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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 6 min ago

In situ metabolomics of aldosterone-producing adenomas.

Fri, 06/09/2019 - 15:29
Related Articles In situ metabolomics of aldosterone-producing adenomas. JCI Insight. 2019 Sep 05;4(17): Authors: Murakami M, Rhayem Y, Kunzke T, Sun N, Feuchtinger A, Ludwig P, Strom TM, Gomez-Sanchez C, Knösel T, Kirchner T, Williams TA, Reincke M, Walch AK, Beuschlein F Abstract Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between KCNJ5- and CACNA1D-mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs. PMID: 31484828 [PubMed - in process]

NMR-Based Metabolomics Profiling for Radical Scavenging and Anti-Aging Properties of Selected Herbs.

Fri, 06/09/2019 - 15:29
Related Articles NMR-Based Metabolomics Profiling for Radical Scavenging and Anti-Aging Properties of Selected Herbs. Molecules. 2019 Sep 03;24(17): Authors: Hussin M, Abdul Hamid A, Abas F, Ramli NS, Jaafar AH, Roowi S, Majid NA, Pak Dek MS Abstract Herbs that are usually recognized as medicinal plants are well known for their therapeutic effects and are traditionally used to treat numerous diseases, including aging. This study aimed to evaluate the metabolite variations among six selected herbs namely Curcurma longa, Oenanthe javanica, Vitex negundo, Pluchea indica, Cosmos caudatus and Persicaria minus using proton nuclear magnetic resonance (1H-NMR) coupled with multivariate data analysis (MVDA). The free radical scavenging activity of the extract was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assay. The anti-aging property was characterized by anti-elastase and anti-collagenase inhibitory activities. The results revealed that P. minus showed the highest radical scavenging activities and anti-aging properties. The partial least squares (PLS) biplot indicated the presence of potent metabolites in P. minus such as quercetin, quercetin-3-O-rhamnoside (quercitrin), myricetin derivatives, catechin, isorhamnetin, astragalin and apigenin. It can be concluded that P. minus can be considered as a potential source for an anti-aging ingredient and also a good free radical eradicator. Therefore, P. minus could be used in future development in anti-aging researches and medicinal ingredient preparations. PMID: 31484470 [PubMed - in process]

The Antialgal Mechanism of Luteolin-7-O-Glucuronide on Phaeocystis globosa by Metabolomics Analysis.

Fri, 06/09/2019 - 15:29
Related Articles The Antialgal Mechanism of Luteolin-7-O-Glucuronide on Phaeocystis globosa by Metabolomics Analysis. Int J Environ Res Public Health. 2019 Sep 03;16(17): Authors: Zhu J, Yang Y, Duan S, Sun D Abstract Antialgal compounds from plants have been identified as promising candidates for controlling harmful algal blooms (HABs). In our previous study, luteolin-7-O-glucuronide was used as a promising algistatic agent to control Phaeocystis globosa (P. globose) blooms; however, its antialgal mechanism on P. globosa have not yet been elaborated in detail. In this study, a liquid chromatography linked to tandem mass spectrometry (LC-MS/MS)-based untargeted metabolomic approach was used to investigate changes in intracellular and extracellular metabolites of P. globosa after exposure to luteolin-7-O-glucuronide. Significant differences in intracellular metabolites profiles were observed between treated and untreated groups; nevertheless, metabolic statuses for extracellular metabolites were similar among these two groups. For intracellular metabolites, 20 identified metabolites showed significant difference. The contents of luteolin, gallic acid, betaine and three fatty acids were increased, while the contents of α-Ketoglutarate and acetyl-CoA involved in tricarboxylic acid cycle, glutamate, and 11 organic acids were decreased. Changes in those metabolites may be induced by the antialgal compound in response to stress. The results revealed that luteolin played a vital role in the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, because luteolin increased the most in the treatment groups and had strong antialgal activity on P. globosa. α-Ketoglutarate and acetyl-CoA were the most inhibited metabolites, indicating that the antialgal compound inhibited the growth through disturbed the tricarboxylic acid (TCA) cycle of algal cells. To summarize, our data provides insights into the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, which can be used to further control P. globosa blooms. PMID: 31484378 [PubMed - in process]

metabolomics; +22 new citations

Thu, 05/09/2019 - 15:20
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 2019/09/05PubMed 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

Wed, 04/09/2019 - 15:12
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 2019/09/04PubMed 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

Wed, 04/09/2019 - 12:12
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 2019/09/04PubMed 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.

Chronic kidney disease: Biomarker diagnosis to therapeutic targets.

Tue, 03/09/2019 - 14:46
Related Articles Chronic kidney disease: Biomarker diagnosis to therapeutic targets. Clin Chim Acta. 2019 Aug 30;: Authors: Wang YN, Ma SX, Chen YY, Chen L, Liu BL, Liu QQ, Zhao YY Abstract Chronic kidney disease (CKD), characterized as renal dysfunction, is recognized as a major public health problem with high morbidity and mortality worldwide. Unfortunately, there are no obvious clinical symptoms in early stage disease until severe damage has occurred. Further complicating early diagnosis and treatment is the lack of sensitive and specific biomarkers. As such, novel biomarkers are urgently needed. Metabolomics has shown an increasing potential for identifying underlying disease mechanisms, facilitating clinical diagnosis and developing pharmaceutical treatments for CKD. Recent advances in metabolomics revealed that CKD was closely associated with the dysregulation of numerous metabolites, such as amino acids, lipids, nucleotides and glycoses, that might be exploited as potential biomarkers. In this review, we summarize recent metabolomic applications based on animal model studies and in patients with CKD and highlight several biomarkers that may play important roles in diagnosis, intervention and development of new therapeutic strategies. PMID: 31476302 [PubMed - as supplied by publisher]

Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.

Tue, 03/09/2019 - 14:46
Related Articles Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation. J Am Heart Assoc. 2019 Sep 03;8(17):e012809 Authors: Choi J, Shoaib M, Yin T, Nayyar G, Shinozaki K, Stevens JF, Becker LB, Kim J Abstract Background Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results Adult male Sprague-Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra-high-performance liquid chromatography-high-accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation. PMID: 31475603 [PubMed - in process]

The Diversity of Nutritional Metabolites: Origin, Dissection, and Application in Crop Breeding.

Tue, 03/09/2019 - 14:46
Related Articles The Diversity of Nutritional Metabolites: Origin, Dissection, and Application in Crop Breeding. Front Plant Sci. 2019;10:1028 Authors: Fang C, Luo J, Wang S Abstract The chemical diversity of plants is very high, and plant-based foods provide almost all the nutrients necessary for human health, either directly or indirectly. With advancements in plant metabolomics studies, the concept of nutritional metabolites has been expanded and updated. Because the concentration of many nutrients is usually low in plant-based foods, especially those from crops, metabolome-assisted breeding techniques using molecular markers associated with the synthesis of nutritional metabolites have been developed and used to improve nutritional quality of crops. Here, we review the origins of the diversity of nutrient metabolites from a genomic perspective and the role of gene duplication and divergence. In addition, we systematically review recent advances in the metabolomic and genetic basis of metabolite production in major crops. With the development of genome sequencing and metabolic detection technologies, multi-omic integrative analysis of genomes, transcriptomes, and metabolomes has greatly facilitated the deciphering of the genetic basis of metabolic pathways and the diversity of nutrient metabolites. Finally, we summarize the application of nutrient diversity in crop breeding and discuss the future development of a viable alternative to metabolome-assisted breeding techniques that can be used to improve crop nutrient quality. PMID: 31475024 [PubMed]

Distinct Morphological, Physiological, and Biochemical Responses to Light Quality in Barley Leaves and Roots.

Tue, 03/09/2019 - 14:46
Related Articles Distinct Morphological, Physiological, and Biochemical Responses to Light Quality in Barley Leaves and Roots. Front Plant Sci. 2019;10:1026 Authors: Klem K, Gargallo-Garriga A, Rattanapichai W, Oravec M, Holub P, Veselá B, Sardans J, Peñuelas J, Urban O Abstract Light quality modulates plant growth, development, physiology, and metabolism through a series of photoreceptors perceiving light signal and related signaling pathways. Although the partial mechanisms of the responses to light quality are well understood, how plants orchestrate these impacts on the levels of above- and below-ground tissues and molecular, physiological, and morphological processes remains unclear. However, the re-allocation of plant resources can substantially adjust plant tolerance to stress conditions such as reduced water availability. In this study, we investigated in two spring barley genotypes the effect of ultraviolet-A (UV-A), blue, red, and far-red light on morphological, physiological, and metabolic responses in leaves and roots. The plants were grown in growth units where the root system develops on black filter paper, placed in growth chambers. While the growth of above-ground biomass and photosynthetic performance were enhanced mainly by the combined action of red, blue, far-red, and UV-A light, the root growth was stimulated particularly by supplementary far-red light to red light. Exposure of plants to the full light spectrum also stimulates the accumulation of numerous compounds related to stress tolerance such as proline, secondary metabolites with antioxidative functions or jasmonic acid. On the other hand, full light spectrum reduces the accumulation of abscisic acid, which is closely associated with stress responses. Addition of blue light induced accumulation of γ-aminobutyric acid (GABA), sorgolactone, or several secondary metabolites. Because these compounds play important roles as osmolytes, antioxidants, UV screening compounds, or growth regulators, the importance of light quality in stress tolerance is unequivocal. PMID: 31475023 [PubMed]

Erratum to "Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder" [Eur Urol Focus 2018;4:907-915].

Tue, 03/09/2019 - 14:46
Related Articles Erratum to "Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder" [Eur Urol Focus 2018;4:907-915]. Eur Urol Focus. 2019 Aug 29;: Authors: Piyarathna DWB, Rajendiran TM, Putluri V, Vantaku V, Soni T, von Rundstedt FC, Donepudi SR, Jin F, Maity S, Ambati CR, Dong J, Gödde D, Roth S, Störkel S, Degener S, Michailidis G, Lerner SP, Pennathur S, Lotan Y, Coarfa C, Sreekumar A, Putluri N PMID: 31474581 [PubMed - as supplied by publisher]

Proton Transfer Reaction Mass Spectrometry for Plant Metabolomics.

Tue, 03/09/2019 - 14:46
Related Articles Proton Transfer Reaction Mass Spectrometry for Plant Metabolomics. Trends Plant Sci. 2019 Aug 29;: Authors: Majchrzak T, Wojnowski W, Wasik A PMID: 31474555 [PubMed - as supplied by publisher]

Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis.

Tue, 03/09/2019 - 14:46
Related Articles Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis. Drug Metab Pharmacokinet. 2019 Aug 02;: Authors: Yi M, Li Q, Zhao Y, Nie S, Wu N, Wang D Abstract The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in comparison between CHD with BSS patients (Group A) and healthy subjects (Group C), 59 significantly differential metabolites in the positive mode and 18 significantly differential metabolites in the negative mode. The metabolite constituents in the plasma of 30 CHD with BSS patients before (group A) and after 30 days of treatment (Group B), and 20 healthy subjects (Group C) were analyzed using LC-Q-TOF/MS and GC-MS. Based on multivariate statistical analysis (PCA, PLS-DA and OPLS-DA), we determined 69 differential metabolites. The levels of hemorheology indexes were significantly down-regulated after treatment. Metabolic pathway attribution analysis showed that lipid metabolism, amino acid metabolism and bile acid metabolism pathways are involved. Our study identifies the metabolic networks of CHD and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effect of XFZYC on CHD. PMID: 31474470 [PubMed - as supplied by publisher]

Characterizing the metabotype and its persistency in lactating Holstein cows: An approach toward metabolic efficiency measures.

Tue, 03/09/2019 - 14:46
Related Articles Characterizing the metabotype and its persistency in lactating Holstein cows: An approach toward metabolic efficiency measures. J Dairy Sci. 2019 Jul;102(7):6559-6570 Authors: Derno M, Nürnberg G, Kuhla B Abstract The variation in feed efficiency among dairy cows is due to differences in fermentation and digestion characteristics, but recent studies have suggested that various aspects of postabsorptive metabolic processes including heat production or the metabolizable energy for maintenance are more crucial. Thus, metabolic efficiency largely determines feed efficiency, but whether divergent feed efficient cows differ in O2 consumption and metabolic CO2 production, directly determining the metabolic rate has not been investigated. Therefore, the objective of the present study was to determine whether variation in ME intake (MEI), O2 consumption, and metabolic CO2 production account for the variation in metabolic efficiency of dairy cows and whether this effect persists across the lactation cycle. Eighteen cows with different German breeding value functional herd life were kept in freestalls with ad libitum access to a total mixed ration that was kept constant in composition throughout the first lactation. Cows were blood sampled and weighed at wk 5, 13, and 42 postpartum (pp) and transferred into respiration chambers. Animals were retrospectively clustered according to MEI, O2 consumption, and metabolic CO2 production, each normalized to metabolic body weight (mBW). Cluster analysis revealed 9 high metabolically efficient (high-Meff) and 9 low metabolically efficient cows. The high-Meff cows had greater MEI and feed conversion efficiency, produced less metabolic CO2 and methane, had a stronger negative energy balance, and tended to have a lower metabolic respiratory quotient. Further, high-Meff cows had lower residual MEI, less heat energy loss, and lower plasma glucose concentrations, but used a greater portion of body reserves instead of feed energy for milk synthesis, particularly at wk 5 and 13 pp. However, these group differences did not persist by wk 42 pp. Cow groups were not different in O2 consumption, milk yield, metabolizable energy for maintenance, or the efficiency of tissue utilization for milk synthesis, but high-Meff cows tended to have the lower German relative breeding value functional herd life, indicating a link between metabolic performance and productive lifespan. In conclusion, the use of a clustering approach involving MEI/mBW, O2/mBW, and CO2/mBW seems to be a promising method to differentiate cows with divergent metabolic efficiency but does not allow identifying an individual metabotype that persists across the whole lactation cycle. PMID: 31103305 [PubMed - indexed for MEDLINE]

A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats.

Tue, 03/09/2019 - 14:46
Related Articles A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats. Molecules. 2019 May 13;24(9): Authors: Luo L, Kang J, He Q, Qi Y, Chen X, Wang S, Liang S Abstract Naodesheng (NDS) is a widely used traditional Chinese medicine (TCM) prescription for the treatment of ischemic stroke. A combination of 10 components is derived from NDS. They are: Notoginsenoside R1, ginsenoside Rg1, ginsenoside b1, ginsenoside Rd, hydroxysafflor yellow A, senkyunolide I, puerarin, daidzein, vitexin, and ferulic acid. This study aimed to investigate the protective effect of the ten-component combination derived from NDS (TCNDS) on ischemic stroke rats with a middle cerebral artery occlusion (MCAO) model by integrating an NMR-based metabonomics approach with biochemical assessment. Our results showed that TCNDS could improve neurobehavioral function, decrease the cerebral infarct area, and ameliorate pathological features in MCAO model rats. In addition, TCNDS was found to decrease plasma lactate dehydrogenase (LDH) and malondialdehyde (MDA) production and increase plasma superoxide dismutase (SOD) production. Furthermore, 1H-NMR metabonomic analysis indicated that TCNDS could regulate the disturbed metabolites in the plasma, urine, and brain tissue of MCAO rats, and the possible mechanisms were involved oxidative stress, energy metabolism, lipid metabolism, amino acid metabolism, and inflammation. Correlation analysis were then performed to further confirm the metabolites involved in oxidative stress. Correlation analysis showed that six plasma metabolites had high correlations with plasma LDH, MDA, and SOD. This study provides evidence that an NMR-based metabonomics approach integrated with biochemical assessment can help to better understand the underlying mechanisms as well as the holistic effect of multiple compounds from TCM. PMID: 31086027 [PubMed - indexed for MEDLINE]

Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein.

Tue, 03/09/2019 - 14:46
Related Articles Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein. Biomacromolecules. 2018 09 10;19(9):3714-3724 Authors: Bücher KS, Yan H, Creutznacher R, Ruoff K, Mallagaray A, Grafmüller A, Dirks JS, Kilic T, Weickert S, Rubailo A, Drescher M, Schmidt S, Hansman G, Peters T, Uetrecht C, Hartmann L Abstract Norovirus infection is the major cause of nonbacterial gastroenteritis in humans and has been the subject of numerous studies investigating the virus's biophysical properties and biochemical function with the aim of deriving novel and highly potent entry inhibitors to prevent infection. Recently, it has been shown that the protruding P domain dimer (P-dimer) of a GII.10 Norovirus strain exhibits two new binding sites for l-fucose in addition to the canonical binding sites. Thus, these sites provide a novel target for the design of multivalent fucose ligands as entry inhibitors of norovirus infections. In this current study, a first generation of multivalent fucose-functionalized glycomacromolecules was synthesized and applied as model structures to investigate the potential targeting of fucose binding sites in human norovirus P-dimer. Following previously established solid phase polymer synthesis, eight precision glycomacromolecules varying in number and position of fucose ligands along an oligo(amidoamine) backbone were obtained and then used in a series of binding studies applying native MS, NMR, and X-ray crystallography. We observed only one fucose per glycomacromolecule binding to one P-dimer resulting in similar binding affinities for all fucose-functionalized glycomacromolecules, which based on our current findings we attribute to the overall size of macromolecular ligands and possibly to steric hindrance. PMID: 30071731 [PubMed - indexed for MEDLINE]

Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults.

Tue, 03/09/2019 - 14:46
Related Articles Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults. Physiol Rep. 2018 07;6(14):e13799 Authors: Hulston CJ, Woods RM, Dewhurst-Trigg R, Parry SA, Gagnon S, Baker L, James LJ, Markey O, Martin NRW, Ferguson RA, van Hall G Abstract Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m2 ) and 8 obese (33.6 ± 1.2 kg/m2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([13 C6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults. PMID: 30009507 [PubMed - indexed for MEDLINE]

Pseudoqc: A Regression-Based Simulation Software for Correction and Normalization of Complex Metabolomics and Proteomics Datasets.

Mon, 02/09/2019 - 14:39
Related Articles Pseudoqc: A Regression-Based Simulation Software for Correction and Normalization of Complex Metabolomics and Proteomics Datasets. Proteomics. 2019 Aug 31;:e1900264 Authors: Wang S, Yang H Abstract Various types of unwanted and uncontrollable signal variations in mass spectrometry (MS)-based metabolomics and proteomics datasets severely disturb the accuracies of metabolite and protein profiling. Therefore, pooled quality control (QC) samples are often employed in quality management processes, which are indispensable to the success of metabolomics and proteomics experiments, especially in high-throughput cases and long-term projects. However, data consistency and QC sample stability are still difficult to guarantee because of the experimental operation complexity and differences between experimenters. To make things worse, numerous proteomics projects do not take QC samples into consideration at the beginning of experimental design. Herein, we present a powerful and interactive web-based software, named pseudoQC, to simulate QC sample data for actual metabolomics and proteomics datasets using four different machine learning-based regression methods. The simulated data are used for correction and normalization of the two published datasets, and the obtained results suggest that nonlinear regression methods perform better than linear ones. Additionally, the above software is available as a web-based graphical user interface (GUI) and can be utilized by scientists without a bioinformatics background. pseudoQC is open-source software and freely available at https://www.omicsolution.org/wukong/pseudoQC/. This article is protected by copyright. All rights reserved. PMID: 31474000 [PubMed - as supplied by publisher]

Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota.

Mon, 02/09/2019 - 14:39
Related Articles Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota. J Nutr Biochem. 2019 Jul 30;72:108218 Authors: Sreng N, Champion S, Martin JC, Khelaifia S, Christensen JE, Padmanabhan R, Azalbert V, Blasco-Baque V, Loubieres P, Pechere L, Landrier JF, Burcelin R, Sérée E Abstract The polyphenols resveratrol (RSV) and curcumin (Cur) are phytoalexines and natural antibiotics with numerous pharmacological functions and metabolic impacts. Recent evidences show a broad control of gut microbiota by polyphenols which could influence glycemic regulation. The aim of this work is to estimate the respective effect of RSV and Cur alone or in association on the control of glycemia and on gut microbiota. A 5-week chronic treatment of hyperglycemic mice with RSV and/or Cur resulted in a differential effect on glucose tolerance test and modified gut microbiome. We precisely identified groups of bacteria representing a specific signature of the glycemic effect of RSV. Inferred metagenomic analysis and metabolic pathway prediction showed that the sulfur and branched-chain amino-acid (BCAA) metabolic activities are tightly correlated with the efficacy of RSV for the control of glycaemia. The impact on BCAA metabolism was further validated by serum metabolomics analysis. Altogether, we show that polyphenols specifically impact gut microbiota and corresponding metabolic functions which could be responsible for their therapeutic role. PMID: 31473511 [PubMed - as supplied by publisher]

A metabolomics study on effects of polyaromatic compounds in oil sand extracts on the respiratory, hepatic and nervous systems using three human cell lines.

Mon, 02/09/2019 - 14:39
Related Articles A metabolomics study on effects of polyaromatic compounds in oil sand extracts on the respiratory, hepatic and nervous systems using three human cell lines. Environ Res. 2019 Aug 19;178:108680 Authors: Sarma SN, Kimpe LE, Doyon VC, Blais JM, Chan HM Abstract Polyaromatic compounds (PACs) are by-products of combustion and are the major pollutants from the oil and gas industry. However, the mechanism of PACs induced toxicity still remains elusive. The aim of this study was to elucidate the effects of a typical mixture of PACs found in oil sand extract (OSE) on the respiratory, hepatic and nervous systems in humans using in vitro cell culture models followed by non-targeted metabolomics analysis. OSE collected from Alberta, Canada was fractionated into PAC and alkane fractions, and their effects after 24 h exposure on the cell viability measured by MTT assay in three human cell lines (A549, HepG2, and SK-N-SH) were studied. The PAC fractions showed significant dose-dependent cytotoxicity. A549 cells showed the highest sensitivity to OSE extracts, followed by SK-N-SH and HepG2. In contrast, the alkane fractions showed no effects on cell viability. The three human cell lines were further exposed with the PACs at 10% and 20% lethal concentration for 24 h. Metabolomics analysis of the cell extracts indicated that PACs treatments showed different disruptions on possible metabolic pathways on the three cell lines. PACs altered the sex steroid hormone metabolism and regulated the levels of leukotrienes metabolites in all three cell types. The amino acids L-cysteine, L-glutamine, L-tyrosine that are known to cause respiratory effects were significantly up-regulated in A549 cells. The PACs treated HepG2 cells showed down-regulation in metabolites responsible for the inflammatory mediation. Treatment of the differentiated SK-N-SH cells showed up-regulated metabolites involved with butanoate, fatty acid, and pyrimidine metabolism. Leukotriene metabolites were found to be significantly increased in all PACs treated cells. In conclusion, our results showed that PACs in OSE can alter the metabolism of the human lung, liver and neuronal cells and may induce toxicity in multiple target organs. PMID: 31473503 [PubMed - as supplied by publisher]

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