PubMed

Related Articles Learning from other diseases: protection and pathology in chronic fungal infections. Semin Immunopathol. 2015 Sep 17; Authors: Zelante T, Pieraccini G, Scaringi L, Aversa F, Romani L Abstract Fungal commensals coexist in a complex milieu of bacteria within the human body. An increased understanding of the importance of microbiota in shaping the host's immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. Metagenomics has revealed the complex interactions between fungal and bacterial commensals that, either directly or through the participation of the host immune system, impact on immune homeostasis at mucosal surfaces that, in turn, lead to secondary fungal infections. Metabolomics has captured the dialogue between the mammalian host and its microbiota. It appears that the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a dominant role in the interplay between tryptophan catabolism by microbial communities, the host's own pathway of metabolite production, and the activation of the aryl hydrocarbon receptor (AhR)/IL-22 axis, eventually impacting on mucosal immune homeostasis and host/fungal symbiosis. Thus, the regulatory loop involving AhR and IDO1 may be exploited for the development of multi-pronged host- and microbiota-directed therapeutic approaches for mucosal and systemic fungal diseases. PMID: 26382631 [PubMed - as supplied by publisher]

Related Articles A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data. Comput Biol Chem. 2015 Sep 1; Authors: Barker BE, Sadagopan N, Wang Y, Smallbone K, Myers CR, Xi H, Locasale JW, Gu Z Abstract A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB. PMID: 26381164 [PubMed - as supplied by publisher]

Related Articles Metabolic youth in middle age - predicting ageing in Caenorhabditis elegans using metabolomics. J Proteome Res. 2015 Sep 18; Authors: Davies SK, Bundy JG, Leroi AM Abstract Many mutations and allelic variants are known that influence the rate at which animals age. But when in life do such variants diverge from normal patterns of ageing? And is this divergence visible in their physiologies? To investigate these questions we have used 1H NMR spectroscopy to study how the metabolome of the nematode Caenorhabditis elegans changes as it grows older. We identify a series of metabolic changes that, collectively, predict the age of wild-type worms. We then show that long-lived mutant daf-2(m41) worms are metabolically youthful compared to wild-type worms - but that this relative youth only appears in middle age. Finally, we show that metabolic age predicts the timing and magnitude of differences in age-specific mortality between these strains. Thus the future mortality of these two genotypes can be predicted long before most of the worms die. PMID: 26381038 [PubMed - as supplied by publisher]

Related Articles Non-invasive assessment of in-vitro embryo quality to improve transfer success. Reprod Biomed Online. 2015 Aug 12; Authors: Rødgaard T, Heegaard PM, Callesen H Abstract Although IVF has been performed routinely for many years to help couples with fertility problems and in relation to modern breeding of farm animals, pregnancy rates after transfer to a recipient have not improved during the last decade. Early prediction of the viability of in-vitro developed embryos before the transfer to a recipient still remains challenging. Presently, the predominant non-invasive technique for selecting viable embryos is based on morphology, where parameters such as rates of cleavage and blastocyst formation as well as developmental kinetics are evaluated mostly subjectively. The simple morphological approach is, however, inadequate for the prediction of embryo quality, and several studies have focused on developing new non-invasive methods using molecular approaches based particularly on proteomics, metabolomics and most recently small non-coding RNA, including microRNA. This review outlines the potential of several non-invasive in-vitro methods based on analysis of spent embryo culture medium. PMID: 26380864 [PubMed - as supplied by publisher]

Related Articles [Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2015 Jul;35(7):823-33 Authors: Zhang L, Zhang Q, You Y, Zhou MX, Wang LH, Chen HB, Yan XZ, Liu XZ, Liu WH Abstract OBJECTIVE: To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome. METHODS: Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose. CONCLUSIONS: ED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process. PMID: 26380446 [PubMed - in process]

Related Articles [Optimization and application of targeted LC-MS metabolomic analyses in photosynthetic cyanobacteria]. Sheng Wu Gong Cheng Xue Bao. 2015 Apr;31(4):577-90 Authors: Niu X, Zhang X, Yu X, Su Y, Chen L, Zhang W Abstract To accurately analyze metabolites in industry-important photosynthetic microbes, LC-MS based metabolomics protocol needs to be optimized specifically for individual species. In this study, an LC-MS based metabolomics method was optimized for cyanobacterium Synechocystis sp. PCC 6803. With the optimized extraction, liquid chromatographic and mass spectral parameters, the method was capable of detecting 24 important metabolites related to central carbohydrate and energy metabolism in Synechocystis sp. PCC 6803. The study laid an important foundation for the metabolomics analysis of cyanobacteria. PMID: 26380414 [PubMed - in process]

Related Articles Prospects of breeding high-quality rice using post-genomic tools. Theor Appl Genet. 2015 Aug;128(8):1449-66 Authors: Anacleto R, Cuevas RP, Jimenez R, Llorente C, Nissila E, Henry R, Sreenivasulu N Abstract KEY MESSAGE: The holistic understanding derived from integrating grain quality and sensory research outcomes in breeding high-quality rice in the light of post-genomics resources has been synthesized. Acceptance of new rice genotypes by producers and consumers hinges not only on their potential for higher yield but recent emphasis has also been on premium-value genotypes that have the ability to satisfy consumer preferences for grain quality. This review article provides insights into how to link grain quality attributes and sensory perception to support breeding superior rice varieties. Recent advances in quality profiling and omics technologies have provided efficient approaches to identify the key genes and biochemical markers involved in rice quality traits. Emphasis has been given to the upcoming area of holistic understanding of grain quality and attributes derived from sensory evaluation to leverage integrative gene discovery strategies that enable breeding programs to efficiently tap the huge genetic diversity in rice for novel genes that enhance rice food quality. PMID: 25993897 [PubMed - indexed for MEDLINE]

Related Articles Detection of reactive metabolites using isotope-labeled glutathione trapping and simultaneous neutral loss and precursor ion scanning with ultra-high-pressure liquid chromatography triple quadruple mass spectrometry. Anal Chem. 2015 Apr 7;87(7):3646-54 Authors: Huang K, Huang L, van Breemen RB Abstract Metabolic activation of drugs to electrophilic species is responsible for over 60% of black box warnings and drug withdrawals from the market place in the United States. Reactive metabolite trapping using glutathione (GSH) and analysis using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) or HPLC with high resolution mass spectrometry (mass defect filtering) have enabled screening for metabolic activation to become routine during drug development. However, current MS-based approaches cannot detect all GSH conjugates present in complex mixtures, especially those present in extracts of botanical dietary supplements. To overcome these limitations, a fast triple quadrupole mass spectrometer-based approach was developed that can detect positively and negatively charged GSH conjugates in a single analysis without the need for advanced knowledge of the elemental compositions of potential conjugates and while avoiding false positives. This approach utilized UHPLC instead of HPLC to shorten separation time and enhance sensitivity, incorporated stable-isotope labeled GSH to avoid false positives, and used fast polarity switching electrospray MS/MS to detect GSH conjugates that form positive and/or negative ions. The general new method was then used to test the licorice dietary supplement Glycyrrhiza glabra, which was found to form multiple GSH conjugates upon metabolic activation. Among the GSH conjugates found in the licorice assay were conjugates with isoliquiritigenin and glabridin, which is an irreversible inhibitor of cytochrome P450 enzymes. PMID: 25774910 [PubMed - indexed for MEDLINE]

Related Articles Non-protein amino acids in Australian acacia seed: implications for food security and recommended processing methods to reduce djenkolic acid. Food Chem. 2015 Jul 15;179:109-15 Authors: Boughton BA, Reddy P, Boland MP, Roessner U, Yates P Abstract Seed of Australian acacia species, Acacia colei, Acacia elecantha, Acacia torulosa, Acacia turmida and Acacia saligna, were analysed for the presence of toxic non-protein amino acids and the levels of essential amino acids. Amines were derivatised with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate before analysis using liquid chromatography electrospray ionisation triple quadrupole mass spectrometry (LC-ESI-QQQ-MS). Multiple reaction monitoring (MRM) with optimised transitions and collision energies for each analyte were employed. The known nephrotoxic compound djenkolic acid was found to be present at elevated levels in all species tested. The lowest levels were in A. colei (0.49% w/w) and the highest in A. saligna (1.85% w/w). Observed levels of djenkolic acid are comparable to measured and reported levels found in the djenkol bean. Subsequent testing of seed processing methods showed djenkolic acid levels can be significantly reduced by over 90% by dry roasting at 180 °C rendering the seed safe for human consumption. PMID: 25722145 [PubMed - indexed for MEDLINE]

Related Articles An efficient TOF-SIMS image analysis with spatial correlation and alternating non-negativity-constrained least squares. Bioinformatics. 2015 Mar 1;31(5):753-60 Authors: Aram P, Shen L, Pugh JA, Vaidyanathan S, Kadirkamanathan V Abstract MOTIVATION: Advances in analytical instrumentation towards acquiring high-resolution images of mass spectrometry constantly demand efficient approaches for data analysis. This is particularly true of time-of-flight secondary ion mass spectrometry imaging where recent advances enable acquisition of high-resolution data in multiple dimensions. In many applications, the distribution of different species from a sampled surface is spatially continuous in nature and a model that incorporates the spatial correlation across the surface would be preferable to estimations at discrete spatial locations. A key challenge here is the capability to analyse the high-resolution multidimensional data to extract relevant information reliably and efficiently. RESULTS: We propose a framework based on alternating non-negativity-constrained least squares which accounts for the spatial correlation across the sample surface. The proposed method also decouples the computational complexity of the estimation procedure from the image resolution, which significantly reduces the processing time. We evaluate the performance of the algorithm with biochemical image datasets generated from mixture of metabolites. PMID: 25452330 [PubMed - indexed for MEDLINE]

Related Articles MetMSLine: an automated and fully integrated pipeline for rapid processing of high-resolution LC-MS metabolomic datasets. Bioinformatics. 2015 Mar 1;31(5):788-90 Authors: Edmands WM, Barupal DK, Scalbert A Abstract UNLABELLED: MetMSLine represents a complete collection of functions in the R programming language as an accessible GUI for biomarker discovery in large-scale liquid-chromatography high-resolution mass spectral datasets from acquisition through to final metabolite identification forming a backend to output from any peak-picking software such as XCMS. MetMSLine automatically creates subdirectories, data tables and relevant figures at the following steps: (i) signal smoothing, normalization, filtration and noise transformation (PreProc.QC.LSC.R); (ii) PCA and automatic outlier removal (Auto.PCA.R); (iii) automatic regression, biomarker selection, hierarchical clustering and cluster ion/artefact identification (Auto.MV.Regress.R); (iv) Biomarker-MS/MS fragmentation spectra matching and fragment/neutral loss annotation (Auto.MS.MS.match.R) and (v) semi-targeted metabolite identification based on a list of theoretical masses obtained from public databases (DBAnnotate.R). AVAILABILITY AND IMPLEMENTATION: All source code and suggested parameters are available in an un-encapsulated layout on http://wmbedmands.github.io/MetMSLine/. Readme files and a synthetic dataset of both X-variables (simulated LC-MS data), Y-variables (simulated continuous variables) and metabolite theoretical masses are also available on our GitHub repository. PMID: 25348215 [PubMed - indexed for MEDLINE]

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Related Articles Missing value imputation strategies for metabolomics data. Electrophoresis. 2015 Sep 16; Authors: Armitage EG, Godzien J, Alonso-Herranz V, López-Gonzálvez Á, Barbas C Abstract The origin of missing values can be caused by different reasons and depending on these origins missing values should be considered differently and dealt with in different ways. In this research, four methods of imputation have been compared with respect to revealing their effects on the normality and variance of data, on statistical significance and on the approximation of a suitable threshold to accept missing data as truly missing. Additionally, the effects of different strategies for controlling familywise error rate or false discovery and how they work with the different strategies for missing value imputation have been evaluated. Missing values were found to affect normality and variance of data and k-means nearest neighbour imputation was the best method tested for restoring this. Bonferroni correction was the best method for maximising true positives and minimising false positives and it was observed that as low as 40% missing data could be truly missing. The range between 40 and 70% missing values was defined as a 'grey area' and therefore a strategy has been proposed that provides a balance between the optimal imputation strategy that was kNN and the best approximation of positioning real zeros. This article is protected by copyright. All rights reserved. PMID: 26376450 [PubMed - as supplied by publisher]

Related Articles Lipidomic Analysis of Chlamydomonas reinhardtii under Nitrogen and Sulfur Deprivation. PLoS One. 2015;10(9):e0137948 Authors: Yang D, Song D, Kind T, Ma Y, Hoefkens J, Fiehn O Abstract Chlamydomonas reinhardtii accumulates lipids under complete nutrient starvation conditions while overall growth in biomass stops. In order to better understand biochemical changes under nutrient deprivation that maintain production of algal biomass, we used a lipidomic assay for analyzing the temporal regulation of the composition of complex lipids in C. reinhardtii in response to nitrogen and sulfur deprivation. Using a chip-based nanoelectrospray direct infusion into an ion trap mass spectrometer, we measured a diversity of lipid species reported for C. reinhardtii, including PG phosphatidylglycerols, PI Phosphatidylinositols, MGDG monogalactosyldiacylglycerols, DGDG digalactosyldiacylglycerols, SQDG sulfoquinovosyldiacylglycerols, DGTS homoserine ether lipids and TAG triacylglycerols. Individual lipid species were annotated by matching mass precursors and MS/MS fragmentations to the in-house LipidBlast mass spectral database and MS2Analyzer. Multivariate statistics showed a clear impact on overall lipidomic phenotypes on both the temporal and the nutrition stress level. Homoserine-lipids were found up-regulated at late growth time points and higher cell density, while triacyclglycerols showed opposite regulation of unsaturated and saturated fatty acyl chains under nutritional deprivation. PMID: 26375463 [PubMed - as supplied by publisher]

Related Articles SCK-3: TARGET METABOLOMICS FOR IMPROVING EARLY PREDICTION OF DEATH IN PATIENTS WITH SEPTIC SHOCK. Shock. 2015 Oct;44 Suppl 2:19-20 Authors: Cambiaghi A, Brunelli L, Caironi P, Ferrario M, Gattinoni L, Latini R, Masson S, Ristagno G, Pastorelli R Abstract INTRODUCTION: Elucidation of early metabolic signatures that predict survival in septic shock might help clinicians in prioritizing individual patient treatment. In this preliminary investigation, we examined plasma metabolome and clinical features in a subset of 20 patients with septic shock, enrolled in the multicenter Albumin Italian Outcome Sepsis (ALBIOS, NCT00707122). METHODS: Patients were divided into two groups according to their 28-days and 90-days survival. A mass spectrometry-based metabolomic approach was used to quantify acylcarnitines, aminoacids, biogenic amines, glycerophospolipids, sphingolipids, sugars. Metabolites were measured one day (d1) and one week (d7) after ICU admission. RESULTS: Profiles of specific metabolites differed markedly between survivors and non-survivors. An overall decrease from d1 to d7 in levels of different species of lysophosphatidylcholines (LPC) and phosphatidylcholines (PC) was observed together with a significant increase in kynurenine (KYN), in non-survivors compared to survivors both at 28- and 90-days (Wilcoxon test p < 0.05, FDR < 0.05). Data-mining techniques were then used to highlight metabolite levels associated with mortality. Twenty-eight days mortality was associated at d1 with increased levels of diacyl-PC-C38:1, butyrylacylcarnitine, but decreased diacyl-PC-C40:6 and diacyl-alkyl-PC-38:0; whereas at d7 with increased diacyl-PC-C42:4, KYN and decreased diacyl-alkyl-PC40:1, LPC-C24:0. Ninety-days mortality was associated only at d7 with elevation of KYN, diacyl-PC-C44:3 and reduction of diacyl- alkyl-PC40:1, LPC-C24:0. CONCLUSION: Our preliminary results suggest that increased KYN, that may contribute to hypotension in sepsis, as well as alterations of different LPC and PC species, able to modulate immune and inflammatory responses, might represent not only a risk factor for septic shock patients but important pathophysiologic mechanisms deserving further investigation. PMID: 26375122 [PubMed - as supplied by publisher]

Related Articles Top-down MALDI-in-source decay-FTICR mass spectrometry of isotopically resolved proteins. Anal Chem. 2015 Mar 17;87(6):3429-37 Authors: Nicolardi S, Switzar L, Deelder AM, Palmblad M, van der Burgt YE Abstract An accurate mass measurement of a known protein provides information on potential amino acid deletions and post-translational modifications. Although this field is dominated by strategies based on electrospray ionization, mass spectrometry (MS) methods using matrix-assisted laser desorption/ionization (MALDI) have the advantage of yielding predominantly singly charged precursor ions, thus avoiding peak overlap from different charge states of multiple species. Such MALDI-MS methods require mass measurement at ultrahigh resolution, which is provided by Fourier transform ion cyclotron resonance (FTICR) mass analyzers. Recently, using a MALDI-FTICR-MS platform equipped with a 15 T magnet, we reported on the mass analysis of intact human serum peptides and small proteins with isotopic resolution up to ∼15 kDa and identified new proteoforms from an accurate measurement of mass distances. In the current study, we have used this FTICR system after an upgrade with a novel dynamically harmonized ICR cell, i.e., ParaCell, for mapping isotopically resolved intact proteins up to about 17 kDa and performed top-down MALDI in-source decay (ISD) analysis. Standard proteins myoglobin (m/z-value 16,950) and ribonuclease B (m/z-value 14,900) were measured with resolving powers of 62,000 and 61,000, respectively. Furthermore, it will be shown that (singly charged) MALDI-ISD fragment ions can be measured at isotopic resolution up to m/z-value 12,000 (e.g., resolving power 39,000 at m/z-value 12,000) providing more reliable identifications. Moreover, examples are presented of pseudo-MS(3) experiments on ISD fragment ions from RNase B by collisional-induced dissociation (CID). PMID: 25719938 [PubMed - indexed for MEDLINE]

Related Articles Essential role for oxidative phosphorylation in cancer progression. Cell Metab. 2015 Jan 6;21(1):11-2 Authors: Maiuri MC, Kroemer G Abstract Cancers are often affected by derangements in mitochondrial (mt) function, as well as mtDNA mutations. In this issue, Tan et al. (2015) demonstrate that only mtDNA-depleted cancer cells capable of recovering mtDNA from the host form metastasizing cancers in vivo, revealing an essential requirement for oxidative phosphorylation in tumor progression. PMID: 25565201 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic analysis of plasma and liver from surplus arginine fed Atlantic salmon. Front Biosci (Elite Ed). 2015;7:67-78 Authors: Andersen SM, Assaad HI, Lin G, Wang J, Aksnes A, Wu G, Espe M Abstract The aim of this study was to determine the metabolic effect of surplus arginine (36.1 g/kg dry matter) compared to a control diet with required arginine (21.1 g/kg dry matter) in adult Atlantic salmon (Salmo salar L.). Although the feeding trial had no significant effect on growth, there were significant differences in the metabolite profile in both plasma and liver in experimental group as compared to the control group. There was increased concentrations of biliverdin, PGF-2 alpha, oxidized glutathione, selenocysteine, two monoacylglycerols and a tripeptide in the liver as well as decreased concentrations of valine and a vitamin D3 metabolite in plasma of arginine supplemented fish. These results indicate that while surplus arginine does not affect growth or body weight, it induces metabolic changes in Atlantic salmon. PMID: 25553364 [PubMed - indexed for MEDLINE]

Related Articles Plasma metabolite profiles following trauma-hemorrhage: effect of posttreatment with resveratrol. Shock. 2015 Feb;43(2):172-7 Authors: Wang YR, Tsai YF, Lau YT, Yu HP Abstract Resveratrol (RSV) has been shown to inhibit the inflammatory reaction and ameliorate the organ damage resulting from trauma-hemorrhage (TH). However, the effects of RSV on the metabolomic profiles under these conditions remain unclear. The aim of this study was to determine the metabolomic profiles of plasma in TH rats and to evaluate the therapeutic effects of RSV using high-performance liquid chromatography-mass spectrometry. Thirty male Sprague-Dawley rats were divided into sham operation (n = 10), sham-operation plus RSV treatment (n = 10), TH (n = 10), and TH plus RSV treatment (n = 10) groups. Plasma samples were obtained at 24 h after surgery. Electrospray ionization-tandem mass spectrometry was used to characterize the plasma metabolomes. The systemic analyses of plasma metabolomes and their targets were determined using a number of computational approaches, including principal component analysis, partial least squares discriminant analysis, and heat map analysis. Using these methods, the effects of RSV on the metabolomic profiles in animals that underwent trauma-hemorrhagic injury were determined. These approaches allowed a clear discrimination of the pathophysiological characteristics among the groups. The results demonstrate RSV treatment significantly reduced the metabolic derangements caused by TH. Compared with the sham-operated rats, the plasma levels of carnitine in the TH rats were relatively lower, but the levels of acetylcarnitine and butyrylcarnitine were higher, suggesting that RSV ameliorated the deranged carnitine metabolism in TH rats. There was a statistically significant increase in carnitine. In addition, RSV treatment reduced ketoacidosis and protein degradation, as evidenced by the attenuation of the elevated plasma branched-chain amino acid levels in the TH rats. Our study showed that the alterations of the metabolomic profiles in the rats subjected to trauma-hemorrhagic shock were attenuated by RSV treatment. In view of the metabolomic evidence, we conclude that RSV exerts beneficial effects in trauma-hemorrhagic shock injury and that these effects are partially mediated by improving energy metabolism and reducing protein degradation. PMID: 25300031 [PubMed - indexed for MEDLINE]

Related Articles High-throughput nucleoside phosphate monitoring in mammalian cell fed-batch cultivation using quantitative matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Biotechnol J. 2015 Jan;10(1):190-8 Authors: Steinhoff RF, Ivarsson M, Habicher T, Villiger TK, Boertz J, Krismer J, Fagerer SR, Soos M, Morbidelli M, Pabst M, Zenobi R Abstract Current methods for monitoring multiple intracellular metabolite levels in parallel are limited in sample throughput capabilities and analyte selectivity. This article presents a novel high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) for monitoring intracellular metabolite levels in fed-batch processes. The MALDI-TOF-MS method presented here is based on a new microarray sample target and allows the detection of nucleoside phosphates and various other metabolites using stable isotope labeled internal standards. With short sample preparation steps and thus high sample throughput capabilities, the method is suitable for monitoring mammalian cell cultures, such as antibody producing hybridoma cell lines in industrial environments. The method is capable of reducing the runtime of standard LC-UV methods to approximately 1 min per sample (including 10 technical replicates). Its performance is exemplarily demonstrated in an 8-day monitoring experiment of independently controlled fed-batches, containing an antibody producing mouse hybridoma cell culture. The monitoring profiles clearly confirmed differences between cultivation conditions. Hypothermia and hyperosmolarity were studied in four bioreactors, where hypothermia was found to have a positive effect on the longevity of the cell culture, whereas hyperosmolarity lead to an arrest of cell proliferation. The results are in good agreement with HPLC-UV cross validation experiments. Subsequent principal component analysis (PCA) clearly separates the different bioreactor conditions based on the measured mass spectral profiles. This method is not limited to any cell line and can be applied as a process analytical tool in biotechnological processes. PMID: 25139677 [PubMed - indexed for MEDLINE]