PubMed

Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation. Nat Microbiol. 2020 Aug 17;: Authors: Deo P, Chow SH, Han ML, Speir M, Huang C, Schittenhelm RB, Dhital S, Emery J, Li J, Kile BT, Vince JE, Lawlor KE, Naderer T Abstract Sensing of microbes activates the innate immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondrial activity by delivering toxins via outer membrane vesicles (OMVs). How macrophages respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages exposed to OMVs from Neisseria gonorrhoeae, uropathogenic Escherichia coli and Pseudomonas aeruginosa induce mitochondrial apoptosis and NLRP3 inflammasome activation. OMVs and toxins that cause mitochondrial dysfunction trigger inhibition of host protein synthesis, which depletes the unstable BCL-2 family member MCL-1 and induces BAK-dependent mitochondrial apoptosis. In parallel with caspase-11-mediated pyroptosis, mitochondrial apoptosis and potassium ion efflux activate the NLRP3 inflammasome after OMV exposure in vitro. Importantly, in the in vivo setting, the activation and release of interleukin-1β in response to N. gonorrhoeae OMVs is regulated by mitochondrial apoptosis. Our data highlight how innate immune cells sense infections by monitoring mitochondrial health. PMID: 32807891 [PubMed - as supplied by publisher]

Addressing the batch effect issue for LC/MS metabolomics data in data preprocessing. Sci Rep. 2020 Aug 17;10(1):13856 Authors: Liu Q, Walker D, Uppal K, Liu Z, Ma C, Tran V, Li S, Jones DP, Yu T Abstract With the growth of metabolomics research, more and more studies are conducted on large numbers of samples. Due to technical limitations of the Liquid Chromatography-Mass Spectrometry (LC/MS) platform, samples often need to be processed in multiple batches. Across different batches, we often observe differences in data characteristics. In this work, we specifically focus on data generated in multiple batches on the same LC/MS machinery. Traditional preprocessing methods treat all samples as a single group. Such practice can result in errors in the alignment of peaks, which cannot be corrected by post hoc application of batch effect correction methods. In this work, we developed a new approach that address the batch effect issue in the preprocessing stage, resulting in better peak detection, alignment and quantification. It can be combined with down-stream batch effect correction methods to further correct for between-batch intensity differences. The method is implemented in the existing workflow of the apLCMS platform. Analyzing data with multiple batches, both generated from standardized quality control (QC) plasma samples and from real biological studies, the new method resulted in feature tables with better consistency, as well as better down-stream analysis results. The method can be a useful addition to the tools available for large studies involving multiple batches. The method is available as part of the apLCMS package. Download link and instructions are at https://mypage.cuhk.edu.cn/academics/yutianwei/apLCMS/ . PMID: 32807888 [PubMed - in process]

Metabolomics in the study of spontaneous animal diseases. J Vet Diagn Invest. 2020 Aug 18;:1040638720948505 Authors: Tran H, McConville M, Loukopoulos P Abstract Using analytical chemistry techniques such as nuclear magnetic resonance (NMR) spectroscopy and liquid or gas chromatography-mass spectrometry (LC/GC-MS), metabolomics allows detection of most endogenous and exogenous metabolites in a biological sample. Metabolomics has a wide range of applications, and has been employed in nutrition science, toxicology, environmental studies, and systems biology. Metabolomics is particularly useful in biomedical science, and has been used for diagnostic laboratory testing, identifying targets for drug development, and monitoring drug metabolism, mode of action, and toxicity. Despite its immense potential, metabolomics remains underutilized in the study of spontaneous animal diseases. Our aim was to comprehensively review the existing literature on the use of metabolomics in spontaneous veterinary diseases. Three databases were used to find journal articles that applied metabolomics in veterinary medicine. A screening process was then conducted to eliminate references that did not meet the eligibility criteria; only primary research studies investigating spontaneous animal disease were included; 38 studies met the inclusion criteria. The main techniques used were NMR and MS. All studies detected metabolite alterations in diseased animals compared with non-diseased animals. Metabolomics was mainly used to study diseases of the digestive, reproductive, and musculoskeletal systems. Inflammatory conditions made up the largest proportion of studies when articles were categorized by disease process. Following a comprehensive analysis of the literature on metabolomics in spontaneous veterinary diseases, we concluded that metabolomics, although in its early stages in veterinary research, is a promising tool regarding diagnosis, biomarker discovery, and in uncovering new insights into disease pathophysiology. PMID: 32807042 [PubMed - as supplied by publisher]

Identifying the Compounds of the Metabolic Elicitors of Pseudomonas fluorescens N 21.4 Responsible for Their Ability to Induce Plant Resistance. Plants (Basel). 2020 Aug 12;9(8): Authors: Martin-Rivilla H, Gutierrez-Mañero FJ, Gradillas A, P Navarro MO, Andrade G, Lucas JA Abstract In this work, the metabolic elicitors extracted from the beneficial rhizobacterium Pseudomonas fluorescens N 21.4 were sequentially fragmented by vacuum liquid chromatography to isolate, purify and identify the compounds responsible for the extraordinary capacities of this strain to induce systemic resistance and to elicit secondary defensive metabolism in diverse plant species. To check if the fractions sequentially obtained were able to increase the synthesis of isoflavones and if, therefore, they still maintained the eliciting capacity of the live strain, rapid and controlled experiments were done with soybean seeds. The optimal action concentration of the fractions was established and all of them elicited isoflavone secondary metabolism-the fractions that had been extracted with n-hexane being more effective. The purest fraction was the one with the highest eliciting capacity and was also tested in Arabidopsis thaliana seedlings to induce systemic resistance against the pathogen Pseudomonas syringae pv. tomato DC 3000. This fraction was then analyzed by UHPLC/ESI-QTOF-MS, and an alkaloid, two amino lipids, three arylalkylamines and a terpenoid were tentatively identified. These identified compounds could be part of commercial plant inoculants of biological and sustainable origin to be applied in crops, due to their potential to enhance the plant immune response and since many of them have putative antibiotic and/or antifungal potential. PMID: 32806693 [PubMed]

Varying Protein Levels Influence Metabolomics and the Gut Microbiome in Healthy Adult Dogs. Toxins (Basel). 2020 Aug 12;12(8): Authors: Ephraim E, Cochrane CY, Jewell DE Abstract The optimal ranges of protein for healthy adult dogs are not known. This study evaluated the impact of long-term consumption of foods containing low, medium, and high levels of protein on serum, urine, and fecal metabolites, and gut microbiome in beagles. Following maintenance on a prefeed food for 14 days, dogs (15 neutered males, 15 spayed females, aged 2-9 years, mean initial weight 11.3 kg) consumed the low (18.99%, dry matter basis), medium (25.34%), or high (45.77%) protein foods, each for 90 days, in a William's Latin Square Design sequence. In serum and/or urine, metabolites associated with inflammation (9,10-dihydroxyoctadecanoic acid (DiHOME)), 12,13-DiHOME) and kidney dysfunction (urea, 5-hydroxyindole sulfate, 7-hydroxyindole sulfate, p-cresol sulfate) increased with higher protein levels in food, while one-carbon pathway metabolites (betaine, dimethylglycine, sarcosine) decreased. Fecal pH increased with protein consumed, and levels of beneficial indoles and short-chain fatty acids decreased while branched-chain fatty acids increased. Beta diversity of the fecal microbiome was significantly different, with increased abundances of proteolytic bacteria with higher protein food. Feeding dogs a high amount of protein leads to a shift to proteolytic gut bacteria, higher fecal pH, and is associated with increased levels of metabolites linked with inflammation and kidney dysfunction. PMID: 32806674 [PubMed - in process]

Related Articles Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy. Nat Commun. 2020 06 02;11(1):2843 Authors: Li M, Parker BL, Pearson E, Hunter B, Cao J, Koay YC, Guneratne O, James DE, Yang J, Lal S, O'Sullivan JF Abstract Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource. PMID: 32487995 [PubMed - indexed for MEDLINE]

Related Articles Acute Hypercapnia/Ischemia Alters the Esterification of Arachidonic Acid and Docosahexaenoic Acid Epoxide Metabolites in Rat Brain Neutral Lipids. Lipids. 2020 01;55(1):7-22 Authors: Otoki Y, Metherel AH, Pedersen T, Yang J, Hammock BD, Bazinet RP, Newman JW, Taha AY Abstract In the brain, approximately 90% of oxylipins are esterified to lipids. However, the significance of this esterification process is not known. In the present study, we (1) validated an aminopropyl solid phase extraction (SPE) method for separating esterified lipids using 100 and 500 mg columns and (2) applied the method to quantify the distribution of esterified oxylipins within phospholipids (PL) and neutral lipids (NL) (i.e. triacylglycerol and cholesteryl ester) in rats subjected to head-focused microwave fixation (controls) or CO2 -induced hypercapnia/ischemia. We hypothesized that oxylipin esterification into these lipid pools will be altered following CO2 -induced hypercapnia/ischemia. Lipids were extracted from control (n = 8) and CO2 -asphyxiated (n = 8) rat brains and separated on aminopropyl cartridges to yield PL and NL. The separated lipid fractions were hydrolyzed, purified with hydrophobic-lipophilic-balanced SPE columns, and analyzed with ultra-high-pressure liquid chromatography coupled to tandem mass spectrometry. Method validation showed that the 500 mg (vs 100 mg) aminopropyl columns yielded acceptable separation and recovery of esterified fatty acid epoxides but not other oxylipins. Two epoxides of arachidonic acid (ARA) were significantly increased, and three epoxides of docosahexaenoic acid (DHA) were significantly decreased in brain NL of CO2 -asphyxiated rats compared to controls subjected to head-focused microwave fixation. PL-bound fatty acid epoxides were highly variable and did not differ significantly between the groups. This study demonstrates that hypercapnia/ischemia alters the concentration of ARA and DHA epoxides within NL, reflecting an active turnover process regulating brain fatty acid epoxide concentrations. PMID: 31691988 [PubMed - indexed for MEDLINE]

Related Articles An exploration of the methods to determine the protein-specific synthesis and breakdown rates in vivo in humans. Physiol Rep. 2019 09;7(17):e14143 Authors: Holm L, Dideriksen K, Nielsen RH, Doessing S, Bechshoeft RL, Højfeldt G, Moberg M, Blomstrand E, Reitelseder S, van Hall G Abstract The present study explores the methods to determine human in vivo protein-specific myofibrillar and collagenous connective tissue protein fractional synthesis and breakdown rates. We found that in human myofibrillar proteins, the protein-bound tracer disappearance method to determine the protein fractional breakdown rate (FBR) (via 2 H2 O ingestion, endogenous labeling of 2 H-alanine that is incorporated into proteins, and FBR quantified by its disappearance from these proteins) has a comparable intrasubject reproducibility (range: 0.09-53.5%) as the established direct-essential amino acid, here L-ring-13 C6 -phenylalanine, incorporation method to determine the muscle protein fractional synthesis rate (FSR) (range: 2.8-56.2%). Further, the determination of the protein breakdown in a protein structure with complex post-translational processing and maturation, exemplified by human tendon tissue, was not achieved in this experimentation, but more investigation is encouraged to reveal the possibility. Finally, we found that muscle protein FBR measured with an essential amino acid tracer prelabeling is inappropriate presumably because of significant and prolonged intracellular recycling, which also may become a significant limitation for determination of the myofibrillar FSR when repeated infusion trials are completed in the same participants. PMID: 31496135 [PubMed - indexed for MEDLINE]

34 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 2020/08/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

34 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 2020/08/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Development of a novel comprehensive analytical method for volatile compounds using supercritical fluid chromatography/mass spectrometry with a highly cross-linked styrene divinylbenzene polymer-based column. J Chromatogr A. 2020 Aug 30;1626:461363 Authors: Fujito Y, Hayakawa Y, Bamba T Abstract Analytical techniques to determine volatile compounds such as flavor, aroma, and fragrances are in high demand due to their wide range of applications in industry, the chemical properties of them are very diverse. Supercritical fluid chromatography (SFC) is capable of high speed, high peak capacity separation and has a high separation coverage. It is also an advantageous for preparative purifications due to its unique mobile phase conditions. However, there is no column commercially available for SFC that is suitable to comprehensively separate volatile compounds. SFC is limited to the use of silica-based columns due to weak retentions and polymer-based column issues such as pressure, swelling and shrinkage tolerances. This study demonstrated comprehensive analytical method for volatile in SFC using a highly cross-linked styrene divinylbenzene (SDVB) polymer-based column, newly developed for SFC. In this study, 23 typical volatile compounds with a wide variety of chemical properties were selected as model compounds. The newly developed SDVB column showed, compared to conventional silica-based columns (k > 0.3), an excellent overall and substantial improved retentions (k > 1.6) under SFC mobile phase conditions. It was also able to retain esters (hydroxy acetate, pentyl butylate, methyl salicylate) and non-polar terpenes (limonene, pinene) that did not show sufficient retention in any other commercially available silica-based columns. Aldehydes reacting on NH2 column due to Schiff base formation were also successfully eluted. It was confirmed that SDVB column provided comprehensive separation and wide coverage for volatile compounds. PMID: 32797842 [PubMed - as supplied by publisher]

Effects of casein, chicken and pork proteins on regulation of body fat and blood inflammatory factors and metabolite patterns are largely dependent on protein level and less attributable to the protein source. J Agric Food Chem. 2020 Aug 14;: Authors: Song S, Xia T, Zhu C, Xue J, Fu Q, Hua C, Hooiveld GJEJ, Muller M, Li CB Abstract The impact of meat protein on metabolic regulation is still disputed, and may be influenced by protein level. This study aimed to explore the effects of casein, pork and chicken proteins at different protein levels (40% E vs. 20% E) on body weight regulation, body fat accumulation, serum hormone levels, and inflammatory factors/metabolites in rats maintained on high-fat (45% E fat) diets for 84 d. Increased protein-levels resulted in a significant reduction in body fat mass and an increase in serum levels of the anti-inflammatory cytokine IL-10, independent of protein source. Analysis of blood via untargeted metabolomics analysis identified 8, 4 and 4 metabolites significantly altered by protein level, protein source, and a protein level*source interaction, respectively. Together, the effects of casein, chicken and pork protein on the regulation of body fat accumulation and blood metabolite profile are largely dependent on protein level, and less attributable to the protein source. PMID: 32797752 [PubMed - as supplied by publisher]

A computational and experimental study of the fragmentation of l-leucine, l-isoleucine and l-allo-isoleucine under collision-induced dissociation tandem mass spectrometry. Analyst. 2020 Aug 14;: Authors: Jiang C, Arthur CJ, Gates PJ Abstract The isomeric amino acids l-leucine, l-isoleucine and l-allo-isoleucine, are essential to many vital biological processes and are therefore of interest to the fields of metabolomics and proteomics. Their discrimination can be problematic however due to their isomeric natue. This study demonstrates a systematic investigation of the fragmentations of l-leucine, l-isoleucine and l-allo-isoleucine in combination with a thorough theoretical rationalisation. Collision induced dissociation (CID) tandem mass spectra (MS/MS) of all three amino acids were collected under a range of different collision energies to identify spontaneous and sequential fragmentation processes. We demonstrate that the three structural isomers can be distinguished by their CID MS/MS spectra, and additional computational modelling is used to rationalise these differences. PMID: 32797137 [PubMed - as supplied by publisher]

Triacylglycerol synthesis enhances macrophage inflammatory function. Nat Commun. 2020 Aug 14;11(1):4107 Authors: Castoldi A, Monteiro LB, van Teijlingen Bakker N, Sanin DE, Rana N, Corrado M, Cameron AM, Hässler F, Matsushita M, Caputa G, Klein Geltink RI, Büscher J, Edwards-Hicks J, Pearce EL, Pearce EJ Abstract Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1β, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation. PMID: 32796836 [PubMed - as supplied by publisher]

Omics Application in Animal Science-A Special Emphasis on Stress Response and Damaging Behaviour in Pigs. Genes (Basel). 2020 Aug 11;11(8): Authors: Kasper C, Ribeiro D, Almeida AM, Larzul C, Liaubet L, Murani E Abstract Increasing stress resilience of livestock is important for ethical and profitable meat and dairy production. Susceptibility to stress can entail damaging behaviours, a common problem in pig production. Breeding animals with increased stress resilience is difficult for various reasons. First, studies on neuroendocrine and behavioural stress responses in farm animals are scarce, as it is difficult to record adequate phenotypes under field conditions. Second, damaging behaviours and stress susceptibility are complex traits, and their biology is not yet well understood. Dissecting complex traits into biologically better defined, heritable and easily measurable proxy traits and developing biomarkers will facilitate recording these traits in large numbers. High-throughput molecular technologies ("omics") study the entirety of molecules and their interactions in a single analysis step. They can help to decipher the contributions of different physiological systems and identify candidate molecules that are representative of different physiological pathways. Here, we provide a general overview of different omics approaches and we give examples of how these techniques could be applied to discover biomarkers. We discuss the genetic dissection of the stress response by different omics techniques and we provide examples and outline potential applications of omics tools to understand and prevent outbreaks of damaging behaviours. PMID: 32796712 [PubMed - as supplied by publisher]

Metabolomics in Radiation Biodosimetry: Current Approaches and Advances. Metabolites. 2020 Aug 11;10(8): Authors: Satyamitra MM, Cassatt DR, Hollingsworth BA, Price PW, Rios CI, Taliaferro LP, Winters TA, DiCarlo AL Abstract Triage and medical intervention strategies for unanticipated exposure during a radiation incident benefit from the early, rapid and accurate assessment of dose level. Radiation exposure results in complex and persistent molecular and cellular responses that ultimately alter the levels of many biological markers, including the metabolomic phenotype. Metabolomics is an emerging field that promises the determination of radiation exposure by the qualitative and quantitative measurements of small molecules in a biological sample. This review highlights the current role of metabolomics in assessing radiation injury, as well as considerations for the diverse range of bioanalytical and sampling technologies that are being used to detect these changes. The authors also address the influence of the physiological status of an individual, the animal models studied, the technology and analysis employed in interrogating response to the radiation insult, and variables that factor into discovery and development of robust biomarker signatures. Furthermore, available databases for these studies have been reviewed, and existing regulatory guidance for metabolomics are discussed, with the ultimate goal of providing both context for this area of radiation research and the consideration of pathways for continued development. PMID: 32796693 [PubMed - as supplied by publisher]

Ruggedness testing of liquid chromatography-tandem mass spectrometry system components using microbiome-relevant methods and matrices. J Microbiol Methods. 2020 Aug 11;:106020 Authors: Horvath TD, Haidacher SJ, Oezguen N, Hoch KM, Auchtung JM, Haag AM Abstract Recently, an opportunity to perform a broad ruggedness assessment of our liquid chromatography-tandem mass spectrometry (LC-MS/MS) system presented itself during the analytical planning phase of a large-scale human fecal microbiome study. The specific aim of this project was to study the microbial-mediated metabolism of a targeted set of bile acids/salts by mixed bacterial communities cultured from the feces of 12 healthy volunteers when grown in a custom growth medium and following exposure to different clinically-relevant antibiotics. The magnitude of this study offered a rare opportunity to significantly stress procedures and LC-MS/MS system components comprised in our bile acid/salt targeted metabolomics method. With this second specific aim in mind, we modified the sample analysis plan to include a series of figure-of-merit (FoM)-based tests that are commonly used in regulated bioanalytical labs to assess LC and MS system ruggedness for a specific assay - these FoM-based testing parameters were monitored continuously over the course of sample analysis and the results are presented in this report. In total, the assessment included 1206 sequential injections (180 calibration standards, 136 blank-internal standard samples, and 890 diluted medium samples) that took place over 8-days. Completion of the 8-days of non-stop sample analysis revealed no critical hardware or software failures, and the analysis of the FoM-based tests indicated no observable degradation of system performance over the number of samples and time tested. The FoM-based test metrics presented may be used as a template to assess the ruggedness of any LC-MS/MS-based targeted metabolomics workflow. PMID: 32795635 [PubMed - as supplied by publisher]

Metabolomics investigation of summer mortality in New Zealand Greenshell™ mussels (Perna canaliculus). Fish Shellfish Immunol. 2020 Aug 11;: Authors: Nguyen TV, Alfaro AC Abstract Increasing water temperatures due to climate change have resulted in more frequent high mortality events of New Zealand Greenshell™ mussels (Perna canaliculus Gmelin 1791). These events have significant impacts within mussel farms which support a major shellfish industry for New Zealand. The present study investigates metabolic responses of farmed mussels during a summer mortality event in order to identify health impacts and elucidate mechanistic effects of external stressors on mussels. A gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach was used to identify metabolic perturbations and flow cytometry assays were used to assess viability, oxidative stress and apoptosis of haemocytes from healthy and unhealthy mussels during a summer mortality event. The results showed significantly higher mortality and apoptosis of haemocytes in unhealthy mussels compared to healthy mussels. Reactive oxygen species (ROS) production, which is an indicator of oxidative stress was very high in both mussel groups, but no differences were observed between the two mussel groups. Metabolomics revealed alterations of many metabolites in both haemolymph and hepatopancreas (digestive gland) of unhealthy mussels compared to healthy mussels, reflecting perturbations in several molecular pathways, including energy metabolism, amino acid metabolism, protein degradation/tissue damage and oxidative stress. Increased levels of itaconic acid, which is an antimicrobial metabolite was observed in haemolymph, but not in hepatopancreas samples. This investigation provides the first detailed metabolic characterization of mussel immune responses to a summer mortality event and illustrates the benefits of using an integrated metabolomics and flow cytometry workflow for mussel health assessment and biomarker identification for summer mortality early detection. PMID: 32795595 [PubMed - as supplied by publisher]

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure. Can J Cardiol. 2020 Mar 28;: Authors: Zhao H, Shui B, Zhao Q, Hu Z, Shu Q, Su M, Zhang Y, Ni Y Abstract BACKGROUND: Heart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined. METHODS: A quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers. RESULTS: The optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro-B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001). CONCLUSIONS: Targeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation. PMID: 32795449 [PubMed - as supplied by publisher]

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 2020/08/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.