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Metabolites, Volume 5, Issue 1 (March 2015) , Pages 1-183

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Open AccessReview Neural Tube Defects: From a Proteomic Standpoint
Metabolites 2015, 5(1), 164-183; https://doi.org/10.3390/metabo5010164
Received: 10 October 2014 / Revised: 8 February 2015 / Accepted: 4 March 2015 / Published: 17 March 2015
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Abstract
Neural tube defects (NTDs) are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene [...] Read more.
Neural tube defects (NTDs) are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene etiology of NTDs has been aided by genetic studies, which have discovered panels of genes mutated in these diseases that encode receptors and cytoplasmic signaling molecules with poorly defined functions. Animal models ranging from flies to mice have been used to determine the function of these genes and identify their associated molecular cascades. More emphasis is now being placed on the identification of biochemical markers from clinical samples and model systems based on mass spectrometry, which open novel avenues in the understanding of NTDs at protein, metabolic and molecular levels. This article reviews how the use of proteomics can push forward the identification of novel biomarkers and molecular networks implicated in NTDs, an indispensable step in the improvement of patient management. Full article
(This article belongs to the Special Issue Inborn Errors of Metabolism)
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Open AccessReview Advances in Electronic-Nose Technologies for the Detection of Volatile Biomarker Metabolites in the Human Breath
Metabolites 2015, 5(1), 140-163; https://doi.org/10.3390/metabo5010140
Received: 29 December 2014 / Revised: 11 February 2015 / Accepted: 23 February 2015 / Published: 2 March 2015
Cited by 61 | Viewed by 4090 | PDF Full-text (312 KB) | HTML Full-text | XML Full-text
Abstract
Recent advancements in the use of electronic-nose (e-nose) devices to analyze human breath profiles for the presence of specific volatile metabolites, known as biomarkers or chemical bio-indicators of specific human diseases, metabolic disorders and the overall health status of individuals, are providing the [...] Read more.
Recent advancements in the use of electronic-nose (e-nose) devices to analyze human breath profiles for the presence of specific volatile metabolites, known as biomarkers or chemical bio-indicators of specific human diseases, metabolic disorders and the overall health status of individuals, are providing the potential for new noninvasive tools and techniques useful to point-of-care clinical disease diagnoses. This exciting new area of electronic disease detection and diagnosis promises to yield much faster and earlier detection of human diseases and disorders, allowing earlier, more effective treatments, resulting in more rapid patient recovery from various afflictions. E-nose devices are particularly suited for the field of disease diagnostics, because they are sensitive to a wide range of volatile organic compounds (VOCs) and can effectively distinguish between different complex gaseous mixtures via analysis of electronic aroma sensor-array output profiles of volatile metabolites present in the human breath. This review provides a summary of some recent developments of electronic-nose technologies, particularly involving breath analysis, with the potential for providing many new diagnostic applications for the detection of specific human diseases associated with different organs in the body, detectable from e-nose analyses of aberrant disease-associated VOCs present in air expired from the lungs. Full article
(This article belongs to the Special Issue Breath Analysis in Metabolomics)
Open AccessArticle A Study of the Effects of Exercise on the Urinary Metabolome Using Normalisation to Individual Metabolic Output
Metabolites 2015, 5(1), 119-139; https://doi.org/10.3390/metabo5010119
Received: 16 December 2014 / Revised: 13 February 2015 / Accepted: 22 February 2015 / Published: 27 February 2015
Cited by 23 | Viewed by 3565 | PDF Full-text (1524 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aerobic exercise, in spite of its multi-organ benefit and potent effect on the metabolome, has yet to be investigated comprehensively via an untargeted metabolomics technology. We conducted an exploratory untargeted liquid chromatography mass spectrometry study to investigate the effects of a one-h aerobic [...] Read more.
Aerobic exercise, in spite of its multi-organ benefit and potent effect on the metabolome, has yet to be investigated comprehensively via an untargeted metabolomics technology. We conducted an exploratory untargeted liquid chromatography mass spectrometry study to investigate the effects of a one-h aerobic exercise session in the urine of three physically active males. Individual urine samples were collected over a 37-h protocol (two pre-exercise and eight post-exercise). Raw data were subjected to a variety of normalization techniques, with the most effective measure dividing each metabolite by the sum response of that metabolite for each individual across the 37-h protocol expressed as a percentage. This allowed the metabolite responses to be plotted on a normalised scale. Our results highlight significant metabolites located in the following systems: purine pathway, tryptophan metabolism, carnitine metabolism, cortisol metabolism, androgen metabolism, amino acid oxidation, as well as metabolites from the gastrointestinal microbiome. Many of the significant changes observed in our pilot investigation mirror previous research studies, of various methodological designs, published within the last 15 years, although they have never been reported at the same time in a single study. Full article
(This article belongs to the Special Issue Biomarkers in Metabolomics)
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Open AccessReview Application of Metabolomics in Drug Resistant Breast Cancer Research
Metabolites 2015, 5(1), 100-118; https://doi.org/10.3390/metabo5010100
Received: 7 February 2014 / Revised: 18 August 2014 / Accepted: 24 December 2014 / Published: 16 February 2015
Cited by 24 | Viewed by 3862 | PDF Full-text (617 KB) | HTML Full-text | XML Full-text
Abstract
The metabolic profiles of breast cancer cells are different from normal mammary epithelial cells. Breast cancer cells that gain resistance to therapeutic interventions can reprogram their endogenous metabolism in order to adapt and proliferate despite high oxidative stress and hypoxic conditions. Drug resistance [...] Read more.
The metabolic profiles of breast cancer cells are different from normal mammary epithelial cells. Breast cancer cells that gain resistance to therapeutic interventions can reprogram their endogenous metabolism in order to adapt and proliferate despite high oxidative stress and hypoxic conditions. Drug resistance in breast cancer, regardless of subgroups, is a major clinical setback. Although recent advances in genomics and proteomics research has given us a glimpse into the heterogeneity that exists even within subgroups, the ability to precisely predict a tumor’s response to therapy remains elusive. Metabolomics as a quantitative, high through put technology offers promise towards devising new strategies to establish predictive, diagnostic and prognostic markers of breast cancer. Along with other “omics” technologies that include genomics, transcriptomics, and proteomics, metabolomics fits into the puzzle of a comprehensive systems biology approach to understand drug resistance in breast cancer. In this review, we highlight the challenges facing successful therapeutic treatment of breast cancer and the innovative approaches that metabolomics offers to better understand drug resistance in cancer. Full article
(This article belongs to the Special Issue Cancer Metabolomics)
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Open AccessArticle Taxonomic and Environmental Variation of Metabolite Profiles in Marine Dinoflagellates of the Genus Symbiodinium
Metabolites 2015, 5(1), 74-99; https://doi.org/10.3390/metabo5010074
Received: 4 September 2014 / Revised: 4 February 2015 / Accepted: 9 February 2015 / Published: 16 February 2015
Cited by 18 | Viewed by 3357 | PDF Full-text (1548 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microorganisms in terrestrial and marine ecosystems are essential to environmental sustainability. In the marine environment, invertebrates often depend on metabolic cooperation with their endosymbionts. Coral reefs, one of the most important marine ecosystems, are based on the symbiosis between a broad diversity of [...] Read more.
Microorganisms in terrestrial and marine ecosystems are essential to environmental sustainability. In the marine environment, invertebrates often depend on metabolic cooperation with their endosymbionts. Coral reefs, one of the most important marine ecosystems, are based on the symbiosis between a broad diversity of dinoflagellates of the genus Symbiodinium and a wide phyletic diversity of hosts (i.e., cnidarian, molluscan, poriferan). This diversity is reflected in the ecology and physiology of the symbionts, yet the underlying biochemical mechanisms are still poorly understood. We examined metabolite profiles of four cultured species of Symbiodinium known to form viable symbioses with reef-building corals, S. microadriaticum (cp-type A194), S. minutum (cp-type B184), S. psygmophilum (cp-type B224) and S. trenchii (cp-type D206). Metabolite profiles were shown to differ among Symbiodinium species and were found to be affected by their physiological response to growth in different temperatures and light regimes. A combined Random Forests and Bayesian analysis revealed that the four Symbiodinium species examined primarily differed in their production of sterols and sugars, including a C29 stanol and the two sterols C28Δ5 and C28Δ5,22, as well as differences in metabolite abundances of a hexose and inositol. Inositol levels were also strongly affected by changes in temperature across all Symbiodinium species. Our results offer a detailed view of the metabolite profile characteristic of marine symbiotic dinoflagellates of the genus Symbiodinium, and identify patterns of metabolites related to several growth conditions. Full article
(This article belongs to the Special Issue Metabolism in Phototrophic Prokaryotes and Algae)
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Open AccessReview The Role of Colonic Bacteria in the Metabolism of the Natural Isoflavone Daidzin to Equol
Metabolites 2015, 5(1), 56-73; https://doi.org/10.3390/metabo5010056
Received: 7 November 2014 / Accepted: 7 January 2015 / Published: 14 January 2015
Cited by 49 | Viewed by 3793 | PDF Full-text (538 KB) | HTML Full-text | XML Full-text
Abstract
Isoflavones are found in leguminous plants, especially soybeans. They have a structural similarity to natural estrogens, which enables them to bind to estrogen receptors and elicit biological activities similar to natural estrogens. They have been suggested to be beneficial for the prevention and [...] Read more.
Isoflavones are found in leguminous plants, especially soybeans. They have a structural similarity to natural estrogens, which enables them to bind to estrogen receptors and elicit biological activities similar to natural estrogens. They have been suggested to be beneficial for the prevention and therapy of hormone-dependent diseases. After soy products are consumed, the bacteria of the intestinal microflora metabolize isoflavones to metabolites with altered absorption, bioavailability, and estrogenic characteristics. Variations in the effect of soy products have been correlated with the isoflavone metabolites found in plasma and urine samples of the individuals consuming soy products. The beneficial effects of the soy isoflavone daidzin, the glycoside of daidzein, have been reported in individuals producing equol, a reduction product of daidzein produced by specific colonic bacteria in individuals called equol producers. These individuals comprise 30% and 60% of populations consuming Western and soy-rich Asian diets, respectively. Since the higher percentage of equol producers in populations consuming soy-rich diets is correlated with a lower incidence of hormone-dependent diseases, considerable efforts have been made to detect the specific colonic bacteria involved in the metabolism of daidzein to the more estrogenic compound, equol, which should facilitate the investigation of the metabolic activities related to this compound. Full article
(This article belongs to the Special Issue Metabolomic Studies of the Human Gut Microbiome)
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Open AccessReview Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview
Metabolites 2015, 5(1), 3-55; https://doi.org/10.3390/metabo5010003
Received: 8 July 2014 / Accepted: 12 December 2014 / Published: 9 January 2015
Cited by 60 | Viewed by 4345 | PDF Full-text (1672 KB) | HTML Full-text | XML Full-text
Abstract
Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly [...] Read more.
Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases. Full article
(This article belongs to the Special Issue Breath Analysis in Metabolomics)
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Open AccessEditorial Acknowledgement to Reviewers of Metabolites in 2014
Metabolites 2015, 5(1), 1-2; https://doi.org/10.3390/metabo5010001
Received: 8 January 2015 / Accepted: 8 January 2015 / Published: 8 January 2015
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Abstract
The editors of Metabolites would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2014:[...] Full article
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