PubMed

Taurine Attenuates Dimethylbenz[a]anthracene-induced Breast Tumorigenesis in Rats: A Plasma Metabolomic Study. Anticancer Res. 2016 Feb;36(2):533-43 Authors: He YU, Li QQ, Guo SC Abstract Breast cancer is the most common malignancy and the leading cause of cancer-related mortality in women worldwide. Taurine, the most abundant free amino acid, plays a role in several biological processes in humans and has been shown to have activity against breast cancer and other tumors. To investigate the role and mechanism of taurine action in breast cancer, we used dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats as a model of breast cancer. The administration of taurine significantly reduced the DMBA-induced breast cancer rate from 80% to 40% in rats (p<0.05). Metabolomic studies using time-of-flight gas chromatography-mass spectrometry identified 23 differential metabolites in the plasma of taurine-administered rats. Bioinformatic analysis further revealed that these metabolites are involved in multiple metabolic pathways, including energy, glucose, amino acid, and nucleic acid metabolism, suggesting that the antitumor activity of taurine in rats is mediated through altered metabolism of breast cancer cells. We propose that these differential metabolites may be potential biomarkers for monitoring cancer therapy and prognosis in the clinic. This study provides a scientific basis for further investigations of the antitumor mechanism of taurine and the development of novel therapeutic strategies to treat breast cancer. PMID: 26851007 [PubMed - in process]

Comparison of Metabolites Variation and Antiobesity Effects of Fermented versus Nonfermented Mixtures of Cudrania tricuspidata, Lonicera caerulea, and Soybean According to Fermentation In Vitro and In Vivo. PLoS One. 2016;11(2):e0149022 Authors: Suh DH, Jung ES, Park HM, Kim SH, Lee S, Jo YH, Lee MK, Jung G, Do SG, Lee CH Abstract We used ultra-performance-liquid-chromatography with quadrupole-time-of-flight mass spectrometry to study the changes in metabolites in the mixture of Cudrania tricuspidata, Lonicera caerulea, and soybean (CLM) during fermentation. Additionally, the antiobesity effects of CLM and fermented-CLM (FCLM) were studied based on the analysis of plasma from high-fat diet (HFD)-fed mice. The levels of cyanidin and the glycosides of luteolin, quercetin, and cyanidin derived from L. caerulea were decreased, whereas the levels of luteolin and quercetin were increased during fermentation. Isoflavone glycosides and soyasaponins originating from the soybean were decreased, whereas their aglycones such as daidzein, glycitein, and genistein were increased. As for prenylated flavonoids from C. tricuspidata, these metabolites were decreased at the early stage of fermentation, and were increased at end of the fermentation. In terms of the functional food product, various metabolites derived from diverse natural products in CLM had complementary effects and demonstrated higher antioxidant and pancreatic lipase inhibition activities after fermentation; these activities were closely related to flavonoid aglycones including genistein, daidzein, glycitein, luteolin, and quercetin. In an in vivo experiment, several clinical parameters affected by HFD were improved by the administration of either CLM or FCLM, but there was a difference in the antiobesity effects. The levels of lysoPCs with C20:4, C16:0, and C22:6 were significantly attenuated by CLM administration, while the attenuated levels of lysoPCs with C20:4 and C18:2 were significantly restored by FCLM administration. These metabolites may explain the above-mentioned differences in antiobesity effects. Although only the changes in plasma lysophospholipids could not fully explain antiobesity effects between non-fermented and fermented plant mixtures from our results, we suggest that metabolomics approach could provide a way to reveal the metabolite alterations in the complex fermentation process and understand the differences or changes in bioactivity according to fermentation. PMID: 26848749 [PubMed - as supplied by publisher]

Global Metabolic Responses to Salt Stress in Fifteen Species. PLoS One. 2016;11(2):e0148888 Authors: Sévin DC, Stählin JN, Pollak GR, Kuehne A, Sauer U Abstract Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species' taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance. PMID: 26848578 [PubMed - as supplied by publisher]

Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer. Oncotarget. 2016 Feb 3; Authors: Fan Y, Zhou X, Xia TS, Chen Z, Li J, Liu Q, Alolga RN, Chen Y, Lai MD, Li P, Zhu W, Qi LW Abstract PURPOSE: This work aims to identify differential metabolites and predicting molecular subtypes of breast cancer (BC). METHODS: Plasma samples were collected from 96 BC patients and 79 normal participants. Metabolic profiles were determined by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry based on multivariate statistical data analysis. RESULTS: We observed 64 differential metabolites between BC and normal group. Compared to human epidermal growth factor receptor 2 (HER2)-negative patients, HER2-positive group showed elevated aerobic glycolysis, gluconeogenesis, and increased fatty acid biosynthesis with reduced Krebs cycle. Compared with estrogen receptor (ER)-negative group, ER-positive patients showed elevated alanine, aspartate and glutamate metabolism, decreased glycerolipid catabolism, and enhanced purine metabolism. A panel of 8 differential metabolites, including carnitine, lysophosphatidylcholine (20:4), proline, alanine, lysophosphatidylcholine (16:1), glycochenodeoxycholic acid, valine, and 2-octenedioic acid, was identified for the classification of BC subtypes. These markers showed potential diagnostic value with average area under the curve at 0.925 (95% CI 0.867-0.983) for the training set (n=51) and 0.893 (95% CI 0.847-0.939) for the test set (n=45). CONCLUSION: Human plasma metabolomics is useful in identifying differential metabolites and predicting breast cancer subtypes. PMID: 26848530 [PubMed - as supplied by publisher]

GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar-dependent connectivity of primary metabolites. Metabolomics. 2016;12:39 Authors: Cuadros-Inostroza A, Ruíz-Lara S, González E, Eckardt A, Willmitzer L, Peña-Cortés H Abstract Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites. PMID: 26848290 [PubMed - as supplied by publisher]

Multi-platform metabolomics analyses of a broad collection of fragrant and non-fragrant rice varieties reveals the high complexity of grain quality characteristics. Metabolomics. 2016;12:38 Authors: Mumm R, Hageman JA, Calingacion MN, de Vos RC, Jonker HH, Erban A, Kopka J, Hansen TH, Laursen KH, Schjoerring JK, Ward JL, Beale MH, Jongee S, Rauf A, Habibi F, Indrasari SD, Sakhan S, Ramli A, Romero M, Reinke RF, Ohtsubo K, Boualaphanh C, Fitzgerald MA, Hall RD Abstract The quality of rice in terms not only of its nutritional value but also in terms of its aroma and flavour is becoming increasingly important in modern rice breeding where global targets are focused on both yield stability and grain quality. In the present paper we have exploited advanced, multi-platform metabolomics approaches to determine the biochemical differences in 31 rice varieties from a diverse range of genetic backgrounds and origin. All were grown under the specific local conditions for which they have been bred and all aspects of varietal identification and sample purity have been guaranteed by local experts from each country. Metabolomics analyses using 6 platforms have revealed the extent of biochemical differences (and similarities) between the chosen rice genotypes. Comparison of fragrant rice varieties showed a difference in the metabolic profiles of jasmine and basmati varieties. However with no consistent separation of the germplasm class. Storage of grains had a significant effect on the metabolome of both basmati and jasmine rice varieties but changes were different for the two rice types. This shows how metabolic changes may help prove a causal relationship with developing good quality in basmati rice or incurring quality loss in jasmine rice in aged grains. Such metabolomics approaches are leading to hypotheses on the potential links between grain quality attributes, biochemical composition and genotype in the context of breeding for improvement. With this knowledge we shall establish a stronger, evidence-based foundation upon which to build targeted strategies to support breeders in their quest for improved rice varieties. PMID: 26848289 [PubMed - as supplied by publisher]

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. Sci Rep. 2016;6:20391 Authors: Ferrario M, Cambiaghi A, Brunelli L, Giordano S, Caironi P, Guatteri L, Raimondi F, Gattinoni L, Latini R, Masson S, Ristagno G, Pastorelli R Abstract Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID: 26847922 [PubMed - in process]

The effects of acute lipopolysaccharide challenge on dairy goat liver metabolism assessed with (1) HNMR metabonomics. J Anim Physiol Anim Nutr (Berl). 2016 Feb 5; Authors: Wang LF, Jia SD, Yang GQ, Liu RY, Yang GY, Li M, Zhu HS, Wang YY, Han LQ Abstract We investigated the mechanisms mediating hepatic metabolic responses to an acute lipopolysaccharide (LPS) challenge in goats. Guanzhong dairy goats (15) were randomly divided into three groups: control (CTL, saline, 0.2 ml/kg BW), lower dose LPS (LPS-L, 20 μg/kg BW) and higher dose LPS (LPS-H, 40 μg/kg BW). All injections were administered intraperitoneally twice with a 24-h interval. Forty-eight hours after the first injection, blood samples were collected to extract plasma for biochemical analysis, and liver tissues were biopsied and stored in liquid nitrogen for metabonomics analysis. We found that plasma levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin increased (p < 0.05) in both LPS-treated groups, whereas plasma triglyceride, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, total protein and albumin levels markedly decreased (p < 0.05). The increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), levels of tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and IL-8 indicated hepatic injury and metabolic dysfunction in some degree. Using proton nuclear magnetic resonance ((1) H-NMR) metabonomics and the Chenomx NMR suite database, 69 metabolites were detected and identified. Metabolic differences among the groups were determined with pattern recognition analyses using principal component analysis and supervised projection to latent structures discriminant analysis. Pattern recognition analysis distinguished and clustered the metabolite variables from the three groups, finding nine of 69 metabolites that differed significantly between two of the three groups: six from the LPS-L or LPS-H groups differed from CTL and three differed between LPS-L and LPS-H groups. These altered metabolites were closely connected with glucose, lipid and amino acid metabolic pathways in hepatocytes. Based on an analysis of these metabolites and their relevant pathways, the mechanisms and degree of hepatic injury were deduced. Therefore, the metabolic profile was used effectively to detect characteristic hepatic metabolites, discriminate metabolic changes induced by LPS, clarify the mechanisms for the resulting metabolic dysfunctions and provide efficient information to diagnose liver injury. PMID: 26847913 [PubMed - as supplied by publisher]

Use of metabolomics for the chemotaxonomy of legume-associated Ascochyta and allied genera. Sci Rep. 2016;6:20192 Authors: Kim W, Peever TL, Park JJ, Park CM, Gang DR, Xian M, Davidson JA, Infantino A, Kaiser WJ, Chen W Abstract Chemotaxonomy and the comparative analysis of metabolic features of fungi have the potential to provide valuable information relating to ecology and evolution, but have not been fully explored in fungal biology. Here, we investigated the chemical diversity of legume-associated Ascochyta and Phoma species and the possible use of a metabolomics approach using liquid chromatography-mass spectrometry for their classification. The metabolic features of 45 strains including 11 known species isolated from various legumes were extracted, and the datasets were analyzed using chemometrics methods such as principal component and hierarchical clustering analyses. We found a high degree of intra-species consistency in metabolic profiles, but inter-species diversity was high. Molecular phylogenies of the legume-associated Ascochyta/Phoma species were estimated using sequence data from three protein-coding genes and the five major chemical groups that were detected in the hierarchical clustering analysis were mapped to the phylogeny. Clusters based on similarity of metabolic features were largely congruent with the species phylogeny. These results indicated that evolutionarily distinct fungal lineages have diversified their metabolic capacities as they have evolved independently. This whole metabolomics approach may be an effective tool for chemotaxonomy of fungal taxa lacking information on their metabolic content. PMID: 26847260 [PubMed - in process]

The peach HECATE3-like gene FLESHY plays a double role during fruit development. Plant Mol Biol. 2016 Feb 5; Authors: Botton A, Rasori A, Ziliotto F, Moing A, Maucourt M, Bernillon S, Deborde C, Petterle A, Varotto S, Bonghi C Abstract Tight control of cell/tissue identity is essential for a correct and functional organ patterning, an important component of overall fruit development and eventual maturation and ripening. Despite many investigations regarding the molecular determinants of cell identity in fruits of different species, a useful model able to depict the regulatory networks governing this relevant part of fruit development is still missing. Here we described the peach fruit as a system to link the phenotype of a slow ripening (SR) selection to an altered transcriptional regulation of genes involved in determination of mesocarp cell identity providing insight toward molecular regulation of fruit tissue formation. Morpho-anatomical observations and metabolomics analyses performed during fruit development on the reference cultivar Fantasia, compared to SR, revealed that the mesocarp of SR maintained typical immaturity traits (e.g. small cell size, high amino acid contents and reduced sucrose) throughout development, along with a strong alteration of phenylpropanoid contents, resulting in accumulation of phenylalanine and lignin. These findings suggest that the SR mesocarp is phenotypically similar to a lignifying endocarp. To test this hypothesis, the expression of genes putatively involved in determination of drupe tissues identity was assessed. Among these, the peach HEC3-like gene FLESHY showed a strongly altered expression profile consistent with pit hardening and fruit ripening, generated at a post-transcriptional level. A double function for FLESHY in channelling the phenylpropanoid pathway to either lignin or flavour/aroma is suggested, along with its possible role in triggering auxin-ethylene cross talk at the start of ripening. PMID: 26846510 [PubMed - as supplied by publisher]

Acute nephrotoxicity of aristolochic acid in vitro: metabolomics study for intracellular metabolic time-course changes. Biomarkers. 2016 Feb 5;:1-10 Authors: Liu X, Liu Y, Cheng M, Xiao H Abstract Time-course metabolic changes of aristolochic acid nephrotoxicity (AAN) was investigated using acute AAN HK-2 model. And the AAN-related biomarkers were selected. In the results, 11 potential identified biomarkers were selected and validated using multivariate method combined with time-course analysis. Several metabolic pathways, including vitamin metabolism, lipids acalytion, trytophan metabolism and protein degradation were found to be associated with AAN pathology. This research will provide a valuable reference for the discovery of more potential biomarkers of AAN progression in clinic. PMID: 26846302 [PubMed - as supplied by publisher]

Pulsed (13)C2-Acetate Protein-SIP Unveils Epsilonproteobacteria as Dominant Acetate Utilizers in a Sulfate-Reducing Microbial Community Mineralizing Benzene. Microb Ecol. 2016 Feb 4; Authors: Starke R, Keller A, Jehmlich N, Vogt C, Richnow HH, Kleinsteuber S, von Bergen M, Seifert J Abstract In a benzene-degrading and sulfate-reducing syntrophic consortium, a clostridium affiliated to the genus Pelotomaculum was previously described to ferment benzene while various sulfate-reducing Deltaproteobacteria and a member of the Epsilonproteobacteria were supposed to utilize acetate and hydrogen as key metabolites derived from benzene fermentation. However, the acetate utilization network within this community was not yet unveiled. In this study, we performed a pulsed (13)C2-acetate protein stable isotope probing (protein-SIP) approach continuously spiking low amounts of acetate (10 μM per day) in addition to the ongoing mineralization of unlabeled benzene. Metaproteomics revealed high abundances of Clostridiales followed by Syntrophobacterales, Desulfobacterales, Desulfuromonadales, Desulfovibrionales, Archaeoglobales, and Campylobacterales. Pulsed acetate protein-SIP results indicated that members of the Campylobacterales, the Syntrophobacterales, the Archaeoglobales, the Clostridiales, and the Desulfobacterales were linked to acetate utilization in descending abundance. The Campylobacterales revealed the fastest and highest (13)C incorporation. Previous experiments suggested that the activity of the Campylobacterales was not essential for anaerobic benzene degradation in the investigated community. However, these organisms were consistently detected in various hydrocarbon-degrading and sulfate-reducing consortia enriched from the same aquifer. Here, we demonstrate that this member of the Campylobacterales is the dominant acetate utilizer in the benzene-degrading microbial consortium. PMID: 26846217 [PubMed - as supplied by publisher]

Single-cell metabolite profiling of stalk and glandular cells of intact trichomes with internal electrode capillary pressure probe electrospray ionization mass spectrometry. Anal Chem. 2016 Feb 4; Authors: Nakashima T, Wada H, Morita S, Erra-Balsells R, Hiraoka K, Nonami H Abstract In this report, we developed the pressure probe electrospray ionization mass spectrometry with internal electrode capillary (IEC-PPESI-MS) which enables high spatial-resolution cell sampling, precise post-sampling manipulation and high detection sensitivity. Using this technique, a comparative in situ single-cell metabolite profiling of stalk and glandular cells, the two adjacent cell types comprising a trichome unit in tomato plants (Solanum lycopersicum L.), were performed to clarify the extent of metabolic differentiation between two cell types as well as among different types of trichomes. Owing to high sensitivity of the system, less than a pico-liter cell sap from a single stalk cell sufficiently yielded a number of peaks of amino acids, organic acids, carbohydrates and flavonoids. The minimal cell sap removal from a stalk cell without severe disturbance of trichome structure enabled sequential analysis of adjacent glandular cell on the same trichome, which showed the presence of striking differences in metabolite compositions between two adjacent cell types. Comparison among different types of trichome also revealed significant variations in metabolite profiles, particularly in flavonoids and acyl sugars compositions. Some metabolites were found only in specific cell types or particular trichome types. Although extensive metabolomics analysis of glandular cells of tomato trichomes has been previously documented, this is the first report describing cell-to-cell variations in metabolite compositions of stalk and glandular cells as well as in different trichome types. Further application of this technique may provide new insights into distinct metabolism in plant cells displaying variations in shape, size, function and physicochemical properties. PMID: 26845634 [PubMed - as supplied by publisher]

Related Articles Quantitative and qualitative shifts in defensive metabolites define chemical defense investment during leaf development in Inga, a genus of tropical trees. Ecol Evol. 2016 Jan;6(2):478-92 Authors: Wiggins NL, Forrister DL, Endara MJ, Coley PD, Kursar TA Abstract Selective pressures imposed by herbivores are often positively correlated with investments that plants make in defense. Research based on the framework of an evolutionary arms race has improved our understanding of why the amount and types of defenses differ between plant species. However, plant species are exposed to different selective pressures during the life of a leaf, such that expanding leaves suffer more damage from herbivores and pathogens than mature leaves. We hypothesize that this differential selective pressure may result in contrasting quantitative and qualitative defense investment in plants exposed to natural selective pressures in the field. To characterize shifts in chemical defenses, we chose six species of Inga, a speciose Neotropical tree genus. Focal species represent diverse chemical, morphological, and developmental defense traits and were collected from a single site in the Amazonian rainforest. Chemical defenses were measured gravimetrically and by characterizing the metabolome of expanding and mature leaves. Quantitative investment in phenolics plus saponins, the major classes of chemical defenses identified in Inga, was greater for expanding than mature leaves (46% and 24% of dry weight, respectively). This supports the theory that, because expanding leaves are under greater selective pressure from herbivores, they rely more upon chemical defense as an antiherbivore strategy than do mature leaves. Qualitatively, mature and expanding leaves were distinct and mature leaves contained more total and unique metabolites. Intraspecific variation was greater for mature leaves than expanding leaves, suggesting that leaf development is canalized. This study provides a snapshot of chemical defense investment in a speciose genus of tropical trees during the short, few-week period of leaf development. Exploring the metabolome through quantitative and qualitative profiling enables a more comprehensive examination of foliar chemical defense investment. PMID: 26843932 [PubMed]

Related Articles A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease. J Ginseng Res. 2016 Jan;40(1):9-17 Authors: Li N, Liu Y, Li W, Zhou L, Li Q, Wang X, He P Abstract BACKGROUND: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. METHODS: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. RESULTS: The impaired cognitive function and increased hippocampal Aβ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. CONCLUSION: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD. PMID: 26843817 [PubMed]

Related Articles Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures. Rapid Commun Mass Spectrom. 2016 Mar 15;30(5):581-93 Authors: Telu KH, Yan X, Wallace WE, Stein SE, Simón-Manso Y Abstract RATIONALE: The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. METHODS: Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). RESULTS: Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) <2%); however, substantial differences were found in the LC/MS patterns originating on different platforms or even using different chromatographic scales (conventional HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. CONLUSIONS: Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID: 26842580 [PubMed - in process]

Related Articles Microbial metabolomics in open microscale platforms. Nat Commun. 2016;7:10610 Authors: Barkal LJ, Theberge AB, Guo CJ, Spraker J, Rappert L, Berthier J, Brakke KA, Wang CC, Beebe DJ, Keller NP, Berthier E Abstract The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid-liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus, a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria. PMID: 26842393 [PubMed - in process]

Related Articles Resistant Starch Alters Gut Microbiome and Metabolomics Profiles Concurrent with Amelioration of Chronic Kidney Disease in Rats. Am J Physiol Renal Physiol. 2016 Feb 3;:ajprenal.00513.2015 Authors: Kieffer DA, Piccolo BD, Vaziri ND, Liu S, Lau WL, Khazaeli M, Nazertehrani S, Moore ME, Marco ML, Martin RJ, Adams SH Abstract Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xeno-metabolites). The fermentable dietary fiber-high amylose maize resistant starch type 2 (HAMRS2)-has been shown to alter the gut milieu, and in CKD rat models leads to markedly improved kidney function. The aim of the current study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function, in order to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine induced CKD were fed a semi-purified low fiber or a high fiber diet (59% w/w of HAMRS2) for 3 weeks (n=9/grp). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes to Firmicutes ratio. Several URS solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances: i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively in HAMRS2-fed rats, and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indices and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. PMID: 26841824 [PubMed - as supplied by publisher]

Related Articles Nutrimetabolomics and Adipocitokines in the "Great Obstetrical Syndromes". Pediatr Endocrinol Rev. 2015 Dec;13(2):546-58 Authors: De Magistris A, Marincola FC, Fanos V, Dessi A Abstract In neonatal medicine, nutritional research is focusing more and more on thrifty phenotype effects, in order to understand and prevent the development of long-term diseases. lschemic placental disease which brings together Gestational diabete, Preeclamptic Toxemia, and Intrauterine Growth Restriction, the "Great Obstetrical Syndromes" (GOS), originates from sugar.and lipid metabolism. Adipokines and metabolomics can be valuable tools for the diagnosis of obstetrical syndromes and addressing nutrition. Inappropriate nutrition, even in the first periods of life, can accelerate the development of chronic metabolic diseases, especially in the pediatric age. The purpose of this review is firstly to critically examine the information provided by the studies of metabolomics on GOS's and better understand their origin. Secondly, it reflects on the IUGR metabolism and on applications of metabolomics in nutrition and its "nutrimetabolomic" effects and then to discuss the principles that guide nutrition of IUGR children in the light of these. PMID: 26841642 [PubMed - in process]

Related Articles The influence of sample collection methodology and sample preprocessing on the blood metabolic profile. Bioanalysis. 2015;7(8):991-1006 Authors: Jørgenrud B, Jäntti S, Mattila I, Pöhö P, Rønningen KS, Yki-Järvinen H, Orešič M, Hyötyläinen T Abstract AIM: Blood serum and plasma have intrinsic differences in their composition and the preprocessing, such as clotting temperature in serum, and storage at room temperature may have further effect on metabolite concentrations. METHODS: The influence of sampling preprocessing on the metabolic profiles in serum and different types of plasma was investigated using liquid chromatography and comprehensive 2D gas chromatography coupled to a mass spectrometer. RESULTS: The profiles of polar metabolites were significantly dependent on the type of the sample, while lipid profiles were similar in serum and different types of plasma. Extended storage of plasma at room temperature resulted in degradation of lipids already after 1 day. Serum clotting at room temperature generally resulted in higher metabolite concentration compared with serum clotting on ice. PMID: 25966010 [PubMed - indexed for MEDLINE]