Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Thermal adaptation strategies of the extremophile bacterium Thermus filiformis based on multi-omics analysis.

Sun, 14/05/2017 - 14:48
Related Articles Thermal adaptation strategies of the extremophile bacterium Thermus filiformis based on multi-omics analysis. Extremophiles. 2017 May 12;: Authors: Mandelli F, Couger MB, Paixão DAA, Machado CB, Carnielli CM, Aricetti JA, Polikarpov I, Prade R, Caldana C, Paes Leme AF, Mercadante AZ, Riaño-Pachón DM, Squina FM Abstract Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot spring in New Zealand. The experimental study of the mechanisms of thermal adaptation is important to unveil response strategies of the microorganism to stress. In this study, the main pathways involved on T. filiformis thermoadaptation, as well as, thermozymes with potential biotechnological applications were revealed based on omics approaches. The strategy adopted in this study disclosed that pathways related to the carbohydrate metabolism were affected in response to thermoadaptation. High temperatures triggered oxidative stress, leading to repression of genes involved in glycolysis and the tricarboxylic acid cycle. During heat stress, the glucose metabolism occurred predominantly via the pentose phosphate pathway instead of the glycolysis pathway. Other processes, such as protein degradation, stringent response, and duplication of aminoacyl-tRNA synthetases, were also related to T. filiformis thermoadaptation. The heat-shock response influenced the carotenoid profile of T. filiformis, favoring the synthesis of thermozeaxanthins and thermobiszeaxanthins, which are related to membrane stabilization at high temperatures. Furthermore, antioxidant enzymes correlated with free radical scavenging, including superoxide dismutase, catalase and peroxidase, and metabolites, such as oxaloacetate and α-ketoglutarate, were accumulated at 77 °C. PMID: 28500387 [PubMed - as supplied by publisher]

The association of the lipidomic profile with features of polycystic ovary syndrome.

Sun, 14/05/2017 - 14:48
Related Articles The association of the lipidomic profile with features of polycystic ovary syndrome. J Mol Endocrinol. 2017 May 12;: Authors: Moran L, Mundra P, Teede H, Miekle PJ Abstract Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI>25 kg/m2; n=92 with PCOS, n=64 without PCOS). Outcomes included the association between the plasma lipidomic profile [325 lipid species (24 classes) using liquid chromatography mass spectrometry] and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex-hormone binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes [4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely [trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine]). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions. PMID: 28500248 [PubMed - as supplied by publisher]

Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database.

Sun, 14/05/2017 - 14:48
Related Articles Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database. J Proteomics. 2017 May 09;: Authors: Komatsu S, Wang X, Yin X, Nanjo Y, Ohyanagi H, Sakata K Abstract The Soybean Proteome Database (SPD) stores data on soybean proteins obtained with gel-based and gel-free proteomic techniques. The database was constructed to provide information on proteins for functional analyses. The majority of the data is focused on soybean (Glycine max 'Enrei'). The growth and yield of soybean are strongly affected by environmental stresses such as flooding. The database was originally constructed using data on soybean proteins separated by two-dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic technique. Since 2015, the database has been expanded to incorporate data obtained by label-free mass spectrometry-based quantitative proteomics, which is a gel-free proteomic technique. Here, the portions of the database consisting of gel-free proteomic data are described. The gel-free proteomic database contains 39,212 proteins identified in 63 sample sets, such as temporal and organ-specific samples of soybean plants grown under flooding stress or non-stressed conditions. In addition, data on organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored. Furthermore, the database integrates multiple omics data such as genomics, transcriptomics, metabolomics, and proteomics. The SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. BIOLOGICAL SIGNIFICANCE: The Soybean Proteome Database stores data obtained from both gel-based and gel-free proteomic techniques. The gel-free proteomic database comprises 39,212 proteins identified in 63 sample sets, such as different organs of soybean plants grown under flooding stress or non-stressed conditions in a time-dependent manner. In addition, organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free proteomics database. A total of 44,704 proteins, including 5490 proteins identified using a gel-based proteomic technique, are stored in the SPD. It accounts for approximately 80% of all predicted proteins from genome sequences, though there are over lapped proteins. Based on the demonstrated application of data stored in the database for functional analyses, it is suggested that these data will be useful for analyses of biological mechanisms in soybean. Furthermore, coupled with recent advances in information and communication technology, the usefulness of this database would increase in the analyses of biological mechanisms. PMID: 28499913 [PubMed - as supplied by publisher]

metabolomics; +24 new citations

Sat, 13/05/2017 - 14:36
24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/05/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury.

Fri, 12/05/2017 - 14:13
Related Articles Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury. Dev Neurosci. 2017 May 12;: Authors: Blaise BJ, Schwendimann L, Chhor V, Degos V, Hodson MP, Dallmann G, Keller M, Gressens P, Fleiss B Abstract Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy. PMID: 28494460 [PubMed - as supplied by publisher]

Metabolomics analysis: Finding out metabolic building blocks.

Fri, 12/05/2017 - 14:13
Related Articles Metabolomics analysis: Finding out metabolic building blocks. PLoS One. 2017;12(5):e0177031 Authors: Alberich R, Castro JA, Llabrés M, Palmer-Rodríguez P Abstract In this paper we propose a new methodology for the analysis of metabolic networks. We use the notion of strongly connected components of a graph, called in this context metabolic building blocks. Every strongly connected component is contracted to a single node in such a way that the resulting graph is a directed acyclic graph, called a metabolic DAG, with a considerably reduced number of nodes. The property of being a directed acyclic graph brings out a background graph topology that reveals the connectivity of the metabolic network, as well as bridges, isolated nodes and cut nodes. Altogether, it becomes a key information for the discovery of functional metabolic relations. Our methodology has been applied to the glycolysis and the purine metabolic pathways for all organisms in the KEGG database, although it is general enough to work on any database. As expected, using the metabolic DAGs formalism, a considerable reduction on the size of the metabolic networks has been obtained, specially in the case of the purine pathway due to its relative larger size. As a proof of concept, from the information captured by a metabolic DAG and its corresponding metabolic building blocks, we obtain the core of the glycolysis pathway and the core of the purine metabolism pathway and detect some essential metabolic building blocks that reveal the key reactions in both pathways. Finally, the application of our methodology to the glycolysis pathway and the purine metabolism pathway reproduce the tree of life for the whole set of the organisms represented in the KEGG database which supports the utility of this research. PMID: 28493998 [PubMed - in process]

shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics.

Fri, 12/05/2017 - 14:13
Related Articles shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics. PLoS One. 2017;12(5):e0176334 Authors: Khomtchouk BB, Hennessy JR, Wahlestedt C Abstract BACKGROUND: Transcriptomics, metabolomics, metagenomics, and other various next-generation sequencing (-omics) fields are known for their production of large datasets, especially across single-cell sequencing studies. Visualizing such big data has posed technical challenges in biology, both in terms of available computational resources as well as programming acumen. Since heatmaps are used to depict high-dimensional numerical data as a colored grid of cells, efficiency and speed have often proven to be critical considerations in the process of successfully converting data into graphics. For example, rendering interactive heatmaps from large input datasets (e.g., 100k+ rows) has been computationally infeasible on both desktop computers and web browsers. In addition to memory requirements, programming skills and knowledge have frequently been barriers-to-entry for creating highly customizable heatmaps. RESULTS: We propose shinyheatmap: an advanced user-friendly heatmap software suite capable of efficiently creating highly customizable static and interactive biological heatmaps in a web browser. shinyheatmap is a low memory footprint program, making it particularly well-suited for the interactive visualization of extremely large datasets that cannot typically be computed in-memory due to size restrictions. Also, shinyheatmap features a built-in high performance web plug-in, fastheatmap, for rapidly plotting interactive heatmaps of datasets as large as 105-107 rows within seconds, effectively shattering previous performance benchmarks of heatmap rendering speed. CONCLUSIONS: shinyheatmap is hosted online as a freely available web server with an intuitive graphical user interface: http://shinyheatmap.com. The methods are implemented in R, and are available as part of the shinyheatmap project at: https://github.com/Bohdan-Khomtchouk/shinyheatmap. Users can access fastheatmap directly from within the shinyheatmap web interface, and all source code has been made publicly available on Github: https://github.com/Bohdan-Khomtchouk/fastheatmap. PMID: 28493881 [PubMed - in process]

Comparative Metabolic Response between Cucumber (Cucumis sativus) and Corn (Zea Mays) to a Cu(OH)2 Nanopesticide.

Fri, 12/05/2017 - 14:13
Related Articles Comparative Metabolic Response between Cucumber (Cucumis sativus) and Corn (Zea Mays) to a Cu(OH)2 Nanopesticide. J Agric Food Chem. 2017 May 11;: Authors: Zhao L, Huang Y, Keller AA Abstract Due to their unique properties, copper-based nanopesticides are emerging in the market. Thus, understanding their effect on crop plants is very important. Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. We selected maize and cucumber as model plants to expose to different doses of Cu(OH)2 nanopesticide. GC-TOF-MS based metabolomics was employed to determine the metabolic response of these two species. Results revealed significant differences in metabolite profile changes between maize and cucumber. Furthermore, the Cu(OH)2 nanopesticide induced metabolic reprogramming in both species, but in a different manner. In maize, several intermediates metabolite of the glycolysis pathway and tricarboxylic acid cycle (TCA) were up-regulated, indicating the energy metabolism was activated. In addition, the levels of aromatic compounds (4-hydroxycinnamic acid and 1,2,4-benzenetriol) and their precursors (phenylalanine, tyrosine) were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense related pathway. In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu(OH)2 nanopesticide. Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. PMID: 28493687 [PubMed - as supplied by publisher]

Overlapping MALDI-Mass Spectrometry Imaging for In-Parallel MS and MS/MS Data Acquisition without Sacrificing Spatial Resolution.

Fri, 12/05/2017 - 14:13
Related Articles Overlapping MALDI-Mass Spectrometry Imaging for In-Parallel MS and MS/MS Data Acquisition without Sacrificing Spatial Resolution. J Am Soc Mass Spectrom. 2017 May 10;: Authors: Hansen RL, Lee YJ Abstract Metabolomics experiments require chemical identifications, often through MS/MS analysis. In mass spectrometry imaging (MSI), this necessitates running several serial tissue sections or using a multiplex data acquisition method. We have previously developed a multiplex MSI method to obtain MS and MS/MS data in a single experiment to acquire more chemical information in less data acquisition time. In this method, each raster step is composed of several spiral steps and each spiral step is used for a separate scan event (e.g., MS or MS/MS). One main limitation of this method is the loss of spatial resolution as the number of spiral steps increases, limiting its applicability for high-spatial resolution MSI. In this work, we demonstrate multiplex MS imaging is possible without sacrificing spatial resolution by the use of overlapping spiral steps, instead of spatially separated spiral steps as used in the previous work. Significant amounts of matrix and analytes are still left after multiple spectral acquisitions, especially with nanoparticle matrices, so that high quality MS and MS/MS data can be obtained on virtually the same tissue spot. This method was then applied to visualize metabolites and acquire their MS/MS spectra in maize leaf cross-sections at 10 μm spatial resolution. Graphical Abstract ᅟ. PMID: 28493035 [PubMed - as supplied by publisher]

Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia.

Fri, 12/05/2017 - 14:13
Related Articles Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia. Cell Death Dis. 2017 May 11;8(5):e2781 Authors: Sun Y, Li T, Xie C, Xu Y, Zhou K, Rodriguez J, Han W, Wang X, Kroemer G, Modjtahedi N, Blomgren K, Zhu C Abstract Mitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial intermembrane space protein that plays a major role in the import of intermembrane proteins and physically interacts with apoptosis-inducing factor (AIF). The purpose of this study was to investigate the impact of CHCHD4 haploinsufficiency on mitochondrial function and brain injury after cerebral hypoxia-ischemia (HI) in neonatal mice. CHCHD4(+/-) and wild-type littermate mouse pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4 haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release from the mitochondria and reduced neuronal cell death. The total brain injury volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in CHCHD4(+/-) mice. However, CHCHD4 haploinsufficiency had no influence on mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or neural progenitor cell differentiation. There were no significant changes in the expression or distribution of p53 protein or p53 pathway-related genes under physiological conditions or after HI. These results suggest that CHCHD4 haploinsufficiency afforded persistent neuroprotection related to reduced release of mitochondrial intermembrane space proteins. The CHCHD4-dependent import pathway might thus be a potential therapeutic target for preventing or treating neonatal brain injury. PMID: 28492551 [PubMed - in process]

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

Fri, 12/05/2017 - 14:13
Related Articles Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations. Nutrients. 2017 May 11;9(5): Authors: Troisi J, Pierri L, Landolfi A, Marciano F, Bisogno A, Belmonte F, Palladino C, Nuzio SG, Campiglia P, Vajro P Abstract To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations. PMID: 28492501 [PubMed - in process]

Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae.

Fri, 12/05/2017 - 14:13
Related Articles Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae. Elife. 2017 May 11;6: Authors: Luzzatto Knaan T, Garg N, Wang M, Glukhov E, Peng Y, Ackermann G, Amir A, Duggan BM, Ryazanov S, Gerwick L, Knight R, Alexandrov T, Bandeira N, Gerwick WH, Dorrestein PC Abstract Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures. However, much is yet underexplored and additional information is hidden in these exceptional collections. We applied untargeted mass spectrometry approaches to capture the chemical space and dispersal patterns of metabolites from an in-house library of marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics signals detected were not found in other available datasets of similar nature, supporting the hypothesis that marine cyanobacteria and algae possess distinctive metabolomes. The data were plotted onto a world map representing 8 major sampling sites, and revealed potential geographic locations with high chemical diversity. We demonstrate the use of these inventories as a tool to explore the diversity and distribution of natural products. Finally, we utilized this tool to guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine cyanobacterium. PMID: 28492366 [PubMed - as supplied by publisher]

METABOLOMICS APPROACH IN THE INVESTIGATION OF METABOLIC CHANGES IN OBESE MEN AFTER 24 WEEKS OF COMBINED TRAINING.

Fri, 12/05/2017 - 14:13
Related Articles METABOLOMICS APPROACH IN THE INVESTIGATION OF METABOLIC CHANGES IN OBESE MEN AFTER 24 WEEKS OF COMBINED TRAINING. J Proteome Res. 2017 May 11;: Authors: Duft RG, Castro A, Bonfante ILP, Brunelli DT, Chacon-Mikahil MPT, Cavaglieri CR Abstract Obesity is associated with comorbidities related to metabolic disorders, due to excess of adipose tissue. Physical exercise has a major role in the prevention of obesity. Combined training (CT), especially, has been shown to improve markers of health. In this study, we used 1H NMR-based metabolomics to investigate changes in the metabolism of obese men, after 24 weeks of CT. Twenty-two obese (Body Mass Index 31 ± 1.4 kg/m²), middle-aged men (48.2 ± 6.1 years) were randomly assigned to a control group (CG, n = 11) or CT group (n = 11). The CT was performed three times a week (resistance and aerobic training) for 24 weeks. Blood samples were collected before and after experimental period. There was an improvement in body composition and physical fitness indices after CT training. Multivariate PCA and PLS-DA models showed a distinct separation between groups. Twenty metabolites with importance for projection (VIP) higher > 1.0 were identified, and four classified as best discriminators (tyrosine, 2-oxoisocaproate, histidine, pyruvate). Some metabolites were correlated with strength, VO2peak, fat and lean body mass, waist circumference and insulin. In conclusion, 24 weeks of CT was effective for functional improvements and metabolic changes in obese middle-aged men. PMID: 28492082 [PubMed - as supplied by publisher]

Corrigendum: Brain Metabolic Changes in Rats following Acoustic Trauma.

Fri, 12/05/2017 - 14:13
Related Articles Corrigendum: Brain Metabolic Changes in Rats following Acoustic Trauma. Front Neurosci. 2017;11:260 Authors: He J, Zhu Y, Aa J, Smith PF, De Ridder D, Wang G, Zheng Y Abstract [This corrects the article on p. 148 in vol. 11, PMID: 28392756.]. PMID: 28491021 [PubMed - in process]

Pharmacometabolomics for predicting variable busulfan exposure in paediatric haematopoietic stem cell transplantation patients.

Fri, 12/05/2017 - 14:13
Related Articles Pharmacometabolomics for predicting variable busulfan exposure in paediatric haematopoietic stem cell transplantation patients. Sci Rep. 2017 May 10;7(1):1711 Authors: Kim B, Lee JW, Hong KT, Yu KS, Jang IJ, Park KD, Shin HY, Ahn HS, Cho JY, Kang HJ Abstract Owing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups. In the high-AUC group, deferoxamine metabolites were detected. Phenylacetylglutamine and two acylcarnitines were significantly lower in the high-AUC group than in the low-AUC group. Deferoxamine, an iron-chelating agent that lowers serum ferritin levels, was detected in the high-AUC group, indicating that those patients had high ferritin levels. Therefore, in a retrospective study of 130 paediatric patients, we confirmed our hypothesis that busulfan clearance (dose/AUC) and serum ferritin level has a negative correlation (r = -0.205, P = 0.019). Ferritin, acylcarnitine, and phenylacetylglutamine are associated with liver damage, including free radical formation, deregulation of hepatic mitochondrial β-oxidation, and hyperammonaemia. Our findings reveal potential biomarkers predictive of busulfan exposure and suggest that liver function may affect busulfan exposure. PMID: 28490733 [PubMed - in process]

The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity.

Fri, 12/05/2017 - 14:13
Related Articles The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity. FASEB J. 2017 May 10;: Authors: Lei S, Huang F, Zhao A, Chen T, Chen W, Xie G, Zheng X, Zhang Y, Yu H, Zhang P, Rajani C, Bao Y, Jia W, Jia W Abstract Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays an important role in the development of metabolic disease. However, BAs in relation to fatty acids have not been fully investigated in obesity (OB)-related metabolic disorders. A targeted metabolomic measurement of serum BA and free fatty acid profiles was applied to sera of 381 individuals in 2 independent studies. The results showed that the ratio of dihomo-γ-linolenic acid (DGLA) to DCA species (DCAs) was significantly increased in OB individuals with type 2 diabetes (T2DM) from a case-control study and decreased in the remission group of OB subjects with T2DM after metabolic surgery. The changes were closely associated with their metabolic status. These results were consistently confirmed in both serum and liver of mice with diet-induced OB, implying that such a metabolic alteration in circulation reflects changes occurring in the liver. In vitro studies of human liver L-02 cell lines under BA treatment revealed that DCA and its conjugated form, TDCA, significantly inhibited mRNA expression of fatty acid transport protein 5 in the presence of DGLA, which was involved in hepatocyte DGLA uptake. Thus, the DGLA: DCAs ratio may be a promising biomarker for metabolic abnormalities in OB.-Lei, S., Huang, F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang, P., Rajani, C., Bao, Y., Jia, W., Jia, W. The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity. PMID: 28490483 [PubMed - as supplied by publisher]

A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls.

Fri, 12/05/2017 - 14:13
Related Articles A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol. 2017 May 11;17(1):88 Authors: Malatji BG, Meyer H, Mason S, Engelke UFH, Wevers RA, van Reenen M, Reinecke CJ Abstract BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease. METHODS: We selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18-22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz (1)H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software. RESULTS AND DISCUSSION: Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites - succinic acid, taurine and creatine - that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis - area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group. CONCLUSION: Our data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS. PMID: 28490352 [PubMed - in process]

Effects of pan cooking on micropollutants in meat.

Fri, 12/05/2017 - 14:13
Related Articles Effects of pan cooking on micropollutants in meat. Food Chem. 2017 Oct 01;232:395-404 Authors: Planche C, Ratel J, Blinet P, Mercier F, Angénieux M, Chafey C, Zinck J, Marchond N, Chevolleau S, Marchand P, Dervilly-Pinel G, Guérin T, Debrauwer L, Engel E Abstract This work presents the effects of pan cooking on PCBs, PCDD/Fs, pesticides and trace elements in meat from a risk assessment perspective. Three different realistic cooking intensities were studied. A GC×GC-TOF/MS method was set up for the multiresidue analysis of 189 PCBs, 17 PCDD/Fs and 16 pesticides whereas Cd, As, Pb and Hg were assayed by ICP-MS. In terms of quantity, average PCB losses after cooking were 18±5% for rare, 30±3% for medium, and 48±2% for well-done meat. In contrast, average PCDD/F losses were not significant. For pesticides, no loss occurred for aldrin, lindane, DDE or DDD, whereas losses exceeding 80% were found for dieldrin, sulfotep or phorate. Losses close to the margin of error were observed for trace elements. These results are discussed in light of the physicochemical properties of the micropollutants as well as of water and fat losses into cooking juice. PMID: 28490090 [PubMed - in process]

Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial differentiation revealed by UPLC-QTOF-MS metabolomics.

Thu, 11/05/2017 - 20:00
Related Articles Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial differentiation revealed by UPLC-QTOF-MS metabolomics. PLoS One. 2017;12(5):e0177464 Authors: Hu W, Pan X, Abbas HMK, Li F, Dong W Abstract Rhizoctonia solani is a causative agent of sheath blight, which results in huge economic losses every year. During its life cycle, the formation of sclerotia helps Rhizoctonia solani withstand a variety of unfavorable factors. Oxidative stress is a key factor that induces sclerotium formation. The differentiated and undifferentiated phenotypes of R. solani AG-1-IA were obtained by controlling aerial conditions. Metabolomics based on the mass spectrometry technique combined with multivariate and univariate analyses was used to investigate the metabolic variation in vegetative, differentiated and undifferentiated mycelia. Our results revealed that during maturation, the metabolic levels of N2-acetyl-L-ornithine, 3,1'-(OH)2-Gamma-carotene, (5Z,7E)-(1S,3R)-24,24-difluoro-24a-homo-9,10-seco-5,7,10(19)-cholestatrien-1,3,25-triol, stoloniferone O, PA(O-18:0/12:0), PA(P-16:0/14:0), PA(P-16:0/16:(19Z)) and PA(P-16:0/17:2(9Z,12Z)) were suppressed in both differentiated and undifferentiated mycelia. The concentrations of PE(20:1(11Z)/14:1(9Z)), PE(P-16:0/20:4(5Z,8Z,11Z,13E)(15OH[S])) and PS(12:0/18:1(9Z)) were increased in the differentiated group, while increased levels of N(gamma)-nitro-L-arginine, tenuazonic acid and 9S,10S,11R-trihydroxy-12Z,15Z-octadecadienoic acid were found in the undifferentiated group. Our results suggest that different levels of these metabolites may act as biomarkers for the developmental stages of R. solani AG-1-IA. Moreover, the mechanisms of sclerotium formation and mycelium differentiation were elucidated at the metabolic level. PMID: 28489938 [PubMed - in process]

Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

Thu, 11/05/2017 - 20:00
Related Articles Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles. Eur J Clin Nutr. 2017 May 10;: Authors: Dias CB, Amigo N, Wood LG, Correig X, Garg ML Abstract BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.European Journal of Clinical Nutrition advance online publication, 10 May 2017; doi:10.1038/ejcn.2017.56. PMID: 28488685 [PubMed - as supplied by publisher]

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