PubMed

Related Articles Multi-omics study for interpretation of genome-wide association study. J Hum Genet. 2020 Sep 18;: Authors: Akiyama M Abstract Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with complex traits, including a wide variety of diseases. Despite the successful identification of associated loci, interpreting GWAS findings remains challenging and requires other biological resources. Omics, including genomics, transcriptomics, proteomics, metabolomics, and epigenomics, are increasingly used in a broad range of research fields. Integrative analyses applying GWAS with these omics data are expected to expand our knowledge of complex traits and provide insight into the pathogenesis of complex diseases and their causative factors. Recently, associations between genetic variants and omics data have been comprehensively evaluated, providing new information on the influence of genetic variants on omics. Furthermore, recent advances in analytic methods, including single-cell technologies, have revealed previously unknown disease mechanisms. To advance our understanding of complex traits, integrative analysis using GWAS with multi-omics data is needed. In this review, I describe successful examples of integrative analyses based on omics and GWAS, discuss the limitations of current multi-omics analyses, and provide a perspective on future integrative studies. PMID: 32948838 [PubMed - as supplied by publisher]

Related Articles Dengue virus dominates lipid metabolism modulations in Wolbachia-coinfected Aedes aegypti. Commun Biol. 2020 Sep 18;3(1):518 Authors: Koh C, Islam MN, Ye YH, Chotiwan N, Graham B, Belisle JT, Kouremenos KA, Dayalan S, Tull DL, Klatt S, Perera R, McGraw EA Abstract Competition between viruses and Wolbachia for host lipids is a proposed mechanism of Wolbachia-mediated virus blocking in insects. Yet, the metabolomic interaction between virus and symbiont within the mosquito has not been clearly defined. We compare the lipid profiles of Aedes aegypti mosquitoes bearing mono- or dual-infections of the Wolbachia wMel strain and dengue virus serotype 3 (DENV3). We found metabolic signatures of infection-induced intracellular events but little evidence to support direct competition between Wolbachia and virus for host lipids. Lipid profiles of dual-infected mosquitoes resemble those of DENV3 mono-infected mosquitoes, suggesting virus-driven modulation dominates over that of Wolbachia. Interestingly, knockdown of key metabolic enzymes suggests cardiolipins are host factors for DENV3 and Wolbachia replication. These findings define the Wolbachia-DENV3 metabolic interaction as indirectly antagonistic, rather than directly competitive, and reveal new research avenues with respect to mosquito × virus interactions at the molecular level. PMID: 32948809 [PubMed - as supplied by publisher]

Related Articles Metabolic Profiling of a Porcine Combat Trauma-Injury Model Using NMR and Multi-Mode LC-MS Metabolomics-A Preliminary Study. Metabolites. 2020 Sep 16;10(9): Authors: Laserna AKC, Lai Y, Fang G, Ganapathy R, Atan MSBM, Lu J, Wu J, Uttamchandani M, Moochhala SM, Li SFY Abstract Profiles of combat injuries worldwide have shown that penetrating trauma is one of the most common injuries sustained during battle. This is usually accompanied by severe bleeding or hemorrhage. If the soldier does not bleed to death, he may eventually succumb to complications arising from trauma hemorrhagic shock (THS). THS occurs when there is a deficiency of oxygen reaching the organs due to excessive blood loss. It can trigger massive metabolic derangements and an overwhelming inflammatory response, which can subsequently lead to the failure of organs and possibly death. A better understanding of the acute metabolic changes occurring after THS can help in the development of interventional strategies, as well as lead to the identification of potential biomarkers for rapid diagnosis of hemorrhagic shock and organ failure. In this preliminary study, a metabolomic approach using the complementary platforms of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS) was used to determine the metabolic changes occurring in a porcine model of combat trauma injury comprising of penetrating trauma to a limb with hemorrhagic shock. Several metabolites associated with the acute-phase reaction, inflammation, energy depletion, oxidative stress, and possible renal dysfunction were identified to be significantly changed after a thirty-minute shock period. PMID: 32948079 [PubMed - as supplied by publisher]

Related Articles Absorption and interaction mechanisms of uranium & cadmium in purple sweet potato(Ipomoea batatas L.). J Hazard Mater. 2020 Dec 05;400:123264 Authors: Lai JL, Zhang-Xuan D, Xiao-Hui JI, Xue-Gang L Abstract The purpose of this study was to reveal the absorption and interaction mechanisms of uranium (U) & cadmium (Cd) in corps. Purple sweet potato (Ipomoea batatas L.) was selected as the experimental material. The absorption behavior of U and Cd in this crop and the effects on mineral nutrition were analyzed in a pot experiment. The interactions between U and Cd in purple sweet potato were analyzed using UPLC-MS metabolome analysis. The pot experiment confirmed that the root tuber of the purple sweet potato had accumulated U (1.68-5.16 mg kg-1) and Cd (0.78-2.02 mg kg-1) and would pose a health risk if consumed. Both U and Cd significantly interfered with the mineral nutrient of the roots. Metabolomics revealed that a total of 4865 metabolites were identified in roots. 643 (419 up; 224 down), 526 (332 up; 194 down) and 634 (428 up; 214 down) different metabolites (DEMs) were identified in the U, Cd, and U + Cd exposure groups. Metabolic pathway analysis showed that U and Cd induced the expression of plant hormones (the first messengers) and cyclic nucleotides (cAMP and cGMP, second messengers) in cells and regulated the primary/secondary metabolism of roots to induce resistance to U and Cd toxicity. PMID: 32947695 [PubMed - as supplied by publisher]

Related Articles Root response in Pisum sativum under naproxen stress: Morpho-anatomical, cytological, and biochemical traits. Chemosphere. 2020 Nov;258:127411 Authors: Svobodníková L, Kummerová M, Zezulka Š, Babula P, Sendecká K Abstract Non-steroidal anti-inflammatory drugs as an important group of emerging environmental contaminants in irrigation water and soils can influence biochemical and physiological processes essential for growth and development in plants as non-target organisms. Plants are able to take up, transport, transform, and accumulate drugs in the roots. Root biomass in ten-days old pea plants was lowered by 6% already under 0.1 mg/L naproxen (NPX) due to a lowered number of lateral roots, although 0.5 mg/L NPX stimulated the total root length by 30% as against control. Higher section area (by 40%) in root tip, area of xylem (by 150%) or stele-to-section ratio (by 10%) in zone of maturation, and lower section area in zone of lateral roots (by 18%) prove the changes in primary root anatomy and its earlier differentiation at 10 mg/L NPX. Accumulated NPX (up to 10 μg/g DW at 10 mg/L) and products of its metabolization in roots increased the amounts of hydrogen peroxide (by 33%), and superoxide (by 62%), which was reflected in elevated lipid peroxidation (by 32%), disruption of membrane integrity (by 89%) and lowering both oxidoreductase and dehydrogenase activities (by up to 40%). Elevated antioxidant capacity (SOD, APX, and other molecules) under low treatments decreased at 10 mg/L NPX (both by approx. 30%). Naproxen was proved to cause changes at both cellular and tissue levels in roots, which was also reflected in their anatomy and morphology. Higher environmental loading through drugs thus can influence even the root function. PMID: 32947668 [PubMed - as supplied by publisher]

Related Articles Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice. Nat Chem Biol. 2020 06;16(6):667-675 Authors: Mock ED, Mustafa M, Gunduz-Cinar O, Cinar R, Petrie GN, Kantae V, Di X, Ogasawara D, Varga ZV, Paloczi J, Miliano C, Donvito G, van Esbroeck ACM, van der Gracht AMF, Kotsogianni I, Park JK, Martella A, van der Wel T, Soethoudt M, Jiang M, Wendel TJ, Janssen APA, Bakker AT, Donovan CM, Castillo LI, Florea BI, Wat J, van den Hurk H, Wittwer M, Grether U, Holmes A, van Boeckel CAA, Hankemeier T, Cravatt BF, Buczynski MW, Hill MN, Pacher P, Lichtman AH, van der Stelt M Abstract N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor. LEI-401 reduced NAE levels in neuroblastoma cells and in the brain of freely moving mice, but not in NAPE-PLD KO cells and mice, respectively. LEI-401 activated the hypothalamus-pituitary-adrenal axis and impaired fear extinction, thereby emulating the effect of a cannabinoid CB1 receptor antagonist, which could be reversed by a fatty acid amide hydrolase inhibitor. Our findings highlight the distinctive role of NAPE-PLD in NAE biosynthesis in the brain and suggest the presence of an endogenous NAE tone controlling emotional behavior. PMID: 32393901 [PubMed - indexed for MEDLINE]

Related Articles Quantitative Analysis of the Cellular Lipidome of Saccharomyces Cerevisiae Using Liquid Chromatography Coupled with Tandem Mass Spectrometry. J Vis Exp. 2020 03 08;(157): Authors: Mohammad K, Jiang H, Hossain MI, Titorenko VI Abstract Lipids are structurally diverse amphipathic molecules that are insoluble in water. Lipids are essential contributors to the organization and function of biological membranes, energy storage and production, cellular signaling, vesicular transport of proteins, organelle biogenesis, and regulated cell death. Because the budding yeast Saccharomyces cerevisiae is a unicellular eukaryote amenable to thorough molecular analyses, its use as a model organism helped uncover mechanisms linking lipid metabolism and intracellular transport to complex biological processes within eukaryotic cells. The availability of a versatile analytical method for the robust, sensitive, and accurate quantitative assessment of major classes of lipids within a yeast cell is crucial for getting deep insights into these mechanisms. Here we present a protocol to use liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for the quantitative analysis of major cellular lipids of S. cerevisiae. The LC-MS/MS method described is versatile and robust. It enables the identification and quantification of numerous species (including different isobaric or isomeric forms) within each of the 10 lipid classes. This method is sensitive and allows identification and quantitation of some lipid species at concentrations as low as 0.2 pmol/µL. The method has been successfully applied to assessing lipidomes of whole yeast cells and their purified organelles. The use of alternative mobile phase additives for electrospray ionization mass spectrometry in this method can increase the efficiency of ionization for some lipid species and can be therefore used to improve their identification and quantitation. PMID: 32202524 [PubMed - indexed for MEDLINE]

Related Articles Plasma metabolite biomarkers related to secondary hyperparathyroidism and parathyroid hormone. J Cell Biochem. 2019 09;120(9):15766-15775 Authors: Shen Q, Xiang W, Ye S, Lei X, Wang L, Jia S, Shao X, Weng C, Shen X, Wang Y, Feng S, Qu L, Wang C, Chen J, Zhang P, Jiang H Abstract BACKGROUND: Hyperphosphatemia, hypocalcemia, and elevation of parathyroid hormone (PTH) are typical abnormalities of uremic patients with Secondary hyperparathyroidism (SHPT). However, metabolic imbalance associated with SHPT is not well understood. METHODS: A total of 15 SHPT patients with an intact parathyroid hormone (iPTH) level > 600 pg/mL were set as preoperative (PR) group, 15 age- and gender-matched controls who had undergone parathyroidectomy plus forearm transplantation because of hyperparathyroidism and achieved an iPTH level <150 pg/mL were set as postoperative (PO) group. Metabolite profiling of these 30 uremic patients and five healthy controls (HC) was performed using ultra performance liquid chromatography-mass spectrometry. RESULTS: Five differential metabolites, including allyl isothiocyanate, L-phenylalanine, D-Aspartic acid, indoleacetaldehyde, and D-galactose correlated with PTH were identified in this study. Taking them as a biomarker signature, PR group can be distinguished from HC group with an area under the curve (AUC) of 0.947 (95% CI, 0.76-1) and PO group with an AUC of 0.6 (95% CI, 0.38-0.807). CONCLUSIONS: The serum metabolome correlated with PTH is successfully demonstrated for a better understanding of the pathogenesis of SHPT. PMID: 31069832 [PubMed - indexed for MEDLINE]

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 2020/09/20PubMed 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.

28 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 2020/09/18PubMed 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.

28 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 2020/09/18PubMed 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.

41 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 2020/09/17PubMed 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.

41 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 2020/09/17PubMed 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.

32 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 2020/09/16PubMed 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.

49 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 2020/09/15PubMed 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.

Antimicrobial and antiproliferative activities of novel synthesized 6-(quinolin-2-ylthio) pyridine derivatives with molecular docking study as multi-targeted JAK2/STAT3 inhibitors. Chem Biol Drug Des. 2020 Sep 12;: Authors: Nafie MS, Mahgoub S, Amer AM Abstract Quinoline derivatives are attracting considerable interest due to their biological importance. In this paper, several 2-amino-4-aryl-6-(quinolin-2-ylthio)pyridine-3,5-dicarbonitrile derivatives are synthesized by adopting a one-pot reaction of quinoline-2-thione, aromatic aldehydes, and malononitrile in the presence of sodium hydroxide in absolute ethanol. The structures of these newly synthesized compounds were determined using different spectroscopic techniques, including elemental analyses, IR, 1H NMR, and MS. The synthesized derivatives were screened for their antimicrobial and cytotoxic activities. Compounds 4a, 4b, 4d, and 4e exhibited promising antimicrobial activity compared to antibacterial and antifungal standard drugs. Additionally, 4f, 4d, and 4g showed potent cytotoxic activity against both MCF-7 and A549 cells with IC50 values (6.39- 9.3 μM). Our molecular docking results of compound 4f proves good binding affinity towards the three tested proteins as Jak2/STATA3 inhibition; are in accordance with the RT-PCR mRNA expressions of the compound against MCF-7 cells which downregulated the Jak2 and STAT3 genes, and this may be the proposed mode of action for anti-breast cancer activity. PMID: 32920942 [PubMed - as supplied by publisher]

MetabolomicDifferences of Exhaled Breath Condensate AmongChildren With and WithoutAsthma. Pediatr Allergy Immunol. 2020 Sep 13;: Authors: Chang-Chien J, Huang HY, Tsai HJ, Lo CJ, Lin WC, Tseng YL, Wang SL, Ho HY, Cheng ML, Yao TC Abstract BACKGROUND: There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community. METHODS: One hundred sixty-fiveAsian children (92 stable asthma and 73 non-asthmatic controls) participating in a population-based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance-based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis. RESULTS: EBC metabolomic signature (lactate, formate, butyrate and isobutyrate) had an area under the Receiver Operator Characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P<0.001) and FEV1 /FVC % predicted (AUC = 0.569; P<0.001). The AUC for EBC metabolomic signature was 0.745 in the validation set, which was slightly but not significantly lower than in the testing set (P = 0.282).We further extrapolated two potentially involved metabolic pathways, including pyruvate (P=1.67×10-3 ; impact: 0.14) and methane (P=1.89×10-3 ; impact: 0.15), as the most likely divergent metabolisms between children with and without asthma. CONCLUSION: This study provided evidence supporting the role of EBC metabolomicsignature to discriminate stable asthma in Asian children in the community, with a discriminative property outperforming conventional clinical tests such asFeNOor spirometry. PMID: 32920883 [PubMed - as supplied by publisher]

A rapid GC method coupled with quadrupole or time of flight mass spectrometry for metabolomics analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Sep 02;1160:122355 Authors: Wang Y, Zhou L, Zhou Y, Zhao C, Lu X, Xu G Abstract Gas chromatography-mass spectrometry (GC-MS) is an ideal tool for analyzing the intermediates of tricarboxylic acid cycle and glycolysis, sugars, organic acids and amino acids, etc. High-throughput metabolomics methods are required by large-scale clinical researches, and time of flight mass spectrometry (TOF MS) having fast scanning rate is preferable for rapid GC. Quadrupole MS (qMS) instruments have 95% market share, and their potential in rapid metabolomics is worth being studied. In this work, a within 15-min GC program was established and matched by qMS scanning for plasma metabolome analysis after N-methyl-N-(trimethylsilyl)-trifluoroacetamide derivatization. Compared to the longer-time program GC-qMS method, the rapid GC-qMS method had nearly no metabolome information loss, and it had excellent profile performance in repeatability, intra-day and inter-day precision, sampling range, linearity and extraction recovery. Compared to TOF MS, qMS achieved similar results in investigating lung cancer serum metabolic disruptions. Partial least squares-discriminant analysis revealed that the two datasets acquired by qMS and TOF MS had very similar model parameters, and most of top ranked differential metabolites were the same. This study provides a rapid and economical GC-qMS metabolomics method for researchers. Still, MS having faster scanning rate and higher sensitivity are recommended, if possible, to detect more small peaks and some co-eluted peaks. PMID: 32920480 [PubMed - as supplied by publisher]

The cardiac protection of Baoyuan decoction via gut-heart axis metabolic pathway. Phytomedicine. 2020 Sep 02;79:153322 Authors: Du Z, Wang J, Lu Y, Ma X, Wen R, Lin J, Zhou C, Song Z, Li J, Tu P, Jiang Y Abstract BACKGROUND: Gut-heart axis has emerged as a novel concept to provide new insights into the complex mechanisms of heart failure (HF) and offer new therapeutic targets. Cardiac hypertrophy (CH) is one of the etiological agents contributing to the development of HF. Baoyuan Decoction (BYD), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating CH and preventing HF. Previously, we have reported that BYD-targeted endogenous metabolites are potentially linked to gut microbiota metabolism, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of BYD remains to be elucidated. PURPOSE: To investigate whether the gut microbiota plays a key role in anti-CH effects of BYD. STUDY DESIGN: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and microflora suppression model was adopted to investigate the links between the microbiota-host metabolic interaction and BYD efficacy in CH rats. METHOD: Firstly, the efficacy evaluation of BYD in treating chronic isoproterenol (ISO)-induced CH rats was performed by using multiple pharmacodynamic approaches. Then, the fecal metabolomics and 16S rRNA sequencing techniques were used to obtain the microbial and metabolic features of BYD against CH. After that, the potential gut-heart axis-based mechanism of BYD against CH was predicted by bioinformatic network analysis and validated by multiple molecular biology approaches. Finally, the antibiotics (AB)-induced gut microbiota suppression was employed to investigate whether the anti-CH effects of BYD is associated with the gut microflora. RESULTS: The fecal microbial communities and metabolic compositions were significantly altered in ISO-induced CH rats, while BYD effectively ameliorated the CH-associated gut microbiota dysbiosis, especially of Firmicutes and Bacteroidetes, and time-dependently alleviated the disturbance of fecal metabolome and reversed the changes of key CH and gut microbiota-related metabolites, such as short/medium chain fatty acids, primary/secondary bile acids, and amino acids. The mechanism study showed that the anti-CH effect of BYD was related to inhibition of the derivatives of arginine and tryptophan and their downstream pro-hypertrophic, pro-inflammatory, and pro-oxidant signaling pathways. The following microflora suppression test showed that BYD-mediated myocardial protection was decreased either in pharmacodynamics or in metabolic modulation. CONCLUSION: This study demonstrates that the protection of BYD against CH is partially gut microbiota dependent, and the regulatory effects of gut metabolism-related tryptophan and arginine derivatives is an important cardioprotection mechanism of BYD. PMID: 32920286 [PubMed - as supplied by publisher]

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery. Nutr Metab Cardiovasc Dis. 2020 Jul 15;: Authors: Dadson P, Rebelos E, Honka H, Juárez-Orozco LE, Kalliokoski KK, Iozzo P, Teuho J, Salminen P, Pihlajamäki J, Hannukainen JC, Nuutila P Abstract BACKGROUND AND AIMS: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. METHODS AND RESULTS: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). CONCLUSION: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01373892. PMID: 32919861 [PubMed - as supplied by publisher]