PubMed

Related Articles Dietary nicotinic acid supplementation ameliorates chronic alcohol-induced fatty liver in rats. Alcohol Clin Exp Res. 2014 Jul;38(7):1982-92 Authors: Li Q, Xie G, Zhang W, Zhong W, Sun X, Tan X, Sun X, Jia W, Zhou Z Abstract BACKGROUND: Alcohol abuse frequently causes niacin deficiency in association with the development of alcoholic liver disease. The objective of the present study was to determine whether dietary nicotinic acid (NA) deficiency exaggerates and whether dietary NA supplementation alleviates alcohol-induced fatty liver. METHODS: Male Sprague-Dawley rats were pair-fed with 4 isocaloric liquid diets: control, ethanol (EtOH), EtOH with dietary NA deficiency, and EtOH with dietary NA supplementation, respectively, for 8 weeks. The control and EtOH diets contained normal levels of NA (7.5 mg/l). Dietary NA deficiency (0 mg NA/l) was achieved by removing NA from the vitamin mix, while NA was added to the liquid diet at 750 mg/l for dietary NA supplementation. RESULTS: Chronic EtOH feeding induced significant lipid accumulation in the liver, which was not worsened by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Liver total NAD, NAD(+) , and NADH levels were remarkably higher in the NA supplemented group than the NA deficient or EtOH alone groups. Dietary NA supplementation to EtOH-fed rats increased the protein levels of hepatic cytochrome P450 4A1 (CYP4A1) and acyl-coenzyme A oxidase 1 without affecting their mRNA levels. Interestingly, we found dietary NA supplementation reduced the ubiquitination level of CYP4A1. In addition, hepatic fatty acid synthase expression was reduced, while the serum β-hydroxybutyrate and adiponectin concentrations were significantly elevated by dietary NA supplementation. Moreover, dietary NA supplementation modulated EtOH-perturbed liver and serum metabolite profiles. CONCLUSIONS: These results demonstrate that alcoholic fatty liver was not exaggerated by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Increased hepatic fatty acid oxidation and decreased hepatic de novo lipogenesis contribute to the effects of dietary NA supplementation. PMID: 24848081 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome. Int J Neuropsychopharmacol. 2014 Aug;17(8):1139-48 Authors: Paredes RM, Quinones M, Marballi K, Gao X, Valdez C, Ahuja SS, Velligan D, Walss-Bass C Abstract Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia. However, SGAs cause metabolic disturbances that can manifest as metabolic syndrome (MetS) in a subset of patients. The causes for these metabolic disturbances remain unclear. We performed a comprehensive metabolomic profiling of 60 schizophrenia patients undergoing treatment with SGAs that puts them at high (clozapine, olanzapine), medium (quetiapine, risperidone), or low (ziprasidone, aripiprazole) risk for developing MetS, compared to a cohort of 20 healthy controls. Multiplex immunoassays were used to measure 13 metabolic hormones and adipokines in plasma. Mass spectrometry was used to determine levels of lipids and polar metabolites in 29 patients and 10 controls. We found that levels of insulin and tumor necrosis factor alpha (TNF-α) were significantly higher (p < 0.005) in patients at medium and high risk for MetS, compared to controls. These molecules are known to be increased in individuals with high body fat content and obesity. On the other hand, adiponectin, a molecule responsible for control of food intake and body weight, was significantly decreased in patients at medium and high risk for MetS (p < 0.005). Further, levels of dyacylglycerides (DG), tryacylglycerides (TG) and cholestenone were increased, whereas α-Ketoglutarate and malate, important mediators of the tricarboxylic acid (TCA) cycle, were significantly decreased in patients compared to controls. Our studies suggest that high- and medium-risk SGAs are associated with disruption of energy metabolism pathways. These findings may shed light on the molecular underpinnings of antipsychotic-induced MetS and aid in design of novel therapeutic approaches to reduce the side effects associated with these drugs. PMID: 24565079 [PubMed - indexed for MEDLINE]

Sebaceous gland - A major player in skin homeostasis. Exp Dermatol. 2015 Apr 11; Authors: Picardo M, Mastrofrancesco A, Bíró T Abstract Structural and functional interactions among different skin cell types maintain cutaneous homeostasis. In normal skin, dermal fibroblasts and basal layer keratinocytes establish the extracellular matrix which provides signalling molecules that promote keratinocyte growth and differentiation. Keratinocytes, in turn, stratify to form the epithelial layers and provide mechanical integrity and barrier function for the tissue, and also signal to fibroblasts for continued tissue homeostasis. This article is protected by copyright. All rights reserved. PMID: 25865503 [PubMed - as supplied by publisher]

Related Articles Cardiac steatosis potentiates angiotensin II effects in the heart. Am J Physiol Heart Circ Physiol. 2015 Feb 15;308(4):H339-50 Authors: Glenn DJ, Cardema MC, Ni W, Zhang Y, Yeghiazarians Y, Grapov D, Fiehn O, Gardner DG Abstract Lipid accumulation in the heart is associated with obesity and diabetes and may play an important role in the pathogenesis of heart failure. The renin-angiotensin system is also thought to contribute to cardiovascular morbidity in obese and diabetic patients. We hypothesized that the presence of lipid within the myocyte might potentiate the cardiomyopathic effects of ANG II in the cardiac diacylglycerol acyl transferase 1 (DGAT1) transgenic mouse model of myocyte steatosis. Treatment with ANG II resulted in a similar increase in blood pressure in both nontransgenic and DGAT1 transgenic mice. However, ANG II in DGAT1 transgenic mice resulted in a marked increase in interstitial fibrosis and a reduction in systolic function compared with nontransgenic littermates. Lipidomic analysis revealed that >20% of lipid species were significantly altered between nontransgenic and DGAT1 transgenic animals, whereas 3% were responsive to ANG II administration. ROS were also increased by ANG II in DGAT1 transgenic hearts. ANG II treatment resulted in increased expression of transforming growth factor (TGF)-β2 and the type I TGF-β receptor as well as increased phosphorylation of Smad2 in DGAT1 transgenic hearts. Injection of neutralizing antibodies to TGF-β resulted in a reduction in fibrosis in DGAT1 transgenic hearts treated with ANG II. These results suggest that myocyte steatosis amplifies the fibrotic effects of ANG II through mechanisms that involve activation of TGF-β signaling and increased production of ROS. PMID: 25485904 [PubMed - indexed for MEDLINE]

Related Articles Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction. Am J Physiol Heart Circ Physiol. 2015 Feb 15;308(4):H269-80 Authors: Lopez EF, Kabarowski JH, Ingle KA, Kain V, Barnes S, Crossman DK, Lindsey ML, Halade GV Abstract Polyunsaturated fatty acid (PUFA) intake has increased over the last 100 yr, contributing to the current obesogenic environment. Obesity and aging are prominent risk factors for myocardial infarction (MI). How obesity interacts with aging to alter the post-MI response, however, is unclear. We tested the hypothesis that obesity in aging mice would impair the resolution of post-MI inflammation. PUFA diet (PUFA aging group) feeding to 12-mo-old C57BL/6J mice for 5 mo showed higher fat mass compared with standard lab chow (LC)-fed young (LC young group; 3-5 mo old) or aging alone control mice (LC aging group). LC young, LC aging, and PUFA aging mice were subjected to coronary artery ligation to induce MI. Despite similar infarct areas post-MI, plasma proteomic profiling revealed higher VCAM-1 in the PUFA aging group compared with LC young and LC aging groups, leading to increased neutrophil infiltration in the PUFA aging group (P<0.05). Macrophage inflammatory protein-1γ and CD40 were also increased at day 1, and myeloperoxidase remained elevated at day 5, an observation consistent with delayed wound healing in the PUFA aging group. Lipidomic analysis showed higher levels of arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid at day 1 post-MI in the PUFA aging group compared with the LC aging group (all P<0.05), thereby mediating neutrophil extravasation in the PUFA aging group. The inflammation-resolving enzymes 5-lipoxygenase, cyclooxygenase-2, and heme oxyegnase-1 were altered to delay wound healing post-MI in the PUFA aging group compared with LC young and LC aging groups. PUFA aging magnifies the post-MI inflammatory response and impairs the healing response by stimulating prolonged neutrophil trafficking and proinflammatory lipid mediators. PMID: 25485899 [PubMed - indexed for MEDLINE]

Related Articles Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring. J Endocrinol. 2015 Feb;224(2):171-82 Authors: Dellschaft NS, Alexandre-Gouabau MC, Gardner DS, Antignac JP, Keisler DH, Budge H, Symonds ME, Sebert SP Abstract Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth. To promote an adverse phenotype in young adulthood, after weaning, offspring were reared under a low-activity obesogenic environment with the exception of a subgroup of IUGR offspring, reared as twins, maintained in a standard activity environment. We assessed glucose tolerance together with leptin and cortisol responses to feeding in young adulthood when the hypothalamus was sampled for assessment of genes regulating appetite control, energy and endocrine sensitivity. Caloric restriction reduced maternal plasma glucose, raised non-esterified fatty acids, and changed the metabolomic profile, but had no effect on insulin, leptin, or cortisol. IUGR offspring whose postnatal growth was enhanced and were obese showed insulin and leptin resistance plus raised cortisol. This was accompanied by increased hypothalamic gene expression for energy and glucocorticoid sensitivity. These long-term adaptations were reduced but not normalized in IUGR offspring whose postnatal growth was not accelerated and remained lean in a standard post-weaning environment. IUGR results in an adverse metabolic phenotype, especially when postnatal growth is enhanced and offspring progress to juvenile-onset obesity. PMID: 25416820 [PubMed - indexed for MEDLINE]

Related Articles Airway metabolic anomalies in adolescents with bronchopulmonary dysplasia: new insights from the metabolomic approach. J Pediatr. 2015 Feb;166(2):234-9.e1 Authors: Carraro S, Giordano G, Pirillo P, Maretti M, Reniero F, Cogo PE, Perilongo G, Stocchero M, Baraldi E Abstract OBJECTIVES: To assess a group of adolescents with bronchopulmonary dysplasia (BPD) from a biochemical-metabolic standpoint, applying the metabolomic approach to studying their exhaled breath condensate (EBC). STUDY DESIGN: Twenty adolescents with BPD (mean age 14.8 years) and 15 healthy controls (mean age 15.2 years) were recruited for EBC collection, exhaled nitric oxide measurement, and spirometry. The EBC samples were analyzed using a metabolomic approach based on mass spectrometry. The obtained spectra were analyzed using multivariate statistical analysis tools. RESULTS: A reliable Orthogonal Projections to Latent Structures-Discriminant Analysis model showed a clear discrimination between cases of BPD and healthy controls (R(2) = 0.95 and Q(2) = 0.92). The search for putative biomarkers identified an altered complex lipid profile in the adolescents with BPD. CONCLUSIONS: The metabolomic analysis of EBC distinguishes cases of BPD from healthy individuals, suggesting that the lung of survivors of BPD is characterized by long-term metabolic abnormalities. The search for putative biomarkers indicated a possible role of an altered surfactant composition, which may persist far beyond infancy. PMID: 25294602 [PubMed - indexed for MEDLINE]

Related Articles Plasma free amino acid profiling of esophageal cancer using high-performance liquid chromatography spectroscopy. World J Gastroenterol. 2014 Jul 14;20(26):8653-9 Authors: Ma H, Hasim A, Mamtimin B, Kong B, Zhang HP, Sheyhidin I Abstract AIM: To perform plasma free amino acid (PFAA) profiling of esophageal squamous cell carcinoma (ESCC) patients at different pathological stages and healthy subjects. METHODS: Plasma samples from ESCC patients (n = 51) and healthy control adults (n = 60) were analyzed by high-performance liquid chromatography (HPLC). The ESCC patients included moderate/poorly-differentiation (n = 24), lymph node metastasis (n = 17) and clinical stage > Ib2 (n = 36). Partial least squares discriminant analysis was performed to demonstrate that the PFAA metabolic patterns enabled discrimination between ESCC patients and controls, and the Student t test was applied to assess significant differences in PFAA concentrations between the two groups. RESULTS: There were significant differences in the PFAA profiles between controls and ESCC patients. Compared with healthy controls, the levels of Asp, Glu, Gly, His, Thr, Tau, Ala, Met, Ile, Leu, and Phe were decreased in ESCC patients, but Cys was increased. There exists a strong correlation between PFAA profiles and clinicopathological characteristics in ESCC patients. The levels of many PFAAs (i.e., Glu, Asp, Ser, Gly, Tau, Ala, Tyr, Val, Ile, and Leu) were related to pathological grading, lymph node metastasis, and ESCC clinical stage. Very good discrimination between ESCC patients and control subjects was achieved by multivariate modeling of plasma profiles. CONCLUSION: HPLC-based plasma profiling analysis was shown to be an effective approach to differentiate between ESCC patients and controls. PFAA profiles may have potential value for screening or diagnosing ESCC. PMID: 25024622 [PubMed - indexed for MEDLINE]

Related Articles Solving the jigsaw puzzle of wound-healing potato cultivars: metabolite profiling and antioxidant activity of polar extracts. J Agric Food Chem. 2014 Aug 6;62(31):7963-75 Authors: Dastmalchi K, Cai Q, Zhou K, Huang W, Serra O, Stark RE Abstract Potato (Solanum tuberosum L.) is a worldwide food staple, but substantial waste accompanies the cultivation of this crop due to wounding of the outer skin and subsequent unfavorable healing conditions. Motivated by both economic and nutritional considerations, this metabolite profiling study aims to improve understanding of closing layer and wound periderm formation and guide the development of new methods to ensure faster and more complete healing after skin breakage. The polar metabolites of wound-healing tissues from four potato cultivars with differing patterns of tuber skin russeting (Norkotah Russet, Atlantic, Chipeta, and Yukon Gold) were analyzed at three and seven days after wounding, during suberized closing layer formation and nascent wound periderm development, respectively. The polar extracts were assessed using LC-MS and NMR spectroscopic methods, including multivariate analysis and tentative identification of 22 of the 24 biomarkers that discriminate among the cultivars at a given wound-healing time point or between developmental stages. Differences among the metabolites that could be identified from NMR- and MS-derived biomarkers highlight the strengths and limitations of each method, also demonstrating the complementarity of these approaches in terms of assembling a complete molecular picture of the tissue extracts. Both methods revealed that differences among the cultivar metabolite profiles diminish as healing proceeds during the period following wounding. The biomarkers included polyphenolic amines, flavonoid glycosides, phenolic acids and glycoalkaloids. Because wound healing is associated with oxidative stress, the free radical scavenging activities of the extracts from different cultivars were measured at each wounding time point, revealing significantly higher scavenging activity of the Yukon Gold periderm especially after 7 days of wounding. PMID: 24998264 [PubMed - indexed for MEDLINE]

Related Articles Neurochemical evaluation of brain function with 1H magnetic resonance spectroscopy in patients with fragile X syndrome. Am J Med Genet A. 2014 Jan;164A(1):99-105 Authors: Utine GE, Akpınar B, Arslan U, Kiper PÖ, Volkan-Salancı B, Alanay Y, Aktaş D, Haliloğlu G, Oğuz KK, Boduroğlu K, Alikaşifoğlu M Abstract Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and (1)H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age- and sex-matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N-acetyl aspartate/Creatine (NAA/Cr), and Choline/N-acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t-test and Mann-Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS. PMID: 24259304 [PubMed - indexed for MEDLINE]

Monitoring tryptophan metabolism after exposure to hexaconazole and the enantioselective metabolism of hexaconazole in rat hepatocytes in vitro. J Hazard Mater. 2015 Apr 3;295:9-16 Authors: Wang Y, Zhu W, Qiu J, Wang X, Zhang P, Yan J, Zhou Z Abstract In the present study, the enantioselective metabolism, cytotoxicity of hexaconazole and its influence on tryptophan metabolism in rat hepatocytes in vitro were investigated. Following the exposure of primary rat hepatocytes to rac-hexaconazole, the concentrations of its enantiomers in the media were determined by chiral high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The half-lives (t1/2) of (+)-hexaconazole and (-)-hexaconazole were 5.17h and 19.80h, respectively, indicating that the metabolic process was enantioselective with (-)-hexaconazole enrichment. Using the MTT method, the EC50 values of rac-hexaconazole, (+)-hexaconazole and (-)-hexaconazole after 12h of exposure were determined to be 71.62, 62.71 and 67.94μM, respectively. Tryptophan metabolism was monitored using metabolomics profiling techniques. Hexaconazole and its enantiomers caused the down-regulation of tryptophan levels and the up-regulation of kynurenine (KYN) levels, suggesting a role for hexaconazole in the activation of the KYN pathway and providing information for the mechanism of its toxicity. PMID: 25863579 [PubMed - as supplied by publisher]

Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic H1N1 Influenza Virus Infection in Mice. J Immunol. 2015 Apr 10; Authors: Milner JJ, Rebeles J, Dhungana S, Stewart DA, Sumner SC, Meyers MH, Mancuso P, Beck MA Abstract Obese individuals are at greater risk for hospitalization and death from infection with the 2009 pandemic H1N1 influenza virus (pH1N1). In this study, diet-induced and genetic-induced obese mouse models were used to uncover potential mechanisms by which obesity increases pH1N1 severity. High-fat diet-induced and genetic-induced obese mice exhibited greater pH1N1 mortality, lung inflammatory responses, and excess lung damage despite similar levels of viral burden compared with lean control mice. Furthermore, obese mice had fewer bronchoalveolar macrophages and regulatory T cells during infection. Obesity is inherently a metabolic disease, and metabolic profiling has found widespread usage in metabolic and infectious disease models for identifying biomarkers and enhancing understanding of complex mechanisms of disease. To further characterize the consequences of obesity on pH1N1 infection responses, we performed global liquid chromatography-mass spectrometry metabolic profiling of lung tissue and urine. A number of metabolites were perturbed by obesity both prior to and during infection. Uncovered metabolic signatures were used to identify changes in metabolic pathways that were differentially altered in the lungs of obese mice such as fatty acid, phospholipid, and nucleotide metabolism. Taken together, obesity induces distinct alterations in the lung metabolome, perhaps contributing to aberrant pH1N1 immune responses. PMID: 25862817 [PubMed - as supplied by publisher]

Human Urinary Composition Controls Siderocalin's Antibacterial Activity. J Biol Chem. 2015 Apr 10; Authors: Shields-Cutler RR, Crowley JR, Hung CS, Stapleton AE, Aldrich CC, Marschall J, Henderson JP Abstract During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well-known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine. PMID: 25861985 [PubMed - as supplied by publisher]

Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS coupled with a pattern recognition approach. Anal Bioanal Chem. 2015 Apr 10; Authors: Dong F, Deng D, Chen H, Cheng W, Li Q, Luo R, Ding S Abstract Metabolomics has become an important tool in distinguishing changes in metabolic pathways and the diagnosis of human disease. Polycystic ovary syndrome (PCOS) is a relatively complicated, heterogeneous endocrine disorder. The etiology and pathogenesis of PCOS remain uncertain. In this study, based on the platform of ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the method of pattern recognition, a comprehensive metabolomics approach has been applied to explore the changes in metabolic profiling between PCOS patients (n = 20) and controls (n = 15) as well as insulin-resistance (IR) PCOS patients (n = 11) and non-IR PCOS subjects (n = 9) in serum. In total, 36 metabolites were found significantly different between PCOS and controls, and 9 metabolites were discovered significantly different between IR and non-IR PCOS patients. Significant increases in the levels of saturated and unsaturated fatty acids (myristic acid, linoleic acid, 9-/13-HODE, etc.), fatty amides (palmitic amide, oleamide), dehydroepiandrosterone sulfate, L-glutamic acid, azelaic acid, L-glyceric acid, pyroglutamic acid, and decreases in the levels of lysophosphatidylethanolamine, lysophosphatidylcholine, uridine, and L-carnitine were found in PCOS patients compared with controls. In IR PCOS patients, linoleic acid, myristic acid, palmitoleic acid, and vaccenic acid also increased significantly compared with non-IR PCOS patients. All these changed metabolites showed abnormalities of steroid hormone biosynthesis, amino acids and nucleosides metabolism, glutathione metabolism, and lipids and carbohydrates metabolism in PCOS patients. The subgroup IR PCOS patients exhibited greater metabolic deviations than non-IR PCOS patients. These findings may help yield promising insights into the pathogenesis and advance the diagnosis and prevention of PCOS. PMID: 25860656 [PubMed - as supplied by publisher]

Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry. Metabolites. 2015;5(2):192-210 Authors: Miyamoto S, Taylor SL, Barupal DK, Taguchi A, Wohlgemuth G, Wikoff WR, Yoneda KY, Gandara DR, Hanash SM, Kim K, Fiehn O Abstract Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection. PMID: 25859693 [PubMed - as supplied by publisher]

A molecular structure matching approach to efficient identification of endogenous mammalian biochemical structures. BMC Bioinformatics. 2015 Mar 18;16(Suppl 5):S11 Authors: Hamdalla MA, Ammar RA, Rajasekaran S Abstract Metabolomics is the study of small molecules, called metabolites, of a cell, tissue or organism. It is of particular interest as endogenous metabolites represent the phenotype resulting from gene expression. A major challenge in metabolomics research is the structural identification of unknown biochemical compounds in complex biofluids. In this paper we present an efficient cheminformatics tool, BioSMXpress that uses known endogenous mammalian biochemicals and graph matching methods to identify endogenous mammalian biochemical structures in chemical structure space. The results of a comprehensive set of empirical experiments suggest that BioSMXpress identifies endogenous mammalian biochemical structures with high accuracy. BioSMXpress is 8 times faster than our previous work BioSM without compromising the accuracy of the predictions made. BioSMXpress is freely available at http://engr.uconn.edu/~rajasek/BioSMXpress.zip. PMID: 25859612 [PubMed - as supplied by publisher]

Species-specific Standardisation of Licorice by Metabolomic Profiling of Flavanones and Chalcones. Phytochem Anal. 2014 Jul-Aug;25(4):378-88 Authors: Simmler C, Jones T, Anderson JR, Nikolić DC, van Breemen RB, Soejarto DD, Chen SN, Pauli GF Abstract INTRODUCTION: Major phenolics from licorice roots (Glycyrrhiza sp.) are glycosides of the flavanone liquiritigenin (F) and its 2′-hydroxychalcone isomer, isoliquiritigenin (C). As the F and C contents fluctuate between batches of licorice, both quality control and standardisation of its preparations become complex tasks. OBJECTIVE: To characterise the F and C metabolome in extracts from Glycyrrhiza glabra L. and Glycyrrhiza uralensis Fisch. ex DC. by addressing their composition in major F–C pairs and defining the total F:C proportion. MATERIAL AND METHODS: Three types of extracts from DNA-authenticated samples were analysed by a validated UHPLC/UV method to quantify major F and C glycosides. Each extract was characterised by the identity of major F–C pairs and the proportion of Fs among all quantified Fs:Cs. RESULTS: The F and C compositions and proportions were found to be constant for all extracts from a Glycyrrhiza species. All G. uralensis extracts contained up to 2.5 more Fs than G. glabra extracts. Major F–C pairs were B-ring glycosidated in G. uralensis, and A-/B-ring apiosyl-glucosidated in the G. glabra extracts. The F:C proportion was found to be linked to the glycosidation site: the more B-ring F-C glycosides were present, the higher was the final F:C proportion in the extract. These results enable the chemical differentiation of extracts from G. uralensis and G. glabra, which are characterised by total F:C proportions of 8.37:1.63 and 7.18:2.82, respectively. CONCLUSION: Extracts from G. glabra and G. uralensis can be differentiated by their respective F and C compositions and proportions, which are both useful for further standardisation of licorice botanicals. PMID: 25859589 [PubMed - in process]

Non-targeted metabolomics and lipidomics LC-MS data from maternal plasma of 180 healthy pregnant women. Gigascience. 2015;4:16 Authors: Luan H, Meng N, Liu P, Fu J, Chen X, Rao W, Jiang H, Xu X, Cai Z, Wang J Abstract BACKGROUND: Metabolomics has the potential to be a powerful and sensitive approach for investigating the low molecular weight metabolite profiles present in maternal fluids and their role in pregnancy. FINDINGS: In this Data Note, LC-MS metabolome, lipidome and carnitine profiling data were collected from 180 healthy pregnant women, representing six time points spanning all three trimesters, and providing sufficient coverage to model the progression of normal pregnancy. CONCLUSIONS: As a relatively large scale, real-world dataset with robust numbers of quality control samples, the data are expected to prove useful for algorithm optimization and development, with the potential to augment studies into abnormal pregnancy. All data and ISA-TAB format enriched metadata are available for download in the MetaboLights and GigaScience databases. PMID: 25859341 [PubMed]

Advances in biomarkers of major depressive disorder. Adv Clin Chem. 2015;68:177-204 Authors: Huang TL, Lin CC Abstract Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction. PMID: 25858873 [PubMed - in process]

Lipidomics: new insight into kidney disease. Adv Clin Chem. 2015;68:153-75 Authors: Zhao YY, Vaziri ND, Lin RC Abstract Due to the incidence of type-2 diabetes and hypertension, chronic kidney disease (CKD) has emerged as a major public health problem worldwide. CKD results in premature death from accelerated cardiovascular disease and various other complications. Early detection, careful monitoring of renal function, and response to therapeutic intervention are critical for prevention of CKD progression and its complications. Unfortunately, traditional biomarkers of renal function are insufficiently sensitive or specific to detect early stages of disease when therapeutic intervention is most effective. Therefore, more sensitive biomarkers of kidney disease are needed for early diagnosis, monitoring, and effective treatment. CKD results in profound changes in lipid and lipoprotein metabolism that, in turn, contribute to progression of CKD and its cardiovascular complications. Lipids and lipid-derived metabolites play diverse and critically important roles in the structure and function of cells, tissues, and biofluids. Lipidomics is a branch of metabolomics, which encompasses the global study of lipids and their biologic function in health and disease including identification of biomarkers for diagnosis, prognosis, prevention, and therapeutic response for various diseases. This review summarizes recent developments in lipidomics and its application to various kidney diseases including chronic glomerulonephritis, IgA nephropathy, chronic renal failure, renal cell carcinoma, diabetic nephropathy, and acute renal failure in clinical and experimental research. Analytical technologies, data analysis, as well as currently known metabolic biomarkers of kidney diseases are addressed. Future perspectives and potential limitations of lipidomics are discussed. PMID: 25858872 [PubMed - in process]