PubMed

LC-MS-Based Metabolomic Investigation of Chemopreventive Phytochemical-Elicited Metabolic Events. Methods Mol Biol. 2016;1379:77-88 Authors: Wang L, Yao D, Chen C Abstract Phytochemicals are under intensive investigation for their potential use as chemopreventive agents in blocking or suppressing carcinogenesis. Metabolic interactions between phytochemical and biological system play an important role in determining the efficacy and toxicity of chemopreventive phytochemicals. However, complexities of phytochemical biotransformation and intermediary metabolism pose challenges for studying phytochemical-elicited metabolic events. Metabolomics has become a highly effective technical platform to detect subtle changes in a complex metabolic system. Here, using green tea polyphenols as an example, we describe a workflow of LC-MS-based metabolomics study, covering the procedures and techniques in sample collection, preparation, LC-MS analysis, data analysis, and interpretation. PMID: 26608291 [PubMed - in process]

Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults. J Appl Physiol (1985). 2015 Nov 25;:jap.00879.2015 Authors: DeVan AE, Johnson LC, Brooks FA, Evans TD, Justice JN, Cruickshank-Quinn C, Reisdorph N, Bryan NS, McQueen MB, Santos-Parker JR, Chonchol MB, Bassett CJ, Sindler AL, Giordano T, Seals DR Abstract Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults, and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc, Inc., randomized, placebo-control, double-blind) increased plasma nitrite acutely (5- to 15-fold, p<0.001 vs. placebo) and chronically (p<0.10), and was well-tolerated without symptomatic hypotension or clinically-relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline (p<0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, p<0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well-tolerated, increases plasma nitrite concentrations, improves endothelial function and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial. PMID: 26607249 [PubMed - as supplied by publisher]

29 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 2015/11/26PubMed comprises more than 24 million 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.

22 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 2015/11/25PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles NMR based metabolic snapshot from Minibronchoalveolar lavage fluid: an approach to unfold human respiratory metabolomics. J Proteome Res. 2015 Nov 20; Authors: Viswan A, Sharma RK, Azim A, Sinha N Abstract Utility of Mini Bronchoalveolar lavage (mBAL) and its applicability in metabolomics has not been explored in the field of human respiratory disease. mBAL "an archetype" of the local lung environment ensures a potent technique to get the snapshot of the epithelial lining fluid afflicted to human lung disorders. Characterization of the mBAL fluid has potential to help in elucidating the composition of the alveoli and airways in the diseased state, yielding diagnostic information of clinical applicability. In this study one of the first attempts has been made to comprehensively assign and detect metabolites in mBAL fluid, extracted from human lungs, by the composite use of 800 MHz one dimensional (1D) and two dimensional (2D) NMR, homonuclear J-resolved, COSY, TOCSY and heteronuclear HSQC correlation methods. A foremost all-inclusive sketch of the 50 metabolites have been corroborated and assigned, which can be a resourceful archive to further lung directed metabolomics, prognosis and diagnosis. Thus NMR based mBALF studies, as proposed in this article, will leverage many more prospective respiratory researches for routine clinical application and proves to be a viable approach to mirror the key predisposing factors contributing to the onset of lung disease. PMID: 26587756 [PubMed - as supplied by publisher]

Related Articles Ion Mobility in Clinical Analysis: Current Progress and Future Perspectives. Clin Chem. 2015 Nov 19; Authors: Chouinard CD, Wei MS, Beekman CR, Kemperman RH, Yost RA Abstract BACKGROUND: Ion mobility spectrometry (IMS) is a rapid separation tool that can be coupled with several sampling/ionization methods, other separation techniques (e.g., chromatography), and various detectors (e.g., mass spectrometry). This technique has become increasingly used in the last 2 decades for applications ranging from illicit drug and chemical warfare agent detection to structural characterization of biological macromolecules such as proteins. Because of its rapid speed of analysis, IMS has recently been investigated for its potential use in clinical laboratories. CONTENT: This review article first provides a brief introduction to ion mobility operating principles and instrumentation. Several current applications will then be detailed, including investigation of rapid ambient sampling from exhaled breath and other volatile compounds and mass spectrometric imaging for localization of target compounds. Additionally, current ion mobility research in relevant fields (i.e., metabolomics) will be discussed as it pertains to potential future application in clinical settings. SUMMARY: This review article provides the authors' perspective on the future of ion mobility implementation in the clinical setting, with a focus on ambient sampling methods that allow IMS to be used as a "bedside" standalone technique for rapid disease screening and methods for improving the analysis of complex biological samples such as blood plasma and urine. PMID: 26585928 [PubMed - as supplied by publisher]

Related Articles Automated Multiplex LC-MS/MS Assay for Quantifying Serum Apolipoproteins A-I, B, C-I, C-II, C-III, and E with Qualitative Apolipoprotein E Phenotyping. Clin Chem. 2015 Nov 19; Authors: van den Broek I, Romijn FP, Nouta J, van der Laarse A, Drijfhout JW, Smit NP, van der Burgt YE, Cobbaert CM Abstract BACKGROUND: Direct and calculated measures of lipoprotein fractions for cardiovascular risk assessment suffer from analytical inaccuracy in certain dyslipidemic and pathological states, most commonly hypertriglyceridemia. LC-MS/MS has proven suitable for multiplexed quantification and phenotyping of apolipoproteins. We developed and provisionally validated an automated assay for quantification of apolipoprotein (apo) A-I, B, C-I, C-II, C-III, and E and simultaneous qualitative assessment of apoE phenotypes. METHODS: We used 5 value-assigned human serum pools for external calibration. Serum proteins were denatured, reduced, and alkylated according to standard mass spectrometry-based proteomics procedures. After trypsin digestion, peptides were analyzed by LC-MS/MS. For each peptide, we measured 2 transitions. We compared LC-MS/MS results to those obtained by an immunoturbidimetric assay or ELISA. RESULTS: Intraassay CVs were 2.3%-5.5%, and total CVs were 2.5%-5.9%. The LC-MS/MS assay correlated (R = 0.975-0.995) with immunoturbidimetric assays with Conformité Européenne marking for apoA-I, apoB, apoC-II, apoC-III, and apoE in normotriglyceridemic (n = 54) and hypertriglyceridemic (n = 46) sera. Results were interchangeable for apoA-I ≤3.0 g/L (Deming slope 1.014) and for apoB-100 ≤1.8 g/L (Deming slope 1.016) and were traceable to higher-order standards. CONCLUSIONS: The multiplex format provides an opportunity for new diagnostic and pathophysiologic insights into types of dyslipidemia and allows a more personalized approach for diagnosis and treatment of lipid abnormalities. PMID: 26585923 [PubMed - as supplied by publisher]

Related Articles AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells. J Endocrinol. 2015 Nov 19; Authors: Kim N, Lee JO, Lee HJ, Lee YW, Kim HI, Kim SJ, Park SH, Lee CS, Ryoo SW, Hwang GS, Kim HS Abstract Isoeugenol exerts various beneficial effects on human health. However, mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased Glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicated that isoeugenol exerted beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in the skeletal muscles. PMID: 26585419 [PubMed - as supplied by publisher]

Related Articles Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial. Cancer Epidemiol Biomarkers Prev. 2015 Nov 19; Authors: Liesenfeld DB, Botma A, Habermann N, Toth R, Weigel C, Popanda O, Klika KD, Potter JD, Lampe JW, Ulrich CM Abstract BACKGROUND: Aspirin use is an effective strategy for the chemoprevention of colorectal cancer, even at low doses. However, in order to implement aspirin interventions, risk-benefit balances and biologic mechanisms need to be better defined; to further this aim, we used a metabolomics approach. METHODS: We metabolically profiled 40 healthy, nonsmoking men and women ages 20 to 45 years enrolled in a randomized, double-blind, crossover trial of 325 mg aspirin/day over a period of 60 days. Gas and liquid chromatography-mass spectrometry were used to comprehensively profile participants' plasma samples after aspirin and placebo interventions. RESULTS: A total of 363 metabolites, covering most human biochemical pathways, were measured. Compared with placebo-treated participants, plasma concentrations of the oncometabolite 2-hydroxyglutarate (R+S) decreased after aspirin treatment in both men and women (P = 0.005). This signal proved robust during 20-fold random splitting of the data using 80% of the samples in each split. We subsequently performed functional follow-up studies using targeted, enantiospecific detection in human colorectal cancer cell lines and observed an aspirin-induced reduction of (R)-2-hydroxyglutarate. We further showed that salicylate, the primary aspirin metabolite, inhibits the hydroxyacid-oxoacid transhydrogenase mediated production of (R)-2-hydroxyglutarate, thereby providing mechanistic evidence for the clinically observed effects of aspirin on total-2-hydroxyglutarate. CONCLUSIONS: Using a metabolomics approach with functional follow-up, we propose that a decrease in the oncometabolite (R)-2-hydroxyglutarate may identify an additional mechanism for aspirin or its metabolites in cancer prevention. IMPACT: Reduction of the oncometabolite (R)-2-hydroxyglutarate identifies a novel, non-COX-inhibition-mediated mechanism of aspirin. Cancer Epidemiol Biomarkers Prev; 1-8. ©2015 AACR. PMID: 26585118 [PubMed - as supplied by publisher]

Related Articles Cold adaptation mechanisms in the ghost moth Hepialus xiaojinensis: metabolic regulation and thermal compensation. J Insect Physiol. 2015 Nov 13; Authors: Zhu W, Zhang H, Li X, Meng Q, Shu R, Wang M, Zhou G, Wang H, Miao L, Zhang J, Qin Q Abstract Ghost moths (Lepidoptera: Hepialidae) are cold-adapted stenothermal species inhabiting alpine meadows on the Tibetan Plateau. They have an optimal developmental temperature of 12-16 °C but can maintain feeding and growth at 0 °C. Their survival strategies have received little attention, but these insects are a promising model for environmental adaptation. Here, biochemical adaptations and energy metabolism in response to cold were investigated in larvae of the ghost moth Hepialus xiaojinensis. Metabolic rate and respiratory quotient decreased dramatically with decreasing temperature (15 to 4 °C), suggesting that the energy metabolism of ghost moths, especially glycometabolism, was sensitive to cold. However, the metabolic rate at 4 °C increased with the duration of cold exposure, indicating thermal compensation to sustain energy budgets under cold conditions. Underlying regulation strategies were studied by analyzing metabolic differences between cold-acclimated (4 °C for 48 h) and control larvae (15 °C). In cold-acclimated larvae, the energy generating pathways of carbohydrates, instead of the overall consumption of carbohydrates, was compensated in the fat body by improving the transcription of related enzymes. The mobilization of lipids was also promoted, with higher diacylglycerol, monoacylglycerol and free fatty acid content in hemolymph. These results indicated that cold acclimation induced a reorganisation on metabolic structure to prioritise energy metabolism. Within the aerobic process, flux throughout the tricarboxylic acid (TCA) cycle was encouraged in the fat body, and the activity of α-ketoglutarate dehydrogenase was the likely compensation target. Increased mitochondrial cristae density was observed in the midgut of cold-acclimated larvae. The thermal compensation strategies in this ghost moth span the entire process of energy metabolism, including degration of metabolic substrate, TCA cycle and oxidative phosphorylation, and from an energy budget perspective explains how ghost moths sustain physiological activity in cold environments. PMID: 26585102 [PubMed - as supplied by publisher]

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics. Placenta. 2015 Nov 5; Authors: Austdal M, Thomsen LC, Tangerås LH, Skei B, Mathew S, Bjørge L, Austgulen R, Bathen TF, Iversen AC Abstract INTRODUCTION: Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking. METHODS: Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. RESULTS: Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. DISCUSSION: HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease. PMID: 26582504 [PubMed - as supplied by publisher]

Integrated Pathway-Based and Network-Based Analysis of GC-MS Rice Metabolomics Data under Diazinon Stress to infer Affected Biological Pathways. Anal Biochem. 2015 Nov 12; Authors: Mahdavi V, Ghanati F, Ghassempour A Abstract Diazinon insecticide is widely applied throughout rice (Oryza sativa L.) fields in Iran. However, concerns are now being raised about its potential adverse impacts on rice fields. In this study, a time-course metabolic change in rice plants was investigated after diazinon treatment using gas chromatography-mass spectrometry (GC-MS) and subsequentely, three different methods, namely MetaboAnalyst, MetaboNetwork, and analysis of reporter reactions, as a potential multivariate method were used to find the underlying changes in metabolism with stronger evidence in order to link differentially expressed metabolites to biological pathways. In a different perception, results clearly showed the similarity Acetylcholinesterase (AChE) of rice plants to that of animals in terms of its inhibitability by diazinon and emphasizes that subsequent accumulation of AChE mainly affects on the metabolism of osmolites and TCA intermediates. PMID: 26582432 [PubMed - as supplied by publisher]

Metabolic changes in transgenic maize mature seeds over-expressing the Aspergillus niger phyA2. Plant Cell Rep. 2015 Nov 18; Authors: Rao J, Yang L, Guo J, Quan S, Chen G, Zhao X, Zhang D, Shi J Abstract KEY MESSAGE: Non-targeted metabolomics analysis revealed only intended metabolic changes in transgenic maize over-expressing the Aspergillus niger phyA2. Genetically modified (GM) crops account for a large proportion of modern agriculture worldwide, raising increasingly the public concerns of safety. Generally, according to substantial equivalence principle, if a GM crop is demonstrated to be equivalently safe to its conventional species, it is supposed to be safe. In this study, taking the advantage of an established non-target metabolomic profiling platform based on the combination of UPLC-MS/MS with GC-MS, we compared the mature seed metabolic changes in transgenic maize over-expressing the Aspergillus niger phyA2 with its non-transgenic counterpart and other 14 conventional maize lines. In total, levels of nine out of identified 210 metabolites were significantly changed in transgenic maize as compared with its non-transgenic counterpart, and the number of significantly altered metabolites was reduced to only four when the natural variations were taken into consideration. Notably, those four metabolites were all associated with targeted engineering pathway. Our results indicated that although both intended and non-intended metabolic changes occurred in the mature seeds of this GM maize event, only intended metabolic pathway was found to be out of the range of the natural metabolic variation in the metabolome of the transgenic maize. Therefore, only when natural metabolic variation was taken into account, could non-targeted metabolomics provide reliable objective compositional substantial equivalence analysis on GM crops. PMID: 26581949 [PubMed - as supplied by publisher]

The biochemistry of blister fluid from pediatric burn injuries: proteomics and metabolomics aspects. Expert Rev Proteomics. 2015 Nov 18; Authors: Zang T, Broszczak DA, Broadbent JA, Cuttle L, Lu H, Parker TJ Abstract Burn injury is a prevalent and traumatic event for pediatric patients. At present, the diagnosis of burn injury severity is subjective and lacks a clinically relevant quantitative measure. This is due in part to a lack of knowledge surrounding the biochemistry of burn injuries and that of blister fluid. A more complete understanding of the blister fluid biochemistry may open new avenues for diagnostic and prognostic development. Burn insult induces a highly complex network of signaling processes and numerous changes within various biochemical systems, which can ultimately be examined using proteome and metabolome measurements. This review reports on the current understanding of burn wound biochemistry and outlines a technical approach for 'omics' profiling of blister fluid from burn wounds of differing severity. PMID: 26581649 [PubMed - as supplied by publisher]

Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner. Am J Clin Nutr. 2015 Nov 18; Authors: Gralka E, Luchinat C, Tenori L, Ernst B, Thurnheer M, Schultes B Abstract BACKGROUND: Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood. OBJECTIVE: We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures. DESIGN: In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly ≤1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups. RESULTS: We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated). CONCLUSION: Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322. PMID: 26581381 [PubMed - as supplied by publisher]

Metabolic Characterization of the Common Marmoset (Callithrix jacchus). PLoS One. 2015;10(11):e0142916 Authors: Go YM, Liang Y, Uppal K, Soltow QA, Promislow DE, Wachtman LM, Jones DP Abstract High-resolution metabolomics has created opportunity to integrate nutrition and metabolism into genetic studies to improve understanding of the diverse radiation of primate species. At present, however, there is very little information to help guide experimental design for study of wild populations. In a previous non-targeted metabolomics study of common marmosets (Callithrix jacchus), Rhesus macaques, humans, and four non-primate mammalian species, we found that essential amino acids (AA) and other central metabolites had interspecies variation similar to intraspecies variation while non-essential AA, environmental chemicals and catabolic waste products had greater interspecies variation. The present study was designed to test whether 55 plasma metabolites, including both nutritionally essential and non-essential metabolites and catabolic products, differ in concentration in common marmosets and humans. Significant differences were present for more than half of the metabolites analyzed and included AA, vitamins and central lipid metabolites, as well as for catabolic products of AA, nucleotides, energy metabolism and heme. Three environmental chemicals were present at low nanomolar concentrations but did not differ between species. Sex and age differences in marmosets were present for AA and nucleotide metabolism and warrant additional study. Overall, the results suggest that quantitative, targeted metabolomics can provide a useful complement to non-targeted metabolomics for studies of diet and environment interactions in primate evolution. PMID: 26581102 [PubMed - as supplied by publisher]

Plasma Metabolic Profiles in Women are Menopause Dependent. PLoS One. 2015;10(11):e0141743 Authors: Ke C, Hou Y, Zhang H, Yang K, Wang J, Guo B, Zhang F, Li H, Zhou X, Li Y, Li K Abstract Menopause is an endocrinological transition that greatly affects health and disease susceptibility in middle-aged and elderly women. To gain new insights into the metabolic process of menopause, plasma metabolic profiles in 115 pre- and post-menopausal women were systematically analyzed by ultra-performance liquid chromatography/mass spectrometry in conjunction with univariate and multivariate statistical analysis. Metabolic signatures revealed considerable differences between pre- and post-menopausal women, and clear separations were observed between the groups in partial least-squares discriminant analysis score plots. In total, 28 metabolites were identified as potential metabolite markers for menopause, including up-regulated acylcarnitines, fatty acids, lysophosphatidylcholines, lysophosphatidylethanolamines, and down-regulated pregnanediol-3-glucuronide, dehydroepiandrosterone sulfate, p-hydroxyphenylacetic acid and dihydrolipoic acid. These differences highlight that significant alterations occur in fatty acid β-oxidation, phospholipid metabolism, hormone metabolism and amino acid metabolism in post-menopausal women. In conclusion, our plasma metabolomics study provides novel understanding of the metabolic profiles related to menopause, and will be useful for investigating menopause-related diseases and assessing metabolomic confounding factors. PMID: 26580805 [PubMed - as supplied by publisher]

Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites. Stem Cells. 2015 Nov 18; Authors: Sakayori N, Kikkawa T, Tokuda H, Kiryu E, Yoshizaki K, Kawashima H, Yamada T, Arai H, Kang JX, Katagiri H, Shibata H, Innis SM, Arita M, Osumi N Abstract Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Although several studies have suggested that a balanced dietary n-6:n-3 ratio is essential for brain development, the underlying cellular and molecular mechanism is poorly understood. Here, we found that feeding pregnant mice an n-6 excess/n-3 deficient diet, which reflects modern human diets, impairs neocortical neurogenesis in the offspring. This impaired neurodevelopment occurs through a precocious fate transition of neural stem cells from the neurogenic to gliogenic lineage. A comprehensive mediator lipidomics screen revealed key mediators, epoxy metabolites, which were confirmed functionally using a neurosphere assay. Importantly, although the offspring were raised on a well-balanced n-6:n-3 diet, they exhibited increased anxiety-related behavior in adulthood. These findings provide compelling evidence that excess maternal consumption of n-6 PUFAs combined with insufficient intake of n-3 PUFAs causes abnormal brain development that can have long-lasting effects on the offspring's mental state. This article is protected by copyright. All rights reserved. PMID: 26580686 [PubMed - as supplied by publisher]

Developments in FTICR-MS and Its Potential for Body Fluid Signatures. Int J Mol Sci. 2015;16(11):27133-27144 Authors: Nicolardi S, Bogdanov B, Deelder AM, Palmblad M, van der Burgt YE Abstract Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the number of FTMS-applications enormously. One recent example involves clinical proteomics using FTICR-MS to discover and validate protein biomarker signatures in body fluids such as serum or plasma. These biological samples are highly complex in terms of the type and number of components, their concentration range, and the structural identity of each species, and thus require extensive sample cleanup and chromatographic separation procedures. Clearly, such an elaborate and multi-step sample preparation process hampers high-throughput analysis of large clinical cohorts. A final MS read-out at ultra-high resolution enables the analysis of a more complex sample and can thus simplify upfront fractionations. To this end, FTICR-MS offers superior ultra-high resolving power with accurate and precise mass-to-charge ratio (m/z) measurement of a high number of peptides and small proteins (up to 20 kDa) at isotopic resolution over a wide mass range, and furthermore includes a wide variety of fragmentation strategies to characterize protein sequence and structure, including post-translational modifications (PTMs). In our laboratory, we have successfully applied FTICR "next-generation" peptide profiles with the purpose of cancer disease classifications. Here we will review a number of developments and innovations in FTICR-MS that have resulted in robust and routine procedures aiming for ultra-high resolution signatures of clinical samples, exemplified with state-of-the-art examples for serum and saliva. PMID: 26580595 [PubMed - as supplied by publisher]

Globally Optimized Targeted Mass Spectrometry (GOT-MS): Reliable Metabolomics Analysis with Broad Coverage. Anal Chem. 2015 Nov 18; Authors: Gu H, Zhang P, Zhu J, Raftery D Abstract Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, Globally Optimized Targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1,890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time of flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ~160 biologically important metabolites, and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach, and should have the potential to significantly advance both basic and clinical metabolic research. PMID: 26579731 [PubMed - as supplied by publisher]