PubMed

Non-occlusive Sweat Collection Combined with Chemical Isotope Labeling LC-MS for Human Sweat Metabolomics and Mapping the Sweat Metabolomes at Different Skin Locations. Anal Chem. 2017 Jul 05;: Authors: Hooton K, Li L Abstract Human sweat is an excellent biofluid candidate for metabolomics due to its non-invasive sample collection and relatively simple matrix. We report a simple and inexpensive method for sweat collection over a defined period (e.g., 24 hr) based on the use of a non-occlusive style sweat patch adhered to a skin. This method was combined with differential chemical isotope labeling (CIL) LC-MS for mapping the metabolome profiles of sweat samples collected from skins of left forearm, lower back, and neck of 20 healthy volunteers. Three 24-hr sweat samples were collected at three different days from each subject for examining day-to-day metabolome variations. A total of 342 LC-MS runs including replicate analyses were carried out (two runs were discarded due to instrumental issue), resulting in the detection and relative quantification of 3140 sweat metabolites with 84 metabolites identified and 2716 metabolites mass-matched to metabolome databases. Multivariate and univariate analyses of the metabolome data revealed a location-dependence characteristic of the sweat metabolome, offering a possibility of mapping the sweat metabolic differences according to skin locations. Significant differences in male and female sweat metabolomes could be detected, demonstrating the possibility of using sweat metabolome to reveal biological variations among different comparative groups. Thus the combination of non-invasive sweat collection and CIL LC-MS is a robust analytical tool for sweat metabolomics with potential applications including daily monitoring of the sweat metabolome as health indicators, discovering sweat-based disease biomarkers, and metabolomic mapping of sweat collected from different areas of skin with and without injuries or diseases. PMID: 28679039 [PubMed - as supplied by publisher]

21st Century Toolkit for Optimizing Population Health through Precision Nutrition. Crit Rev Food Sci Nutr. 2017 Jul 05;:0 Authors: O'Sullivan A, Henrick B, Dixon B, Barile D, Zivkovic A, Smilowitz J, Lemay D, Martin W, German JB, Schaefer SE Abstract Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of "big data" to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individual's unique phenotype, or the current state of health, as determined by the interactions among biology, environment and behavior. The tools of Precision Nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health. PMID: 28678528 [PubMed - as supplied by publisher]

Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. Int J Mol Sci. 2017 Jul 05;18(7): Authors: Sbirkov Y, Kwok C, Bhamra A, Thompson AJ, Gil V, Zelent A, Petrie K Abstract Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML. PMID: 28678185 [PubMed - in process]

Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints? Mar Drugs. 2017 Jul 04;15(7): Authors: Farag MA, Fekry MI, Al-Hammady MA, Khalil MN, El-Seedi HR, Meyer A, Porzel A, Westphal H, Wessjohann LA Abstract Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10-60 µg/mL. No obvious correlation between the extracts' IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels. PMID: 28677625 [PubMed - in process]

A Concise Review on Multi-Omics Data Integration for Terroir Analysis in Vitis vinifera. Front Plant Sci. 2017;8:1065 Authors: Fabres PJ, Collins C, Cavagnaro TR, Rodríguez López CM Abstract Vitis vinifera (grapevine) is one of the most important fruit crops, both for fresh consumption and wine and spirit production. The term terroir is frequently used in viticulture and the wine industry to relate wine sensory attributes to its geographic origin. Although, it can be cultivated in a wide range of environments, differences in growing conditions have a significant impact on fruit traits that ultimately affect wine quality. Understanding how fruit quality and yield are controlled at a molecular level in grapevine in response to environmental cues has been a major driver of research. Advances in the area of genomics, epigenomics, transcriptomics, proteomics and metabolomics, have significantly increased our knowledge on the abiotic regulation of yield and quality in many crop species, including V. vinifera. The integrated analysis of multiple 'omics' can give us the opportunity to better understand how plants modulate their response to different environments. However, 'omics' technologies provide a large amount of biological data and its interpretation is not always straightforward, especially when different 'omic' results are combined. Here we examine the current strategies used to integrate multi-omics, and how these have been used in V. vinifera. In addition, we also discuss the importance of including epigenomics data when integrating omics data as epigenetic mechanisms could play a major role as an intermediary between the environment and the genome. PMID: 28676813 [PubMed - in process]

Screening Specific Biomarkers of Herbs Using a Metabolomics Approach: A Case Study of Panax ginseng. Sci Rep. 2017 Jul 04;7(1):4609 Authors: Wang HP, Liu Y, Chen C, Xiao HB Abstract Medicinal herbs belonging to the same genus are always easily confused due to their extremely similar morphology and metabolites. Previously, to differentiate them, inherently specific biomarkers were screened out via intuitive comparison of their metabolite profiles. Unfortunately, the selected biomarkers have worked only partially. Most significant specific biomarkers have been neglected. Herein, a novel method for screening specific biomarkers of medicinal herbs using a metabolomics technique was developed. Firstly, the profiles of a group of easily confused herbs belonging to the same genus were analyzed by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry to detect all components, including low-response metabolites. Then, all components were compared between the different samples, and specific biomarkers were extracted by the metabolomics techniques of alignment, normalization, defining the sample sets, filtering by frequency and Venn diagram analysis with Mass Profiler Professional (MPP) software. Thirdly, the correlations of these biomarkers were investigated via partial correlational analysis to obtain the most representative specific biomarkers. As an example, selection of specific biomarkers for ginseng (Panax ginseng) was performed, and three specific biomarkers including chikusetsusaponin IVa, ginsenoside Rf and ginsenoside Rc were finally selected and verified as the most representative specific biomarkers of Panax ginseng. PMID: 28676690 [PubMed - in process]

Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition. BMC Med. 2017 Jul 05;15(1):122 Authors: Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, Gicquiau A, Gunter MJ, Ferrari P, Kaaks R, Kühn T, Floegel A, Boeing H, Trichopoulou A, Lagiou P, Anifantis E, Agnoli C, Palli D, Trevisan M, Tumino R, Bueno-de-Mesquita HB, Agudo A, Larrañaga N, Redondo-Sánchez D, Barricarte A, Huerta JM, Quirós JR, Wareham N, Khaw KT, Perez-Cornago A, Johansson M, Cross AJ, Tsilidis KK, Riboli E, Key TJ, Travis RC Abstract BACKGROUND: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62-0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40-0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4. CONCLUSIONS: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations. PMID: 28676103 [PubMed - in process]

Related Articles Acetate-mediated novel survival strategy against drought in plants. Nat Plants. 2017 Jun 26;3:17097 Authors: Kim JM, To TK, Matsui A, Tanoi K, Kobayashi NI, Matsuda F, Habu Y, Ogawa D, Sakamoto T, Matsunaga S, Bashir K, Rasheed S, Ando M, Takeda H, Kawaura K, Kusano M, Fukushima A, Endo TA, Kuromori T, Ishida J, Morosawa T, Tanaka M, Torii C, Takebayashi Y, Sakakibara H, Ogihara Y, Saito K, Shinozaki K, Devoto A, Seki M Abstract Water deficit caused by global climate changes seriously endangers the survival of organisms and crop productivity, and increases environmental deterioration(1,2). Plants' resistance to drought involves global reprogramming of transcription, cellular metabolism, hormone signalling and chromatin modification(3-8). However, how these regulatory responses are coordinated via the various pathways, and the underlying mechanisms, are largely unknown. Herein, we report an essential drought-responsive network in which plants trigger a dynamic metabolic flux conversion from glycolysis into acetate synthesis to stimulate the jasmonate (JA) signalling pathway to confer drought tolerance. In Arabidopsis, the ON/OFF switching of this whole network is directly dependent on histone deacetylase HDA6. In addition, exogenous acetic acid promotes de novo JA synthesis and enrichment of histone H4 acetylation, which influences the priming of the JA signalling pathway for plant drought tolerance. This novel acetate function is evolutionarily conserved as a survival strategy against environmental changes in plants. Furthermore, the external application of acetic acid successfully enhanced the drought tolerance in Arabidopsis, rapeseed, maize, rice and wheat plants. Our findings highlight a radically new survival strategy that exploits an epigenetic switch of metabolic flux conversion and hormone signalling by which plants adapt to drought. PMID: 28650429 [PubMed - indexed for MEDLINE]

Related Articles Infectious Agents and Neurodegenerative Diseases: Exploring the Links. Curr Top Med Chem. 2017;17(12):1390-1399 Authors: Alam MZ, Alam Q, Kamal MA, Jiman-Fatani AA, Azhar EI, Khan MA, Haque A Abstract Recent studies have shown that bacterial and viral infections are risk factors for various neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), Alzheimer's disease (AD), and Lyme disease (LD). However, it is still controversial how the infections play a role in neurological diseases progression. Infections in central nervous system may lead multiple damages in infected and neighboring cells. The infection leads to the activation of inflammatory processes and host immune responses, which acts as defense mechanism and also causes damage to the host neuronal functions and viability. Several bacterial and viral pathogens have been reported for neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in combination with other factors, like aging, metabolic diseases and the genetic makeup of the host. We will focus in this review on the possible link between neurodegeneration and infections particularly Chlamydophila pneumoniae, Borrelia burgdorferi, Mycoplasma etc. PMID: 28049398 [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 2017/07/05PubMed comprises more than millions of 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.

Lipidomics to investigate the pharmacologic mechanisms of ginkgo folium in the hyperuricemic rat model. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jun 20;1060:407-415 Authors: Zhang S, Zhuang J, Yue G, Wang Y, Liu M, Zhang B, Du Z, Ma Q Abstract Hyperuricemia caused by purine metabolic abnormalities is reported to have close correlation with lipid metabolic disorders. Ginkgo folium, a frequently-used lipid-lowering medicine, has significant anti-hyperuricemia effects. However, it is poorly known about the interaction between lowering uric acid and regulation of lipid metabolic disorders. In this study, hyperuricemic rat model was induced by orally administration with fructose. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with pattern recognition approaches were used to determine different lipid metabolites in serum of control group, model group, and different doses of ginkgo folium groups. Principal component analysis (PCA) was applied to analyze the MS data to assess the establishment of model, partial least squares-discriminate analysis (PLS-DA) and independent samples T-test were performed to indicate the differences between different groups of rats and to find biomarkers. Metabolomics pathway analysis (MetPA) was introduced to reveal the pharmacologic mechanisms of ginkgo folium. 19 potential biomarkers associated with hyperuricemia were found. After intervened by ginkgo folium, these biomarkers were returning to normal level. Among these biomarkers, 13 lipid biomarkers were significantly reversed. Ginkgo filum can lower uric acid via adjusting back the level of PCs and LPCs, which suggested that its treatment mechanisms may be related to reducing the activity of PLA2. In sum, the lipidomics analysis in the system level have enhanced our understanding to pathogenesis of hyperuricemia and the results suggested that ginkgo folium could alleviate the abnormal metabolic status of hyperuricemia. These results demonstrated a new mechanism for lowering uric acid, which was helpful to the early treatment for hyperuricemia. PMID: 28672255 [PubMed - as supplied by publisher]

Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain. Chem Biodivers. 2017 Jul 03;: Authors: Tawfike AF, Tate R, Abbott G, Young L, Viegelmann C, Schumacher M, Diederich M, Edrada-Ebel RA Abstract Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate anticancer secondary metabolites from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimised method suitable for up-scaling. The optimised culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HRESI-MS, 1D and 2D-NMR. This study introduced a new method of dereplication utilising both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field. This article is protected by copyright. All rights reserved. PMID: 28672096 [PubMed - as supplied by publisher]

Metabolomics combined with pattern recognition and bioinformatics analysis methods for the development of pharmacodynamic biomarkers on liver fibrosis. Mol Biosyst. 2017 Jul 03;: Authors: Fang J, Wang L, Wang Y, Qiu M, Zhang Y Abstract The major obstacle for the development of targeted therapies is the lack of pharmacodynamic (PD) biomarkers to provide an early readout of biological activities. As the modulation of metabolites may reflect the biological changes occurring in the targets, metabolomics is promising to be an efficient way to explore PD biomarkers. In the present study, a liver fibrosis rat model was established by intraperitoneal injection of CCl4 twice weekly for 6 weeks, the treatment of total aglycone extracts of Scutellaria baicalensis (TAES) was begun 4 weeks after the modeling, and gas chromatography-mass spectrometry (GC-MS) based metabolomics combined with pattern recognition and network analysis were carried out for the research on PD biomarkers of TAES on liver fibrosis. After 2 weeks of treatment, TAES shows positive effects on CCl4-induced liver fibrosis. In the metabolomics study, 63 urinary metabolites contributing to liver fibrosis were identified. Six metabolic pathways significantly enriched in metabolomics data were mapped onto a network to determine global patterns of metabolic alterations in liver fibrosis. By topological analysis, 6 metabolites with high centrality in the metabolic sub-network were selected as potential PD biomarkers. Within 24 h of the final administration, the 6 identified urine metabolic biomarkers with response to time variation of TAES were validated as PD biomarkers. This integrative study presents an attractive strategy to explore PD biomarkers, which may give insight into the actual pharmacological effect of target drugs, and the information from PD biomarkers can be combined with pharmacokinetics to select the optimal dose and a schedule of administration for the drugs. PMID: 28671700 [PubMed - as supplied by publisher]

Extracellular vesicles are independent metabolic units with asparaginase activity. Nat Chem Biol. 2017 Jul 03;: Authors: Iraci N, Gaude E, Leonardi T, Costa ASH, Cossetti C, Peruzzotti-Jametti L, Bernstock JD, Saini HK, Gelati M, Vescovi AL, Bastos C, Faria N, Occhipinti LG, Enright AJ, Frezza C, Pluchino S Abstract Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1). Critically, we show that Asrgl1 activity is selective for asparagine and is devoid of glutaminase activity. We found that mouse and human NSC EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment. PMID: 28671681 [PubMed - as supplied by publisher]

Volatile compounds in blood headspace and nasal breath. J Breath Res. 2017 Jul 03;: Authors: Ross BM, Babgi R Abstract Breath analysis is a form of metabolomics that utilises the identification and quantification of volatile chemicals to provide information about physiological or pathological processes occurring within the body. An inherent assumption of such analyses is that the concentration of the exhaled gases correlates with the concentration of the same gas in the tissue of interest. In this study we have investigated this assumption by quantifying some volatile compounds in peripheral venous blood headspace, and in nasal breath collected in Tedlar bags obtained at the same time from 30 healthy volunteers, prior to analysis by Selected Ion Flow Tube Mass Spectrometry. Some endogenous compounds were significantly correlated between blood headspace and nasal breath such as isoprene (rp = 0.68) and acetone (rp = 0.63), however many, such as propanal (rp = -0.26) and methanol (rp = 0.23), were not. Furthermore, the relative concentrations of volatiles in blood and breath varied markedly between compounds, with some, such as isoprene and acetone having similar concentrations in each, others such as acetic acid, ammonia and methanol being significantly more abundant in breath, and others, such as methanal, being detectable in breath alone. We also observed that breath propanol and acetic acid concentrations were higher in male compared to female participants, and that the blood headspace methanol concentration was negatively correlated to body mass index. No relationship between volatile concentrations and age was observed. Our data suggest that breath concentrations of volatiles do not necessarily give information about the same compound in the blood stream. This was likely due to the upper airway contributing compounds over and above that originating in the circulation. An investigation of the relationship between breath volatile concentrations and that in the tissue(s) of interest should therefore become a routine part of the development process of breath-based biomarkers. PMID: 28671107 [PubMed - as supplied by publisher]

Neonatal Meningitis: Overcoming Challenges in Diagnosis, Prognosis, and Treatment with Omics. Front Pediatr. 2017;5:139 Authors: Gordon SM, Srinivasan L, Harris MC Abstract Neonatal meningitis is a devastating condition. Prognosis has not improved in decades, despite the advent of improved antimicrobial therapy and heightened index of suspicion among clinicians caring for affected infants. One in ten infants die from meningitis, and up to half of survivors develop significant lifelong complications, including seizures, impaired hearing and vision, and delayed or arrested development of such basic skills as talking and walking. At present, it is not possible to predict which infants will suffer poor outcomes. Early treatment is critical to promote more favorable outcomes, though diagnosis of meningitis in infants is technically challenging, time-intensive, and invasive. Profound neuronal injury has long been described in the setting of neonatal meningitis, as has elevated levels of many pro- and anti-inflammatory cytokines. Mechanisms of the host immune response that drive clearance of the offending organism and underlie brain injury due to meningitis are not well understood, however. In this review, we will discuss challenges in diagnosis, prognosis, and treatment of neonatal meningitis. We will highlight transcriptomic, proteomic, and metabolomic data that contribute to suggested mechanisms of inflammation and brain injury in this setting with a view toward fruitful areas for future investigation. PMID: 28670576 [PubMed - in process]

Urinary metabolomic analysis of intrahepatic cholestasis of pregnancy based on high performance liquid chromatography/mass spectrometry. Clin Chim Acta. 2017 Jun 29;: Authors: Ma L, Zhang X, Pan F, Cui Y, Yang T, Deng L, Shao Y, Ding M Abstract BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mothers and fetuses. Metabolomic approach has been applied to maternal-fetal medicine. The global metabolomic alterations that are specific in ICP as yet have not been investigated. METHODS: Based on high performance liquid chromatography/hybrid quadrupole time-of-flight (HPLC/Q-TOF) mass spectrometry, the untargeted metabolomics was used to analyze the changes of urinary metabolites between ICP group and the control group. RESULTS: One hundred nine variables in positive model and 119 variables in negative model were significantly different (p<0.05) between the ICP group and the control group, with the VIP (variable importance in the project) score>1 by the orthogonal partial least squares discriminant analysis (OPLS-DA). 14 metabolites in positive model and 18 metabolites in negative model were selected and identified based on HMDB (human metabolome database). Most of these metabolites were involved in bile acids biosynthesis and metabolism, hormone metabolism and lipid metabolism. A metabolite panel (MG (22:5), LysoPE (22:5), l-homocysteine sulfonic acid, glycocholic acid and chenodeoxycholic acid 3-sulfate) was contrusted by the binary logistic regression analysis with high diagnostic accuracy for ICP. The area under the receiver operating characteristic curve was 0.988 with the sensitivity of 90.0% and specificity of 93.3%. CONCLUSIONS: Urinary metabolites allow for the discrimination of ICP from the controls by orthogonal partial least squares discriminant analysis. Therefore, these findings may provide deep insights for the etiopathogenesis of ICP. Moreover, the maternal urinary metabolite panel has the potential to be used as non-invasive biomarkers for the diagnosis of ICP. PMID: 28669684 [PubMed - as supplied by publisher]

Orthogonal partial least squares/projections to latent structures regression-based metabolomics approach for identification of gene targets for improvement of 1-butanol production in Escherichia coli. J Biosci Bioeng. 2017 Jun 29;: Authors: Nitta K, Laviña WA, Pontrelli S, Liao JC, Putri SP, Fukusaki E Abstract Metabolomics is the comprehensive analysis of metabolites in biological systems that uses multivariate analyses such as principal component analysis (PCA) or partial least squares/projections to latent structures regression (PLSR) to understand the metabolome state and extract important information from biological systems. In this study, orthogonal PLSR (OPLSR) model-based metabolomics approach was applied to 1-butanol producing Escherichia coli to facilitate in strain improvement strategies. Here, metabolite data obtained by liquid chromatography/mass spectrometry (LC/MS) was used to construct an OPLSR model to correlate metabolite changes with 1-butanol production and rationally identify gene targets for strain improvement. Using this approach, acetyl-CoA was determined as the rate-limiting step of the pathway while free CoA was found to be insufficient for 1-butanol production. By resolving the problems addressed by the OPLSR model, higher 1-butanol productivity was achieved. In this study, the usefulness of OPLSR-based metabolomics approach for understanding the whole metabolome state and determining the most relevant metabolites was demonstrated. Moreover, it was able to provide valuable insights for selection of rational gene targets for strain improvement. PMID: 28669528 [PubMed - as supplied by publisher]

Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis. Diabetes Metab. 2017 Jun 29;: Authors: Friedrich N, Skaaby T, Pietzner M, Budde K, Thuesen BH, Nauck M, Linneberg A Abstract AIM: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. METHODS: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by (1)H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. RESULTS: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. CONCLUSION: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome. PMID: 28669514 [PubMed - as supplied by publisher]

Related Articles Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study. J Agric Food Chem. 2017 Jun 21;65(24):5056-5063 Authors: Shen G, Zhou L, Liu W, Cui Y, Xie W, Chen H, Yu W, Li W, Li H Abstract Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure. PMID: 28609104 [PubMed - indexed for MEDLINE]