PubMed

Related Articles An integrated analysis for determining the geographical origin of medicinal herbs using ICP-AES/ICP-MS and (1)H NMR analysis. Food Chem. 2014 Oct 15;161:168-75 Authors: Kwon YK, Bong YS, Lee KS, Hwang GS Abstract ICP-MS and (1)H NMR are commonly used to determine the geographical origin of food and crops. In this study, data from multielemental analysis performed by ICP-AES/ICP-MS and metabolomic data obtained from (1)H NMR were integrated to improve the reliability of determining the geographical origin of medicinal herbs. Astragalus membranaceus and Paeonia albiflora with different origins in Korea and China were analysed by (1)H NMR and ICP-AES/ICP-MS, and an integrated multivariate analysis was performed to characterise the differences between their origins. Four classification methods were applied: linear discriminant analysis (LDA), k-nearest neighbour classification (KNN), support vector machines (SVM), and partial least squares-discriminant analysis (PLS-DA). Results were compared using leave-one-out cross-validation and external validation. The integration of multielemental and metabolomic data was more suitable for determining geographical origin than the use of each individual data set alone. The integration of the two analytical techniques allowed diverse environmental factors such as climate and geology, to be considered. Our study suggests that an appropriate integration of different types of analytical data is useful for determining the geographical origin of food and crops with a high degree of reliability. PMID: 24837936 [PubMed - indexed for MEDLINE]

Related Articles A powerful methodological approach combining headspace solid phase microextraction, mass spectrometry and multivariate analysis for profiling the volatile metabolomic pattern of beer starting raw materials. Food Chem. 2014 Oct 1;160:266-80 Authors: Gonçalves JL, Figueira JA, Rodrigues FP, Ornelas LP, Branco RN, Silva CL, Câmara JS Abstract The volatile metabolomic patterns from different raw materials commonly used in beer production, namely barley, corn and hop-derived products - such as hop pellets, hop essential oil from Saaz variety and tetra-hydro isomerized hop extract (tetra hop), were established using a suitable analytical procedure based on dynamic headspace solid-phase microextraction (HS-SPME) followed by thermal desorption gas chromatography-quadrupole mass spectrometry detection (GC-qMS). Some SPME extraction parameters were optimized. The best results, in terms of maximum signal recorded and number of isolated metabolites, were obtained with a 50/30 μm DVB/CAR/PDMS coating fiber at 40 °C for 30 min. A set of 152 volatile metabolites comprising ketones (27), sesquiterpenes (26), monoterpenes (19), aliphatic esters (19), higher alcohols (15), aldehydes (11), furan compounds (11), aliphatic fatty acids (9), aliphatic hydrocarbons (8), sulphur compounds (5) and nitrogen compounds (2) were positively identified. Each raw material showed a specific volatile metabolomic profile. Monoterpenes in hop essential oil and corn, sesquiterpenes in hop pellets, ketones in tetra hop and aldehydes and sulphur compounds in barley were the predominant chemical families in the targeted beer raw materials. β-Myrcene was the most dominant volatile metabolite in hop essential oil, hop pellets and corn samples while, in barley, the predominant volatile metabolites were dimethyl sulphide and 3-methylbutanal and, in tetra hop, 6-methyl-2-pentanone and 4-methyl-2-pentanone. Principal component analysis (PCA) showed natural sample grouping among beer raw materials. PMID: 24799238 [PubMed - indexed for MEDLINE]

Related Articles Whole genome data for omics-based research on the self-fertilizing fish Kryptolebias marmoratus. Mar Pollut Bull. 2014 Aug 30;85(2):532-41 Authors: Rhee JS, Lee JS Abstract Genome resources have advantages for understanding diverse areas such as biological patterns and functioning of organisms. Omics platforms are useful approaches for the study of organs and organisms. These approaches can be powerful screening tools for whole genome, proteome, and metabolome profiling, and can be used to understand molecular changes in response to internal and external stimuli. This methodology has been applied successfully in freshwater model fish such as the zebrafish Danio rerio and the Japanese medaka Oryzias latipes in research areas such as basic physiology, developmental biology, genetics, and environmental biology. However, information is still scarce about model fish that inhabit brackish water or seawater. To develop the self-fertilizing killifish Kryptolebias marmoratus as a potential model species with unique characteristics and research merits, we obtained genomic information about K. marmoratus. We address ways to use these data for genome-based molecular mechanistic studies. We review the current state of genome information on K. marmoratus to initiate omics approaches. We evaluate the potential applications of integrated omics platforms for future studies in environmental science, developmental biology, and biomedical research. We conclude that information about the K. marmoratus genome will provide a better understanding of the molecular functions of genes, proteins, and metabolites that are involved in the biological functions of this species. Omics platforms, particularly combined technologies that make effective use of bioinformatics, will provide powerful tools for hypothesis-driven investigations and discovery-driven discussions on diverse aspects of this species and on fish and vertebrates in general. PMID: 24759509 [PubMed - indexed for MEDLINE]

Related Articles Molecular profiling and the reclassification of cancer: divide and conquer. Am Soc Clin Oncol Educ Book. 2013;:127-34 Authors: Munoz J, Swanton C, Kurzrock R Abstract Cancer is one of the leading causes of mortality in the world. Choosing the best treatment is dependent on making the right diagnosis. The diagnostic process has been based on light microscopy and the identification of the organ of tumor origin. Yet we now know that cancer is driven by molecular processes, and that these do not necessarily segregate by organ of origin. Fortunately, revolutionary changes in technology have enabled rapid genomic profiling. It is now apparent that neoplasms classified uniformly (e.g., non-small cell lung cancer) are actually comprised of up to 100 different molecular entities. For instance, tumors bearing ALK alterations make up about 4% of non-small cell lung cancers, and tumors bearing epidermal growth factor receptor (EGFR) mutations, approximately 5% to 10%. Importantly, matching patients to therapies targeted against their driver molecular aberrations has resulted in remarkable response rates. There is now a wealth of evidence supporting a divide-and-conquer strategy. Herein, we provide a concise primer on the current state-of-the-art of molecular profiling in the cancer clinic. PMID: 23714478 [PubMed - indexed for MEDLINE]

Related Articles Characterisation of the cell-free DNA released by cultured cancer cells. Biochim Biophys Acta. 2015 Oct 31; Authors: Bronkhorst AJ, Wentzel JF, Aucamp J, van Dyk E, du Plessis L, Pretorius PJ Abstract The most prominent factor that delays the translation of cell-free DNA (cfDNA) analyses to clinical practice is the lack of knowledge regarding its origin and composition. The elucidation of the former is complicated by the seemingly random fluctuation of quantitative and qualitative characteristics of cfDNA in the blood of healthy and diseased individuals. Besides methodological discrepancies, this could be ascribed to a web of cellular responses to various environmental cues and stressors. Since all cells release cfDNA, it follows that the cfDNA in the blood of cancer patients is not only representative of tumour derived DNA, but also of DNA released by healthy cells under different conditions. Additionally, cfDNA released by malignant cells is not necessarily just aberrant, but likely includes non-mutated chromosomal DNA fragments. This may cause false positive/negative results. Although many have acknowledged that this is a major problem, few have addressed it. We propose that many of the current stumbling blocks encountered in in vivo cfDNA studies can be partially circumvented by in vitro models. Accordingly, the purpose of this work was to evaluate the release of cfDNA from cultured cells and to gauge its potential use for elucidating the nature of cfDNA. Results suggest that the occurrence of cfDNA is not a consequence of apoptosis or necrosis, but primarily a result of actively secreted DNA, perhaps in association with a protein complex. This study demonstrates the potential of in vitro cell culture models to obtain useful information about the phenomenon of cfDNA. PMID: 26529550 [PubMed - as supplied by publisher]

Related Articles In vitro nematicidal activity of aryl hydrazones and comparative GC-MS metabolomics analysis. J Agric Food Chem. 2015 Nov 3; Authors: Eloh K, Demurtas M, Deplano A, Ngoutane Mfopa A, Murgia A, Maxia A, Onnis V, Caboni P Abstract A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-knot nematode Meloidogyne incognita. The phenylhydrazones of thiophene-2-carboxyaldehyde 5, 3-methyl-2-thiophenecarboxyaldehyde 6 and salicylaldehyde 2, were the most potent with EC50/48h values of 16.6 ± 2.2, 23.2 ± 2.7, and 24.3 ± 1.4 mg/L, respectively. A GC-MS metabolomics analysis, after in vitro nematode treatment with hydrazone 6 at 100 mg/L for 12 h, revealed elevated levels of fatty acids such as lauric acid, stearic acid, 2-octenoic acid and palmitic acid. While control samples showed highest levels of monoacylglycerols such us monostearin and 2-monostearin. Surprisingly, after 2h treatment with hydrazone 6, nematodes excreted three times the levels of ammonia eliminated in the same conditions by controls. Thus, phenylhydrazones may represent a good scaffold in the discovery and synthesis of new nematicidal compounds while a metabolomics approach may be helpful in understanding their mechanisms of toxicity and mode of action. PMID: 26528945 [PubMed - as supplied by publisher]

Related Articles Rumen microbial communities influence metabolic phenotypes in lambs. Front Microbiol. 2015;6:1060 Authors: Morgavi DP, Rathahao-Paris E, Popova M, Boccard J, Nielsen KF, Boudra H Abstract The rumen microbiota is an essential part of ruminants shaping their nutrition and health. Despite its importance, it is not fully understood how various groups of rumen microbes affect host-microbe relationships and functions. The aim of the study was to simultaneously explore the rumen microbiota and the metabolic phenotype of lambs for identifying host-microbe associations and potential biomarkers of digestive functions. Twin lambs, separated in two groups after birth were exposed to practices (isolation and gavage with rumen fluid with protozoa or protozoa-depleted) that differentially restricted the acquisition of microbes. Rumen microbiota, fermentation parameters, digestibility and growth were monitored for up to 31 weeks of age. Microbiota assembled in isolation from other ruminants lacked protozoa and had low bacterial and archaeal diversity whereas digestibility was not affected. Exposure to adult sheep microbiota increased bacterial and archaeal diversity independently of protozoa presence. For archaea, Methanomassiliicoccales displaced Methanosphaera. Notwithstanding, protozoa induced differences in functional traits such as digestibility and significantly shaped bacterial community structure, notably Ruminococcaceae and Lachnospiraceae lower up to 6 folds, Prevotellaceae lower by ~40%, and Clostridiaceae and Veillonellaceae higher up to 10 folds compared to microbiota without protozoa. An orthogonal partial least squares-discriminant analysis of urinary metabolome matched differences in microbiota structure. Discriminant metabolites were mainly involved in amino acids and protein metabolic pathways while a negative interaction was observed between methylotrophic methanogens Methanomassiliicoccales and trimethylamine N-oxide. These results stress the influence of gut microbes on animal phenotype and show the potential of metabolomics for monitoring rumen microbial functions. PMID: 26528248 [PubMed]

Related Articles Phenotypes associated with the essential diadenylate cyclase CdaA and its potential regulator CdaR in the human pathogen Listeria monocytogenes. J Bacteriol. 2015 Nov 2; Authors: Rismondo J, Gibhardt J, Rosenberg J, Kaever V, Halbedel S, Commichau FM Abstract Cyclic diadenylate monophosphate (c-di-AMP) is a second messenger utilized by diverse bacteria. In many species, including the Gram-positive human pathogen Listeria monocytogenes, c-di-AMP is essential for growth. Here we show that the single diadenylate cyclase of L. monocytogenes, CdaA, is an integral membrane protein that interacts with its potential regulatory protein, CdaR, via the transmembrane protein domain. The presence of the CdaR protein is not required for membrane localization and abundance of CdaA. We have also found that CdaR negatively influences CdaA activity in L. monocytogenes and that the role of CdaR is most evident at high growth temperature. Interestingly, a cdaR mutant strain is less susceptible to lysozyme. Moreover, CdaA contributes to cell division and cells depleted for CdaA are prone to lysis. The observation that the growth defect of a CdaA depletion strain can be partially restored by increasing osmolarity of the growth medium suggests that c-di-AMP is important for maintaining the integrity of the protective cell envelope. Overall, this work provides new insights into the relationship between CdaA and CdaR. IMPORTANCE: Cyclic diadenylate monophosphate (c-di-AMP) is a recently identified second messenger that is utilized by the Gram-positive human pathogen Listeria monocytogenes. Here we show that the single diadenylate cyclase of L. monocytogenes, CdaA, is an integral membrane protein that interacts with CdaR, its potential regulatory protein. We show that CdaR is not required for membrane localization or abundance of the diadenylate cyclase, but modulates its activity. Moreover, CdaA seems to contribute to cell division. Overall, this work provides new insights into the relationship between CdaA and CdaR and their involvement in cell growth. PMID: 26527648 [PubMed - as supplied by publisher]

Related Articles Metabolomics Identifies Biomarker Pattern for Early Diagnosis of Hepatocellular Carcinoma: from Diethylnitrosamine Treated Rats to Patients. Sci Rep. 2015;5:16101 Authors: Zeng J, Huang X, Zhou L, Tan Y, Hu C, Wang X, Niu J, Wang H, Lin X, Yin P Abstract Early diagnosis of hepatocellular carcinoma (HCC) remains challenging to date. Characteristic metabolic deregulations of HCC may enable novel biomarkers discovery for early diagnosis. A capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics approach was performed to discover and validate potential biomarkers for HCC from the diethylnitrosamine-induced rat hepatocarcinogenesis model to human subjects. Time series sera from the animal model were evaluated using multivariate and univariate analyses to reveal dynamic metabolic changes. Two independent human cohorts (populations I and II) containing 122 human serum specimens were enrolled for validations. A novel biomarker pattern of ratio creatine/betaine which reflects the balance of methylation was identified. This biomarker pattern achieved effective classification of pre-HCC and HCC stages in animal model. It was still effective in the diagnosis of HCC from high-risk patients with cirrhotic nodules, achieving AUC values of 0.865 and 0.905 for two validation cohorts, respectively. The diagnosis of small HCC from cirrhosis with an AUC of 0.928 highlighted the potential for early diagnosis. This ratio biomarker can also improve the diagnostic performance of α-fetoprotein (AFP). This study demonstrates the efficacy of present strategy for biomarker discovery, and the potential of metabolomics approach to provide novel insights for disease study. PMID: 26526930 [PubMed - in process]

Related Articles Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Anal Chim Acta. 2015 Oct 22;898:85-92 Authors: Chen Y, Gao D, Liu H, Lin S, Jiang Y Abstract Currently, there has been a growing need for developing in vitro models to better reflect organism response to chemotherapy at tissue level. For this reason, a microfluidic platform was developed for mimicking physiological microenvironment of solid tumor with multicellular tumor spheroids (MTS) for anticancer drug screening. Importantly, the power of this system over traditional systems is that it is simple to operate and high integration in a more physiologically relevant context. As a proof of concept, long-term MTS cultures with uniform structure were realized on the microfluidic based platform. The response of doxorubicin and paclitaxel on different types of spheroids were simultaneously performed by in situ Live/Dead fluorescence stain to provide spatial distribution of dead cells as well as cytotoxicity information. In addition, the established platform combined with microplate reader was capable to determine the cytotoxicity of different sized MTS, showing a more powerful tool than cell staining examination at the end-point of assay. The HCT116 spheroids were then lysed on chip followed by signaling transduction pathway analysis. To our knowledge, the on chip drug screening study is the first to address the drug susceptibility testing and the offline detailed drug signaling pathway analysis combination on one system. Thus, this novel microfluidic platform provides a useful tool for drug screening with tumor spheroids, which is crucial for drug discovery and development. PMID: 26526913 [PubMed - in process]

Related Articles A novel approach for LC-MS/MS-based chiral metabolomics fingerprinting and chiral metabolomics extraction using a pair of enantiomers of chiral derivatization reagents. Anal Chim Acta. 2015 Oct 22;898:73-84 Authors: Takayama T, Mochizuki T, Todoroki K, Min JZ, Mizuno H, Inoue K, Akatsu H, Noge I, Toyo'oka T Abstract Chiral metabolites are found in a wide variety of living organisms and some of them are understood to be physiologically active compounds and biomarkers. However, the overall analysis of chiral metabolomics is quite difficult due to the high number of metabolites, the significant diversity in their physicochemical properties, and concentration range from metabolite-to-metabolite. To solve this difficulty, we developed a novel approach for chiral metabolomics fingerprinting and chiral metabolomics extraction, which is based on the labeling of a pair of enantiomers of chiral derivatization reagents (i.e., DMT-(S,R)-Pro-OSu and DMT-3(S,R)-Apy) and precursor ion scan chromatography of the derivatives. The multivariate statistics is also required for this strategy. The proposed procedures were evaluated by the detection of a diagnostic marker (i.e., d-lactic acid) using the saliva of diabetic patients. This method was used for the determination of biomarker candidates of chiral amines and carboxyls in Alzheimer's disease (AD) brain homogenates. As the results, l-phenylalanine (L-Phe) and l-lactic acid (L-LA) were identified as the decreased and increased biomarker candidates in the AD brain, respectively. Therefore, the proposed approach seems to be helpful for the determination of non-target chiral metabolomics possessing amines and carboxyls. PMID: 26526912 [PubMed - in process]

Related Articles Quantification of (1)H NMR Spectra from Human Plasma. Metabolomics. 2015 Dec;11(6):1702-1707 Authors: de Graaf RA, Prinsen H, Giannini C, Caprio S, Herzog RI Abstract Human plasma is a biofluid that is high in information content, making it an excellent candidate for metabolomic studies. (1)H NMR has been a popular technique to detect several dozen metabolites in blood plasma. In order for (1)H NMR to become an automated, high-throughput method, challenges related to (1) the large signal from lipoproteins and (2) spectral overlap between different metabolites have to be addressed. Here diffusion-weighted (1)H NMR is used to separate lipoprotein and metabolite signals based on their large difference in translational diffusion. The metabolite (1)H NMR spectrum is then quantified through spectral fitting utilizing full prior knowledge on the metabolite spectral signatures. Extension of the scan time by 3 minutes or 15% per sample allowed the acquisition of a (1)H NMR spectrum with high diffusion weighting. The metabolite (1)H NMR spectra could reliably be modeled with 28 metabolites. Excellent correlation was found between results obtained with diffusion NMR and ultrafiltration. The combination of minimal sample preparation together with minimal user interaction during processing and quantification provides a metabolomics technique for automated, quantitative (1)H NMR of human plasma. PMID: 26526515 [PubMed - as supplied by publisher]

Related Articles Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis. Acta Pharmacol Sin. 2015 Nov;36(11):1356-66 Authors: Chang C, Guo ZG, He B, Yao WZ Abstract AIM: To character the specific metabolomics profiles in the sera of Chinese patients with mild persistent asthma and to explore potential metabolic biomarkers. METHODS: Seventeen Chinese patients with mild persistent asthma and age- and sex-matched healthy controls were enrolled. Serum samples were collected, and serum metabolites were analyzed using GC-MS coupled with a series of multivariate statistical analyses. RESULTS: Clear intergroup separations existed between the asthmatic patients and control subjects. A list of differential metabolites and several top altered metabolic pathways were identified. The levels of succinate (an intermediate in tricarboxylic acid cycle) and inosine were highly upregulated in the asthmatic patients, suggesting a greater effort to breathe during exacerbation and hypoxic stress due to asthma. Other differential metabolites, such as 3,4-dihydroxybenzoic acid and phenylalanine, were also identified. Furthermore, the differential metabolites possessed higher values of area under the ROC curve (AUC), suggesting an excellent clinical ability for the prediction of asthma. CONCLUSION: Metabolic activity is significantly altered in the sera of Chinese patients with mild persistent asthma. The data might be helpful for identifying novel biomarkers and therapeutic targets for asthma. PMID: 26526201 [PubMed - in process]

Related Articles [Metabolome Analysis of Human Serum: Implications for Early Detection of Colorectal Cancer]. Rinsho Byori. 2015 Mar;63(3):328-35 Authors: Yamazaki Y Abstract With the recent development of novel technologies capable of comprehensively detecting and accurately identifying small molecules within biological samples--the field of metabolomics--new information about disease biology is emerging. A comprehensive metabolomics strategy was used to discover novel small molecules which were significantly decreased in the serum of colorectal cancer (CRC) patients relative to normal individuals. The metabolite markers, hydroxylated polyunsaturated ultra long-chain fatty acids (hPULCFAs), were characterized using HPLC-coupled tandem mass spectrometry, and a high-throughput screening (HTS) method compatible with conventional triple-quadrupole mass spectrometers in clinical labs. around the world was developed. The HTS method was used to determine serum levels of the 28 carbon-containing hPULCFA C28H46O4 (named GTA-446) in independent clinical validation studies to investigate the effect of tumor removal after surgery, chemo- or radiation therapy and the correlation with age. We have also obtained results from a two-year prospective trial. Serum samples from a representative cohort of physician-referred colonoscopy subjects (n = 4,923) were collected between July 2008 and August 2010. Ninety-eight new CRC cases were detected in the colonoscopy cohort. Overall sensitivity in this cohort was 85.7%, with 86.5% in the early stage (0-II) and 84.8% in the late-stage (III-IV). This trial represents the first prospective study of this magnitude investigating a metabolic biomarker for CRC. The results indicate that pre-colonoscopy screening using serum GTA-446 levels is a viable approach to detecting early-stage CRC. PMID: 26524856 [PubMed - in process]

Related Articles Accumulation of Glycoconjugates of 3-Methyl-4-hydroxyoctanoic Acid in Fruits, Leaves, and Shoots of Vitis vinifera cv. Monastrell following Foliar Applications of Oak Extract or Oak Lactone. J Agric Food Chem. 2015 May 13;63(18):4533-8 Authors: Pardo-Garcia AI, Wilkinson KL, Culbert JA, Lloyd ND, Alonso GL, Salinas MR Abstract Grapevines are capable of absorbing volatile compounds present in the vineyard during the growing season, and in some cases, volatiles have been found to accumulate in fruits or leaves in glycoconjugate forms, that is, with one or more sugar moieties attached. The presence of oak lactone in wine is usually attributable to oak maturation, but oak lactone has been detected in wines made with fruit from grapevines treated with oak extract or oak lactone. This study investigated the accumulation of glycoconjugates of 3-methyl-4-hydroxyoctanoic acid (i.e., the ring-opened form of oak lactone) in the fruits, leaves, and shoots of Monastrell grapevines following foliar application of either oak extract or oak lactone at approximately 7 days postveraison. Fruits, leaves, and shoots were collected at three different time points, including at maturity. The oak lactone content of fruit was determined by gas chromatography-mass spectrometry, with declining concentrations observed in fruit from grapevines treated with oak lactone with ripening. The concentrations of a β-d-glucopyranoside of 3-methyl-4-hydroxyoctanoic acid in fruits, leaves, and shoots was determined by liquid chromatography-tandem mass spectrometry, with the highest oak lactone glucoside levels observed in leaves of grapevines treated with oak lactone. A glucose-glucose disaccharide was also tentatively identified. These results demonstrate both ring-opening and glycosylation of oak lactone occurred after experimental treatments were imposed. PMID: 25912091 [PubMed - indexed for MEDLINE]

Related Articles Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat Commun. 2014;5:5712 Authors: Müller J, Krijgsman O, Tsoi J, Robert L, Hugo W, Song C, Kong X, Possik PA, Cornelissen-Steijger PD, Foppen MH, Kemper K, Goding CR, McDermott U, Blank C, Haanen J, Graeber TG, Ribas A, Lo RS, Peeper DS Abstract Increased expression of the Microphthalmia-associated transcription factor (MITF) contributes to melanoma progression and resistance to BRAF pathway inhibition. Here we show that the lack of MITF is associated with more severe resistance to a range of inhibitors, while its presence is required for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlate with the expression of several activated receptor tyrosine kinases, most frequently AXL. The MITF-low/AXL-high/drug-resistance phenotype is common among mutant BRAF and NRAS melanoma cell lines. The dichotomous behaviour of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and -low clones in a relapsed patient. Furthermore, drug cocktails containing AXL inhibitor enhance melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas. PMID: 25502142 [PubMed - indexed for MEDLINE]

Related Articles Clinical and non-targeted metabolomic profiling of homozygous carriers of Transcription Factor 7-like 2 variant rs7903146. Sci Rep. 2014;4:5296 Authors: Wagner R, Li J, Kenar E, Kohlbacher O, Machicao F, Häring HU, Fritsche A, Xu G, Lehmann R Abstract An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion. PMID: 24925104 [PubMed - indexed for MEDLINE]

Related Articles Cherry tomatoes metabolic profile determined by ¹H-High Resolution-NMR spectroscopy as influenced by growing season. Food Chem. 2014 Nov 1;162:215-22 Authors: Masetti O, Ciampa A, Nisini L, Valentini M, Sequi P, Dell'Abate MT Abstract The content of the most valuable metabolites present in the lipophilic fraction of Protected Geographical Indication cherry tomatoes produced in Pachino (Italy) was observed for 2 cultivated varieties, i.e. cv. Naomi and cv. Shiren, over a period of 3 years in order to observe variations due to relevant climatic parameters, e.g. solar radiation and average temperature, characterising different seasons. (1)H-NMR spectroscopy was applied and spectral data were processed by means of Principal Component Analysis (PCA). We found that the metabolic profile was different for the two considered cultivated varieties and they were differently affected by climatic conditions. Major metabolites influenced by cropping period were α-tocopherol and the unsaturated lipid fraction in Naomi cherry tomatoes, and chlorophylls and phospholipids in Shiren variety, respectively. These results furnished useful information on seasonal dynamics of such important nutritional metabolites contained in tomatoes, confirming also NMR spectroscopy as powerful tool to define a complete metabolic profiling. PMID: 24874378 [PubMed - indexed for MEDLINE]

Related Articles Impaired metabolic reactivity to oxidative stress in early psychosis patients. Schizophr Bull. 2014 Sep;40(5):973-83 Authors: Fournier M, Ferrari C, Baumann PS, Polari A, Monin A, Bellier-Teichmann T, Wulff J, Pappan KL, Cuenod M, Conus P, Do KQ Abstract Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors. PMID: 24687046 [PubMed - indexed for MEDLINE]

Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry. Clin Chim Acta. 2015 Oct 30; Authors: Takayama T, Tsutsui H, Shimizu I, Toyama T, Yoshimoto N, Endo Y, Inoue K, Todoroki K, Min JZ, Mizuno H, Toyo'oka T Abstract BACKGROUND: Breast cancer is one of the most fearful diseases due to its increasing worldwide prevalence. A number of screening tests has been employed including clinical examinations and mammography. However, another screening method, which is a simple, not embarrassing, and low cost, is highly desired. Based on these findings, we are currently investigating the determination of polyamines including their acetylated structures for the diagnosis of breast cancer patients. We established a diagnostic approach to breast cancer patients based on the ratios of polyamines in saliva by a UPLC-MS/MS analysis. METHODS: Twelve polyamines including their acetylated form were labeled with DBD-F, separated by a reversed-phase chromatography and detected by a Xevo TQ-S tandem mass spectrometer. RESULTS: Eight polyamines (e.g., SPM, CAD, Ac-SPM, N1-Ac-SPD, N8-Ac-SPD) strongly correlated with the cancer patients. A simple 1-order equation was developed for the discrimination of the breast cancer patients and healthy persons (Y=0.5XSPM-3XAc-SPM-0.15XSPD-3.5XN8-Ac-SPD+0.5XN1-Ac-SPD+0.04XCAD). The concordance rate of the breast cancer patients and the healthy persons by the equation was 88% and 76% on the training set, respectively, whereas those on the validation set was both 88%. The score Y in the equation tended to correlate with the cancer stage of the patients and increased with the more serious conditions. The determination of polyamines in the saliva after the cancer patient operations was also performed to identify the concentration change before and after the surgical treatment. The discriminant analysis using 6 polyamines (i.e., N8-Ac-SPD, N1-Ac-SPD, CAD, DAc-SPD, PUT, and Ac-PUT), which were the most influenced molecules derived from the ROC analysis, was performed using the relative percentage. Both the sensitivity and specificity indicated nearly 80% from the ROC analysis result using the ratio of N8-Ac-SPD/(N1-Ac-SPD+N8-Ac-SPD). CONCLUSION: The discrimination equation appears to be useful for the diagnosis of breast cancer patients. Furthermore, the ratio of N8-Ac-SPD/(N1-Ac-SPD+N8-Ac-SPD) may be adopted as an index of the health status after the surgical treatment. PMID: 26523874 [PubMed - as supplied by publisher]