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

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]

A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients.

Thu, 11/05/2017 - 20:00
Related Articles A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients. Mol Med Rep. 2017 Apr 28;: Authors: Pamungkas AD, Medriano CA, Sim E, Lee S, Park YH Abstract The most common type of lung cancer is non‑small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high‑resolution metabolomics (HRM) using liquid chromatography‑mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally‑invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome‑wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5‑methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N‑succinyl‑L‑glutamate‑5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer. PMID: 28487968 [PubMed - as supplied by publisher]

New tools and approaches to newborn screening: ready to open Pandora's box?

Thu, 11/05/2017 - 20:00
Related Articles New tools and approaches to newborn screening: ready to open Pandora's box? Cold Spring Harb Mol Case Stud. 2017 May;3(3):a001842 Authors: Ficicioglu C Abstract The landscape of newborn screening (NBS) is changing as new tools are developed. We must acknowledge that NBS is a very important and extraordinarily positive initiative especially for rare and serious inherited disorders; however, lessons learned from current NBS should guide the future of NBS as we enter the era of "omics" that will expand NBS for many other genetic disorders. In this article, I will first discuss new tools such as genomics and metabolomics for NBS. I will then turn to assessing how best to take advantage of new technical developments while considering the best interests of patients and the success of newborn screening. PMID: 28487886 [PubMed - in process]

Finger Millet: A "Certain" Crop for an "Uncertain" Future and a Solution to Food Insecurity and Hidden Hunger under Stressful Environments.

Thu, 11/05/2017 - 20:00
Related Articles Finger Millet: A "Certain" Crop for an "Uncertain" Future and a Solution to Food Insecurity and Hidden Hunger under Stressful Environments. Front Plant Sci. 2017;8:643 Authors: Gupta SM, Arora S, Mirza N, Pande A, Lata C, Puranik S, Kumar J, Kumar A Abstract Crop growth and productivity has largely been vulnerable to various abiotic and biotic stresses that are only set to be compounded due to global climate change. Therefore developing improved varieties and designing newer approaches for crop improvement against stress tolerance have become a priority now-a-days. However, most of the crop improvement strategies are directed toward staple cereals such as rice, wheat, maize etc., whereas attention on minor cereals such as finger millet [Eleusine coracana (L.) Gaertn.] lags far behind. It is an important staple in several semi-arid and tropical regions of the world with excellent nutraceutical properties as well as ensuring food security in these areas even during harsh environment. This review highlights the importance of finger millet as a model nutraceutical crop. Progress and prospects in genetic manipulation for the development of abiotic and biotic stress tolerant varieties is also discussed. Although limited studies have been conducted for genetic improvement of finger millets, its nutritional significance in providing minerals, calories and protein makes it an ideal model for nutrition-agriculture research. Therefore, improved genetic manipulation of finger millets for resistance to both abiotic and biotic stresses, as well as for enhancing nutrient content will be very effective in millet improvement. Key message: Apart from the excellent nutraceutical value of finger millet, its ability to tolerate various abiotic stresses and resist pathogens make it an excellent model for exploring vast genetic and genomic potential of this crop, which provide us a wide choice for developing strategies for making climate resilient staple crops. PMID: 28487720 [PubMed - in process]

A Combined Comparative Transcriptomic, Metabolomic, and Anatomical Analyses of Two Key Domestication Traits: Pod Dehiscence and Seed Dormancy in Pea (Pisum sp.).

Thu, 11/05/2017 - 20:00
Related Articles A Combined Comparative Transcriptomic, Metabolomic, and Anatomical Analyses of Two Key Domestication Traits: Pod Dehiscence and Seed Dormancy in Pea (Pisum sp.). Front Plant Sci. 2017;8:542 Authors: Hradilová I, Trněný O, Válková M, Cechová M, Janská A, Prokešová L, Aamir K, Krezdorn N, Rotter B, Winter P, Varshney RK, Soukup A, Bednář P, Hanáček P, Smýkal P Abstract The origin of the agriculture was one of the turning points in human history, and a central part of this was the evolution of new plant forms, domesticated crops. Seed dispersal and germination are two key traits which have been selected to facilitate cultivation and harvesting of crops. The objective of this study was to analyze anatomical structure of seed coat and pod, identify metabolic compounds associated with water-impermeable seed coat and differentially expressed genes involved in pea seed dormancy and pod dehiscence. Comparative anatomical, metabolomics, and transcriptomic analyses were carried out on wild dormant, dehiscent Pisum elatius (JI64, VIR320) and cultivated, indehiscent Pisum sativum non-dormant (JI92, Cameor) and recombinant inbred lines (RILs). Considerable differences were found in texture of testa surface, length of macrosclereids, and seed coat thickness. Histochemical and biochemical analyses indicated genotype related variation in composition and heterogeneity of seed coat cell walls within macrosclereids. Liquid chromatography-electrospray ionization/mass spectrometry and Laser desorption/ionization-mass spectrometry of separated seed coats revealed significantly higher contents of proanthocyanidins (dimer and trimer of gallocatechin), quercetin, and myricetin rhamnosides and hydroxylated fatty acids in dormant compared to non-dormant genotypes. Bulk Segregant Analysis coupled to high throughput RNA sequencing resulted in identification of 770 and 148 differentially expressed genes between dormant and non-dormant seeds or dehiscent and indehiscent pods, respectively. The expression of 14 selected dormancy-related genes was studied by qRT-PCR. Of these, expression pattern of four genes: porin (MACE-S082), peroxisomal membrane PEX14-like protein (MACE-S108), 4-coumarate CoA ligase (MACE-S131), and UDP-glucosyl transferase (MACE-S139) was in agreement in all four genotypes with Massive analysis of cDNA Ends (MACE) data. In case of pod dehiscence, the analysis of two candidate genes (SHATTERING and SHATTERPROOF) and three out of 20 MACE identified genes (MACE-P004, MACE-P013, MACE-P015) showed down-expression in dorsal and ventral pod suture of indehiscent genotypes. Moreover, MACE-P015, the homolog of peptidoglycan-binding domain or proline-rich extensin-like protein mapped correctly to predicted Dpo1 locus on PsLGIII. This integrated analysis of the seed coat in wild and cultivated pea provides new insight as well as raises new questions associated with domestication and seed dormancy and pod dehiscence. PMID: 28487704 [PubMed - in process]

Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease.

Thu, 11/05/2017 - 20:00
Related Articles Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease. World J Gastroenterol. 2017 Apr 21;23(15):2771-2784 Authors: Dong S, Zhan ZY, Cao HY, Wu C, Bian YQ, Li JY, Cheng GH, Liu P, Sun MY Abstract AIM: To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. METHODS: Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis. RESULTS: Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH. CONCLUSION: These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions. PMID: 28487615 [PubMed - in process]

Changes in human hepatic metabolism in steatosis and cirrhosis.

Thu, 11/05/2017 - 20:00
Related Articles Changes in human hepatic metabolism in steatosis and cirrhosis. World J Gastroenterol. 2017 Apr 21;23(15):2685-2695 Authors: Schofield Z, Reed MA, Newsome PN, Adams DH, Günther UL, Lalor PF Abstract AIM: To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue. METHODS: We have carried out pilot study using (1)H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries. RESULTS: Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach. CONCLUSION: Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance. PMID: 28487605 [PubMed - in process]

Dioxin-induced increase in leukotriene B4 biosynthesis through the aryl hydrocarbon receptor and its relevance to hepatotoxicity owing to neutrophil infiltration.

Thu, 11/05/2017 - 20:00
Related Articles Dioxin-induced increase in leukotriene B4 biosynthesis through the aryl hydrocarbon receptor and its relevance to hepatotoxicity owing to neutrophil infiltration. J Biol Chem. 2017 May 09;: Authors: Takeda T, Komiya Y, Koga T, Ishida T, Ishii Y, Kikuta Y, Nakaya M, Kurose H, Yokomizo T, Shimizu T, Uchi H, Furue M, Yamada H Abstract Dioxin and related chemicals alter the expression of a number of genes by activating the aryl hydrocarbon receptors (AHRs) to produce a variety of disorders including hepatotoxicity. However, it remains largely unknown how these changes in gene expression are linked to toxicity. To address this issue, we initially examined the effect of 2,3,7,8-tetrachrolodibenzo-p-dioxin (TCDD), a most toxic dioxin, on the hepatic and serum metabolome in male pubertal rats. The results obtained showed that TCDD causes many changes in the level of fatty acids, bile acids, amino acids and their metabolites. Among them, we discovered that TCDD increases the content of leukotriene (LT) B4, an inflammation-inducer due to the activation of leukocytes, in the liver of rats and mice. Further analyses suggested that an increase in LTB4 comes from a dual mechanism consisting of an induction of arachidonate lipoxygenase-5, a rate-limiting enzyme in LTB4 synthesis, and down-regulation of LTC4 synthase, an enzyme converting LTA4 to LTC4. The above changes require AHR activation, because the same was not observed in AHR-knockout rats. In agreement with LTB4 accumulation, TCDD caused the marked infiltration of neutrophils into the liver. However, deleting LTB4 receptors (BLT1) blocked this effect. A TCDD-produced increase in the mRNA expression of inflammatory markers including tumor-necrosis factor and hepatic damage was also suppressed in BLT1-null mice. A series of the above observations focusing on metabolomic changes provides novel evidence that TCDD accumulates LTB4 in the liver by an AHR-dependent induction of LTB4 biosynthesis to cause hepatotoxicity through neutrophil activation. PMID: 28487374 [PubMed - as supplied by publisher]

Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles.

Thu, 11/05/2017 - 20:00
Related Articles Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles. Pancreatology. 2017 May 03;: Authors: Xiao H, Huang JH, Zhang XW, Ahmed R, Xie QL, Li B, Zhu YM, Cai X, Peng QH, Qin YH, Huang HY, Wang W Abstract Acute pancreatitis (AP) is defined as an acute inflammation of pancreas that may cause damage to other tissues and organs depending upon the severity of symptoms. The diagnosis of AP is usually made by detection of raised circulating pancreatic enzyme levels, but there are occasional false positive and false negative diagnoses and such tests are often normal in delayed presentations. More accurate biomarkers would help in such situations. In this study, the global metabolites' changes of AP patients (APP) were profiled by using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition techniques were used to establish the classification models to distinguish APP from healthy participants (HP). Some significant metabolites including 3-hydroxybutyric acid, phosphoric acid, glycerol, citric acid, d-galactose, d-mannose, d-glucose, hexadecanoic acid and serotonin were selected as potential biomarkers for helping clinical diagnosis of AP. Furthermore, the metabolite changes in APP with severe and mild symptoms were also analyzed. Based on the selected biomarkers, some relevant pathways were also identified. Our results suggested that GC-MS based serum metabolomics method can be used in the clinical diagnosis of AP by profiling potential biomarkers. PMID: 28487129 [PubMed - as supplied by publisher]

Design of strategies to study the metabolic profile of highly polar compounds in plasma by reversed-phase liquid chromatography-high resolution mass spectrometry.

Thu, 11/05/2017 - 20:00
Related Articles Design of strategies to study the metabolic profile of highly polar compounds in plasma by reversed-phase liquid chromatography-high resolution mass spectrometry. J Chromatogr A. 2017 Mar 24;1490:156-165 Authors: Sánchez-López E, Crego AL, Marina ML Abstract Amino acids and related compounds are paramount analytes which are involved in numerous metabolic pathways. Most of these compounds are unable to be retained on Liquid Chromatography with Reversed-Phase stationary phases due to their high hydrophilic character. An interesting strategy is to reduce their polarity through their derivatization with a labelling reagent, such as the commercially available 9-fluorenylmethyloxycarbonyl (FMOC) which forms stable complexes with primary and secondary amine moieties rapidly. Although some derivatization reagents have been employed in the study of metabolic profiles, as far as we know, FMOC has never been employed for this purpose. In this work, it is demonstrated that the use of RP-LCMS(TOF) using a C18 column and FMOC as labelling agent enables the determination of a larger number of hydrophilic compounds (proteinogenic amino acids, non-proteinogenic amino acids, and biogenic amines) when compared to the use of a fully-wettable pentafluorophenyl column in fully-aqueous conditions (gradient starting in 0% of organic solvent) and HILIC column, both without using compound derivatization. Different strategies for plasma protein elimination were also carefully evaluated. Results revealed that ultrafiltration (UF) offered a lower variability from sample to sample when compared to the protein precipitation (PP) method (from 2 to 12 times lower variability found in UF). Additionally, UF preserved a larger number of possible compounds when compared to the PP approach: 4631 unique molecular features with UF, 666 unique molecular features with PP. PMID: 28238323 [PubMed - indexed for MEDLINE]

metabolomics; +44 new citations

Wed, 10/05/2017 - 13:23
44 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 2017/05/10PubMed 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.

Salinity affects metabolomic profiles of different trophic levels in a food chain.

Sun, 07/05/2017 - 18:32
Salinity affects metabolomic profiles of different trophic levels in a food chain. Sci Total Environ. 2017 May 02;599-600:198-206 Authors: Nam KH, Kim YJ, Moon YS, Pack IS, Kim CG Abstract Salinization is one of the most important abiotic stressors in an ecosystem. To examine how exposing a host plant to excess salt affects the consequent performance and metabolism of insects in a food chain, we determined the life history traits and the metabolite profiles in rice (Oryza sativa), the herbivore Sitobion avenae, and its predator Harmonia axyridis. When compared with performance under normal (non-stressed) conditions, exposing plants to 50mM NaCl significantly delayed the timing of development for S. avenae fed on rice and H. axyridis and also reduced the body mass of the latter. Our GC-MS-based analysis revealed clear differences in metabolite profiles between trophic levels or treatment conditions. Salinity apparently increased the levels of main components in rice, but decreased levels of major components in S. avenae and H. axyridis. In addition, 16 metabolites showed salinity-related contrasts in this trophic interaction for our rice-S. avenae-H. axyridis system. Salinity impeded the accumulation of metabolites, especially several sugars, amino acids, organic acids, and fatty acids in both insects, a response that was possibly associated with the negative impacts on their growth and reproduction under stress conditions. PMID: 28475913 [PubMed - as supplied by publisher]

DNA Damage in Stem Cells.

Sun, 07/05/2017 - 18:32
DNA Damage in Stem Cells. Mol Cell. 2017 May 04;66(3):306-319 Authors: Vitale I, Manic G, De Maria R, Kroemer G, Galluzzi L Abstract Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions. Such a resistance contributes to the genetic drift of evolving tumors as well as to their limited sensitivity to chemo- and radiotherapy. Here, we discuss the pathophysiological and therapeutic implications of the molecular pathways through which stem cells cope with DNA damage. PMID: 28475867 [PubMed - in process]

NMR-based metabolomic analysis for the effects of creatine supplementation on mouse myoblast cell line C2C12.

Sun, 07/05/2017 - 18:32
NMR-based metabolomic analysis for the effects of creatine supplementation on mouse myoblast cell line C2C12. Acta Biochim Biophys Sin (Shanghai). 2017 May 05;:1-11 Authors: Xu W, Lin D, Huang C Abstract Creatine (Cr) supplementation has drawn much attention from researchers owing to its widespread efficacy in sports, and more recently, in therapeutic fields. However, the underlying molecular mechanisms remain elusive. Here, we performed nuclear magnetic resonance-based metabolomic analysis to address the metabolic profile of aqueous extracts from the mouse myoblast cell line C2C12 exposed to 2 mM Cr for 24 h (the Cr-treated group). Results showed that Cr supplementation facilitated the proliferation of C2C12 myoblasts. Both pattern recognition and hierarchical cluster analyses demonstrated that the metabolic profiles of the Cr-treated and control groups were distinctly different. We identified 13 characteristic metabolites significantly responsible for the discrimination of metabolic profiles between the two groups, through orthogonal projection to latent structures discriminant analysis and independent samples t-test. We further verified the discrimination performances of these metabolites by conducting univariate receiver operating characteristic curve analysis. Compared with the control group, the Cr-treated group exhibited increased levels of Cr, phosphocreatine (PCr), glutathione (GSH), and glucose, but decreased levels of leucine, valine, isoleucine, phenylalanine, methionine, choline, O-phosphocholine, sn-glycero-3-phosphocholine, and glycerol. Our results demonstrated that Cr supplementation upregulated PCr and glucose, promoted trichloroacetic acid cycle anaplerotic flux and GSH-mediated antioxidant capacity, and stabilized lipid membranes through suppressing glycerophospholipid metabolism. Our work provides new clues to the molecular mechanisms underlying the pleiotropic effects of Cr in muscle cells. PMID: 28475656 [PubMed - as supplied by publisher]

Pages