PubMed

Related Articles Cultural and Metabolomic Studies of a New Phtalides Producer, Lignomyces vetlinianus (Agaricomycetes). Int J Med Mushrooms. 2018;20(11):1031-1045 Authors: Sazanova KV, Psurtseva NV, Shavarda AL Abstract Culture characteristics and metabolomic profiling (on the basis of gas chromatography-mass spectrometry) of 3 strains of Lignomyces vetlinianus were studied. Growth rate, macromorphology, and micromorphology of mycelia grown on various media are described. More than 60 compounds were detected in the mycelial extracts, including amino acids, organic acids that are active during the tricarboxylic acid cycle, sugars, fatty acids, sugar alcohols, and sugar acids. Principal component analysis of low-molecular-weight compounds in mycelial methanol extracts of L. vetlinianus strains at different stages of growth demonstrated that the pattern of mycelial metabolomes grouped by age of the culture indicates a significant relation between the development of the culture and the specificity of its metabolite spectrum. Slow-growing cultures develop gradually and are characterized by several changes in metabolite states. The pattern of points is grouped more tightly for fast-growing strains. The production of crystal-like aggregates was observed for aging mycelia at the stationary phase of growth. These aggregates were isolated from mycelia and identified as clusters of 4,6-dimethoxy-phthalide. The molecular structure of this substance was confirmed by nuclear magnetic resonance analysis. The results show that the concentration of 4,6-dimethoxy-phthalide increased during cultivation. Fruiting bodies contained very small amounts of 4,6-dimethoxy-phthalide compared with amounts in mycelia. It can be assumed that L. vetlinianus is a powerful natural producer of phthalides of biotech-nological interest and can be used as a model to study phenolic metabolism in fungi. PMID: 30806228 [PubMed - indexed for MEDLINE]

20 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 2019/06/05PubMed 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.

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 2019/06/04PubMed 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.

Related Articles CDK9 Inhibition Induces a Metabolic Switch that Renders Prostate Cancer Cells Dependent on Fatty Acid Oxidation. Neoplasia. 2019 May 28;21(7):713-720 Authors: Itkonen HM, Poulose N, Walker S, Mills IG Abstract Cyclin-dependent kinase 9 (CDK9), a key regulator of RNA-polymeraseII, is a candidate drug target for cancers driven by transcriptional deregulation. Here we report a multi-omics-profiling of prostate cancer cell responses to CDK9 inhibition to identify synthetic lethal interactions. These interactions were validated using live-cell imaging, mitochondrial flux-, viability- and cell death activation assays. We show that CDK9 inhibition induces acute metabolic stress in prostate cancer cells. This is manifested by a drastic down-regulation of mitochondrial oxidative phosphorylation, ATP depletion and induction of a rapid and sustained phosphorylation of AMP-activated protein kinase (AMPK), the key sensor of cellular energy homeostasis. We used metabolomics to demonstrate that inhibition of CDK9 leads to accumulation of acyl-carnitines, metabolic intermediates in fatty acid oxidation (FAO). Acyl-carnitines are produced by carnitine palmitoyltransferase enzymes 1 and 2 (CPT), and we used both genetic and pharmacological tools to show that inhibition of CPT-activity is synthetically lethal with CDK9 inhibition. To our knowledge this is the first report to show that CDK9 inhibition dramatically alters cancer cell metabolism. PMID: 31151054 [PubMed - as supplied by publisher]

Related Articles The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children. J Nutr Biochem. 2019 Apr 24;70:38-46 Authors: Belardo A, Gevi F, Zolla L Abstract Autism spectrum disorder (ASD) is characterized by severe and persistent difficulties in social communication and social interaction at multiple levels. Recently, metabolic disorders have been associated with most cases of patients with ASD. The aim of this study was to investigate, through a new and more sophisticated mass technique, such as UHPLC-mass spectrometry (Q-exactive analyzer), alteration in metabolisms analyzing ASD children urine samples from children showing simultaneous vitamin B6, B9 and B12 deficiencies. This in order to study how these concurrent deficiencies may influence some phenotypic aspects of autistic disorder. Thus, urinary metabolic patterns specific to ASD were explored at an early age in 60 children with ASD, showing lower three vitamins levels, and 60 corresponding controls (age group 3-8, M: F=42:18). The results showed significant block of cystathionine formation with consequent accumulation of homocysteine. A lower glutathione levels (GSH), with reduction of essential intracellular reducing environment required for normal immune function, detoxification capacity and redox-sensitive enzyme activity. Increased concentration of 5-methyltetrahydrofolate, which leads to a lower availability of methyl group and significant decrease in urinary methionine and S-adenosyl-L-methionine (SAM) concentrations, the major methyl donor. The latter justify the well-known reduction in protein and DNA methylation reported in autistic children. As a final consideration, the concomitant deficiencies of all three B vitamins, recorded in a significant number of autistic children, suggests that intestinal dysbiosis in these patients may be the main cause of a reduction in their absorption, in addition to the genetic mutation of a specific gene. PMID: 31151052 [PubMed - as supplied by publisher]

Related Articles Metabolic adaptation to feed restriction on the green sturgeon (Acipenser medirostris) fingerlings. Sci Total Environ. 2019 May 11;684:78-88 Authors: Lin CY, Huang LH, Deng DF, Lee SH, Liang HJ, Hung SSO Abstract Food restriction may cause severe biological effects on wildlife and lead to population decline and extinction. The objective of the current study was to examine the metabolic effects on green sturgeon in response to feed restriction. Green sturgeon fingerlings were fed for two weeks at 12.5, 25, 50 and 100% of the optimum feeding rate (OFR), which corresponded to 0.25, 0.50, 1.00, and 2.00% body weight per day. We characterized the changes in hydrophilic and hydrophobic metabolites from extracts of muscle, liver, and kidney using nuclear magnetic resonance spectroscopy followed by multivariate statistical analysis. The results of principal component analysis (PCA) score plots from the analyses of hydrophilic metabolites showed that they exhibited a greater response to feed restriction than hydrophobic metabolites. In general, the hydrophilic metabolites in tissues from fish fed ≦25% of the OFR were separated from those fed 100% of the OFR in the PCA score plots. Among the three types of tissues examined, the overall metabolite changes showed a greater response to feed restriction in kidney tissue than in liver or muscle tissues. Numerous glucogenic amino acids in muscle and most amino acids in the kidney were decreased under feed restriction conditions. A significant decrease in ketone bodies (3-hydroxyisobutyrate) was observed in the muscle. Most fatty acids except for glycerol, phospholipid and cholesterol in the liver and kidney tissues were decreased under feed restriction conditions. Creatine phosphate, taurine and glycine were also significantly increased in tissues under feed restriction conditions. In conclusion, this study suggests that the manipulation of feed restriction under the current conditions perturbed metabolites related to energy metabolism, osmolality regulation, and antioxidation capacity in the sturgeon. PMID: 31150878 [PubMed - as supplied by publisher]

Related Articles Hazard assessment of Maerua subcordata (Gilg) DeWolf. For selected endpoints using a battery of in vitro tests. J Ethnopharmacol. 2019 May 28;:111978 Authors: Gebrelibanos Hiben M, Kamelia L, de Haan L, Spenkelink B, Wesseling S, Vervoort J, Rietjens IMCM Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Maerua subcordata (Gilg) DeWolf is a medicinal and wild food plant growing mainly in east Africa. Especially its root tuber is widely used in traditional medicine to treat several infectious and chronic diseases but also in some toxicity implications like use as abortifacient. AIM OF THE STUDY: the present study applied in silico and in vitro tests to identify possible hazards of M. subcordata (fruit, leaf, root, seed) methanol extracts focusing on developmental toxicity. MATERIALS AND METHODS: Ames test, estrogen receptor alpha (ERα) assay, aryl hydrocarbon receptor (AhR) assay, embryonic stem cell test (EST), and zebrafish embryotoxicity test (ZET) were employed. Besides, a Derek Nexus toxicity prediction was performed on candidate structures obtained from metabolomics profiling of the extracts using liquid chromatography coupled to multistage mass spectroscopy (LC/MSn) and a MAGMa software based structural annotation. RESULTS: Glucosinolates, which degrade to isothiocyanates, and biogenic amines were among the candidate molecules identified in the extracts by LC/MSn - MAGMa software structural annotation. Isothiocyanates and some other candidate molecules suggested a positive mutagenicity alert in Derek toxicity predictions. All the extracts showed negative mutagenicity in the Ames test. However, the Derek predictions also identified endocrine and developmental toxicity as possible endpoints of concern. This was further assessed using in vitro tests. Results obtained reveal that leaf extract shows AhR and ERα agonist activities, inhibited differentiation of ES-D3 stem cells into contracting cardiomyocytes in the EST (p < 0.001) as well as inhibited hatching (p < 0.01) and showed acute toxicity (p < 0.01) in the ZET. Also, the fruit extract showed toxicity (p < 0.05) towards zebrafish embryos and both fruit and seed extracts showed AhR agonist activities while root extract was devoid of activity in all in vitro assays. CONCLUSION: The leaf extract tests positive in in vitro tests that this may point towards a developmental toxicity hazard. The current evaluations did not raise concerns of genotoxicity or developmental toxicity for the fruit, seed and root extracts. This is important given the use of especially these parts of M. subcordata, in traditional medicine and/or as (famine) food. PMID: 31150796 [PubMed - as supplied by publisher]

Related Articles Defining the Independence of the Liver Circadian Clock. Cell. 2019 May 30;177(6):1448-1462.e14 Authors: Koronowski KB, Kinouchi K, Welz PS, Smith JG, Zinna VM, Shi J, Samad M, Chen S, Magnan CN, Kinchen JM, Li W, Baldi P, Benitah SA, Sassone-Corsi P Abstract Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function. PMID: 31150621 [PubMed - in process]

Related Articles Untargeted metabolomic profiling of urine from healthy dogs and dogs with chronic hepatic disease. PLoS One. 2019;14(5):e0217797 Authors: Lawrence YA, Guard BC, Steiner JM, Suchodolski JS, Lidbury JA Abstract Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography-quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility. PMID: 31150490 [PubMed - in process]

Related Articles An automatic UPLC-HRMS data analysis platform for plant metabolomics. Plant Biotechnol J. 2019 May 31;: Authors: Liu P, Zhou H, Zheng Q, Lu P, Yu YJ, Cao P, Chen W, Chen Q Abstract Here we want to introduce our new automatic data analysis platform for untargeted metabolomic analysis of complex plant samples. Many laboratories across the world have adopted ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) as they seek to thoroughly characterize metabolites in complex plant samples, with the larger aim of identifying compounds with impactful biological functions. This article is protected by copyright. All rights reserved. PMID: 31150147 [PubMed - as supplied by publisher]

Related Articles 12-Hydroxy-jasmonoyl-L-isoleucine is an active jasmonate that signals through CORONATINE INSENSITIVE 1 and contributes to the wound response in Arabidopsis. Plant Cell Physiol. 2019 May 31;: Authors: Poudel AN, Holtsclaw RE, Kimberlin A, Sen S, Zeng S, Joshi T, Lei Z, Sumner LW, Singh K, Matsuura H, Koo AJ Abstract 12-hydroxy-jasmonoyl-isoleucine (12OH-JA-Ile) is a metabolite in the catabolic pathway of the plant hormone jasmonate, and is synthesized by the cytochrome P450 subclade 94 enzymes. Contrary to the well-established function of jasmonoyl-isoleucine (JA-Ile) as the endogenous bioactive form of jasmonate, the function of 12OH-JA-Ile is unclear. Here, the potential role of 12OH-JA-Ile in jasmonate signaling and wound response was investigated. Exogenous application of 12OH-JA-Ile mimicked several JA-Ile effects including marker gene expression, anthocyanin accumulation and trichome induction in Arabidopsis thaliana. Genome-wide transcriptomics and untargeted metabolite analyses showed large overlaps between those affected by 12OH-JA-Ile and JA-Ile. 12OH-JA-Ile signaling was blocked by mutation in CORONATINE INSENSITIVE 1. Increased anthocyanin accumulation by 12OH-JA-Ile was additionally observed in tomato and sorghum, and was disrupted by the COI1 defect in tomato jai1 mutant. In silico ligand docking predicted that 12OH-JA-Ile can maintain many of the key interactions with COI1-JAZ1 residues identified earlier by crystal structure studies using JA-Ile as ligand. Genetic alternation of jasmonate metabolic pathways in Arabidopsis to deplete both JA-Ile and 12OH-JA-Ile displayed enhanced jasmonate deficient wound phenotypes and was more susceptible to insect herbivory than that depleted in only JA-Ile. Conversely, mutants overaccumulating 12OH-JA-Ile showed intensified wound responses compared to wild-type with similar JA-Ile content. These data are indicative of 12OH-JA-Ile functioning as an active jasmonate signal and contributing to wound and defense response in higher plants. PMID: 31150089 [PubMed - as supplied by publisher]

31 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 2019/05/31PubMed 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.

20 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 2019/05/30PubMed 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.

20 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 2019/05/30PubMed 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.

Related Articles GC-MS Method for Metabolic Profiling of Mouse Femoral Head Articular Cartilage Reveals Distinct Effects of Tissue Culture and Development. Osteoarthritis Cartilage. 2019 May 25;: Authors: Batushansky A, Lopes EBP, Zhu S, Humphries KM, Griffin TM Abstract OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum. We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between 5 to 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted 6 out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development. PMID: 31136803 [PubMed - as supplied by publisher]

Related Articles Schistosoma mansoni venom allergen-like proteins: phylogenetic relationships, stage-specific transcription and tissue localization as predictors of immunological cross-reactivity. Int J Parasitol. 2019 May 25;: Authors: Farias LP, Chalmers IW, Perally S, Rofatto HK, Jackson CJ, Brown M, Khouri MI, Barbosa MMF, Hensbergen PJ, Hokke CH, Leite LCC, Hoffmann KF Abstract Schistosoma mansoni venom allergen-like proteins (SmVALs) are part of a diverse protein superfamily partitioned into two groups (group 1 and group 2). Phylogenetic analyses of group 1 SmVALs revealed that members could be segregated into subclades (A-D); these subclades share similar gene expression patterns across the parasite lifecycle and immunological cross-reactivity. Furthermore, whole-mount in situ hybridization demonstrated that the phylogenetically, transcriptionally and immunologically-related SmVAL4, 10, 18 and 19 (subclade C) were all localized to the pre-acetabular glands of immature cercariae. Our results suggest that SmVAL group 1 phylogenetic relationships, stage-specific transcriptional profiles and tissue localization are predictive of immunological cross-reactivity. PMID: 31136745 [PubMed - as supplied by publisher]

Related Articles Decreased plasma serotonin and other metabolite changes in healthy adults after consumption of wholegrain rye: an untargeted metabolomics study. Am J Clin Nutr. 2019 Jun 01;109(6):1630-1639 Authors: Keski-Rahkonen P, Kolehmainen M, Lappi J, Micard V, Jokkala J, Rosa-Sibakov N, Pihlajamäki J, Kirjavainen PV, Mykkänen H, Poutanen K, Gunter MJ, Scalbert A, Hanhineva K Abstract BACKGROUND: Wholegrain consumption has been associated with beneficial health effects including reduction of diabetes and cancer risk; however, the underlying mechanisms are not fully understood. OBJECTIVE: The aim of this study was to characterize the effects of wholegrain rye intake on circulating metabolites in a human intervention study using untargeted metabolomics. METHODS: The intervention consisted of 2 successive 4-wk periods in a randomized crossover design, where 15 adults consumed wholegrain rye bread (WGR) or white wheat bread enriched with fermented rye bran (WW+RB), following a 4-wk rye-free period with white wheat bread (WW). Fasting plasma samples were collected at the end of each period and analyzed using liquid chromatography-mass spectrometry. Metabolic profiles were compared to identify compounds discriminating WGR from the WW+RB and WW periods. Because peripheral serotonin is produced mainly in the gut, a hypothesis of its altered biosynthesis as a response to increased cereal fiber intake was tested by measuring intestinal serotonin of mice fed for 9 wk on a high-fat diet supplemented with different sources of fiber (rye bran flour, ground wheat aleurone, or powdered cellulose). RESULTS: Five endogenous metabolites and 15 rye phytochemicals associated with WGR intake were identified. Plasma concentrations of serotonin, taurine, and glycerophosphocholine were significantly lower after the WGR than WW period (Q < 0.05). Concentrations of 2 phosphatidylethanolamine plasmalogens, PE(18:2/P-18:0) and PE(18:2/P-16:0), were lower after the WGR period than the WW+RB period (Q < 0.05). The concentration of serotonin was significantly lower in the colonic tissue of mice that consumed rye bran or wheat aleurone compared with cellulose (P < 0.001). CONCLUSIONS: Wholegrain rye intake decreases plasma serotonin in healthy adults when compared with refined wheat. Intake of rye bran and wheat aleurone decreases colonic serotonin in mice. These results suggest that peripheral serotonin could be a potential link between wholegrain consumption and its associated health effects.Data used in the study were derived from a trial registered at www.clinicaltrials.gov as NCT03550365. PMID: 31136658 [PubMed - in process]

Related Articles Transcriptomic and Metabolomic Profiling of Camellia sinensis L. cv. 'Suchazao' Exposed to Temperature Stresses Reveals Modification in Protein Synthesis and Photosynthetic and Anthocyanin Biosynthetic Pathways. Tree Physiol. 2019 May 28;: Authors: Shen J, Zhang D, Zhou L, Zhang X, Liao J, Duan Y, Wen B, Ma Y, Wang Y, Fang W, Zhu X Abstract To determine the mechanisms in tea plants responding to temperature stresses (heat and cold), we examined the global transcriptomic and metabolomic profiles of the tea plant cultivar 'Suchazao' under moderately low temperature (ML), severely low temperature (SL), moderately high temperature (MH), and severely high temperature (SH) using RNA-Seq and HPLC-MS/MS, respectively. The identified differentially expressed genes indicated that the synthesis of stress-resistance protein might be redirected to cope with the temperature stresses. We found that heat shock protein genes Hsp90 and Hsp70 played more critical roles in tea plants in adapting to thermal stress than cold, while LEA played a greater role under cold than heat stress, more types of zinc finger genes were induced under cold stress as well. In addition, energy metabolisms were inhibited by SH, SL, and ML. Furthermore, the mechanisms of anthocyanin synthesis were different under the cold and heat stresses. Indeed, the CsUGT75C1gene, encoding UDP-glucose: anthocyanin 5-O-glucosyl transferase, was up-regulated in the SL-treated leaves but down-regulated in SH. Metabolomics analysis also showed that anthocyanin monomer levels increased under SL. These results indicate that the tea plants share certain foundational mechanisms to adjust to both cold and heat stresses. They also developed some specific mechanisms for surviving the cold or heat stresses. Our study provides effective information about the different mechanisms tea plants employing in surviving cold and heat stresses, as well as the different mechanisms of anthocyanin synthesis, which could speed up the genetic breeding of heat- and cold-tolerant tea varieties. PMID: 31135909 [PubMed - as supplied by publisher]

Related Articles Association of Nonfasting vs Fasting Lipid Levels With Risk of Major Coronary Events in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm. JAMA Intern Med. 2019 May 28;: Authors: Mora S, Chang CL, Moorthy MV, Sever PS Abstract Importance: Recent guidelines have recommended nonfasting for routine testing of lipid levels based on comparisons of nonfasting and fasting populations. However, no previous study has examined the association of cardiovascular outcomes with fasting vs nonfasting lipid levels measured in the same individuals. Objective: To compare the association of nonfasting and fasting lipid levels with prospectively ascertained coronary and vascular outcomes and to evaluate whether a strategy of using nonfasting instead of fasting lipid level measurement would result in misclassification of risk for individuals undergoing evaluation for initiation of statin therapy. Design, Setting, and Participants: This post hoc prospective follow-up of a randomized clinical trial included 8270 of 10 305 participants from the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) with nonfasting and fasting lipid levels measured 4 weeks apart (including 6855 participants with no prior vascular disease) (median follow-up, 3.3 years; interquartile range, 2.8-3.6 years). Data were collected from February 1, 1998, to December 31, 2002, and analyzed from February 1, 2016, to November 30, 2018. Multivariable Cox models, adjusted for cardiovascular risk factors, were calculated for 40-mg/dL (1-mmol/L) higher values of nonfasting and fasting lipids. Main Outcomes and Measures: The trial's primary end point consisted of major coronary events (nonfatal myocardial infarction [MI] and fatal coronary heart disease [212 events]). Secondary analyses examined atherosclerotic cardiovascular disease (ASCVD) events (including MI, stroke, and ASCVD death [351 events]). Results: Among the 8270 participants (82.1% male; mean [SD] age, 63.4 [8.5] years), nonfasting samples had modestly higher triglyceride levels and similar cholesterol levels compared to fasting samples. Associations of nonfasting lipid levels with coronary events were similar to those for fasting lipid levels. For example, adjusted hazard ratios (HRs) per 40-mg/dL of low-density lipoprotein cholesterol were 1.32 (95% CI, 1.08-1.61; P = .007) for nonfasting levels and 1.28 (95% CI, 1.07-1.55; P = .008) for fasting levels. For the primary prevention group, adjusted HRs were 1.42 (95% CI, 1.13-1.78; P = .003) for nonfasting levels and 1.37 (95% CI, 1.11-1.69; P = .003) for fasting levels. Results were consistent by randomized treatment arm (atorvastatin calcium, 10 mg/d, or placebo) and similar for ASCVD events. Concordance of fasting and nonfasting lipid levels for classifying participants into appropriate ASCVD risk categories was high (94.8%). Conclusions and Relevance: Measurement of nonfasting and fasting lipid levels yields similar results in the same individuals for association with incident coronary and ASCVD events. These results suggest that routine measurement of nonfasting lipid levels may help facilitate ASCVD risk screening and treatment, including consideration of when to initiate statin therapy. PMID: 31135812 [PubMed - as supplied by publisher]

Related Articles A robust intracellular metabolite extraction protocol for human neutrophil metabolic profiling. PLoS One. 2018;13(12):e0209270 Authors: Chokesuwattanaskul S, Phelan MM, Edwards SW, Wright HL Abstract Neutrophils are phagocytic innate immune cells that play essential roles in host defence, but are also implicated in inflammatory diseases such as rheumatoid arthritis (RA) where they contribute to systemic inflammation and joint damage. Transcriptomic analysis of neutrophils has revealed significant changes in gene expression in neutrophils activated in vitro by cytokines and in vivo during inflammation in RA. However, there are no reports on the global metabolomic changes that occur as a consequence of this activation. The aim of this study was to establish protocols for the study of changes in the metabolome of human neutrophils using 1H NMR spectroscopy. Sample preparation and spectral analysis protocols were optimised using neutrophils isolated by Ficoll-Paque, with decreased washing steps and inclusion of a heat-shock step to quench metabolite turnover. Cells were incubated ± PMA for 15 min in HEPES-free media and samples were analysed by NMR using a 700 MHz NMR Avance IIIHD Bruker NMR spectrometer equipped with a TCI cryoprobe. Chenomx, Bruker TopSpin and AMIX software were used to process spectra and identify metabolites. Principal Component Analysis (PCA) and signalling pathway analysis was carried out using Metaboanalyst. Cell number and number of scans (NS) were optimised as >3.6 million cells and 512 NS. 327 spectral bins were defined in the neutrophil spectra, of which 287 (87.7%) were assigned to 110 metabolites that included: amino acids, peptides and analogues; carbohydrates, carbonyls and alcohols; nucleotides, nucleosides and analogues; lipids and lipid-like molecules; benzenoids; and other organic compounds. 43 metabolites changed at least 1.5 fold (increase or decrease) after the addition of PMA for 5 or 15 min. Pathway analysis revealed that PMA affected nicotinate and nicotinamide metabolism, aminoacyl-tRNA biosynthesis and glycolysis, suggesting a redirection of glucose metabolism from glycolysis to the pentose phosphate pathway and production of NADPH for activation of the NADPH oxidase and subsequent respiratory burst. We have developed protocols for the study of human neutrophils by 1H NMR spectroscopy. Importantly, this methodology has sufficient sensitivity and reproducibility to detect changes in metabolite abundance from cell numbers typically collected from clinical samples or experiments with multiple assay conditions. PMID: 30571714 [PubMed - indexed for MEDLINE]