PubMed

Microbiota Metabolite Regulation of Host Immune Homeostasis: A Mechanistic Missing Link. Curr Allergy Asthma Rep. 2015 May;15(5):524 Authors: Steinmeyer S, Lee K, Jayaraman A, Alaniz RC Abstract Metazoans predominantly co-exist with symbiotic microorganisms called the microbiota. Metagenomic surveys of the microbiota reveal a diverse ecosystem of microbes particularly in the gastrointestinal (GI) tract. Perturbations in the GI microbiota in higher mammals (i.e., humans) are linked to diseases with variegated symptomology including inflammatory bowel disease, asthma, and auto-inflammatory disorders. Indeed, studies using germ-free mice (lacking a microbiota) confirm that host development and homeostasis are dependent on the microbiota. A long-known key feature of the GI tract microbiota is metabolizing host indigestible dietary matter for maximum energy extraction; however, host signaling pathways are greatly influenced by the microbiota as well. In line with these observations, recent research has revealed that metabolites produced strictly by select microbiota members are mechanistic regulators of host cell functions. In this review, we discuss two major classes of microbiota-produced metabolites: short-chain fatty acids and tryptophan metabolites. We describe the known important roles for these metabolites in shaping host immunity and comment on the current status and future directions for microbiota metabolomics research. PMID: 26139332 [PubMed - in process]

Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children. Clin Pharmacokinet. 2015 Jul 3; Authors: Rodieux F, Wilbaux M, van den Anker JN, Pfister M Abstract Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80 % of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children. PMID: 26138291 [PubMed - as supplied by publisher]

[Chinmedomics: a new strategy for research of traditional Chinese medicine]. Zhongguo Zhong Yao Za Zhi. 2015 Feb;40(4):569-76 Authors: Zhang AH, Sun H, Yan GL, Wang P, Han Y, Wang XJ Abstract Syndrome and formulae (or prescription) are two key issues in traditional Chinese medicine (TCM) and the premise research for material basis of TCM. However, vagueness of syndromes and complexity of formulae greatly limited the evaluation to syndromes and effective substance basis of prescription. Therefore, how to solve the evaluation of syndromes, confirming the efficacy material basis in prescription are the current hot issues of international concern. To solve these problems, establishing chinmedomics by integrated serum pharmacochemistry of TCM with metabolomics technology, that is a unique method of TCM research, made outstanding contributions in solving international concerns such as the effectiveness and security aspects of TCM. On the basis of the biological characterization of syndrome, the metabolic profiling of animal models of TCM syndrome, and related metabolic fingerprints as well as metabolic biomarkers were established to evaluate the overall effects of TCM formulae and corresponding relationship of syndrome-formulae. The active constituents were screened using the plotting of correlation between (endogenous) marker metabolites and (exogenous) serum constituents (PCMS), and is ongoing verification by further biological experiments. Correlation analysis between the ingredients in the body after oral formulae and endogenous markers in vivo can be used to clarify the active ingredients and synergistic properties. This method was successfully applied for rapid discovery of potentially bioactive components and metabolites from TCM, and through a series of studies on the chinmedomics, it proved that the established method could help to explore the effective substance for further research of TCM. As a new research approach, Chinmedomics is the best method to fit the holistic concept of TCM, and it can not only interpret the essence of syndrome but also elucidate the scientific connotation of Chinese medical formulae. PMID: 26137671 [PubMed - in process]

Related Articles Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism. J Nutr. 2015 May;145(5):1123S-1130S Authors: Duffy LC, Raiten DJ, Hubbard VS, Starke-Reed P Abstract Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery. PMID: 25833886 [PubMed - indexed for MEDLINE]

Related Articles Data integration reveals key homeostatic mechanisms following low dose radiation exposure. Toxicol Appl Pharmacol. 2015 May 15;285(1):1-11 Authors: Tilton SC, Matzke MM, Sowa MB, Stenoien DL, Weber TJ, Morgan WF, Waters KM Abstract The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time - with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24-72h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. PMID: 25655199 [PubMed - indexed for MEDLINE]

21 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 2015/07/03PubMed 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.

Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins. J Vis Exp. 2015;(100) Authors: Sanchez SE, Cuevas DA, Rostron JE, Liang TY, Pivaroff CG, Haynes MR, Nulton J, Felts B, Bailey BA, Salamon P, Edwards RA, Burgin AB, Segall AM, Rohwer F Abstract Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented. PMID: 26132888 [PubMed - as supplied by publisher]

Personalized medicine in idiopathic pulmonary fibrosis: facts and promises. Curr Opin Pulm Med. 2015 Jun 30; Authors: Spagnolo P, Tzouvelekis A, Maher TM Abstract PURPOSE OF REVIEW: In this article, we summarize and discuss the most recent literature on personalized medicine in idiopathic pulmonary fibrosis (IPF), a chronic progressive and almost invariably lethal disease of unknown cause. This review is timely as major advances in our understanding of disease pathobiology and improvements in molecular techniques have recently led to the identification of potential surrogates of diagnosis, prognosis and response to treatment. RECENT FINDINGS: The most promising and advanced candidate biomarkers are presented based on their proposed mechanistic pathways (e.g. alveolar epithelial cell dysfunction, immune dysregulation, microbiome, extracellular matrix remodeling and fibroproliferation, epigenetic markers and metabolomics). Recent data suggest that components of the immune system may contribute to the development of IPF. A potential role for infections as a cofactor in disease development and progression or as a trigger in disease exacerbation has also recently been proposed. SUMMARY: Clinical management of IPF is unsatisfactory because of limited availability of truly effective therapies, lack of accurate predictors of disease behavior and absence of simple short-term measures of therapeutic response. A number of putative biomarkers have been identified in patients with IPF, although none has been validated to the standard necessary for their use in either therapeutic trials or clinical practice. Currently, ongoing prospective longitudinal studies will hopefully permit such validation. PMID: 26132817 [PubMed - as supplied by publisher]

Conferring high-temperature tolerance to nontransgenic tomato scions using graft transmission of RNA silencing of the fatty acid desaturase gene. Plant Biotechnol J. 2015 Jul 1; Authors: Nakamura S, Hondo K, Kawara T, Okazaki Y, Saito K, Kobayashi K, Yaeno T, Yamaoka N, Nishiguchi M Abstract We investigated graft transmission of high-temperature tolerance in tomato scions to nontransgenic scions from transgenic rootstocks, where the fatty acid desaturase gene (LeFAD7) was RNA-silenced. Tomato was transformed with a plasmid carrying an inverted repeat of LeFAD7 by Agrobacterium. Several transgenic lines showed the lower amounts of LeFAD7 RNA and unsaturated fatty acids, while nontransgenic control did not, and siRNA was detected in the transgenic lines, but not in control. These lines grew under conditions of high temperature, while nontransgenic control did not. Further, the nontransgenic plants were grafted onto the silenced transgenic plants. The scions showed less of the target gene RNA, and siRNA was detected. Under high-temperature conditions, these grafted plants grew, while control grafted plants did not. Thus, it was shown that high-temperature tolerance was conferred in the nontransgenic scions after grafting onto the silenced rootstocks. PMID: 26132723 [PubMed - as supplied by publisher]

Integrating transcriptomic and metabolomic analysis to understand natural leaf senescence in sunflower. Plant Biotechnol J. 2015 Jul 1; Authors: Moschen S, Bengoa Luoni S, Di Rienzo JA, Caro MD, Tohge T, Watanabe M, Hollmann J, González S, Rivarola M, García-García F, Dopazo J, Hopp HE, Hoefgen R, Fernie AR, Paniego N, Fernández P, Heinz RA Abstract Leaf senescence is a complex process, which has dramatic consequences on crop yield. In sunflower, gap between potential and actual yields reveals the economic impact of senescence. Indeed, sunflower plants are incapable of maintaining their green leaf area over sustained periods. This study characterizes the leaf senescence process in sunflower through a systems biology approach integrating transcriptomic and metabolomic analyses: plants being grown under both glasshouse and field conditions. Our results revealed a correspondence between profile changes detected at the molecular, biochemical and physiological level throughout the progression of leaf senescence measured at different plant developmental stages. Early metabolic changes were detected prior to anthesis and before the onset of the first senescence symptoms, with more pronounced changes observed when physiological and molecular variables were assessed under field conditions. During leaf development, photosynthetic activity and cell growth processes decreased, whereas sucrose, fatty acid, nucleotide and amino acid metabolisms increased. Pathways related to nutrient recycling processes were also up-regulated. Members of the NAC, AP2-EREBP, HB, bZIP and MYB transcription factor families showed high expression levels, and their expression level was highly correlated, suggesting their involvement in sunflower senescence. The results of this study thus contribute to the elucidation of the molecular mechanisms involved in the onset and progression of leaf senescence in sunflower leaves as well as to the identification of candidate genes involved in this process. PMID: 26132509 [PubMed - as supplied by publisher]

Proteome analysis in thyroid pathology. Expert Rev Proteomics. 2015 Jul 1;:1-16 Authors: Pagni F, L'Imperio V, Bono F, Garancini M, Roversi G, De Sio G, Galli M, Smith AJ, Chinello C, Magni F Abstract The incidence of thyroid cancer has continuously increased due to its detection in the preclinical stage. Clinical research in thyroid pathology is focusing on the development of new diagnostic tools to improve the stratification of nodules that have biological, practical and economic consequences on the management of patients. Several clinical questions related to thyroid carcinoma remain open and the use of proteomic research in the hunt for new targets with potential diagnostic applications has an important role in the solutions. Many different proteomic approaches are used to investigate thyroid lesions, including mass spectrometry profiling and imaging technologies. These approaches have been applied to different human tissues (cytological specimens, frozen sections, formalin-fixed paraffin embedded tissue or Tissue Micro Arrays). Moreover, other specimens are used for biomarker discovery, such as cell lines and the secretome. Alternative approaches, such as metabolomics and lipidomics, are also used and integrated within proteomics. PMID: 26132359 [PubMed - as supplied by publisher]

Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases. Biochemistry. 2015 Jul 1; Authors: Vann KR, Sedgeman CA, Gopas J, Golan-Goldhirsh A, Osheroff N Abstract Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. In order to identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. Based on previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10- to 100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons: 1) the activity of the metabolites was abrogated by a reducing agent, 2) compounds inhibited topoisomerase II activity when incubated with the enzyme prior to the addition of DNA, and 3) compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID: 26132160 [PubMed - as supplied by publisher]

Related Articles A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study. Mutagenesis. 2015 Jun 30; Authors: Assi N, Fages A, Vineis P, Chadeau-Hyam M, Stepien M, Duarte-Salles T, Byrnes G, Boumaza H, Knüppel S, Kühn T, Palli D, Bamia C, Boshuizen H, Bonet C, Overvad K, Johansson M, Travis R, Gunter MJ, Lund E, Dossus L, Elena-Herrmann B, Riboli E, Jenab M, Viallon V, Ferrari P Abstract Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation. PMID: 26130468 [PubMed - as supplied by publisher]

Related Articles Distinct metabolomic profiles of papillary thyroid carcinoma and benign thyroid adenoma. J Proteome Res. 2015 Jul 1; Authors: Xu Y, Zheng X, Qiu Y, Jia W, Wang J, Yin S Abstract Papillary thyroid carcinoma (PTC) and benign thyroid adenoma (BTA) are the most common head and neck tumors. However, the metabolic differences between PTC and BTA have not been characterized. The aim of this study was to identify the metabolic profiles of these two types of tumors using a metabolomics approach. Tumors and adjacent non-tumor specimens collected from 57 patients with PTC and 48 patients with BTA were profiled using gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A panel of 46 and 44 differentially expressed metabolites were identified in the PTC and BTA specimens, respetively, and compared with non-tumor tissues. Common metabolic signatures, as characterized by increased glycolysis, amino acid metabolism, one carbon metabolism and tryptophan metabolism, were found in both types of tumors. Purine and pyrimidine metabolism was significantly elevated in the PTC specimens, and taurine and hypotaurine levels were also higher in the PTC tissues. Increased fatty acid and bile acid levels were found, especially in the BTA tissues. The metabolic profiles of the PTC and BTA tissues include both similar and remarkably different metabolites, suggesting the presence of common and unique mechanistic pathways in these types of tumors during tumorigenesis. PMID: 26130307 [PubMed - as supplied by publisher]

Related Articles Metabolic Responses in Candida tropicalis to Complex Inhibitors During Xylitol Bioconversion. Fungal Genet Biol. 2015 Jun 27; Authors: Wang S, Li H, Fan X, Zhang J, Tang P, Yuan Q Abstract During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1, 3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1, 3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. PMID: 26127015 [PubMed - as supplied by publisher]

Related Articles Metabolic study of enrofloxacin and metabolic profile modifications in broiler chicken tissues after drug administration. Food Chem. 2015 Apr 1;172:30-9 Authors: Morales-Gutiérrez FJ, Barbosa J, Barrón D Abstract In this work, the identification and distribution of the metabolites from enrofloxacin (ENR) in liver, kidney and muscle tissues from broiler chickens subjected to a pharmacological treatment was studied. In addition, qualitative analyses of changes in the metabolic profile in those tissues after drug administration were also investigated. As a result, a total of 31 different metabolites from ENR were identified, which ciprofloxacin (CIP) and desethylene-ENR were the major metabolites. After four days of withdrawal period, most of the metabolites were excreted, but residues of ENR and CIP still persisted in tissues at a concentration under the permitted maximum residue limit (MRL). Non-medicated, medicated and post-treatment samples of chicken tissues were clearly clustered according to their metabolite profile by principal component analysis and partial least squares discriminant analysis, which indicates that endogenous metabolites have not returned to their original levels after the withdrawal period. A total of 22 relevant mass features contributing to this separation as potential markers of chicken samples were tentatively identified. PMID: 25442520 [PubMed - indexed for MEDLINE]

Related Articles Lipidomics applications for discovering biomarkers of diseases in clinical chemistry. Int Rev Cell Mol Biol. 2014;313:1-26 Authors: Zhao YY, Cheng XL, Lin RC Abstract Lipids are the fundamental components of biological membranes as well as the metabolites of organisms. Lipids play diverse and important roles in biologicals. The lipid imbalance is closely associated with numerous human lifestyle-related diseases, such as atherosclerosis, obesity, diabetes, and Alzheimer's disease. Lipidomics or lipid profiling is a system-based study of all lipids aiming at comprehensive analysis of lipids in the biological system. Lipidomics has been accepted as a lipid-related research tool in lipid biochemistry, clinical biomarker discovery, disease diagnosis, and in understanding disease pathology. Lipidomics will not only provide insights into the specific functions of lipid species in health and disease, but will also identify potential biomarkers for establishing preventive or therapeutic programs for human diseases. This review presents an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical technologies, data analysis, and clinical research in cancer, neuropsychiatric disease, cardiovascular disease, kidney disease, and respiratory disease. We describe the current status of the identification of metabolic biomarkers in different diseases. We also discuss the lipidomics for the future perspectives and their potential problems. The application of lipidomics in clinical studies may provide new insights into lipid profiling and pathophysiological mechanisms. PMID: 25376488 [PubMed - indexed for MEDLINE]

Related Articles Disposition and metabolic profiling of [(14)C]cerlapirdine using accelerator mass spectrometry. Drug Metab Dispos. 2014 Dec;42(12):2023-32 Authors: Tse S, Leung L, Raje S, Seymour M, Shishikura Y, Obach RS Abstract Cerlapirdine (SAM-531, PF-05212365) is a selective, potent, full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine and other 5-HT6 receptor antagonists have been in clinical development for the symptomatic treatment of Alzheimer's disease. A human absorption, distribution, metabolism, and excretion study was conducted to gain further understanding of the metabolism and disposition of cerlapirdine. Because of the low amount of radioactivity administered, total (14)C content and metabolic profiles in plasma, urine, and feces were determined using accelerator mass spectrometry (AMS). After a single, oral 5-mg dose of [(14)C]cerlapirdine (177 nCi), recovery of total (14)C was almost complete, with feces being the major route of elimination of the administered dose, whereas urinary excretion played a lesser role. The extent of absorption was estimated to be at least 70%. Metabolite profiling in pooled plasma samples showed that unchanged cerlapirdine was the major drug-related component in circulation, representing 51% of total (14)C exposure in plasma. One metabolite (M1, desmethylcerlapirdine) was detected in plasma, and represented 9% of the total (14)C exposure. In vitro cytochrome P450 reaction phenotyping studies showed that M1 was formed primarily by CYP2C8 and CYP3A4. In pooled urine samples, three major drug-related peaks were detected, corresponding to cerlapirdine-N-oxide (M3), cerlapirdine, and desmethylcerlapirdine. In feces, cerlapirdine was the major (14)C component excreted, followed by desmethylcerlapirdine. The results of this study demonstrate that the use of the AMS technique enables comprehensive quantitative elucidation of the disposition and metabolic profiles of compounds administered at a low radioactive dose. PMID: 25217486 [PubMed - indexed for MEDLINE]

Related Articles MetabNet: An R Package for Metabolic Association Analysis of High-Resolution Metabolomics Data. Front Bioeng Biotechnol. 2015;3:87 Authors: Uppal K, Soltow QA, Promislow DE, Wachtman LM, Quyyumi AA, Jones DP Abstract Liquid-chromatography high-resolution mass spectrometry provides capability to measure >40,000 ions derived from metabolites in biologic samples. This presents challenges to confirm identities of known chemicals and delineate potential metabolic pathway associations of unidentified chemicals. We provide an R package for metabolic network analysis, MetabNet, to perform targeted metabolome-wide association study of specific metabolites to facilitate detection of their related metabolic pathways and network structures. PMID: 26125020 [PubMed]

Related Articles Chronic inflammation: is it the driver or is it paving the road for malignant transformation? Genes Cancer. 2015 May;6(5-6):214-9 Authors: Afrasiabi K, Zhou YH, Fleischman A Abstract Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone. PMID: 26124920 [PubMed]