due to significant relation with various risk indexes of MM in both BM and plasma. SIGNIFICANCE: The perturbed glutamate metabolism and carnitine synthesis in BM of MM patients provided a new sight on pathogenesis of MM. The plasma level of aspartate and threonine may become a preferential metabolic marker for diagnosis and risk prediction of MM, respectively. PMID: 33278388 [PubMed - as supplied by publisher]

Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison.

Sun, 06/12/2020 - 14:30
Related Articles Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison. Anal Bioanal Chem. 2020 Dec 05;: Authors: Piga I, Capitoli G, Clerici F, Mahajneh A, Brambilla V, Smith A, Leni D, L'Imperio V, Galimberti S, Pagni F, Magni F Abstract Fine needle aspiration (FNA) is the reference standard for the diagnosis of thyroid nodules. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been successfully used to discriminate the proteomic profiles of benign and malignant thyroid FNAs within the scope of providing support to pathologists for the classification of morphologically borderline cases. However, real FNAs provide a limited amount of material due to sample collection restrictions. Ex vivo FNAs could represent a valuable alternative, increasing sample size and the power of statistical conclusions. In this study, we compared the real and ex vivo MALDI-MSI proteomic profiles, extracted from thyrocyte containing regions of interest, of 13 patients in order to verify their similarity. Statistical analysis demonstrated the mass spectra similarity of the proteomic profiles by performing intra-patient comparison, using statistical similarity systems. In conclusion, these results show that post-surgical FNAs represent a possible alternative source of material for MALDI-MSI proteomic investigations in instances where pre-surgical samples are unavailable or the number of cells is scarce. PMID: 33277997 [PubMed - as supplied by publisher]

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]

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