PubMed

Related Articles Translational systems pharmacology studies in pregnant women. CPT Pharmacometrics Syst Pharmacol. 2017 Dec 14;: Authors: Quinney SK, Gullapelli R, Haas DM Abstract Pregnancy involves rapid physiological adaptation and complex interplay between mother and fetus. New analytic technologies provide large amounts of genomic, proteomic, and metabolomics data. The integration of these data through bioinformatics, statistical, and systems pharmacology techniques can improve our understanding of the mechanisms of normal maternal physiologic changes and fetal development. New insights into the mechanisms of pregnancy-related disorders, such as preterm birth (PTB), may lead to the development of new therapeutic interventions and novel biomarkers. PMID: 29239132 [PubMed - as supplied by publisher]

Related Articles 13C-assisted metabolic flux analysis to investigate heterotrophic and mixotrophic metabolism in Cupriavidus necator H16. Metabolomics. 2018;14(1):9 Authors: Alagesan S, Minton NP, Malys N Abstract Introduction: Cupriavidus necator H16 is a gram-negative bacterium, capable of lithoautotrophic growth by utilizing hydrogen as an energy source and fixing carbon dioxide (CO2) through Calvin-Benson-Bassham (CBB) cycle. The potential to utilize synthesis gas (Syngas) and the prospects of rerouting carbon from polyhydroxybutyrate synthesis to value-added compounds makes C. necator an excellent chassis for industrial application. Objectives: In the context of lack of sufficient quantitative information of the metabolic pathways and to advance in rational metabolic engineering for optimized product synthesis in C. necator H16, we carried out a metabolic flux analysis based on steady-state 13C-labelling. Methods: In this study, steady-state carbon labelling experiments, using either d-[1-13C]fructose or [1,2-13C]glycerol, were undertaken to investigate the carbon flux through the central carbon metabolism in C. necator H16 under heterotrophic and mixotrophic growth conditions, respectively. Results: We found that the CBB cycle is active even under heterotrophic condition, and growth is indeed mixotrophic. While Entner-Doudoroff (ED) pathway is shown to be the major route for sugar degradation, tricarboxylic acid (TCA) cycle is highly active in mixotrophic condition. Enhanced flux is observed in reductive pentose phosphate pathway (redPPP) under the mixotrophic condition to supplement the precursor requirement for CBB cycle. The flux distribution was compared to the mRNA abundance of genes encoding enzymes involved in key enzymatic reactions of the central carbon metabolism. Conclusion: This study leads the way to establishing 13C-based quantitative fluxomics for rational pathway engineering in C. necator H16. PMID: 29238275 [PubMed]

Related Articles Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis. Circ Cardiovasc Genet. 2017 Dec;10(6): Authors: Borges MC, Barros AJD, Ferreira DLS, Casas JP, Horta BL, Kivimaki M, Kumari M, Menon U, Gaunt TR, Ben-Shlomo Y, Freitas DF, Oliveira IO, Gentry-Maharaj A, Fourkala E, Lawlor DA, Hingorani AD Abstract BACKGROUND: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. METHODS AND RESULTS: We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. CONCLUSIONS: Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. PMID: 29237687 [PubMed - in process]

Related Articles Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial). Circ Cardiovasc Genet. 2017 Dec;10(6): Authors: Kofink D, Eppinga RN, van Gilst WH, Bakker SJL, Dullaart RPF, van der Harst P, Asselbergs FW Abstract BACKGROUND: Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the metabolic pathway that produces cholesterol and other isoprenoids. Little is known about their effects on metabolite and lipoprotein subclass profiles. We, therefore, investigated the molecular changes associated with pravastatin treatment compared with placebo administration using a nuclear magnetic resonance-based metabolomics platform. METHODS AND RESULTS: We performed metabolic profiling of 231 lipoprotein and metabolite measures in the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial) study, a placebo-controlled randomized clinical trial designed to test the effects of pravastatin (40 mg once daily) on cardiovascular risk. Metabolic profiles were assessed at baseline and after 3 months of treatment. Pravastatin lowered low-density lipoprotein cholesterol (change in SD units [95% confidence interval]: -1.01 [-1.14, -0.88]), remnant cholesterol (change in SD units [95% confidence interval]: -1.03 [-1.17, -0.89]), and apolipoprotein B (change in SD units [95% confidence interval]: -0.98 [-1.11, -0.86]) with similar effect magnitudes. In addition, pravastatin globally lowered levels of lipoprotein subclasses, with the exception of high-density lipoprotein subclasses, which displayed a more heterogeneous response pattern. The lipid-lowering effect of pravastatin was accompanied by selective changes in lipid composition, particularly in the cholesterol content of very-low-density lipoproteinparticles. In addition, pravastatin reduced levels of several fatty acids but had limited effects on fatty acid ratios. CONCLUSIONS: These randomized clinical trial data demonstrate the widespread effects of pravastatin treatment on lipoprotein subclass profiles and fatty acids. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03073018. PMID: 29237679 [PubMed - in process]

Related Articles Integrated metabolomics and proteomics analysis of hippocampus in a rat model of depression. Neuroscience. 2017 Dec 10;: Authors: Zhang Y, Yuan S, Pu J, Yang L, Zhou X, Liu L, Jiang X, Zhang H, Teng T, Tian L, Xie P Abstract Major depressive disorder (MDD) is a prevalent and serious mental disorder with high rates of suicide and disability. However, the underlying pathogenesis of MDD is complicated and remains largely unclear. An integrated analysis of multiple types of omics data may improve comprehensive understanding of the entire molecular mechanism of MDD. In this study, we applied an integrated analysis of gas chromatography/mass spectrometry (GC-MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to investigate changes in the hippocampus in the chronic unpredictable mild stress (CUMS) rat model of depression. Only the stress-susceptible rats in the CUMS group were selected for profiling against controls. Differential analysis identified 30 metabolites and 170 proteins between the two groups. The integrated analyses revealed four major changes in the hippocampus of CUMS rats: (1) impairment in amino acid metabolism and protein synthesis/degradation; (2) dysregulation of glutamate and glycine metabolism and their transport/catabolism related proteins; (3) disturbances in fatty acid and glycerophospholipid metabolism accompanied by alterations in the corresponding metabolic enzymes; (4) abnormal expression of synapse-associated proteins. These results provide further important insights into the pathophysiology of depression and may help identify potential targets for antidepressant drugs. PMID: 29237567 [PubMed - as supplied by publisher]

Assessing Public Metabolomics Metadata, Towards Improving Quality. J Integr Bioinform. 2017 Dec 13;14(4): Authors: Ferreira JD, Inácio B, Salek RM, Couto FM Abstract Public resources need to be appropriately annotated with metadata in order to make them discoverable, reproducible and traceable, further enabling them to be interoperable or integrated with other datasets. While data-sharing policies exist to promote the annotation process by data owners, these guidelines are still largely ignored. In this manuscript, we analyse automatic measures of metadata quality, and suggest their application as a mean to encourage data owners to increase the metadata quality of their resources and submissions, thereby contributing to higher quality data, improved data sharing, and the overall accountability of scientific publications. We analyse these metadata quality measures in the context of a real-world repository of metabolomics data (i.e. MetaboLights), including a manual validation of the measures, and an analysis of their evolution over time. Our findings suggest that the proposed measures can be used to mimic a manual assessment of metadata quality. PMID: 29236679 [PubMed - in process]

Increased levels of circulating fatty acids are associated with protective effects against future cardiovascular events in non-diabetics. J Proteome Res. 2017 Dec 13;: Authors: Kamleh MA, McLeod O, Checa A, Baldassarre D, Veglia F, Gertow K, Humphries SE, Rauramaa R, deFaire U, Smit AJ, Giral P, Kurl S, Mannarino E, Tremoli E, Silveira A, Orvik J, Hamsten A, Wheelock CE Abstract Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Non-targeted metabolomics analysis was performed by LC-HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort were included in a case-control study design. Following data processing, the three metabolite datasets were concatenated to produce a single dataset of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p=0.026). From this factor, we identified a free fatty acid signature (n=10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in non-diabetics only (OR=0.65, 0.27-0.80 95% CI, p=0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the non-diabetic population, further highlighting the need for patient stratification in clinical investigations. PMID: 29235871 [PubMed - as supplied by publisher]

A metabolomic signature of endometrial cancer. J Proteome Res. 2017 Dec 13;: Authors: Troisi J, Sarno L, Landolfi A, Scala G, Martinelli P, Venturella R, Di Cello A, Zullo F, Guida M Abstract Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed Countries. At the moment, no effective screening system is available. Here, we evaluate the diagnostic performance of a serum metabolomic signature. Two enrollments were carried out: one constituted of 168 subjects: 88 with EC and 80 healthy women, was used for building the classification models. The second (used to establish the performance of the classification algorithm) was constituted of 120 subjects: 30 with EC, 30 with ovarian cancer, 10 with benign endometrial disease and 50 healthy controls. Two ensemble models were built, one with all EC vs. controls (Model I) and one in which EC patients were aggregated according to their histotype (Model II). Serum metabolomic analysis was conducted via gas chromatography-mass spectrometry, while classification was done by an ensemble learning machine. Accuracy ranged from 62% to 99% for the Model I and from 67% to 100% for the Model II. Ensemble model showed an accuracy of 100% both for Model I and II. The most important metabolites in class separation were: lactic acid, progesterone, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, and valine. The serum metabolomics signature of endometrial cancer patients is peculiar because it differs from that of healthy controls and from that of benign endometrial disease and from other gynecological cancers (such as ovarian cancer). PMID: 29235868 [PubMed - as supplied by publisher]

Related Articles Post genomics era for orchid research. Bot Stud. 2017 Dec 12;58(1):61 Authors: Tsai WC, Dievart A, Hsu CC, Hsiao YY, Chiou SY, Huang H, Chen HH Abstract Among 300,000 species in angiosperms, Orchidaceae containing 30,000 species is one of the largest families. Almost every habitats on earth have orchid plants successfully colonized, and it indicates that orchids are among the plants with significant ecological and evolutionary importance. So far, four orchid genomes have been sequenced, including Phalaenopsis equestris, Dendrobium catenatum, Dendrobium officinale, and Apostaceae shengen. Here, we review the current progress and the direction of orchid research in the post genomics era. These include the orchid genome evolution, genome mapping (genome-wide association analysis, genetic map, physical map), comparative genomics (especially receptor-like kinase and terpene synthase), secondary metabolomics, and genome editing. PMID: 29234904 [PubMed]

Related Articles 1H-NMR Based Serum Metabolomics Study to Investigate Hepatoprotective Effect of Qin-Jiao on Carbon Tetrachloride-Induced Acute Hepatotoxicity in Rats. Evid Based Complement Alternat Med. 2017;2017:6091589 Authors: Li Z, Li Y, Lu L, Yang Z, Xue W, Tian X, Zhang X Abstract Gentiana macrophylla Radix, commonly known as Qin-Jiao (QJ), was recorded alone to treat jaundice in Compendium of Materia Medica and has been frequently prescribed for treatment of liver disease in China. However, the underlying mechanism remains unknown. In the present work, QJ of 1,2 g/kg or silybin of 40 mg/kg (positive control) was orally given to rats for 7 days to verify the protective effect on acute liver damage induced by tetrachloride (CCl4). Together with serum biochemistry and histopathological examination, 1H-NMR based metabolomics work was carried out to investigate the efficacy. It turned out that QJ of 2 g/kg exerted comparable protective effect with positive control and partially recovered disturbed metabolism by CCl4. Multivariate analysis was conducted and metabolites altered significantly among groups were assigned and discussed, including betaine, glucose, lactate, creatine, and LDL/VLDL. Metabolic regulations involved in QJ or silybin treatment were as follows: tricarboxylic acid (TCA) cycle, synthesis of LDL/VLDL, and gluconeogenesis were enhanced, while betaine metabolism, glycolysis, creatine metabolism, synthesis of ketone bodies, amino acids metabolism, and β-oxidation of fatty acids were suppressed. For the first time hepatoprotective effect of QJ on acute liver damage was revealed by 1H-NMR based metabolomics, prompting understanding of the underlying mechanism. PMID: 29234415 [PubMed]

Related Articles Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats. Evid Based Complement Alternat Med. 2017;2017:2979760 Authors: Ali MY, Paul S, Tanvir EM, Hossen MS, Rumpa NN, Saha M, Bhoumik NC, Aminul Islam M, Hossain MS, Alam N, Gan SH, Khalil MI Abstract The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions. PMID: 29234381 [PubMed]

Related Articles From Discovery to Translation: Characterization of C-Mannosyltryptophan and Pseudouridine as Markers of Kidney Function. Sci Rep. 2017 Dec 12;7(1):17400 Authors: Sekula P, Dettmer K, Vogl FC, Gronwald W, Ellmann L, Mohney RP, Eckardt KU, Suhre K, Kastenmüller G, Oefner PJ, Köttgen A Abstract Using a non-targeted metabolomics platform, we recently identified C-mannosyltryptophan and pseudouridine as non-traditional kidney function markers. The aims of this study were to obtain absolute concentrations of both metabolites in blood and urine from individuals with and without CKD to provide reference ranges and to assess their fractional excretions (FE), and to assess the agreement with their non-targeted counterparts. In individuals without/with CKD, mean plasma and urine concentrations for C-mannosyltryptophan were 0.26/0.72 µmol/L and 3.39/4.30 µmol/mmol creatinine, respectively. The respective concentrations for pseudouridine were 2.89/5.67 µmol/L and 39.7/33.9 µmol/mmol creatinine. Median (25th, 75th percentiles) FEs were 70.8% (65.6%, 77.8%) for C-mannosyltryptophan and 76.0% (68.6%, 82.4%) for pseudouridine, indicating partial net reabsorption. Association analyses validated reported associations between single metabolites and eGFR. Targeted measurements of both metabolites agreed well with the non-targeted measurements, especially in urine. Agreement for composite nephrological measures FE and urinary metabolite-to-creatinine ratio was lower, but could be improved by replacing non-targeted creatinine measurements with a standard clinical creatinine test. In summary, targeted quantification and additional characterization in relevant populations are necessary steps in the translation of non-traditional biomarkers in nephrology from non-targeted discovery to clinical application. PMID: 29234020 [PubMed - in process]

Related Articles N- and O-glycosylation analysis of human C1-inhibitor reveals extensive mucin-type O-glycosylation. Mol Cell Proteomics. 2017 Dec 12;: Authors: Stavenhagen K, Kayili HM, Holst S, Koeleman C, Engel R, Wouters D, Zeerleder S, Salih B, Wuhrer M Abstract Human C1-inhibitor (C1-Inh) is a serine protease inhibitor and the major regulator of the contact activation pathway as well as the classical and lectin complement pathways. It is known to be a highly glycosylated plasma glycoprotein. However, both the structural features and biological role of C1-Inh glycosylation are largely unknown. Here, we performed for the first time an in-depth site-specific N- and O-glycosylation analysis of C1-Inh combining various mass spectrometric approaches, including C18-porous graphitized carbon (PGC)-LC-ESI-QTOF-MS/MS applying stepping-energy collision-induced dissociation (CID) and electron-transfer dissociation (ETD). Various proteases were applied, partly in combination with PNGase F and exoglycosidase treatment, in order to analyze the (glyco)peptides. The analysis revealed an extensively O-glycosylated N-terminal region. Five novel and five known O-glycosylation sites were identified, carrying mainly core1-type O-glycans. In addition, we detected a heavily O-glycosylated portion spanning from Thr82-Ser121 with up to 16 O-glycans attached. Likewise, all known six N-glycosylation sites were covered and confirmed by this site-specific glycosylation analysis. The glycoforms were in accordance with results on released N-glycans by MALDI-TOF/TOF-MS/MS. The comprehensive characterization of C1-Inh glycosylation described in this study will form the basis for further functional studies on the role of these glycan modifications. PMID: 29233911 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis of alloxan-induced diabetes in mice using UPLC-Q-TOF-MS after Crassostrea gigas polysaccharide treatment. Int J Biol Macromol. 2017 Dec 09;: Authors: Zhao G, Hou X, Li X, Qu M, Tong C, Li W Abstract Diabetes has become a global and serious health issues which causes a variety of complications. This study aims to explore the hypoglycemic effect of Crassostrea gigas polysaccharide (CGPS) and the dynamic changes in the the endogenous small molecule metabolites of urine from normal group, model group and CGPS high dose group by metabolomic approach (UPLC-Q-TOF-MS). In our study, the CGPS treatment could reduce the fasting blood glucose levels and recover the triglycerides (TG), total cholesterol (TC) and glycosylated serum protein (GSP) levels in serum of diabetic mice. Urine samples in normal group, model group and CGPS high dose group were dispersed in the PLS-DA score plots. Nineteen metabolites in urine such as L-carnitine, hippuric acid, pantothenate and ornithine were selected as potential therapeutic biomarkers and related metabolic pathways of CGPS for treating diabetes. They were mainly involved in amino acid metabolism, carbohydrate metabolism and purine metabolism. These data suggested that CGPS has antidiabetic activity and urine metabolites provided new understanding of CGPS for treating diabetes and its complications. PMID: 29233709 [PubMed - as supplied by publisher]

Related Articles HPLC-Based Metabolomic Analysis of Normal and Inflamed Gut. Methods Mol Biol. 2016;1422:63-75 Authors: Kao DJ, Lanis JM, Alexeev E, Kominsky DJ Abstract The idiopathic inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are multifactorial chronic conditions that result in numerous perturbations of metabolism in the gastrointestinal mucosa. Thus, methodologies for the qualitative and quantitative analysis of small molecule metabolites in mucosal tissues are important for further elucidation of mechanisms driving inflammation and the metabolic consequences of inflammation. High-performance liquid chromatography (HPLC) is a ubiquitous analytical technique that can be adapted for both targeted and non-targeted metabolomic analysis. Here, protocols for reversed-phase (RP) HPLC-based methods using two different detection modalities are presented. Ultraviolet detection is used for the analysis of adenine nucleotide metabolites, whereas electrochemical detection is used for the analysis of multiple amino acid metabolites. These methodologies provide platforms for further characterization of the metabolic changes that occur during gastrointestinal inflammation. PMID: 27246023 [PubMed - indexed for MEDLINE]

Related Articles Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms. Amino Acids. 2016 Aug;48(8):1969-81 Authors: Zervou S, Yin X, Nabeebaccus AA, O'Brien BA, Cross RL, McAndrew DJ, Atkinson RA, Eykyn TR, Mayr M, Neubauer S, Lygate CA Abstract Mice over-expressing the creatine transporter have elevated myocardial creatine levels [Cr] and are protected against ischaemia/reperfusion injury via improved energy reserve. However, mice with very high [Cr] develop cardiac hypertrophy and dysfunction. To investigate these contrasting effects, we applied a non-biased hypothesis-generating approach to quantify global protein and metabolite changes in the LV of mice stratified for [Cr] levels: wildtype, moderately elevated, and high [Cr] (65-85; 100-135; 160-250 nmol/mg protein, respectively). Male mice received an echocardiogram at 7 weeks of age with tissue harvested at 8 weeks. RV was used for [Cr] quantification by HPLC to select LV tissue for subsequent analysis. Two-dimensional difference in-gel electrophoresis identified differentially expressed proteins, which were manually picked and trypsin digested for nano-LC-MS/MS. Principal component analysis (PCA) showed efficient group separation (ANOVA P ≤ 0.05) and peptide sequences were identified by mouse database (UniProt 201203) using Mascot. A total of 27 unique proteins were found to be differentially expressed between normal and high [Cr], with proteins showing [Cr]-dependent differential expression, chosen for confirmation, e.g. α-crystallin B, a heat shock protein implicated in cardio-protection and myozenin-2, which could contribute to the hypertrophic phenotype. Nuclear magnetic resonance (¹H-NMR at 700 MHz) identified multiple strong correlations between [Cr] and key cardiac metabolites. For example, positive correlations with α-glucose (r² = 0.45; P = 0.002), acetyl-carnitine (r² = 0.50; P = 0.001), glutamine (r² = 0.59; P = 0.0002); and negative correlations with taurine (r² = 0.74; P < 0.0001), fumarate (r² = 0.45; P = 0.003), aspartate (r² = 0.59; P = 0.0002), alanine (r² = 0.66; P < 0.0001) and phosphocholine (r² = 0.60; P = 0.0002). These findings suggest wide-ranging and hitherto unexpected adaptations in substrate utilisation and energy metabolism with a general pattern of impaired energy generating pathways in mice with very high creatine levels. PMID: 27143170 [PubMed - indexed for MEDLINE]

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 2017/12/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2017/12/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2017/12/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very-Low-Density Lipoproteins. J Am Heart Assoc. 2017 Dec 09;6(12): Authors: Lawler PR, Akinkuolie AO, Harada P, Glynn RJ, Chasman DI, Ridker PM, Mora S Abstract BACKGROUND: It is uncertain whether pharmacological reductions in very-low-density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low-density lipoprotein cholesterol (LDL-C) has been adequately lowered. We examined whether individuals with greater on-statin reductions in VLDL-related measures-beyond reductions in LDL-C-were at further reduced risk of ASCVD. METHODS AND RESULTS: In 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400-MHz proton nuclear magnetic resonance spectroscopy-measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin-allocated participants who achieved minimal (<median) or greater (≥median) marker reductions using adjusted Cox models. On-statin changes in VLDL-related markers were only modestly correlated (Spearman r≤0.29) with change in LDL-C. On-statin median LDL-C was 54 mg/dL and triglyceride was 101 mg/dL. Dose-response reductions in ASCVD risk were observed for greater reductions in LDL-C, VLDL cholesterol mass, and small VLDL lipoprotein particle concentration; the latter 2 remained significant after incremental adjustment for change in LDL-C (P≤0.006). Conversely, there was no further risk reduction with greater reductions in triglycerides or large/medium VLDL lipoprotein particle concentration. CONCLUSIONS: Pharmacological reduction in small, cholesterol-enriched, triglyceride-depleted VLDL was associated with reduction in ASCVD risk. Chemically measured triglycerides may not sufficiently capture risk related to VLDL pathways. These findings also support broader profiling of lipid and lipoprotein changes in response to statins as prognostic markers of individual benefit, supporting more precision-medicine, individualized approaches to cardiovascular risk reduction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681. PMID: 29223956 [PubMed - in process]