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

Metabolite profiling of Epinephelus fuscoguttatus infected with vibriosis reveals Omega 9 as potential metabolite biomarker.

Thu, 28/03/2019 - 11:07
Related Articles Metabolite profiling of Epinephelus fuscoguttatus infected with vibriosis reveals Omega 9 as potential metabolite biomarker. Fish Physiol Biochem. 2019 Mar 26;: Authors: Nurdalila AA, Mayalvanan Y, Baharum SN Abstract In this study, we report the starvation effect and vibriosis infection on a tropical fish, the tiger grouper (Epinephelus fuscoguttatus). The tiger groupers were infected with Vibrio vulnificus for 21 days. Gas chromatography-mass spectrometry combined with multivariate analysis was used to assess the variation in metabolite profiles of E. fuscoguttatus. Metabolite productions in infected fishes were significantly influenced by fatty acid production. The Omega 9 (ω-9) was abundant under the challenged conditions compared to Omega 3 (ω-3) and Omega 6 (ω-6). A total of six fatty acids from the ω-9 group were detected in high concentration in the infected fishes compared to the control groupers. These metabolites are Oleic acid, Palmitoleic acid, 6,9-Octadecenoic acid, 8,11-Eicosadienoic acid, cis-Erucic acid and 5,8,11-Eicosatrienoic acid. The production of ω-9 differed significantly (p ≤ 0.001) in the challenged samples. The detected ω-9 compounds were quantified based on three different extraction techniques with Supelco 37-component FAME mix (Supelco, USA). The highest concentration of ω-9 groups compared to the other fatty acids detected is 1320.79 mg/4 g and the lowest is 939 mg/4 g in challenged-starved; meanwhile, in challenged-fed, the highest concentration detected is 1220.87 mg/4 g and the lowest is 917.25 mg/4 g. These changes demonstrate that ω-9 can be used as a biomarker of infection in fish. PMID: 30915615 [PubMed - as supplied by publisher]

Comparative Metabonomic Investigations of Schistosoma japonicum From SCID Mice and BALB/c Mice: Clues to Developmental Abnormality of Schistosome in the Immunodeficient Host.

Thu, 28/03/2019 - 11:07
Related Articles Comparative Metabonomic Investigations of Schistosoma japonicum From SCID Mice and BALB/c Mice: Clues to Developmental Abnormality of Schistosome in the Immunodeficient Host. Front Microbiol. 2019;10:440 Authors: Liu R, Cheng WJ, Tang HB, Zhong QP, Ming ZP, Dong HF Abstract The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches. PMID: 30915055 [PubMed]

Metabolomics Profiling on Different Stages of Colorectal Cancer: A Systematic Review.

Thu, 28/03/2019 - 11:07
Related Articles Metabolomics Profiling on Different Stages of Colorectal Cancer: A Systematic Review. Malays J Med Sci. 2018 Sep;25(5):16-34 Authors: Yusof HM, Ab-Rahim S, Suddin LS, Saman MSA, Mazlan M Abstract Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Early diagnosis and accurate staging of the disease is vital to improve the prognosis. Metabolomics has been used to identify changes in metabolite profiles in the different stages of cancer in order to introduce new non-invasive molecular tools for staging. In this systematic review, we aim to identify the common metabolite changes in human biological samples and the dominant metabolic pathways associated with CRC progression. A broad systematic search was carried out from selected databases. Four reviewers screened and reviewed the titles, abstracts, and full-text articles according to the inclusion and exclusion criteria. Quality assessment was conducted on the eight articles which met the criteria. Data showed that the metabolites involved with redox status, energy metabolism and intermediates of amino acids, choline and nucleotides metabolism were the most affected during CRC progression. However, there were differences in the levels of individual metabolites detected between the studies, and this might be due to the study population, sample preparation, analytical platforms used and statistical tools. In conclusion, this systematic review highlights the changes in metabolites from early to late stages of CRC. Moreover, biomarkers for prognosis are important to reduce CRC-related mortality. PMID: 30914860 [PubMed]

Metabolomic profiling highlights the metabolic bases of acute-on-chronic and post-hepatectomy liver failure.

Thu, 28/03/2019 - 11:07
Related Articles Metabolomic profiling highlights the metabolic bases of acute-on-chronic and post-hepatectomy liver failure. HPB (Oxford). 2019 Mar 23;: Authors: Faitot F, Ruhland E, Oncioiu C, Besch C, Addeo P, Cicek AE, Bachellier P, Namer IJ Abstract BACKGROUND: Posthepatectomy liver failure (PHLF) is the main limitation to extending liver resection but its pathophysiology is not yet fully understood. The aim of the study was to describe the metabolic adaptations that occur with PHLF. METHODS: A retrospective study of 82 patients using nuclear magnetic resonance metabolomics to identify and quantify intra-hepatic metabolites was performed. The metabolite levels were compared using metabolic network analysis ADEMA between fatal PHLF (FLF) and non fatal PHLF and according to PHLF/ACLF grading. RESULTS: Metabolomic profiles were significantly different between patients presenting FLF and non FLF or grade 3 ACLF versus < grade 3 ACLF. In the patients undergoing hepatectomy, valine, alanine and glycerophosphocholine were identified as powerful biomarkers to predict FLF (AUROC 0.806, 0.802 and 0.856 respectively). Network analysis showed an activation of aerobic glycolysis with glutaminolysis as observed in highly proliferating systems. Inversely, ACLF3 showed deprivation of glucose and lactate compared to lower ACLF grade. CONCLUSION: Clinical andbiological severity of ACLF and PHLF correlate with specific metabolic adaptations. Metabolomics can predict fatal liver failure after hepatectomy and underline significant differences in the metabolic patterns of ACLF and PHLF. PMID: 30914156 [PubMed - as supplied by publisher]

Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.

Thu, 28/03/2019 - 11:07
Related Articles Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial. Nutrients. 2019 Jan 23;11(2): Authors: Washburn RL, Cox JE, Muhlestein JB, May HT, Carlquist JF, Le VT, Anderson JL, Horne BD Abstract Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day. Two pathways were investigated, with trimethylamine N-oxide (TMAO) levels measured due to their association with elevated risk of CAD, along with conductance of a broad panel of metabolic analytes. Measurements were made at baseline, at the end of the fasting day, and at the end of the fed day. A fasting mean of 14.3 ng in TMAO was found versus the baseline mean of 27.1 ng with p = 0.019, although TMAO levels returned to baseline on refeeding. Further, acute alterations in levels of proline, tyrosine, galactitol, and urea plasma levels were observed along with changes in 24 other metabolites during the fasting period. These acute changes reveal short-term mechanisms which, with consistent repeated episodes of IF, may lead to improved health and reduced risk of CAD and diabetes. PMID: 30678028 [PubMed - indexed for MEDLINE]

MDM2-TP53 Crossregulation: An Underestimated Target to Promote Loss of TP53 Function and Cell Survival.

Thu, 28/03/2019 - 11:07
Related Articles MDM2-TP53 Crossregulation: An Underestimated Target to Promote Loss of TP53 Function and Cell Survival. Trends Cancer. 2018 09;4(9):602-605 Authors: Soussi T, Kroemer G Abstract Half of human cancers bear inactivating mutations of the tumor suppressor gene TP53, but the other half do not. In a recent issue of Cancer Cell, Dhar et al. and Zhu et al. reported that, in liver cancer and medulloblastoma, MDM2 is constitutively activated, causing a loss of TP53 function that does not require TP53 mutation. On theoretical grounds, such cancer would be amenable to treatment with MDM2 inhibitors. PMID: 30149877 [PubMed - indexed for MEDLINE]

metabolomics; +17 new citations

Wed, 27/03/2019 - 14:00
17 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 2019/03/27PubMed 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.

metabolomics; +21 new citations

Tue, 26/03/2019 - 13:38
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/03/26PubMed 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.

metabolomics; +17 new citations

Mon, 25/03/2019 - 19:15
17 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 2019/03/25PubMed 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.

metabolomics; +18 new citations

Sat, 23/03/2019 - 12:26
18 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 2019/03/23PubMed 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.

metabolomics; +16 new citations

Fri, 22/03/2019 - 12:11
16 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 2019/03/22PubMed 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.

metabolomics; +26 new citations

Thu, 21/03/2019 - 14:57
26 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 2019/03/21PubMed 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.

metabolomics; +26 new citations

Thu, 21/03/2019 - 11:57
26 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 2019/03/21PubMed 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.

metabolomics; +30 new citations

Wed, 20/03/2019 - 14:41
30 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 2019/03/20PubMed 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.

metabolomics; +30 new citations

Wed, 20/03/2019 - 11:37
30 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 2019/03/20PubMed 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.

metabolomics; +25 new citations

Tue, 19/03/2019 - 14:29
25 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 2019/03/19PubMed 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.

metabolomics; +25 new citations

Tue, 19/03/2019 - 11:25
25 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 2019/03/19PubMed 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.

The association of sleep with metabolic pathways and metabolites: evidence from the Dietary Approaches to Stop Hypertension (DASH)-sodium feeding study.

Mon, 18/03/2019 - 11:09
The association of sleep with metabolic pathways and metabolites: evidence from the Dietary Approaches to Stop Hypertension (DASH)-sodium feeding study. Metabolomics. 2019 Mar 16;15(4):48 Authors: Gordon-Dseagu VLZ, Derkach A, Xiao Q, Williams I, Sampson J, Stolzenberg-Solomon RZ Abstract INTRODUCTION: Sleep is increasingly being viewed as an issue of public health concern, yet few epidemiologic studies have explored associations between sleep habits and metabolomic profile. OBJECTIVES: To assess the association between sleep and blood metabolites. METHODS: We examined the association between sleep and 891 fasting plasma metabolites in a subgroup of 106 participants from the Dietary Approaches to Stop Hypertension (DASH)-Sodium feeding trial (1997-1999). We produced two sleep variables to analyze, sleep midpoint (median time between bedtime and waketime) and sleep duration, as well as bedtime and wake time. Metabolites were measured using liquid and gas chromatography, coupled with mass spectrometry. We assessed associations between sleep variables and log transformed metabolites using linear mixed-effects models. We combined the resulting p-values using Fisher's method to calculate associations between sleep and 38 metabolic pathways. RESULTS: Sixteen pathways were associated (p < 0.05) with midpoint. Only the γ-glutamyl amino acid metabolism pathway reached Bonferroni-corrected threshold (0.0013). Eighty-three metabolites were associated with midpoint (FDR < 0.20). Similar associations were found for wake time. Neither bed time nor duration were strongly associated. The top metabolites (pathways given in brackets) associated with sleep were erythrulose (advanced glycation end-product) (positive association) and several γ-glutamyl pathway metabolites, including CMPF (fatty acid, dicarboxylate), isovalerate (valine, leucine and isoleucine and fatty acid metabolism) and HWESASXX (polypeptide) (inverse association). CONCLUSION: Within our study, several metabolites that have previously been linked to inflammation and oxidative stress (processes involved in diseases such as cardiovascular disease and cancer) were found to be associated with sleep. PMID: 30879189 [PubMed - in process]

High-throughput quantitative analysis of phytohormones in sorghum leaf and root tissue by ultra-performance liquid chromatography-mass spectrometry.

Mon, 18/03/2019 - 11:09
High-throughput quantitative analysis of phytohormones in sorghum leaf and root tissue by ultra-performance liquid chromatography-mass spectrometry. Anal Bioanal Chem. 2019 Mar 16;: Authors: Sheflin AM, Kirkwood JS, Wolfe LM, Jahn CE, Broeckling CD, Schachtman DP, Prenni JE Abstract Plant development, growth, and adaptation to stress are regulated by phytohormones, which can influence physiology even at low concentrations. Phytohormones are chemically grouped according to both structure and function as auxins, cytokinins, abscisic acid, jasmonates, salicylates, gibberellins, and brassinosteroids, among others. This chemical diversity and requirement for highly sensitive detection in complex matrices create unique challenges for comprehensive phytohormone analysis. Here, we present a robust and efficient quantitative UPLC-MS/MS assay for 17 phytohormones, including jasmonates, salicylates, abscisic acid, gibberellins, cytokinins, and auxins. Using this assay, 12 phytohormones were detected and quantified in sorghum plant tissue without the need for solid phase extraction (SPE) or liquid-liquid extraction. Variation of phytohormone profiles was explored in both root and leaf tissues between three genotypes, harvested at two different developmental time points. The results highlight the importance of tissue type, sampling time, and genetic factors when designing experiments that involve phytohormone analysis of sorghum. This research lays the groundwork for future studies, which can combine phytohormone profiling with other datasets such as transcriptome, soil microbiome, genome, and metabolome data, to provide important functional information about adaptation to stress and other environmental variables. PMID: 30879116 [PubMed - as supplied by publisher]

An untargeted metabolomic strategy based on liquid chromatography-mass spectrometry to study high glucose-induced changes in HK-2 cells.

Mon, 18/03/2019 - 11:09
An untargeted metabolomic strategy based on liquid chromatography-mass spectrometry to study high glucose-induced changes in HK-2 cells. J Chromatogr A. 2019 Mar 06;: Authors: Bernardo-Bermejo S, Sánchez-López E, Castro-Puyana M, Benito S, Lucio-Cazaña FJ, Marina ML Abstract Diabetes mellitus is a major health concern nowadays. It is estimated that 40% of diabetics are affected by diabetic nephropathy, one of the complications derived from high glucose blood levels which can lead to chronic loss of kidney function. It is now clear that the renal proximal tubule plays a critical role in the progression of diabetic nephropathy but research focused on studying the molecular mechanisms involved is still needed. The aim of this work was to develop a liquid chromatography-mass spectrometry platform to carry out, for the first time, the untargeted metabolomic analysis of high glucose-induced changes in cultured human proximal tubular HK-2 cells. In order to find the metabolites which were affected by high glucose and to expand the metabolite coverage, intra- and extracellular fluid from HK-2 cells exposed to high glucose (25 mM), normal glucose (5.5 mM) or osmotic control (5.5 mM glucose +19.5 mM mannitol) were analyzed by two complementary chromatographic modes: hydrophilic interaction and reversed-phase liquid chromatography. Non-supervised principal components analysis showed a good separation among the three groups of samples. Statistically significant variables were chosen for further metabolite identification. Different metabolic pathways were affected mainly those derived from amino acidic, polyol, and nitrogenous bases metabolism. PMID: 30878178 [PubMed - as supplied by publisher]

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