PubMed

Related Articles Metabolic Profiling of healthy and cancerous tissues in 2D and 3D. Sci Rep. 2017 11 10;7(1):15285 Authors: Russell S, Wojtkowiak J, Neilson A, Gillies RJ Abstract Metabolism is a compartmentalized process, and it is apparent in studying cancer that tumors, like normal tissues, demonstrate metabolic cooperation between different cell types. Metabolic profiling of cells in 2D culture systems often fails to reflect the metabolism occurring within tissues in vivo due to lack of other cell types and 3D interaction. We designed a tooling and methodology to metabolically profile and compare 2D cultures with cancer cell spheroids, and microtissue slices from tumors, and normal organs. We observed differences in the basal metabolism of 2D and 3D cell cultures in response to metabolic inhibitors, and chemotherapeutics. The metabolic profiles of microtissues derived from normal organs (heart, kidney) were relatively consistent when comparing microtissues derived from the same organ. Treatment of heart and kidney microtissues with cardio- or nephro-toxins had early and marked effects on tissue metabolism. In contrast, microtissues derived from different regions of the same tumors exhibited significant metabolic heterogeneity, which correlated to histology. Hence, metabolic profiling of complex microtissues is necessary to understand the effects of metabolic co-operation and how this interaction, not only can be targeted for treatment, but this method can be used as a reproducible, early and sensitive measure of drug toxicity. PMID: 29127321 [PubMed - indexed for MEDLINE]

Related Articles Zdhhc13-dependent Drp1 S-palmitoylation impacts brain bioenergetics, anxiety, coordination and motor skills. Sci Rep. 2017 10 16;7(1):12796 Authors: Napoli E, Song G, Liu S, Espejo A, Perez CJ, Benavides F, Giulivi C Abstract Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn2+-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls. Loss of Zdhhc13 in cortex and cerebellum from 3- and 24 m old hetero- and homozygous male mutant mice resulted in lower levels of Drp1 S-palmitoylation accompanied by altered mitochondrial dynamics, increased glycolysis, glutaminolysis and lactic acidosis, and neurotransmitter imbalances. Employing in vivo and in vitro models, we identified that Zdhhc13-dependent Drp1 S-palmitoylation, which acting alone or in concert, enables the normal occurrence of the fission-fusion process. In vitro and in vivo direct Zdhhc13-Drp1 protein interaction was observed, confirming Drp1 as a substrate of Zdhhc13. Abnormal fission-fusion processes result in disrupted mitochondria morphology and distribution affecting not only mitochondrial ATP output but neurotransmission and integrity of synaptic structures in the brain, setting the basis for the behavioral abnormalities described in the Zdhhc13-deficient mice. PMID: 29038583 [PubMed - indexed for MEDLINE]

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 2019/07/03PubMed 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.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/07/02PubMed 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.

Related Articles Identification of urine biomarkers for calcium-oxalate urolithiasis in adults based on UPLC-Q-TOF/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jun 21;1124:290-297 Authors: Wang X, Wang M, Ruan J, Zhao S, Xiao J, Tian Y Abstract Urolithiasis is a common urological disease with a high morbidity and recurrence rate, of which calcium oxalate (CaOx) is the most common type of stone that underlies the disease. However, the potential metabolic mechanisms of CaOx urolithiasis remain unclear. The present study aimed to seek potential biomarkers and metabolic mechanisms of CaOx urolithiasis in adults. Urine samples were collected from 36 healthy individuals and 36 patients diagnosed with bilateral upper-urinary-tract stones. All of the stones were composed of CaOx. Ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to perform a metabolic fingerprinting analysis. Principal component analysis (PCA) and orthogonal partial least-squares determinant analysis (OPLS-DA) were carried out to analyze the multivariate data. There were 18 differential metabolites identified, which mainly involved caffeine, phenylalanine, galactose, and tyrosine metabolism. The results revealed potential urinary biomarkers, via metabolic fingerprinting of adults with CaOx urolithiasis, which may help to improve future metabolic evaluation of urolithiasis. The elucidated metabolic pathways may have potential applications as novel treatment targets of CaOx urolithiasis. Additionally, our study suggests that the UPLC-Q-TOF/MS platform may offer new insights into the pathobiology of urolithiasis. PMID: 31255901 [PubMed - as supplied by publisher]

Related Articles Non-targeted metabolomics reveals diagnostic biomarker in the tongue coating of patients with chronic gastritis. J Pharm Biomed Anal. 2019 Jun 20;174:541-551 Authors: Mu X, Ji C, Wang Q, Liu K, Hao X, Zhang G, Shi X, Zhang Y, Gonzalez FJ, Wang Q, Wang Y Abstract Analysis of the properties of the tongue has been used in traditional Chinese medicine for disease diagnosis. Notably, tongue analysis, which is non-invasive and convenient compared with gastroscopy and pathological examination, can be used to assess chronic gastritis (CG). In order to find potential diagnostic biomarkers and study the metabolic mechanisms of the endogenous small molecules in the tongue coating related to CG, a non-targeted metabolomic analysis method was developed using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). It was performed using two different columns in positive and negative ion scanning modes separately. The stability of the samples was evaluated and the age and gender factors of the subjects were excluded to ensure the reliability of the data in this study. Finally, under the four analysis models, 130, 229, 113 and 92 differential compounds were found using multivariate statistical methods respectively. 37 potential biomarkers were putatively identified after removing the duplicate compounds and five potential diagnostic biomarkers were putatively identified by receiver operating characteristic (ROC) curve analysis, including inosine, oleamide, adenosine, N-acetylglucosamine (GlcNAc) and xanthine. The main metabolic pathways associated with CG were purine metabolism, amino acid metabolism, sphingolipid metabolism and energy metabolism, which suggested that oxygen free radicals and energy metabolism were altered in patients with CG. These results provided a potential new basis for the quantitative diagnosis and pathogenesis of CG. PMID: 31255854 [PubMed - as supplied by publisher]

Related Articles Metabolomics in plasma of Malawian children 7 years after surviving severe acute malnutrition: "ChroSAM" a cohort study. EBioMedicine. 2019 Jun 26;: Authors: Bourdon C, Lelijveld N, Thompson D, Dalvi PS, Gonzales GB, Wang D, Alipour M, Wine E, Chimwezi E, Wells JC, Kerac M, Bandsma R, Nyirenda MJ Abstract BACKGROUND: More children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM. METHODS: We followed-up children (n = 352) treated for SAM in 2006-2007, at Queen Elizabeth Central Hospital, in Malawi. Using nuclear magnetic resonance spectroscopy, tandem mass spectrometry and enzyme-linked immunosorbent assay, we measured circulating metabolites in fasting blood in a subset of SAM survivors (n = 69, 9·6 ± 1·6 years), siblings (n = 44, 10·5 ± 2·7 years), and age and sex-matched community controls (n = 37, 9·4 ± 1·8 years). Data were analysed using univariate and sparse partial least square (sPLS) methods. Differences associated with SAM survival, oedema status, and anthropometry were tested, adjusting for age, sex, HIV, and wealth index. FINDINGS: Based on 194 measured metabolites, the profiles of SAM survivors were similar to those of siblings and community controls. IGF1, creatinine, and FGF21, had loading values >0·3 and ranked stably in the top 10 distinguishing metabolites, but did not differ between SAM survivors and controls with univariate analysis. Current stunting was associated with IGF1 (β = 15·2, SE = 3·5, partial R2 = 12%, p < 0·0001) and this relationship could be influenced by early childhood SAM (β = 17·4, SE = 7·7, partial R2 = 2·8%, p = 0·025). No metabolites were associated with oedema status, duration of hospital stay, anthropometry measured during hospitalization, nor with changes in anthropometry since hospitalization. INTERPRETATION: In this group of survivors, SAM was not associated with longer-term global metabolic changes 7 years after treatment. However, SAM may influence the relationship between current stunting and IGF1. Further risk markers for NCDs in SAM survivors may only be revealed by direct metabolic challenge or later in life. PMID: 31255658 [PubMed - as supplied by publisher]

Related Articles Investigation of betaine as a novel psychotherapeutic for schizophrenia. EBioMedicine. 2019 Jun 06;: Authors: Ohnishi T, Balan S, Toyoshima M, Maekawa M, Ohba H, Watanabe A, Iwayama Y, Fujita Y, Tan Y, Hisano Y, Shimamoto-Mitsuyama C, Nozaki Y, Esaki K, Nagaoka A, Matsumoto J, Hino M, Mataga N, Hayashi-Takagi A, Hashimoto K, Kunii Y, Kakita A, Yabe H, Yoshikawa T Abstract BACKGROUND: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. METHODS: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. FINDINGS: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. INTERPRETATION: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY). PMID: 31255657 [PubMed - as supplied by publisher]

Related Articles Identifying metabolomic profiles of inflammatory diets in postmenopausal women. Clin Nutr. 2019 Jun 17;: Authors: Tabung FK, Liang L, Huang T, Balasubramanian R, Zhao Y, Chandler PD, Manson JE, Cespedes Feliciano EM, Hayden KM, Van Horn L, Clish CB, Giovannucci EL, Rexrode KM Abstract BACKGROUND: We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets. METHODS: This baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women's Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P < 0.05. RESULTS: After adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein. CONCLUSION: Metabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study. PMID: 31255351 [PubMed - as supplied by publisher]

Related Articles Lymphocytes exposed to vegetables grown in waters contaminated by anticancer drugs: metabolome alterations and genotoxic risks for human health. Mutat Res. 2019 Jun;842:125-131 Authors: Russo C, Graziani V, Lavorgna M, D'Abrosca B, Piscitelli C, Fiorentino A, Scognamiglio M, Isidori M Abstract Wastewater irrigation of crops may be effective to avoid depletion (about 70%) of freshwater resources. However, the use of reclaimed waters containing persistent microcontaminants such as antineoplastic drugs is of high environmental concern. These active compounds may affect human health with potentially severe adverse effects. To better understand the impact on human health following irrigation of crops with reused contaminated waters, we exposed four edible plants, Brassica rapa, Lactuca sativa, Raphanus sativus, and Triticum durum, to two commonly used antitumoral drugs: 5-fluorouracil (5-FU), and Cisplatin (CDDP), using metabolomics as a potential functional genomics tool to combine with genotoxicity experiments. The metabolome of the treated and untreated plants was analysed to detect biochemical alterations associated to the exposure, and the potential genotoxic damage related to human exposure to the treated plants was evaluated using the comet assay in human lymphocytes, which are characterized by high sensitivity to genotoxic substances. The edible species were able to assimilate 5-FU and CDDP during the treatment, affecting the biochemical pathways of these plants with subsequent metabolome modifications. These metabolic alterations differed according to the specific species used for the test. Furthermore, all vegetables treated with two concentrations of the selected drugs (10 and 100 μg/L) caused significant (p < 0.0001) genotoxic damage in the cells of the immune system at a higher level than in the lymphocytes directly exposed to single antineoplastic drugs. PMID: 31255220 [PubMed - in process]

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/30PubMed 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.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/28PubMed 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.

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/27PubMed 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.

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/27PubMed 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.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/25PubMed 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.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/25PubMed 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.

Targeted metabolomics to investigate antimicrobial activity of itaconic acid in marine molluscs. Metabolomics. 2019 Jun 22;15(7):97 Authors: Van Nguyen T, Alfaro AC Abstract INTRODUCTION: Itaconic acid (ITA) has recently been identified as an antimicrobial metabolite in mammalian immune cells. The presence of ITA was also reported in different tissues of marine molluscs, indicating its role as an endogenous metabolite of molluscs. In addition, the accumulation of ITA has been observed in different tissues of mussels following pathogen challenges. However, the concentration of ITA in mussel tissues and the possible role of this metabolite in the molluscan innate immune system remain unknown. OBJECTIVES: This study aims to quantitatively measure ITA levels in different tissues of marine mussels following an experimental challenge with Vibrio sp. DO1 isolate, and to identify the antimicrobial role of ITA in the innate immune system through the measurement of metabolic and immune alterations in tissues following the challenge. METHODS: In this study, adult Perna canaliculus mussels were experimentally challenged with a pathogenic Vibrio sp. DO1 isolate. The metabolite profiles of five different tissues, including mantle, gill, muscle, hepatopancreas and haemolymph were obtained, and levels of ITA in each tissue were characterized using a gas chromatography-mass spectrometry (GC-MS) metabolomics approach. Flow cytometry was also employed to measure cell health parameters, including oxidative stress via reactive oxygen species (ROS) production, apoptosis via changes in mitochondrial membrane potential (MMP) and haemocyte viability. RESULTS: The ITA levels in mantle, gill, muscle and hepatopancreas tissues at 18-h post infection (hpi) with Vibrio sp. were 40.31, 41.71, 11.61 and 41.66 ng mg-1, respectively. In haemolymph, the level of ITA was significantly increased from 95.25 ng ml-1 at 6 hpi to 174.36 ng ml-1 at 18 hpi and 572.12 ng ml-1 at 60 hpi. In line with the accumulation of ITA, we observed increased levels of metabolites within the tricarboxylic acid (TCA) cycle, anti-inflammatory metabolites and alterations of other metabolites associated with immune responses of the host. The flow cytometry analyses revealed increases in ROS production, apoptotic cells and decreases in cell viability. CONCLUSIONS: We reported on the production of ITA in different tissues of P. canaliculus mussels challenged with a marine pathogen which confirmed ITA as an antimicrobial metabolite. The findings revealed insights into the biosynthesis of ITA and suggests its role in antimicrobial and anti-inflammatory activities in the innate immune system. This study also provided insights into the innate immune system of bivalves and highlighted the potential use of ITA as a biomarker for shellfish health assessment in aquaculture. PMID: 31230148 [PubMed - in process]

Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes. Clin Chim Acta. 2019 Jun 20;: Authors: Reddy P, Lent-Schochet D, Ramakrishnan N, McLaughlin M, Jialal I Abstract Metabolic syndrome (MetS) describes a cluster of cardio-metabolic factors that predispose to type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). While 35% of Americans suffer from this disorder, the specific pathways related to this disease are largely underexplored. The prevailing consensus is that inflammatory pathways contribute to the pathogenesis of this disease, and therefore new research has uncovered how inflammation plays a critical role in the development and progression of MetS. The purpose of this review is to understand the role of major inflammatory mechanisms and their role in MetS. Our review identifies that adipose tissue (AT) contributes to the inflammatory pathways through the release of pro-inflammatory adipokines such as leptin and chemerin and dysregulation of anti-inflammatory adiponectin. Chemokines and cytokines deriving from monocytes are also altered and promote inflammation and insulin resistance. Circulating inflammatory biomarkers including C-reactive protein (CRP), fibrinogen, Serum amyloid A (SAA), cytokines, and chemokines have also been linked to the pathogenesis of MetS. Researchers have identified the significance of CRP levels in predicting future sequelae of MetS such as ASCVD. Mast cells in subcutaneous adipose tissue (SAT) promote both inflammation and fibrosis. Thus, both AT and phagocyte activity define MetS as an inflammatory disorder. PMID: 31229566 [PubMed - as supplied by publisher]

Corrigendum to 'The regulation mechanisms of soluble starch and glycerol for production of azaphilone pigments in Monascus purpureus FAFU618 as revealed by comparative proteomic and transcriptional analyses' [Food Research International 106: 626-635]. Food Res Int. 2019 Aug;122:564-565 Authors: Huang ZR, Zhou WB, Yang XL, Tong AJ, Hong JL, Jia RB, Lin J, Li TT, Pan YY, Lv XC, Liu B PMID: 31229114 [PubMed - in process]

1H NMR-based metabolomics profiling and taste of boneless dry-cured hams during processing. Food Res Int. 2019 Aug;122:114-122 Authors: Zhang J, Yi Y, Pan D, Zhou G, Wang Y, Dang Y, He J, Li G, Cao J Abstract Boneless dry-cured hams were processed by raw material treatment (deboned and tumbled), salting (vacuum packed; 4 °C and 60-70% RH for 3.5 months), resting (vacuum packed; 15 °C and 60-70% RH for 1.5 months) and ripening (vacuum packed; 15 °C and 60-70% RH for 1.5 months). To explore the mechanisms that contributed to the taste of boneless dry-cured hams, 1H NMR-based metabolomics combined with multivariate data analysis was applied to investigate metabolite changes during processing. A total of 28 metabolites, including amino acids, peptide, organic acids, nucleic acids and their derivatives, sugars and others were identified. PC1 and PC2 explained a total of 77.6% and 18.0% of variables, and thus they could well reflect the main characteristics of all samples. The contents of most metabolites had an upward trend during the processing. Amino acids (isoleucine, valine, alanine, glutamate and histidine), organic acids (lactate, acetate, succinate, citrate and formate) and nucleotide derivative (hypoxanthine) were the major contributors to the taste in our final product. We concluded that the processing time (within 6.5 months) had a positive effect on the development of taste of boneless dry-cured hams. PMID: 31229062 [PubMed - in process]