PubMed

Related Articles Seeing the forest for the trees: Retrieving plant secondary biochemical pathways from metabolome networks. Comput Struct Biotechnol J. 2021;19:72-85 Authors: Desmet S, Brouckaert M, Boerjan W, Morreel K Abstract Over the last decade, a giant leap forward has been made in resolving the main bottleneck in metabolomics, i.e., the structural characterization of the many unknowns. This has led to the next challenge in this research field: retrieving biochemical pathway information from the various types of networks that can be constructed from metabolome data. Searching putative biochemical pathways, referred to as biotransformation paths, is complicated because several flaws occur during the construction of metabolome networks. Multiple network analysis tools have been developed to deal with these flaws, while in silico retrosynthesis is appearing as an alternative approach. In this review, the different types of metabolome networks, their flaws, and the various tools to trace these biotransformation paths are discussed. PMID: 33384856 [PubMed]

Related Articles Molecular investigation of Tuscan sweet cherries sampled over three years: gene expression analysis coupled to metabolomics and proteomics. Hortic Res. 2021 Jan 01;8(1):12 Authors: Berni R, Charton S, Planchon S, Legay S, Romi M, Cantini C, Cai G, Hausman JF, Renaut J, Guerriero G Abstract Sweet cherry (Prunus avium L.) is a stone fruit widely consumed and appreciated for its organoleptic properties, as well as its nutraceutical potential. We here investigated the characteristics of six non-commercial Tuscan varieties of sweet cherry maintained at the Regional Germplasm Bank of the CNR-IBE in Follonica (Italy) and sampled ca. 60 days post-anthesis over three consecutive years (2016-2017-2018). We adopted an approach merging genotyping and targeted gene expression profiling with metabolomics. To complement the data, a study of the soluble proteomes was also performed on two varieties showing the highest content of flavonoids. Metabolomics identified the presence of flavanols and proanthocyanidins in highest abundance in the varieties Morellona and Crognola, while gene expression revealed that some differences were present in genes involved in the phenylpropanoid pathway during the 3 years and among the varieties. Finally, proteomics on Morellona and Crognola showed variations in proteins involved in stress response, primary metabolism and cell wall expansion. To the best of our knowledge, this is the first multi-pronged study focused on Tuscan sweet cherry varieties providing insights into the differential abundance of genes, proteins and metabolites. PMID: 33384418 [PubMed]

Related Articles Plasma and serum oxylipin, endocannabinoid, bile acid, steroid, fatty acid and nonsteroidal anti-inflammatory drug quantification in a 96-well plate format. Anal Chim Acta. 2021 Jan 25;1143:189-200 Authors: Pedersen TL, Gray IJ, Newman JW Abstract The goal of this research was to develop a high-throughput, cost-effective method for metabolic profiling of lipid mediators and hormones involved in the regulation of inflammation and energy metabolism, along with polyunsaturated fatty acids and common over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs). We describe a 96-well plate protein precipitation and filtration procedure for 50 μL of plasma or serum in the presence of 37 deuterated analogs and 2 instrument internal standards. Data is acquired in two back-to-back UPLC-MS/MS analyses using electrospray ionization with positive/negative switching and scheduled multiple reaction monitoring for the determination of 145 compounds, including oxylipins, endocannabinoids and like compounds, bile acids, glucocorticoids, sex steroids, polyunsaturated fatty acids, and 3 NSAIDs. Intra- and inter-batch variability was <25% for >70% of metabolites above the LOQ in both matrices, but higher inter-batch variability was observed for serum oxylipins and some bile acids. Results for NIST Standard Reference Material 1950, compared favorably with the 20 certified metabolite values covered by this assay, and we provide new data for oxylipins, N-acylethanolamides, glucocorticoids, and 17-hydroxy-progesterone in this material. Application to two independent cohorts of elderly men and women showed the routine detection of 86 metabolites, identified fasting state influences on essential fatty acid-derived oxylipins, N-acylethanolamides and conjugated bile acids, identified rare presence of high and low testosterone levels and the presence of NSAIDs in ∼10% of these populations. The described method appears valuable for investigations in large cohort studies to provide insight into metabolic cross-talk between the array of mediators assessed here. PMID: 33384117 [PubMed - in process]

Related Articles Anion exchange chromatography - Mass spectrometry for monitoring multiple quality attributes of erythropoietin biopharmaceuticals. Anal Chim Acta. 2021 Jan 25;1143:166-172 Authors: van Schaick G, Gstöttner C, Büttner A, Reusch D, Wuhrer M, Domínguez-Vega E Abstract Assessment of critical quality attributes of the biopharmaceutical erythropoietin (EPO) prior to product release requires the use of several analytical methods. We developed an MS-compatible anion exchange (AEX) method for monitoring multiple quality attributes of EPO biopharmaceuticals. AEX was performed using a stationary phase with quaternary ammonium functional groups and a pH gradient for elution. Baseline separation of charge variants and high-quality MS data were achieved using 30 mM ammonium formate pH 5.5 and 30 mM formic acid pH 2.5 as mobile phases. In a single experiment, assessment of critical quality attributes, such as charge heterogeneity, sialic acid content and number of N-acetyllactosamine units, was possible while providing additional information on other modifications such as O-acetylation and deamidation. In addition, good repeatability and robustness for the relative areas of the individual glycoforms and average number of Neu5Ac per EPO molecule were observed. The results were comparable to common pharmacopeia and standard methods with the advantage of requiring fewer analytical methods and less sample treatment saving time and costs. PMID: 33384114 [PubMed - in process]

Related Articles Single cell metabolomics using mass spectrometry: Techniques and data analysis. Anal Chim Acta. 2021 Jan 25;1143:124-134 Authors: Liu R, Yang Z Abstract Mass spectrometry (MS) based techniques are gaining popularity for metabolomics research due to their high sensitivity, wide detection range, and capability of molecular identification. Utilizing such powerful technique to explore the cellular metabolism at the single cell level not only appreciates the subtle cell-to-cell difference (i.e., cell heterogeneity), but also gains biological merits corresponding to individual cells or small cell subpopulations. In this review article, we first briefly summarize recent advances in single cell MS experimental techniques, and then emphasize on the single cell metabolomics data analysis approaches. Through implementation of statistical analysis and more advanced data analysis methods, single cell metabolomics is expected to find more potential applications in the translational and clinical fields in the future. PMID: 33384110 [PubMed - in process]

Related Articles Effects of a Synbiotic Formula on Functional Bowel Disorders and Gut Microbiota Profile during Long-Term Home Enteral Nutrition (LTHEN): A Pilot Study. Nutrients. 2020 Dec 29;13(1): Authors: D'Onofrio V, Del Chierico F, Belci P, Vernocchi P, Quagliariello A, Reddel S, Conta G, Mancino MV, Fadda M, Scigliano MC, Morelli R, De Francesco A, Guagnini F, Fassio F, Galletti R, Putignani L Abstract Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients. PMID: 33383954 [PubMed - in process]

Related Articles Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson's Disease. Metabolites. 2020 Dec 29;11(1): Authors: Lokhov PG, Maslov DL, Lichtenberg S, Trifonova OP, Balashova EE Abstract A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson's disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since 'omics' tests, to which the metabolomic LDT belongs, cover a variety of them. PMID: 33383698 [PubMed]

Related Articles Offspring susceptibility to metabolic alterations due to maternal high-fat diet and the impact of inhaled ozone used as a stressor. Sci Rep. 2020 10 01;10(1):16353 Authors: Snow SJ, Broniowska K, Karoly ED, Henriquez AR, Phillips PM, Ledbetter AD, Schladweiler MC, Miller CN, Gordon CJ, Kodavanti UP Abstract The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors. PMID: 33004997 [PubMed - in process]

Related Articles Data-driven multivariate population subgrouping via lipoprotein phenotypes versus apolipoprotein B in the risk assessment of coronary heart disease. Atherosclerosis. 2020 02;294:10-15 Authors: Ohukainen P, Kuusisto S, Kettunen J, Perola M, Järvelin MR, Mäkinen VP, Ala-Korpela M Abstract BACKGROUND AND AIMS: Population subgrouping has been suggested as means to improve coronary heart disease (CHD) risk assessment. We explored here how unsupervised data-driven metabolic subgrouping, based on comprehensive lipoprotein subclass data, would work in large-scale population cohorts. METHODS: We applied a self-organizing map (SOM) artificial intelligence methodology to define subgroups based on detailed lipoprotein profiles in a population-based cohort (n = 5789) and utilised the trained SOM in an independent cohort (n = 7607). We identified four SOM-based subgroups of individuals with distinct lipoprotein profiles and CHD risk and compared those to univariate subgrouping by apolipoprotein B quartiles. RESULTS: The SOM-based subgroup with highest concentrations for non-HDL measures had the highest, and the subgroup with lowest concentrations, the lowest risk for CHD. However, apolipoprotein B quartiles produced better resolution of risk than the SOM-based subgroups and also striking dose-response behaviour. CONCLUSIONS: These results suggest that the majority of lipoprotein-mediated CHD risk is explained by apolipoprotein B-containing lipoprotein particles. Therefore, even advanced multivariate subgrouping, with comprehensive data on lipoprotein metabolism, may not advance CHD risk assessment. PMID: 31931463 [PubMed - in process]

Related Articles Alternative splicing of UCP1 by non-cell-autonomous action of PEMT. Mol Metab. 2020 01;31:55-66 Authors: Johnson JM, Verkerke ARP, Maschek JA, Ferrara PJ, Lin CT, Kew KA, Neufer PD, Lodhi IJ, Cox JE, Funai K Abstract OBJECTIVE: Phosphatidylethanolamine methyltransferase (PEMT) generates phosphatidylcholine (PC), the most abundant phospholipid in the mitochondria and an important acyl chain donor for cardiolipin (CL) biosynthesis. Mice lacking PEMT (PEMTKO) are cold-intolerant when fed a high-fat diet (HFD) due to unclear mechanisms. The purpose of this study was to determine whether PEMT-derived phospholipids are important for the function of uncoupling protein 1 (UCP1) and thus for maintenance of core temperature. METHODS: To test whether PEMT-derived phospholipids are important for UCP1 function, we examined cold-tolerance and brown adipose (BAT) mitochondria from PEMTKO mice with or without HFD feeding. We complemented these studies with experiments on mice lacking functional CL due to tafazzin knockdown (TAZKD). We generated several conditional mouse models to study the tissue-specific roles of PEMT, including mice with BAT-specific knockout of PEMT (PEMT-BKO). RESULTS: Chow- and HFD-fed PEMTKO mice completely lacked UCP1 protein in BAT, despite a lack of difference in mRNA levels, and the mice were accordingly cold-intolerant. While HFD-fed PEMTKO mice exhibited reduced mitochondrial CL content, this was not observed in chow-fed PEMTKO mice or TAZKD mice, indicating that the lack of UCP1 was not attributable to CL deficiency. Surprisingly, the PEMT-BKO mice exhibited normal UCP1 protein levels. Knockout of PEMT in the adipose tissue (PEMT-AKO), liver (PEMT-LKO), or skeletal muscle (PEMT-MKO) also did not affect UCP1 protein levels, suggesting that lack of PEMT in other non-UCP1-expressing cells communicates to BAT to suppress UCP1. Instead, we identified an untranslated UCP1 splice variant that was triggered during the perinatal period in the PEMTKO mice. CONCLUSIONS: PEMT is required for UCP1 splicing that yields functional protein. This effect is derived by PEMT in nonadipocytes that communicates to BAT during embryonic development. Future research will focus on identifying the non-cell-autonomous PEMT-dependent mechanism of UCP1 splicing. PMID: 31918922 [PubMed - in process]

38 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 2021/01/01PubMed 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.

38 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 2021/01/01PubMed 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.

47 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 2020/12/31PubMed 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.

47 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 2020/12/31PubMed 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.

19 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 2020/12/30PubMed 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.

65 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 2020/12/29PubMed 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.

Related Articles LC-MS based plasma metabolomics study of the intervention effect of different polar parts of Hawthorn on hyperlipidemia rats. J Sep Sci. 2020 Dec 22;: Authors: Zeng L, Luo L, Xue Q, He Q, Chen X, Meng J, Wang S, Liang S Abstract Hawthorn, a well-known traditional Chinese medicine is used for treatment of dyspepsia syndrome, cardiovascular disease and hyperlipidemia. Hawthorn has complex composition, therefore, the effective fraction and mechanisms of action in alleviating hyperlipidemia are unknown. Therefore, the aim of this study was to evaluate effects of four different polar components of hawthorn on hyperlipidemia rats, and to explore underlying mechanisms of action through LC-MS based plasma metabolomics. Hyperlipidemia rat model was established by feeding rats using high-fat diet. High-fat model rats were then treated with 4 polar components of hawthorn for 14 consecutive days. Plasma samples were collected and subjected to biochemical and metabolomics analysis. Biochemical analysis showed that hawthorn n-butanol and ethyl acetate extracts had the highest efficacy on hyperlipidemia rats. Water fraction showed a partial effect, whereas petroleum ether extract was not effective against hyperlipidemia rats. Furthermore, LC-MS metabolomics analysis showed that the most effective fraction of hawthorn reversed the metabolic disorder in plasma of hyperlipidemia rats. Metabolomics analysis showed that hawthorn exerts its activity by modulating lipid metabolism, energy metabolism, oxidative stress and amino acid metabolism. This article is protected by copyright. All rights reserved. PMID: 33354898 [PubMed - as supplied by publisher]

Related Articles Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort. Epigenet Insights. 2020;13:2516865720977888 Authors: Goodrich JM, Hector EC, Tang L, LaBarre JL, Dolinoy DC, Mercado-Garcia A, Cantoral A, Song PX, Téllez-Rojo MM, Peterson KE Abstract Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth (IGF2, H19, HSD11B2) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR q < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with HSD11B2, 103 with H19, and 4 with IGF2. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or H19 methylation at q < 0.05) and 1-octadecanoyl-rac-glycerol (q < 0.0001 for association with H19 and q = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity (P < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between H19 and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence. PMID: 33354655 [PubMed]

Related Articles Skin Metabolomics. Trends Endocrinol Metab. 2020 Dec 19;: Authors: Elpa DP, Chiu HY, Wu SP, Urban PL Abstract Skin retains numerous low-molecular-weight compounds (metabolites). Some of these compounds fulfill specific physiological roles, while others are by-products of metabolism. The skin surface can be sampled to detect and quantify skin metabolites related to diseases. Miniature probes have been developed to detect selected high-abundance metabolites secreted with sweat. To characterize a broad spectrum of skin metabolites, specimens are collected with one of several available methods, and the processed specimens are analyzed by chromatography, mass spectrometry (MS), or other techniques. Diseases for which skin-related biomarkers have been found include cystic fibrosis (CF), psoriasis, Parkinson's disease (PD), and lung cancer. To increase the clinical significance of skin metabolomics, it is desirable to verify correlations between metabolite levels in skin and other biological tissues/matrices. PMID: 33353809 [PubMed - as supplied by publisher]

Related Articles Data-Independent Acquisition for the Quantification and Identification of Metabolites in Plasma. Metabolites. 2020 Dec 18;10(12): Authors: van der Laan T, Boom I, Maliepaard J, Dubbelman AC, Harms AC, Hankemeier T Abstract A popular fragmentation technique for non-targeted analysis is called data-independent acquisition (DIA), because it provides fragmentation data for all analytes in a specific mass range. In this work, we demonstrated the strengths and weaknesses of DIA. Two types of chromatography (fractionation/3 min and hydrophilic interaction liquid chromatography (HILIC)/18 min) and three DIA protocols (variable sequential window acquisition of all theoretical mass spectra (SWATH), fixed SWATH and MSALL) were used to evaluate the performance of DIA. Our results show that fast chromatography and MSALL often results in product ion overlap and complex MS/MS spectra, which reduces the quantitative and qualitative power of these DIA protocols. The combination of SWATH and HILIC allowed for the correct identification of 20 metabolites using the NIST library. After SWATH window customization (i.e., variable SWATH), we were able to quantify ten structural isomers with a mean accuracy of 103% (91-113%). The robustness of the variable SWATH and HILIC method was demonstrated by the accurate quantification of these structural isomers in 10 highly diverse blood samples. Since the combination of variable SWATH and HILIC results in good quantitative and qualitative fragmentation data, it is promising for both targeted and untargeted platforms. This should decrease the number of platforms needed in metabolomics and increase the value of a single analysis. PMID: 33353236 [PubMed]