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

The use of PAH, metabolite and lipid profiling to assess exposure and effects of produced water discharges on pelagic copepods.

Mon, 27/01/2020 - 14:12
Related Articles The use of PAH, metabolite and lipid profiling to assess exposure and effects of produced water discharges on pelagic copepods. Sci Total Environ. 2020 Jan 15;714:136674 Authors: Hansen BH, Sørensen L, Størseth TR, Altin D, Gonzalez SV, Skancke J, Rønsberg MU, Nordtug T Abstract Several laboratory studies have demonstrated that exposure to oil components cause toxicity to copepods, however, this has never been shown in natural populations of copepods. In the present study, we sampled copepods in an area of the North Sea with high density of oil production platforms discharging produced water. Environmental modelling was used to predict produced water and copepod trajectories prior to copepod sampling in situ. To maximise output from a minimal number of field samples, a novel and combined methodology was developed to allow exploitation of the same extract for several purposes; contaminant body burden, lipidomics, and metabolomics analysis. PAH body burdens were low compared to laboratory experiments where correlations between PAH body burden and acute toxicity, reproduction and molecular endpoints had been established. Still, station-specific PAH profiles strongly indicated copepod exposure to PW. NMR metabolomics, focusing on water-soluble metabolites, suggested no correlation between metabolites and stations. Interestingly, lipidomics analyses suggested site-specific fingerprints and profiles displayed for acyl-glycerols and wax esters. Potential effects of produced water exposure on lipid metabolism in copepods cannot be ruled out and deserves more attention. Our study exemplifies the importance of incorporating novel and improved analytical methodologies in environmental monitoring. PMID: 31982742 [PubMed - as supplied by publisher]

Metabolomic analysis of Cyrtopodium glutiniferum extract by UHPLC-MS/MS and in vitro antiproliferative and genotoxicity assessment.

Mon, 27/01/2020 - 14:12
Related Articles Metabolomic analysis of Cyrtopodium glutiniferum extract by UHPLC-MS/MS and in vitro antiproliferative and genotoxicity assessment. J Ethnopharmacol. 2020 Jan 23;:112607 Authors: Araújo-Lima CF, Paula da Silva Oliveira J, Coscarella IL, Fortes Aiub CA, Felzenszwalb I, Caprini Evaristo GP, Macedo AF Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of orchids have been traditionally used as human phytotherapeutics. Cyrtopodium flavum, for example, is used to heal skin lesions in the Brazilian folk medicine, and it is focus of research due to the analgesic and anti-inflammatory properties. The pseudobulbs of Cyrtopodium glutiniferum, an orchid species found in Brazilian southeastern rainforest, are known to synthesize anti-inflammatory compounds, such as glucomannans and other potentially therapeutic compounds. AIM OF THE STUDY: We have reported the first metabolomic analysis focused on the phenols expression of the neotropical orchid Cyrtopodium glutiniferum Raddi, besides free radical scavenging, anti-inflammatory and antiproliferative activities, and the genotoxicity properties of the aqueous extract. MATERIALS AND METHODS: The metabolomics of C. glutiniferum aqueous extract was performed through UHPLC-MSn acquisition. We have detected the scavenging potential of the extract using DPPH assay. The genotoxic potential was performed by Ames Test (0-5000 μg mL-1) and micronucleous assay (0-5000 μg mL-1) in RAW264.7 cells. The cytotoxic potential of the extract against RAW264.7 was tested by WST-1 assay (0-500 μg mL-1). And after all, the RAW264.7 cells were treated with non-cytotoxic concentrations of C. glutiniferum (0-50 μg mL-1) to evaluate the antiproliferative and anti-inflammatory potential, besides the mitochondrial activity. RESULTS: From the 55 molecules identified, 45.5% belonged to the phenolic compounds database from Phenol Explorer, 29% to an in-house built Orchidaceae molecules database, and 25.5% to both. Among the identified phenolic compounds, 18 subclasses were discriminated, being phenanthrenes the most abundant. Doses-dependent of C. glutiniferum extract were able to induce DPPH free radicals scavenging and also to increase TA100 His+ revertants, in metabolic environment, showing mutagenicity just in the highest concentration, of 5000 μg/plate. On Eukaryotic cell models, the extract also has induced dose-response and time-response cytotoxicity against RAW264.7 macrophages, mainly after 48 h and 72 h, even though the extract has not been able to induce the increase of micronucleated cells and mitotic index alteration on Micronucleus assay. The activation and proliferation of macrophages cultures were downregulated after 24 h and 48 h by the non-cytotoxic concentrations of the extract in a dose-dependent manner. CONCLUSIONS: The Cyrtopodium glutiniferum metabolomics, anti-inflammatory and anti-proliferative properties observed in this study have suggested a therapeutic efficacy of the orchid extract applied in folk medicine. PMID: 31982517 [PubMed - as supplied by publisher]

A urinary metabolomic study from subjects after long-term occupational exposure to low concentration acrylamide using UPLC-QTOF/MS.

Mon, 27/01/2020 - 14:12
Related Articles A urinary metabolomic study from subjects after long-term occupational exposure to low concentration acrylamide using UPLC-QTOF/MS. Arch Biochem Biophys. 2020 Jan 23;:108279 Authors: Wang SY, Han D, Pan YL, Yu CP, Zhou XR, Xin R, Wang R, Ma WW, Wang C, Wu YH Abstract Because long-term occupational exposure to low concentrations of acrylamide (ACR) has the potential to cause neurological damage, it is important to identify biomarkers that can be used to evaluate this risk. In the present study, urine metabolomics of the ACR-exposed and non-exposed groups to identify potential metabolites was carried out using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. Serum biochemical indexes of the exposed and non-exposed groups were also determined. Principal component analysis showed a differential separation between exposed group and non-exposed group and a total of 7 metabolites were identified in positive and negative ionization modes; Area under curve of anthranilic acid, β-guanidinopropionic acid and mesobilirubinogen were 0.980, 0.843 and 0.801 respectively and these metabolites showed high sensitivity and specificity. The 13 biochemical indexes were divided into three classes based on physiological functions. Only biomarkers of dysregulated liver function including alanine aminotransferase, aspartic transaminase, total bilirubin, direct bilirubin and triglyceride were significantly higher in the exposed group than in the non-exposed group. This study identifies important related metabolic changes in the bodies of workers after long-term occupational exposure to low concentration ACR and suggests new biomarkers of nervous system injury caused by ACR. The study also provides a sound basis for exploring the biochemical mechanisms and metabolic pathways of nervous system toxicity caused by ACR. PMID: 31982394 [PubMed - as supplied by publisher]

metabolomics; +17 new citations

Sun, 26/01/2020 - 13:48
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 2020/01/26PubMed 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; +25 new citations

Sat, 25/01/2020 - 13:35
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 2020/01/25PubMed 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; +16 new citations

Fri, 24/01/2020 - 13:24
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 2020/01/24PubMed 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; +22 new citations

Thu, 23/01/2020 - 16:17
22 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 2020/01/23PubMed 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; +22 new citations

Thu, 23/01/2020 - 13:15
22 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 2020/01/23PubMed 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; +22 new citations

Wed, 22/01/2020 - 16:02
22 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 2020/01/22PubMed 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; +22 new citations

Wed, 22/01/2020 - 13:02
22 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 2020/01/22PubMed 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; +17 new citations

Tue, 21/01/2020 - 15:50
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 2020/01/21PubMed 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; +17 new citations

Tue, 21/01/2020 - 12:49
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 2020/01/21PubMed 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.

Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency.

Mon, 20/01/2020 - 12:39
Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2020 Jan 18;: Authors: Bleeker JC, Visser G, Clarke K, Ferdinandusse S, de Haan FH, Houtkooper RH, IJlst L, Kok IL, Langeveld M, van der Pol WL, de Sain-van der Velden MGM, Sibeijn-Kuiper A, Takken T, Wanders RJA, van Weeghel M, Wijburg FA, van der Woude LH, Wüst RCI, Cox PJ, Jeneson JAL Abstract BACKGROUND: A maladaptive shift from fat to carbohydrate (CHO) oxidation during exercise is thought to underlie myopathy and exercise-induced rhabdomyolysis in patients with fatty acid oxidation (FAO) disorders. We hypothesized that ingestion of a ketone ester (KE) drink prior to exercise could serve as an alternative oxidative substrate supply to boost muscular ATP homeostasis. To establish a rational basis for therapeutic use of KE supplementation in FAO, we tested this hypothesis in patients deficient in Very Long-Chain acyl-CoA Dehydrogenase (VLCAD). METHODS: Five patients (range 17-45 y; 4M/1F) patients were included in an investigator-initiated, randomized, blinded, placebo-controlled, 2-way cross-over study. Patients drank either a KE+CHO mix or an isocaloric CHO equivalent and performed 35 min upright cycling followed by 10 minutes supine cycling inside a Magnetic Resonance scanner at individual maximal FAO work rate (fatmax; ~40% VO2 max). The protocol was repeated after a one-week interval with the alternate drink. Primary outcome measures were quadriceps phosphocreatine (PCr), Pi and pH dynamics during exercise and recovery assayed by in vivo 31 P-MR spectroscopy. Secondary outcomes included plasma and muscle metabolites and respiratory gas exchange recordings. RESULTS: Ingestion of KE rapidly induced mild ketosis and increased muscle BHB content. During exercise at FATMAX, VLCADD-specific plasma acylcarnitine levels, quadriceps glycolytic intermediate levels and in vivo Pi/PCr ratio were all lower in KE+CHO than CHO. CONCLUSION: These results provide a rational basis for future clinical trials of synthetic ketone ester supplementation therapy in patients with FAO disorders. This article is protected by copyright. All rights reserved. PMID: 31955429 [PubMed - as supplied by publisher]

Metabolomics, sleepiness, and sleep duration in sleep apnea.

Mon, 20/01/2020 - 12:39
Metabolomics, sleepiness, and sleep duration in sleep apnea. Sleep Breath. 2020 Jan 18;: Authors: Diallo I, Pak VM Abstract PURPOSE: Although the mechanism is unclear, daytime sleepiness, a common sequela of obstructive sleep apnea (OSA), has been found to be correlated with a adverse cardiovascular outcomes. Reviewing metabolomics mechanisms of sleep disturbances and cardiovascular disease may help to explain this correlation. METHODS: This review examines the current literature on the relationships between sleepiness, sleep duration, and metabolites in sleep apnea. RESULTS: Although there is a lack of comprehensive literature in this emerging area, existing studies point to a variety of metabolites in different pathways that are associated with sleepiness and sleep duration. CONCLUSION: Advancing metabolomics research in sleep apnea will guide symptom research and provide alternate and novel opportunities for effective treatment for patients with OSA. PMID: 31955318 [PubMed - as supplied by publisher]

Canine metabolomics advances.

Mon, 20/01/2020 - 12:39
Canine metabolomics advances. Metabolomics. 2020 Jan 18;16(2):16 Authors: Carlos G, Dos Santos FP, Fröehlich PE Abstract INTRODUCTION: Canis lupus familiaris is a domestic dog and many owners consider their pets as a family member. Medical bills with dogs are overcame only by the health care received by humans. Medical care is constantly progressing, and so is veterinary care. Metabolomics is the ''omic" technique aimed to the study of metabolome, low-molecular weight molecules, through biofluids or tissue samples. And it also allows to evaluate disease diagnosis and prognosis, therapeutic evaluation and toxicological studies. OBJECTIVES: The goal of this paper is to review the current and potential applications of metabolomics in domestic dogs. METHOD: ScienceDirect, Scopus, Reaxys and PubMed were searched for papers that performed canine metabolomics in any research area. RESULTS: We analysed 38 papers, published until April 2019 in canine metabolomics approach. Metabolomic research in dogs so far can be divided into three areas: (a) Metabolomics studies in veterinary science, such as improving pet dogs health and welfare. (b) Diet, breeds and species discrimination. (c) Use of dogs as animal model in different diseases and drug development (evaluation toxicity and effect). CONCLUSIONS: The results of this review showed that interest in metabolomics is growing in veterinary research. Several canine diseases have been evaluated with some promise for potential biomarker and/or disease mechanism discovery. Because canine metabolomics is a relatively new area, the researches spread across different research areas and with few studies in each area. PMID: 31955274 [PubMed - in process]

Untargeted and targeted metabolomics strategy for the classification of strong aroma-type baijiu (liquor) according to geographical origin using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

Mon, 20/01/2020 - 12:39
Untargeted and targeted metabolomics strategy for the classification of strong aroma-type baijiu (liquor) according to geographical origin using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. Food Chem. 2019 Dec 30;314:126098 Authors: Song X, Jing S, Zhu L, Ma C, Song T, Wu J, Zhao Q, Zheng F, Zhao M, Chen F Abstract A metabolomics strategy was developed to differentiate strong aroma-type baijiu (SAB) (distilled liquor) from the Sichuan basin (SCB) and Yangtze-Huaihe River Basin (YHRB) through liquid-liquid extraction coupled with GC×GC-TOFMS. PCA effectively separated the samples from these two regions. The PLS-DA training model was excellent, with explained variation and predictive capability values of 0.988 and 0.982, respectively. As a result, the model demonstrated its ability to perfectly differentiate all the unknown SAB samples. Twenty-nine potential markers were located by variable importance in projection values, and twenty-four of them were identified and quantitated. Discrimination ability is closely correlated to the characteristic flavor compounds, such as acid, esters, furans, alcohols, sulfides and pyrazine. Most of the marker compounds were less abundant in the SCB samples than in the YHRB samples. The quantitated markers were further processed using hierarchical cluster analysis for targeted analysis, indicating that the markers had great discrimination power to differentiate the SAB samples. PMID: 31954940 [PubMed - as supplied by publisher]

The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes.

Mon, 20/01/2020 - 12:39
The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes. Mol Genet Metab. 2020 Jan 09;: Authors: Welsink-Karssies MM, van Weeghel M, Hollak CEM, Elfrink HL, Janssen MCH, Lai K, Langendonk JG, Oussoren E, Ruiter JPN, Treacy EP, de Vries M, Ferdinandusse S, Bosch AM Abstract BACKGROUND: The high variability in clinical outcome of patients with Classical Galactosemia (CG) is poorly understood and underlines the importance of prognostic biomarkers, which are currently lacking. The aim of this study was to investigate if residual galactose metabolism capacity is associated with clinical and biochemical outcomes in CG patients with varying geno- and phenotypes. METHODS: Galactose Metabolite Profiling (GMP) was used to determine residual galactose metabolism in fibroblasts of CG patients. The association between the galactose index (GI) defined as the ratio of the measured metabolites [U13C]Gal-1-P/ [13C6]UDP-galactose, and both intellectual and neurological outcome and galactose-1-phosphate (Gal-1-P) levels was investigated. RESULTS: GMP was performed in fibroblasts of 28 patients and 3 control subjects. The GI of the classical phenotype patients (n = 22) was significantly higher than the GI of four variant patients detected by newborn screening (NBS) (p = .002), two homozygous p.Ser135Leu patients (p = .022) and three controls (p = .006). In the classical phenotype patients, 13/18 (72%) had a poor intellectual outcome (IQ < 85) and 6/12 (50%) had a movement disorder. All the NBS detected variant patients (n = 4) had a normal intellectual outcome (IQ ≥ 85) and none of them has a movement disorder. In the classical phenotype patients, there was no significant difference in GI between patients with a poor and normal clinical outcome. The NBS detected variant patients had significantly lower GI levels and thus higher residual galactose metabolism than patients with classical phenotypes. There was a clear correlation between Gal-1-P levels in erythrocytes and the GI (p = .001). CONCLUSIONS: The GI was able to distinguish CG patients with varying geno- and phenotypes and correlated with Gal-1-P. The data of the NBS detected variant patients demonstrated that a higher residual galactose metabolism may result in a more favourable clinical outcome. Further research is needed to enable individual prognostication and treatment in all CG patients. PMID: 31954591 [PubMed - as supplied by publisher]

metabolomics; +34 new citations

Sun, 19/01/2020 - 15:22
34 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 2020/01/19PubMed 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; +34 new citations

Sun, 19/01/2020 - 12:19
34 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 2020/01/19PubMed 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.

Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena.

Sat, 18/01/2020 - 12:03
Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena. J Hazard Mater. 2020 Jan 10;388:122034 Authors: Yan S, Wang D, Teng M, Meng Z, Yan J, Li R, Jia M, Tian S, Zhou Z, Zhu W Abstract The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 μg/kg bw/day and 300 μg/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet- specific. Then the 1H NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the diet-specificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP. PMID: 31951990 [PubMed - as supplied by publisher]

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