PubMed

Related Articles A combined metabolomic and phylogenetic study reveals putatively prebiotic effects of high molecular weight arabino-oligosaccharides when assessed by in vitro fermentation in bacterial communities derived from humans. Anaerobe. 2014 Aug;28:68-77 Authors: Sulek K, Vigsnaes LK, Schmidt LR, Holck J, Frandsen HL, Smedsgaard J, Skov TH, Meyer AS, Licht TR Abstract Prebiotic oligosaccharides are defined by their selective stimulation of growth and/or activity of bacteria in the digestive system in ways claimed to be beneficial for health. However, apart from the short chain fatty acids, little is known about bacterial metabolites created by fermentation of prebiotics, and the significance of the size of the oligosaccharides remains largely unstudied. By in vitro fermentations in human fecal microbial communities (derived from six different individuals), we studied the effects of high-mass (HA, >1 kDa), low-mass (LA, <1 kDa) and mixed (BA) sugar beet arabino-oligosaccharides (AOS) as carbohydrate sources. Fructo-oligosaccharides (FOS) were included as reference. The changes in bacterial communities and the metabolites produced in response to incubation with the different carbohydrates were analyzed by quantitative PCR (qPCR) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. All tested carbohydrate sources resulted in a significant increase of Bifidobacterium spp. between 1.79 fold (HA) and 1.64 fold (FOS) in the microbial populations after fermentation, and LC-MS analysis suggested that the bifidobacteria contributed to decomposition of the arabino-oligosaccharide structures, most pronounced in the HA fraction, resulting in release of the essential amino acid phenylalanine. Abundance of Lactobacillus spp. correlated with the presence of a compound, most likely a flavonoid, indicating that lactobacilli contribute to release of such health-promoting substances from plant structures. Additionally, the combination of qPCR and LC-MS revealed a number of other putative interactions between intestinal microbes and the oligosaccharides, which contributes to the understanding of the mechanisms behind prebiotic impact on human health. PMID: 24905430 [PubMed - indexed for MEDLINE]

Related Articles Water shortage and quality of fleshy fruits--making the most of the unavoidable. J Exp Bot. 2014 Aug;65(15):4097-117 Authors: Ripoll J, Urban L, Staudt M, Lopez-Lauri F, Bidel LP, Bertin N Abstract Extreme climatic events, including drought, are predicted to increase in intensity, frequency, and geographic extent as a consequence of global climate change. In general, to grow crops successfully in the future, growers will need to adapt to less available water and to take better advantage of the positive effects of drought. Fortunately, there are positive effects associated with drought. Drought stimulates the secondary metabolism, thereby potentially increasing plant defences and the concentrations of compounds involved in plant quality, particularly taste and health benefits. The role of drought on the production of secondary metabolites is of paramount importance for fruit crops. However, to manage crops effectively under conditions of limited water supply, for example by applying deficit irrigation, growers must consider not only the impact of drought on productivity but also on how plants manage the primary and secondary metabolisms. This question is obviously complex because during water deficit, trade-offs among productivity, defence, and quality depend upon the intensity, duration, and repetition of events of water deficit. The stage of plant development during the period of water deficit is also crucial, as are the effects of other stressors. In addition, growers must rely on relevant indicators of water status, i.e. parameters involved in the relevant metabolic processes, including those affecting quality. Although many reports on the effects of drought on plant function and crop productivity have been published, these issues have not been reviewed thus far. Here, we provide an up-to-date review of current knowledge of the effects of different forms of drought on fruit quality relative to the primary and secondary metabolisms and their interactions. We also review conventional and less conventional indicators of water status that could be used for monitoring purposes, such as volatile compounds. We focus on fruit crops owing to the importance of secondary metabolism in fruit quality and the importance of fruits in the human diet. The issue of defence is also briefly discussed. PMID: 24821951 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/04/01PubMed 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.

68 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 2015/03/31PubMed 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.

A Promising Raman Spectroscopy Technique for the Investigation of trans and cis Cholesteryl Ester Isomers in Biological Samples. Appl Spectrosc. 2015 Apr 1; Authors: Melchiorre M, Ferreri C, Tinti A, Chatgilialoglu C, Torreggiani A Abstract Lipid geometry is an important issue in biology and medicine. The cis-trans geometry conversion of double bonds in lipids is an endogenous process that can be mediated by sulfur-centered free radicals. Trans isomers of polyunsaturated fatty acids can be used as biological markers of free radical stress, and their presence in biological samples can be determined by synthesis and characterization of appropriate reference compounds. Fractions of plasma lipids, such as cholesteryl linoleate and arachidonate esters, are interesting targets because of their connection with membrane phospholipid turnover and their roles in cardiovascular health. In this context, Raman spectroscopy can provide a useful contribution, since Raman analysis can be performed directly on the lipid extracts without any derivatization reaction, is nondestructive, and can rapidly supply biochemical information. This study focused on the build up of Raman spectral libraries of different cis and trans isomers of cholesteryl esters to be used as references for the examination of complex biological samples and to facilitate isomer recognition. Unsaturated cholesteryl esters obtained by chemical synthesis and with different alkyl chain lengths, double bond numbers, or both, were analyzed. The potential of Raman analysis for trans isomer detection in biological samples was successfully tested on some cholesteryl ester lipid fractions from human serum. The data suggest promising applications of Raman spectroscopy in metabolomics and lipidomics. PMID: 25812111 [PubMed - as supplied by publisher]

Identification of Small Molecules that Disrupt Signaling between ABL and Its Positive Regulator RIN1. PLoS One. 2015;10(3):e0121833 Authors: Ting PY, Damoiseaux R, Titz B, Bradley KA, Graeber TG, Fernández-Vega V, Bannister TD, Chase P, Nair R, Scampavia L, Hodder P, Spicer TP, Colicelli J Abstract Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML). Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Förster resonance energy transfer (TR-FRET) -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1. This assay was used in a high throughput screen (HTS) of two small molecule libraries totaling 444,743 compounds. 708 confirmed hits were counter-screened to eliminate off-target inhibitors and reanalyzed to prioritize compounds with IC50 values below 10 μM. The CML cell line K562 was then used to identify five compounds that decrease MAPK1/3 phosphorylation, which we determined to be an indicator of RIN1-dependent ABL signaling. One of these compounds is a thiadiazole, and the other four are structurally related acyl piperidine amides. Notably, these five compounds lower cellular BCR-ABL1 kinase activity by blocking a positive regulatory interaction rather than directly inhibiting ABL catalytic function. PMID: 25811598 [PubMed - as supplied by publisher]

Endo-Lysosomal Dysfunction in Human Proximal Tubular Epithelial Cells Deficient for Lysosomal Cystine Transporter Cystinosin. PLoS One. 2015;10(3):e0120998 Authors: Ivanova EA, De Leo MG, Van Den Heuvel L, Pastore A, Dijkman H, De Matteis MA, Levtchenko EN Abstract Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC) deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles. PMID: 25811383 [PubMed - as supplied by publisher]

PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 2015 Mar 25;:ajpcell.00322.2014 Authors: Abu Aboud O, Donohoe D, Bultman S, Fitch M, Riiff T, Hellerstein M, Weiss RH Abstract Kidney cancer (RCC) is the 6(th) most common cancer in the US and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 years due to the development of therapeutic resistance. We previously identified PPARα as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced both apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as an siRNA specific to PPARα, attenuate the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis which has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific glycolysis inhibition corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model with minimal obvious toxicity, a finding associated with the expected on-target effects upon c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent glycolysis inhibition, is a potential novel and effective therapeutic approach for RCC which targets metabolic reprogramming in this tumor. PMID: 25810260 [PubMed - as supplied by publisher]

Metabolites profiling of Chrysanthemum pacificum Nakai parts using UPLC-PDA-MS coupled to chemometrics. Nat Prod Res. 2015 Mar 26;:1-8 Authors: Farag NF, Farag MA, Abdelrahman EH, Azzam SM, El-Kashoury ES Abstract Methanol-soluble constituents from the flowers, non-flowering aerial parts and roots of Chrysanthemum pacificum Nakai were analysed via high resolution UPLC-PDA-qTOF-MS followed by chemometrics. Forty-seven chromatographic peaks belonging to various metabolite classes were detected. Most metabolite classes showed qualitative and quantitative differences across parts, with luteolin conjugates being mostly enriched in flowers whereas non-flowering aerial parts contained mostly quercetin and methoxylated flavone conjugates. Root sample ranked the lowest for all flavones and dicaffeoylquinic acids. In contrast, 1,5-di-caffeoylquinic acid levels were found at high levels in flowers and aerial parts reaching 3145 and 1390 μg/g, respectively, suggesting that C. pacificum could serve as a natural resource of this well-recognised anti-hepatotoxic phenolic. Principal component analysis was further used for organs classification in an untargeted manner. This study provides the first map of secondary metabolites distribution in C. pacificum Nakai organs. PMID: 25810048 [PubMed - as supplied by publisher]

In vivo determination of the volatile metabolites of saprotroph fungi by comprehensive two-dimensional gas chromatography. J Sep Sci. 2015 Mar 23; Authors: de Lima PF, Furlan MF, Ribeiro FA, Pascholati SF, Augusto F Abstract In this work, we discuss the use of multi-way principal component analysis combined with comprehensive two-dimensional gas chromatography to study the volatile metabolites of the saprophytic fungus Memnoniella sp. isolated in vivo by headspace solid-phase microextraction. This fungus has been identified as having the ability to induce plant resistance against pathogens, possibly through its volatile metabolites. Adequate culture media was inoculated, and its headspace was then sampled with a solid-phase microextraction fiber and chromatographed every 24 h over seven days. The raw chromatogram processing using multi-way principal component analysis allowed the determination of the inoculation period, during which the concentration of volatile metabolites was maximized, as well as the discrimination of the appropriate peaks from the complex culture media background. Several volatile metabolites not previously described in the literature on biocontrol fungi were observed, as well as sesquiterpenes and aliphatic alcohols. These results stress that, due to the complexity of multidimensional chromatographic data, multivariate tools might be mandatory even for apparently trivial tasks, such as the determination of the temporal profile of metabolite production and extinction. However, when compared with conventional gas chromatography, the complex data processing yields a considerable improvement in the information obtained from the samples. This article is protected by copyright. All rights reserved. PMID: 25808238 [PubMed - as supplied by publisher]

Pathologic metabolism: An exploratory study of the plasma metabolome of critical injury. J Trauma Acute Care Surg. 2015 Apr;78(4):742-751 Authors: Peltz ED, D'Alessandro A, Moore EE, Chin T, Silliman CC, Sauaia A, Hansen KC, Banerjee A Abstract BACKGROUND: Severe trauma is associated with massive alterations in metabolism. Thus far, investigations have relied on traditional bioanalytic approaches including calorimetry or nuclear magnetic resonance. However, recent strides in mass spectrometry (MS)-based metabolomics present enhanced analytic opportunities to characterize a wide range of metabolites in the critical care setting. METHODS: MS-based metabolomics analyses were performed on plasma samples from severely injured patients' trauma activation field blood and plasma samples obtained during emergency department thoracotomy. These were compared against the metabolic profiles of healthy controls. RESULTS: Few significant alterations were observed between trauma activation field blood and emergency department thoracotomy patients. In contrast, we identified trauma-dependent metabolic signatures, which support a state of hypercatabolism, driven by sugar consumption, lipolysis and fatty acid use, accumulation of ketone bodies, proteolysis and nucleoside breakdown, which provides carbon and nitrogen sources to compensate for trauma-induced energy consumption and negative nitrogen balance. Unexpectedly, metabolites of bacterial origin (including tricarballylate and citramalate) were detected in plasma from trauma patients. CONCLUSION: In the future, the correlation between metabolomics adaptation and recovery outcomes could be studied by MS-based approaches, and this work can provide a method for assessing the efficacy of alternative resuscitation strategies. PMID: 25807403 [PubMed - as supplied by publisher]

Enhanced acylcarnitine annotation in high-resolution mass spectrometry data: fragmentation analysis for the classification and annotation of acylcarnitines. Front Bioeng Biotechnol. 2015;3:26 Authors: van der Hooft JJ, Ridder L, Barrett MP, Burgess KE Abstract Metabolite annotation and identification are primary challenges in untargeted metabolomics experiments. Rigorous workflows for reliable annotation of mass features with chemical structures or compound classes are needed to enhance the power of untargeted mass spectrometry. High-resolution mass spectrometry considerably improves the confidence in assigning elemental formulas to mass features in comparison to nominal mass spectrometry, and embedding of fragmentation methods enables more reliable metabolite annotations and facilitates metabolite classification. However, the analysis of mass fragmentation spectra can be a time-consuming step and requires expert knowledge. This study demonstrates how characteristic fragmentations, specific to compound classes, can be used to systematically analyze their presence in complex biological extracts like urine that have undergone untargeted mass spectrometry combined with data dependent or targeted fragmentation. Human urine extracts were analyzed using normal phase liquid chromatography (hydrophilic interaction chromatography) coupled to an Ion Trap-Orbitrap hybrid instrument. Subsequently, mass chromatograms and collision-induced dissociation and higher-energy collisional dissociation (HCD) fragments were annotated using the freely available MAGMa software. Acylcarnitines play a central role in energy metabolism by transporting fatty acids into the mitochondrial matrix. By filtering on a combination of a mass fragment and neutral loss designed based on the MAGMa fragment annotations, we were able to classify and annotate 50 acylcarnitines in human urine extracts, based on high-resolution mass spectrometry HCD fragmentation spectra at different energies for all of them. Of these annotated acylcarnitines, 31 are not described in HMDB yet and for only 4 annotated acylcarnitines the fragmentation spectra could be matched to reference spectra. Therefore, we conclude that the use of mass fragmentation filters within the context of untargeted metabolomics experiments is a valuable tool to enhance the annotation of small metabolites. PMID: 25806366 [PubMed]

Metabolomics and partial least square discriminant analysis to predict history of myocardial infarction of self-claimed healthy subjects: validity and feasibility for clinical practice. J Clin Bioinforma. 2015;5:3 Authors: Mohamad N, Ismet RI, Rofiee M, Bannur Z, Hennessy T, Selvaraj M, Ahmad A, Nor F, Abdul Rahman T, Md Isa K, Ismail A, Teh LK, Salleh MZ Abstract BACKGROUND: The dynamics of metabolomics in establishing a prediction model using partial least square discriminant analysis have enabled better disease diagnosis; with emphasis on early detection of diseases. We attempted to translate the metabolomics model to predict the health status of the Orang Asli community whom we have little information. The metabolite expressions of the healthy vs. diseased patients (cardiovascular) were compared. A metabotype model was developed and validated using partial least square discriminant analysis (PLSDA). Cardiovascular risks of the Orang Asli were predicted and confirmed by biochemistry profiles conducted concurrently. RESULTS: Fourteen (14) metabolites were determined as potential biomarkers for cardiovascular risks with receiver operating characteristic of more than 0.7. They include 15S-HETE (AUC = 0.997) and phosphorylcholine (AUC = 0.995). Seven Orang Asli were clustered with the patients' group and may have ongoing cardiovascular risks and problems. This is supported by biochemistry tests results that showed abnormalities in cholesterol, triglyceride, HDL and LDL levels. CONCLUSIONS: The disease prediction model based on metabolites is a useful diagnostic alternative as compared to the current single biomarker assays. The former is believed to be more cost effective since a single sample run is able to provide a more comprehensive disease profile, whilst the latter require different types of sampling tubes and blood volumes. PMID: 25806102 [PubMed]

Associations of cord blood metabolites with early childhood obesity risk. Int J Obes (Lond). 2015 Mar 25; Authors: Isganaitis E, Rifas-Shiman SL, Oken E, Dreyfuss J, Gall W, Gillman MW, Patti ME Abstract BACKGROUND/OBJECTIVE: Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. METHODS: We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 mo and BMI >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age- and sex-matched, had normal postnatal weight gain (2(nd) or 3(rd) quartile of change in weight-for-age 0-6 mo) and normal mid-childhood weight (BMI 25(th)-75(th) percentile). Cord blood metabolites were measured using untargeted LC/MS; individual metabolites and pathways differing between cases vs. controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI, and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). RESULTS: Of 415 detected metabolites, 16 were altered in cases vs. controls (T-test, nominal P<0.05). 3 metabolites were related to tryptophan: serotonin, tryptophan betaine, and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of 2 methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16% respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine, and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age, and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case vs. control status. CONCLUSIONS: Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study.International Journal of Obesity accepted article preview online, 25 March 2015. doi:10.1038/ijo.2015.39. PMID: 25804930 [PubMed - as supplied by publisher]

Optimising ketocarotenoid production in potato tubers: Effect of genetic background, transgene combinations and environment. Plant Sci. 2015 May;234:27-37 Authors: Campbell R, Morris WL, Mortimer CL, Misawa N, Ducreux LJ, Morris JA, Hedley PE, Fraser PD, Taylor MA Abstract Astaxanthin is a high value carotenoid produced by some bacteria, a few green algae, several fungi but only a limited number of plants from the genus Adonis. Astaxanthin has been industrially exploited as a feed supplement in poultry farming and aquaculture. Consumption of ketocarotenoids, most notably astaxanthin, is also increasingly associated with a wide range of health benefits, as demonstrated in numerous clinical studies. Currently astaxanthin is produced commercially by chemical synthesis or from algal production systems. Several studies have used a metabolic engineering approach to produce astaxanthin in transgenic plants. Previous attempts to produce transgenic potato tubers biofortified with astaxanthin have met with limited success. In this study we have investigated approaches to optimising tuber astaxanthin content. It is demonstrated that the selection of appropriate parental genotype for transgenic approaches and stacking carotenoid biosynthetic pathway genes with the cauliflower Or gene result in enhanced astaxanthin content, to give six-fold higher tuber astaxanthin content than has been achieved previously. Additionally we demonstrate the effects of growth environment on tuber carotenoid content in both wild type and astaxanthin-producing transgenic lines and describe the associated transcriptome and metabolome restructuring. PMID: 25804807 [PubMed - in process]

Multiple biomarkers of biological effects induced by cadmium in clam Ruditapes philippinarum. Fish Shellfish Immunol. 2015 Mar 21; Authors: Ji C, Wu H, Zhou M, Zhao J Abstract Cadmium (Cd) is a known heavy metal pollutant in the Bohai Sea. Manila clam Ruditapes philippinarum is an important fishery species along the Bohai coast. In this study, the biological effects induced by two concentrations (20 and 200 μg/L) of Cd were characterized using multiple biochemical indices in the digestive glands of clam R. philippinarum. The total haemocyte counts, reactive oxygen species productions and antioxidant enzyme activities exhibited that Cd induced dose-dependent immune and oxidative stresses in clam digestive glands. Metabolic responses indicated that both Cd exposures caused immune stress marked by the elevated branched chain amino acids (valine, leucine and isoleucine), together with the disturbance in energy metabolism. The differential metabolic biomarkers related to osmotic stress, including homarine, betaine, tyrosine and phenylalanine, suggested the differential responsive mechanisms in clam digestive glands induced by Cd exposures. In addition, both Cd treatments enhanced the anaerobiosis metabolism in clam digestive glands via differential metabolic pathways. PMID: 25804494 [PubMed - as supplied by publisher]

Untargeted Metabolomic Analysis of Human Plasma Indicates Differentially Affected Polyamine and L-Arginine Metabolism in Mild Cognitive Impairment Subjects Converting to Alzheimer's Disease. PLoS One. 2015;10(3):e0119452 Authors: Graham SF, Chevallier OP, Elliott CT, Hölscher C, Johnston J, McGuinness B, Kehoe PG, Passmore AP, Green BD Abstract This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification. PMID: 25803028 [PubMed - as supplied by publisher]

Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field. Biomed Res Int. 2015;2015:254076 Authors: Denihan NM, Boylan GB, Murray DM Abstract Metabolomics, the latest "omic" technology, is defined as the comprehensive study of all low molecular weight biochemicals, "metabolites" present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field. PMID: 25802843 [PubMed - as supplied by publisher]

Combined mass spectrometric and chromatographic methods for in-depth analysis of phenolic secondary metabolites in barley leaves. J Mass Spectrom. 2015 Mar;50(3):513-32 Authors: Piasecka A, Sawikowska A, Krajewski P, Kachlicki P Abstract Structural analysis via HPLC-ESI-MSn, UPLC-HESI-MS/MS and NMR reported 152 phenolic secondary metabolites in spring barley seedlings (Hordeum vulgare L.). Flavonoids with various patterns of glycosylation and acylation, as well as hydroxycinnamic acid glycosides, esters and amides, were identified in methanolic extracts from leaves of nine varieties of barley originating from different regions of the world. Hordatines derivatives, flavones acylated directly on the aglycone, and hydroxyferulic acid derivatives deserve special attention. Preparative chromatography enabled characterization of a number of compounds at trace levels with the 6-C-[6″-O-glycosyl]-glycosides and the 6-C-[2″,6″-di-O-glycosides]-glucoside structure of flavones. Derivatives of flavonols, quercetin and isorhamnetin were observed only in Syrian varieties. The ultra performance liquid chromatography profiles of UV-absorbing secondary metabolites were used for chemotaxonomic comparison between nine varieties of barley from different climatic conditions. The hierarchical clustering of bred lines from the Fertile Crescent and European and American varieties indicates a great diversity of chemical phenotypes within barley species. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 25800187 [PubMed - in process]

Analytical methods in untargeted metabolomics: state of the art in 2015. Front Bioeng Biotechnol. 2015;3:23 Authors: Alonso A, Marsal S, Julià A Abstract Metabolomics comprises the methods and techniques that are used to measure the small molecule composition of biofluids and tissues, and is actually one of the most rapidly evolving research fields. The determination of the metabolomic profile - the metabolome - has multiple applications in many biological sciences, including the developing of new diagnostic tools in medicine. Recent technological advances in nuclear magnetic resonance and mass spectrometry are significantly improving our capacity to obtain more data from each biological sample. Consequently, there is a need for fast and accurate statistical and bioinformatic tools that can deal with the complexity and volume of the data generated in metabolomic studies. In this review, we provide an update of the most commonly used analytical methods in metabolomics, starting from raw data processing and ending with pathway analysis and biomarker identification. Finally, the integration of metabolomic profiles with molecular data from other high-throughput biotechnologies is also reviewed. PMID: 25798438 [PubMed]