PubMed

Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit. PLoS One. 2015;10(11):e0140993 Authors: Garcia-Simon M, Morales JM, Modesto-Alapont V, Gonzalez-Marrachelli V, Vento-Rehues R, Jorda-Miñana A, Blanquer-Olivas J, Monleon D Abstract Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID: 26565633 [PubMed - as supplied by publisher]

Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema. Clin Sci (Lond). 2015 Nov 12; Authors: Conlon TM, Bartel J, Ballweg K, Günter S, Prehn C, Krumsiek J, Meiners S, Theiss FJ, Adamski J, Eickelberg O, Yildirim AO Abstract Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodeling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema we used mass spectrometry-based approaches to quantitate the lung, bronchoalveolar-lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared to PBS controls. Partial Least Square analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung specific L-carnitine, a metabolite critical for transporting long chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro , stimulation of the ATII-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared to PBS treated controls (lung compliance; 0.067±0.008ml/cmH20 vs 0.035±0.005ml/cmH20, p<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, p<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD. PMID: 26564208 [PubMed - as supplied by publisher]

High-resolution NMR-based metabolic detection of microgram biopsies using a 1 mm HRμMAS probe. Analyst. 2015 Nov 13; Authors: Nishiyama Y, Endo Y, Nemoto T, Bouzier-Sore AK, Wong A Abstract A prototype 1 mm High-Resolution micro-Magic Angle Spinning (HRμMAS) probe is described. High quality (1)H NMR spectra were obtained from 490 μg of heterogeneous biospecimens, offering a rich-metabolite profiling. The results demonstrate the potential of HRμMAS as a new NMR analytical tool in metabolomics. PMID: 26563772 [PubMed - as supplied by publisher]

Compound identification in forensic toxicological analysis with untargeted LC-MS-based techniques. Bioanalysis. 2015 Nov 13; Authors: Oberacher H, Arnhard K Abstract Untargeted LC-MS/MS techniques have become indispensable tools for systematic toxicological analysis. Compound identification is based on the mass spectrometric information obtained, and this may include m/z, isotopic pattern, retention time and fragmentation information. All these different kinds of analytical features can be stored in libraries and databases. Currently, the most competent approach for compound identification involves tandem mass spectral library search. State-of-the-art databases were shown to be sensitive, specific, robust and instrument-independent. Low- and high-resolution instruments can both be used to develop efficient screening workflows. For automated and unattended acquisition of tandem mass spectral data, data-dependent acquisition control is the method of choice. Due to their impressive detection sensitivity, data-independent acquisition techniques are finding increased applicability. PMID: 26563687 [PubMed - as supplied by publisher]

Biotechnological advances in tea (Camellia sinensis [L.] O. Kuntze): a review. Plant Cell Rep. 2015 Nov 13; Authors: Mukhopadhyay M, Mondal TK, Chand PK Abstract KEY MESSAGE: This article presents a comprehensive review on the success and limitations of biotechnological approaches aimed at genetic improvement of tea with a purpose to explore possibilities to address challenging areas. Tea is a woody perennial tree with a life span of more than 100 years. Conventional breeding of tea is slow and limited primarily to selection which leads to narrowing down of its genetic base. Harnessing the benefits of wild relatives has been negligible due to low cross-compatibility, genetic drag and undesirable alleles for low yield. Additionally, being a recalcitrant species, in vitro propagation of tea is constrained too. Nevertheless, maneuvering with tissue/cell culture techniques, a considerable success has been achieved in the area of micropropagation, somatic embryogenesis as well as genetic transformation. Besides, use of molecular markers, "expressomics" (transcriptomics, proteomics, metabolomics), map-based cloning towards construction of physical maps, generation of expressed sequenced tags (ESTs) have facilitated the identification of QTLs and discovery of genes associated with abiotic or biotic stress tolerance and agronomic traits. Furthermore, the complete genome (or at least gene space) sequence of tea is expected to be accessible in the near future which will strengthen combinational approaches for improvement of tea. This review presents a comprehensive account of the success and limitations of the biotechnological tools and techniques hitherto applied to tea and its wild relatives. Expectedly, this will form a basis for making further advances aimed at genetic improvement of tea in particular and of economically important woody perennials in general. PMID: 26563347 [PubMed - as supplied by publisher]

Related Articles Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS. PLoS One. 2014;9(7):e103811 Authors: Kruh-Garcia NA, Wolfe LM, Chaisson LH, Worodria WO, Nahid P, Schorey JS, Davis JL, Dobos KM Abstract The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states. PMID: 25080351 [PubMed - indexed for MEDLINE]

Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia-A Case of Novel Weapons? Int J Mol Sci. 2015;16(11):26721-26737 Authors: Skoneczny D, Weston PA, Zhu X, Gurr GM, Callaway RM, Weston LA Abstract Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant's capacity to deter natural enemies in its invaded range through production of novel weapons. PMID: 26561809 [PubMed - as supplied by publisher]

Metabolomics-Based Analysis of Banana and Pear Ingestion on Exercise Performance and Recovery. J Proteome Res. 2015 Nov 12; Authors: Nieman DC, Gillitt ND, Sha W, Meaney MP, John C, Pappan KL, Kinchen JM Abstract Bananas and pears vary in sugar and phenolic profiles, and metabolomics was utilized to measure their influence on exercise performance and recovery. Male athletes (N=20) cycled for 75 km while consuming water (WATER), bananas (BAN), or pears (PEAR) (0.6 g carbohydrate/kg each hour) in randomized order. UPLC-MS/MS and the library of purified standards maintained by Metabolon (Durham, NC) were used to analyze metabolite shifts in pre- and post-exercise (0-h, 1.5-h, 21-h) blood samples. Performance times were 5.0% and 3.3% faster during BAN and PEAR versus WATER (P=0.018 and P=0.091, respectively), with reductions in cortisol, IL-10, and total leukocytes, and increases in blood glucose, insulin, and FRAP. Partial Least Square Discriminant Analysis (PLS-DA) showed a distinct separation between trials immediately- (R2Y=0.877, Q2Y=0.457) and 1.5-h-post-exercise (R2Y=0.773, Q2Y=0.441). A total of 107 metabolites (primarily lipid-related) increased more than 2-fold during WATER, with a 48% and 52% reduction in magnitude during BAN and PEAR recovery (P<0.001). Increases in metabolites unique to BAN and PEAR included fructose and fruit constituents, and sulfated phenolics that were related to elevated FRAP. These data indicate that BAN and PEAR ingestion improves 75-km cycling performance, attenuates fatty acid utilization and oxidation, and contributes unique phenolics that augment antioxidant capacity. PMID: 26561314 [PubMed - as supplied by publisher]

MYC-induced reprogramming of glutamine catabolism supports optimal virus replication. Nat Commun. 2015;6:8873 Authors: Thai M, Thaker SK, Feng J, Du Y, Hu H, Ting Wu T, Graeber TG, Braas D, Christofk HR Abstract Viruses rewire host cell glucose and glutamine metabolism to meet the bioenergetic and biosynthetic demands of viral propagation. However, the mechanism by which viruses reprogram glutamine metabolism and the metabolic fate of glutamine during adenovirus infection have remained elusive. Here, we show MYC activation is necessary for adenovirus-induced upregulation of host cell glutamine utilization and increased expression of glutamine transporters and glutamine catabolism enzymes. Adenovirus-induced MYC activation promotes increased glutamine uptake, increased use of glutamine in reductive carboxylation and increased use of glutamine in generating hexosamine pathway intermediates and specific amino acids. We identify glutaminase (GLS) as a critical enzyme for optimal adenovirus replication and demonstrate that GLS inhibition decreases replication of adenovirus, herpes simplex virus 1 and influenza A in cultured primary cells. Our findings show that adenovirus-induced reprogramming of glutamine metabolism through MYC activation promotes optimal progeny virion generation, and suggest that GLS inhibitors may be useful therapeutically to reduce replication of diverse viruses. PMID: 26561297 [PubMed - in process]

Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis. J Pediatr Surg. 2015 Oct 22; Authors: Demehri FR, Frykman PK, Cheng Z, Ruan C, Wester T, Nordenskjöld A, Kawaguchi A, Hui TT, Granström AL, Funari V, Teitelbaum DH, HAEC Collaborative Research Group (HCRG) Abstract PURPOSE: Children with Hirschsprung disease (HD) who have a history of enterocolitis (HAEC) have a shift in colonic microbiota, many of which are necessary for short chain fatty acid (SCFA) production. As SCFAs play a critical role in colonic mucosal preservation, we hypothesized that fecal SCFA composition is altered in children with HAEC. METHODS: A multicenter study enrolled 18 HD children, abstracting for history of feeding, antibiotic/probiotic use, and enterocolitis symptoms. HAEC status was determined per Pastor et al. criteria (12). Fresh feces were collected for microbial community analysis via 16S sequencing as well as SCFA analysis by gas chromatography-mass spectrometry. RESULTS: Nine patients had a history of HAEC, and nine had never had HAEC. Fecal samples from HAEC children showed a 4-fold decline in total SCFA concentration vs. non-HAEC HD patients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAEC children. Finally, we measured relative abundance of SCFA-producing fecal microbiota. Interestingly, 10 of 12 butyrate-producing genera as well as 3 of 4 acetate-producing genera demonstrated multi-fold expansion. CONCLUSION: Children with HAEC history have reduced fecal SCFAs and altered SCFA profile. These findings suggest a complex interplay between the colonic metabolome and changes in microbiota, which may influence the pathogenesis of HAEC. PMID: 26561246 [PubMed - as supplied by publisher]

Tryptophan oxidation catabolite, N-formylkynurenine (NFK), in photo degraded cell culture medium results in reduced cell culture performance. Biotechnol Prog. 2015 Nov 11; Authors: McElearney K, Ali A, Zang L, Gilbert A, Kshirsagar R Abstract Chemically defined media have been widely used in the biopharmaceutical industry to enhance cell culture productivities and ensure process robustness. These media, which are quite complex, often contain a mixture of many components such as vitamins, amino acids, metals and other chemicals. Some of these components are known to be sensitive to various stress factors including photodegradation. Previous work has shown that small changes in impurity concentrations induced by these potential stresses can have a large impact on the cell culture process including growth and product quality attributes. Furthermore, it has been shown to be difficult to detect these modifications analytically due to the complexity of the cell culture media and the trace level of the degradant products. Here we describe work performed to identify the specific chemical(s) in photodegraded medium that affect cell culture performance. First, we developed a model system capable of detecting changes in cell culture performance. Second, we used these data and applied an LC-MS analytical technique to characterize the cell culture media and identify degradant products which affect cell culture performance. Riboflavin limitation and N-formylkynurenine (NFK), a tryptophan oxidation catabolite, were identified as chemicals which results in a reduction in cell culture performance. This article is protected by copyright. All rights reserved. PMID: 26560839 [PubMed - as supplied by publisher]

Molecular histology of arteries: mass spectrometry imaging as a novel ex vivo tool to investigate atherosclerosis. Expert Rev Proteomics. 2015 Nov 11; Authors: Martin-Lorenzo M, Alvarez-Llamas G, McDonnell LA, Vivanco F Abstract Atherosclerosis is usually the underlying cause of a fatal event such as myocardial infarction or ictus. The atherome plaque develops silently and asymptomatically within the arterial intima layer. In this context, the possibility to analyze the molecular content of arterial tissue while preserving each molecule's specific localization is of great interest as it may reveal further insights into the physiopathological changes taking place. Mass spectrometry imaging (MSI) enables the spatially-resolved molecular analysis of proteins, peptides, metabolites, lipids and drugs directly in tissue, with a resolution sufficient to reveal molecular features specific to distinct arterial structures. MSI represents a novel ex vivo imaging tool still underexplored in cardiovascular diseases. This review focuses on the MSI technique applied to cardiovascular disease and covers the main contributions to date, ongoing efforts, the main challenges and current limitations of MSI. PMID: 26558814 [PubMed - as supplied by publisher]

1H-NMR-Based Metabolomic Study for Identifying Serum Profiles Associated with the Response to Etanercept in Patients with Rheumatoid Arthritis. PLoS One. 2015;10(11):e0138537 Authors: Priori R, Casadei L, Valerio M, Scrivo R, Valesini G, Manetti C Abstract OBJECTIVE: A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients. METHODS: Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months' follow-up. Each patient was evaluated by the same rheumatologist before and after six months of treatment. At this time, the clinical response (good, moderate, none) was determined according to the EUropean League Against Rheumatism (EULAR) criteria, based on both erythrocyte sedimentation rate (EULAR-ESR) and C-reactive protein (EULAR-CRP). Sera collected prior and after six months of etanercept were analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate data analysis. RESULTS: Twenty-seven patients were enrolled: 18 had a good/moderate response and 9 were non responders according to both EULAR-ESR and EULAR-CRP after six months of etanercept. Metabolomic analysis at baseline was able to discriminate good, moderate, and non-responders with a very good predictivity (Q2 = 0.68) and an excellent sensitivity, specificity, and accuracy (100%). In good responders, we found an increase in isoleucine, leucine, valine, alanine, glutamine, tyrosine, and glucose levels and a decrease in 3-hydroxybutyrate levels after six months of treatment with etanercept with respect to baseline. CONCLUSION: Our study confirms the potential of metabolomic analysis to predict the response to biological agents. Changes in metabolic profiles during treatment may help elucidate their mechanism of action. PMID: 26558759 [PubMed - in process]

Related Articles Discriminating precursors of common fragments for large-scale metabolite profiling by triple quadrupole mass spectrometry. Bioinformatics. 2015 Jun 15;31(12):2017-23 Authors: Nikolskiy I, Siuzdak G, Patti GJ Abstract MOTIVATION: The goal of large-scale metabolite profiling is to compare the relative concentrations of as many metabolites extracted from biological samples as possible. This is typically accomplished by measuring the abundances of thousands of ions with high-resolution and high mass accuracy mass spectrometers. Although the data from these instruments provide a comprehensive fingerprint of each sample, identifying the structures of the thousands of detected ions is still challenging and time intensive. An alternative, less-comprehensive approach is to use triple quadrupole (QqQ) mass spectrometry to analyze predetermined sets of metabolites (typically fewer than several hundred). This is done using authentic standards to develop QqQ experiments that specifically detect only the targeted metabolites, with the advantage that the need for ion identification after profiling is eliminated. RESULTS: Here, we propose a framework to extend the application of QqQ mass spectrometers to large-scale metabolite profiling. We aim to provide a foundation for designing QqQ multiple reaction monitoring (MRM) experiments for each of the 82 696 metabolites in the METLIN metabolite database. First, we identify common fragmentation products from the experimental fragmentation data in METLIN. Then, we model the likelihoods of each precursor structure in METLIN producing each common fragmentation product. With these likelihood estimates, we select ensembles of common fragmentation products that minimize our uncertainty about metabolite identities. We demonstrate encouraging performance and, based on our results, we suggest how our method can be integrated with future work to develop large-scale MRM experiments. AVAILABILITY AND IMPLEMENTATION: Our predictions, Supplementary results, and the code for estimating likelihoods and selecting ensembles of fragmentation reactions are made available on the lab website at http://pattilab.wustl.edu/FragPred. PMID: 25691443 [PubMed - indexed for MEDLINE]

Flatography: Detection of gastrointestinal diseases by faecal gas analysis. World J Gastrointest Pharmacol Ther. 2015 Nov 6;6(4):111-3 Authors: de Groot EF, de Meij TG, Berkhout DJ, van der Schee MP, de Boer NK Abstract Patients presenting with gastro-intestinal symptoms might suffer from a range of possible underlying diseases. An unmet need exists for novel cost-effective, reproducible, easy-to-perform and non-invasive tests. Hippocrates used body odours to diagnose diseases circa 460 before Christ. The art of diagnostic smelling is making a promising high-tech come-back with portable "electronic diagnostic noses". Analysis of faecal volatile organic compounds is a novel field in metabolomics with considerable potential to improve the diagnosis, phenotyping and monitoring of gastro-intestinal disease. Challenges will be to mature over the coming years by development of a standardized methodology for stool sample collection, storage, handling and analysis. Furthermore, key volatiles need to be identified to improve test accuracy and sensitivity by development of sensors tailored toward the accurate identification of disease specific volatiles. If these challenges are adequately faced, analysis of faecal volatiles has realistic potential to considerably improve screening, diagnosis and disease monitoring for gastro-intestinal diseases. PMID: 26558144 [PubMed]

Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants. Front Bioeng Biotechnol. 2015;3:167 Authors: Hill CB, Czauderna T, Klapperstück M, Roessner U, Schreiber F Abstract Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions. PMID: 26557642 [PubMed]

Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat. Metabolomics. 2015 Oct 1;11(5):1082-1094 Authors: Mak TD, Tyburski JB, Krausz KW, Kalinich JF, Gonzalez FJ, Fornace AJ Abstract The potential for exposures to ionizing radiation has increased in recent years. Although advances have been made, understanding the global metabolic response as a function of both dose and exposure time is challenging considering the complexity of the responses. Herein we report our findings on the dose- and time-dependency of the urinary response to ionizing radiation in the male rat using radiation metabolomics. Urine samples were collected from adult male rats, exposed to 0.5 to 10 Gy γ-radiation, both before from 6 to 72 h following exposures. Samples were analyzed by liquid chromatography coupled with time-of-flight mass spectrometry, and deconvoluted mass chromatographic data were initially analyzed by principal component analysis. However, the breadth and complexity of the data necessitated the development of a novel approach to summarizing biofluid constituents after exposure, called Visual Analysis of Metabolomics Package (VAMP). VAMP revealed clear urine metabolite profile differences to as little as 0.5 Gy after 6 h exposure. Via VAMP, it was discovered that the response to radiation exposure found in rat urine is characterized by an overall net down-regulation of ion excretion with only a modest number of ions excreted in excess over pre-exposure levels. Our results show both similarities and differences with the published mouse urine response and a dose- and time-dependent net decrease in urine ion excretion associated with radiation exposure. These findings mark an important step in the development of minimally invasive radiation biodosimetry. VAMP should have general applicability in metabolomics to visualize overall differences and trends in many sample sets. PMID: 26557048 [PubMed - as supplied by publisher]

Chemical Shifts to Metabolic Pathways: Identifying Metabolic Pathways Directly from a Single 2D NMR Spectrum. Anal Chem. 2015 Nov 10; Authors: Dubey A, Rangarajan A, Pal D, Atreya HS Abstract Identifying cellular processes in terms of metabolic pathways is one of the avowed goals of metabolomics studies. Currently this is done after relevant metabolites are identified to allow their mapping onto specific pathways. This task is daunting due to the complex nature of cellular processes and the difficulty in establishing the identity of individual metabolites. We propose here a new method: ChemSMP (Chemical Shifts to Metabolic Pathways), which facilitates rapid analysis by identifying the active metabolic pathways directly from chemical shifts obtained from a single two-dimensional (2D) [13C-1H] correlation NMR spectrum, without the need for identification and assignment of individual metabolites. ChemSMP uses a novel indexing and scoring system comprising of a 'uniqueness score' and a 'coverage score'. Our method is demonstrated on metabolic pathways data from Small Molecule Pathway Database (SMPDB) and chemical shifts from Human Metabolome Database (HMDB). Benchmarks show that ChemSMP has a positive prediction rate of >90% in presence of de-cluttered data and can sustain the same at 60 - 70% even in presence of noise such as deletions of peaks and chemical shift deviations. The method tested on NMR data acquired for a mixture of 20 amino acids shows a success rate of 93% in correct recovery of pathways. When used on data obtained from cell lysate of an unexplored oncogenic cell line, it revealed active metabolic pathways responsible for regulating energy homeostasis of cancer cells. Our unique tool is thus expected to significantly enhance analysis of NMR based metabolomics data by reducing existing impediments. PMID: 26556218 [PubMed - as supplied by publisher]

Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study. J Lipid Res. 2015 Nov 10; Authors: Oni-Orisan A, Edin ML, Lee JA, Wells MA, Christensen ES, Vendrov KC, Lih FB, Tomer KB, Bai X, Taylor JM, Stouffer GA, Zeldin DC, Lee CR Abstract Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD (no apparent CAD [N=39], nonobstructive CAD [N=51], obstructive CAD [N=72]) were evaluated. A significant relationship between free EET levels and CAD extent was observed (P=0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P=0.013), and with a biomarker of EET biosynthesis (P<0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared to other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise in patients with obstructive CAD. PMID: 26555503 [PubMed - as supplied by publisher]

ANALYTICAL APPROACHES FOR LIPIDOMICS AND ITS POTENTIAL APPLICATIONS IN NEUROPSYCHIATRIC DISORDERS. World J Biol Psychiatry. 2015 Nov 10;:1-49 Authors: Sethi S, Hayashi M, Sussulini A, Tasic L, Brietzke E Abstract OBJECTIVES: In this review, the authors discuss an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical techniques and clinical research in neuropsychiatric disorders. METHODS: Lipidomics is a lipid-targeted metabolomics approach aiming at the comprehensive analysis of lipids in biological systems. Recent technological advancements in mass spectrometry and chromatography have greatly enhanced the development and applications of metabolic profiling of diverse lipids in complex biological samples. RESULTS: An effective evaluation of the clinical course of diseases requires the application of very precise diagnostic and assessment approaches as early as possible. In order to achieve this, "omics" strategies offer new opportunities for biomarker identification and/or discovery in complex diseases and may provide pathological pathways understanding for diseases beyond traditional methodologies. CONCLUSIONS: This review highlights the importance of lipidomics for the future perspectives as a tool for biomarker identification and discovery and its clinical application. PMID: 26555297 [PubMed - as supplied by publisher]