PubMed

Related Articles Targeting bioactive compounds in natural extracts - Development of a comprehensive workflow combining chemical and biological data. Anal Chim Acta. 2019 Sep 06;1070:29-42 Authors: Ory L, Nazih EH, Daoud S, Mocquard J, Bourjot M, Margueritte L, Delsuc MA, Bard JM, Pouchus YF, Bertrand S, Roullier C Abstract In natural product drug discovery, several strategies have emerged to highlight specifically bioactive compound(s) within complex mixtures (fractions or crude extracts) using metabolomics tools. In this area, a great deal of interest has raised among the scientific community on strategies to link chemical profiles and associated biological data, leading to the new field called "biochemometrics". This article falls into this emerging research by proposing a complete workflow, which was divided into three major steps. The first one consists in the fractionation of the same extract using four different chromatographic stationary phases and appropriated elution conditions to obtain five fractions for each column. The second step corresponds to the acquisition of chemical profiles using HPLC-HRMS analysis, and the biological evaluation of each fraction. The last step evaluates the links between the relative abundances of molecules present in fractions (peak area) and the global bioactivity level observed for each fraction. To this purpose, an original bioinformatics script (encoded with R Studio software) using the combination of four statistical models (Spearman, F-PCA, PLS, PLS-DA) was here developed leading to the generation of a "Super list" of potential bioactive compounds together with a predictive score. This strategy was validated by its application on a marine-derived Penicillium chrysogenum extract exhibiting antiproliferative activity on breast cancer cells (MCF-7 cells). After the three steps of the workflow, one main compound was highlighted as responsible for the bioactivity and identified as ergosterol. Its antiproliferative activity was confirmed with an IC50 of 0.10 μM on MCF-7 cells. The script efficiency was further demonstrated by comparing the results obtained with a different recently described approach based on NMR profiling and by virtually modifying the data to evaluate the computational tool behaviour. This approach represents a new and efficient tool to tackle some of the bottlenecks in natural product drug discovery programs. PMID: 31103165 [PubMed - in process]

Related Articles Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin. Microbiome. 2019 May 18;7(1):76 Authors: Veach AM, Morris R, Yip DZ, Yang ZK, Engle NL, Cregger MA, Tschaplinski TJ, Schadt CW Abstract BACKGROUND: Plants have developed defense strategies for phytopathogen and herbivore protection via coordinated metabolic mechanisms. Low-molecular weight metabolites produced within plant tissues, such as salicylic acid, represent one such mechanism which likely mediates plant - microbe interactions above and below ground. Salicylic acid is a ubiquitous phytohormone at low levels in most plants, yet are concentrated defense compounds in Populus, likely acting as a selective filter for rhizosphere microbiomes. We propagated twelve Populus trichocarpa genotypes which varied an order of magnitude in salicylic acid (SA)-related secondary metabolites, in contrasting soils from two different origins. After four months of growth, plant properties (leaf growth, chlorophyll content, and net photosynthetic rate) and plant root metabolomics specifically targeting SA metabolites were measured via GC-MS. In addition, rhizosphere microbiome composition was measured via Illumina MiSeq sequencing of 16S and ITS2 rRNA-genes. RESULTS: Soil origin was the primary filter causing divergence in bacterial/archaeal and fungal communities with plant genotype secondarily influential. Both bacterial/archaeal and fungal evenness varied between soil origins and bacterial/archaeal diversity and evenness correlated with at least one SA metabolite (diversity: populin; evenness: total phenolics). The production of individual salicylic acid derivatives that varied by host genotype resulted in compositional differences for bacteria /archaea (tremuloidin) and fungi (salicylic acid) within one soil origin (Clatskanie) whereas soils from Corvallis did not illicit microbial compositional changes due to salicylic acid derivatives. Several dominant bacterial (e.g., Betaproteobacteria, Acidobacteria, Verrucomicrobia, Chloroflexi, Gemmatimonadete, Firmicutes) and one fungal phyla (Mortierellomycota) also correlated with specific SA secondary metabolites; bacterial phyla exhibited more negative interactions (declining abundance with increasing metabolite concentration) than positive interactions. CONCLUSIONS: These results indicate microbial communities diverge most among soil origin. However, within a soil origin, bacterial/archaeal communities are responsive to plant SA production within greenhouse-based rhizosphere microbiomes. Fungal microbiomes are impacted by root SA-metabolites, but overall to a lesser degree within this experimental context. These results suggest plant defense strategies, such as SA and its secondary metabolites, may partially drive patterns of both bacterial/archaeal and fungal taxa-specific colonization and assembly. PMID: 31103040 [PubMed - in process]

Related Articles High temperature-induced proteomic and metabolomic profiles of a thermophilic Bacillus manusensis isolated from the deep-sea hydrothermal field of Manus Basin. J Proteomics. 2019 May 15;:103380 Authors: Sun QL, Sun YY, Zhang J, Luan ZD, Lian C, Liu SQ, Yu C Abstract Thermophiles are organisms that grow optimally at 50 °C-80 °C and studies on the survival mechanisms of thermophiles have drawn great attention. Bacillus manusensis S50-6 is the type strain of a new thermophilic species isolated from hydrothermal vent in Manus Basin. In this study, we examined the growth and global responses of S50-6 to high temperature on molecular level using multi-omics method (genomics, proteomics, and metabolomics). S50-6 grew optimally at 50 °C (Favorable, F) and poorly at 65 °C (Non-Favorable, NF); it formed spores at F but not at NF condition. At NF condition, S50-6 formed long filaments containing undivided cells. A total of 1621 proteins were identified at F and NF conditions, and 613 proteins were differentially expressed between F and NF. At NF condition, proteins of glycolysis, rRNA mature and modification, and DNA/protein repair were up-regulated, whereas proteins of sporulation and amino acid/nucleotide metabolism were down-regulated. Consistently, many metabolites associated with amino acid and nucleotide metabolic processes were down-regulated at NF condition. Our results revealed molecular strategies of deep-sea B. manusensis to survive at unfavorable high temperature and provided new insights into the thermotolerant mechanisms of thermophiles. SIGNIFICANCE: In this study, we systematically characterized the genomic, proteomic and metabolomic profiles of a thermophilic deep-sea Bacillus manusensis under different temperatures. Based on these analysis, we propose a model delineating the global responses of B. manusensis to unfavorable high temperature. Under unfavorable high temperature, glycolysis is a more important energy supply pathway; protein synthesis is subjected to more stringent regulation by increased tRNA modification; protein and DNA repair associated proteins are enhanced in production to promote heat survival. In contrast, energy-costing pathways, such as sporulation, are repressed, and basic metabolic pathways, such as amino acid and nucleotide metabolisms, are slowed down. Our results provide new insights into the thermotolerant mechanisms of thermophilic Bacillus. PMID: 31102757 [PubMed - as supplied by publisher]

Related Articles Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum. Reprod Toxicol. 2019 May 15;: Authors: Hu X, Li S, Cirrilo P, Krigbaum N, Tran V, Ishikawa T, La Merrill MA, Jones DP, Cohn B Abstract The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p,p'-DDT, o,p'-DDT and p,p'-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p,p'-DDT and p,p'-DDE. Amino acids such arginine had a strong association with p,p'-DDT and o,p'-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p,p'-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine and fatty acid metabolism on the causal disease pathway should be examined. PMID: 31102720 [PubMed - as supplied by publisher]

Related Articles Capturing the complex interplay between drugs and the intestinal microbiome. Clin Pharmacol Ther. 2019 May 18;: Authors: Birer C, Wright ES Abstract Predicting drug interactions, disposition, and side effects is central to the practice of clinical pharmacology. Until recently, the human microbiome has been an underappreciated player in the dynamics of drug metabolism. It is now clear that humans are 'superorganisms' with about tenfold more microbial cells than human cells and harboring an immense diversity of microbial enzymes. Owing to the advent of new technologies, we are beginning to understand the human microbiome's impact on clinical pharmacology. This article is protected by copyright. All rights reserved. PMID: 31102465 [PubMed - as supplied by publisher]

Related Articles Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease. Eur Heart J. 2019 May 18;: Authors: Tzoulaki I, Castagné R, Boulangé CL, Karaman I, Chekmeneva E, Evangelou E, Ebbels TMD, Kaluarachchi MR, Chadeau-Hyam M, Mosen D, Dehghan A, Moayyeri A, Ferreira DLS, Guo X, Rotter JI, Taylor KD, Kavousi M, de Vries PS, Lehne B, Loh M, Hofman A, Nicholson JK, Chambers J, Gieger C, Holmes E, Tracy R, Kooner J, Greenland P, Franco OH, Herrington D, Lindon JC, Elliott P Abstract AIMS: To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). METHODS AND RESULTS: We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05). CONCLUSION: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis. PMID: 31102408 [PubMed - as supplied by publisher]

Related Articles A comparative analysis of egg provisioning using mass spectrometry during rapid life history evolution in sea urchins. Evol Dev. 2019 May 17;: Authors: Davidson PL, Thompson JW, Foster MW, Moseley MA, Byrne M, Wray GA Abstract A dramatic life history switch that has evolved numerous times in marine invertebrates is the transition from planktotrophic (feeding) to lecithotrophic (nonfeeding) larval development-an evolutionary tradeoff with many important developmental and ecological consequences. To attain a more comprehensive understanding of the molecular basis for this switch, we performed untargeted lipidomic and proteomic liquid chromatography-tandem mass spectrometry on eggs and larvae from three sea urchin species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph Heliocidaris tuberculata, and the distantly related planktotroph Lytechinus variegatus. We identify numerous molecular-level changes possibly associated with the evolution of lecithotrophy in H. erythrogramma. We find the massive lipid stores of H. erythrogramma eggs are largely composed of low-density, diacylglycerol ether lipids that, contrary to expectations, appear to support postmetamorphic development and survivorship. Rapid premetamorphic development in this species may instead be powered by upregulated carbohydrate metabolism or triacylglycerol metabolism. We also find proteins involved in oxidative stress regulation are upregulated in H. erythrogramma eggs, and apoB-like lipid transfer proteins may be important for echinoid oogenic nutrient provisioning. These results demonstrate how mass spectrometry can enrich our understanding of life history evolution and organismal diversity by identifying specific molecules associated with distinct life history strategies and prompt new hypotheses about how and why these adaptations evolve. PMID: 31102332 [PubMed - as supplied by publisher]

Related Articles Alternative outlets for sustaining photosynthetic electron transport during dark-to-light transitions. Proc Natl Acad Sci U S A. 2019 May 17;: Authors: Saroussi S, Karns DAJ, Thomas DC, Bloszies C, Fiehn O, Posewitz MC, Grossman AR Abstract Environmental stresses dramatically impact the balance between the production of photosynthetically derived energetic electrons and Calvin-Benson-Bassham cycle (CBBC) activity; an imbalance promotes accumulation of reactive oxygen species and causes cell damage. Hence, photosynthetic organisms have developed several strategies to route electrons toward alternative outlets that allow for storage or harmless dissipation of their energy. In this work, we explore the activities of three essential outlets associated with Chlamydomonas reinhardtii photosynthetic electron transport: (i) reduction of O2 to H2O through flavodiiron proteins (FLVs) and (ii) plastid terminal oxidases (PTOX) and (iii) the synthesis of starch. Real-time measurements of O2 exchange have demonstrated that FLVs immediately engage during dark-to-light transitions, allowing electron transport when the CBBC is not fully activated. Under these conditions, we quantified maximal FLV activity and its overall capacity to direct photosynthetic electrons toward O2 reduction. However, when starch synthesis is compromised, a greater proportion of the electrons is directed toward O2 reduction through both the FLVs and PTOX, suggesting an important role for starch synthesis in priming/regulating CBBC and electron transport. Moreover, partitioning energized electrons between sustainable (starch; energetic electrons are recaptured) and nonsustainable (H2O; energetic electrons are not recaptured) outlets is part of the energy management strategy of photosynthetic organisms that allows them to cope with the fluctuating conditions encountered in nature. Finally, unmasking the repertoire and control of such energetic reactions offers new directions for rational redesign and optimization of photosynthesis to satisfy global demands for food and other resources. PMID: 31101712 [PubMed - as supplied by publisher]

Related Articles ROIMCR: a powerful analysis strategy for LC-MS metabolomic datasets. BMC Bioinformatics. 2019 May 17;20(1):256 Authors: Gorrochategui E, Jaumot J, Tauler R Abstract BACKGROUND: The analysis of LC-MS metabolomic datasets appears to be a challenging task in a wide range of disciplines since it demands the highly extensive processing of a vast amount of data. Different LC-MS data analysis packages have been developed in the last few years to facilitate this analysis. However, most of these strategies involve chromatographic alignment and peak shaping and often associate each "feature" (i.e., chromatographic peak) with a unique m/z measurement. Thus, the development of an alternative data analysis strategy that is applicable to most types of MS datasets and properly addresses these issues is still a challenge in the metabolomics field. RESULTS: Here, we present an alternative approach called ROIMCR to: i) filter and compress massive LC-MS datasets while transforming their original structure into a data matrix of features without losing relevant information through the search of regions of interest (ROIs) in the m/z domain and ii) resolve compressed data to identify their contributing pure components without previous alignment or peak shaping by applying a Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) analysis. In this study, the basics of the ROIMCR method are presented in detail and a detailed description of its implementation is also provided. Data were analyzed using the MATLAB (The MathWorks, Inc., www.mathworks.com ) programming and computing environment. The application of the ROIMCR methodology is described in detail, with an example of LC-MS data generated in a lipidomic study and with other examples of recent applications. CONCLUSIONS: The methodology presented here combines the benefits of data filtering and compression based on the searching of ROI features, without the loss of spectral accuracy. The method has the benefits of the application of the powerful MCR-ALS data resolution method without the necessity of performing chromatographic peak alignment or modelling. The presented method is a powerful alternative to other existing data analysis approaches that do not use the MCR-ALS method to resolve LC-MS data. The ROIMCR method also represents an improved strategy compared to the direct applications of the MCR-ALS method that use less-powerful data compression strategies such as binning and windowing. Overall, the strategy presented here confirms the usefulness of the ROIMCR chemometrics method for analyzing LC-MS untargeted metabolomics data. PMID: 31101001 [PubMed - in process]

Related Articles Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer. Cancers (Basel). 2019 May 16;11(5): Authors: Loras A, Suárez-Cabrera C, Martínez-Bisbal MC, Quintás G, Paramio JM, Martínez-Máñez R, Gil S, Ruiz-Cerdá JL Abstract Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up. PMID: 31100982 [PubMed]

Related Articles Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells. Cancers (Basel). 2019 May 16;11(5): Authors: Iyer RV, Maguire O, Kim M, Curtin LI, Sexton S, Fisher DT, Schihl SA, Fetterly G, Menne S, Minderman H Abstract The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials. PMID: 31100868 [PubMed]

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 2019/05/18PubMed 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.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/05/17PubMed 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.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/05/17PubMed 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.

35 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 2019/05/16PubMed 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.

35 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 2019/05/16PubMed 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.

Related Articles Mass spectral databases for metabolomics: How to build a consistently annotated mass spectral database from pure reference compounds analyzed under electrospray ionization conditions? J Mass Spectrom. 2019 May 13;: Authors: Damont A, Olivier MF, Warnet A, Lyan B, Pujos-Guillot E, Jamin EL, Debrauwer L, Bernillon S, Junot C, Tabet JC, Fenaille F Abstract Nowadays, high-resolution mass spectrometry is widely used for metabolomic studies. Thanks to its high sensitivity, it enables the detection of a large range of metabolites. In metabolomics, the continuous quest for a metabolite identification as complete and accurate as possible has led during the last decade to an ever increasing development of public MS databases (including LC-MS data) concomitantly with bioinformatic tool expansion. To facilitate the annotation process of MS profiles obtained from biological samples, but also to ease data sharing, exchange and exploitation, the standardization and harmonization of the way to describe and annotate mass spectra seemed crucial to us. Indeed, under electrospray (ESI) conditions, a single metabolite does not produce a unique ion corresponding to its protonated or deprotonated form but could lead to a complex mixture of signals. These MS signals result from the existence of different natural isotopologues of the same compound and also to the potential formation of adduct ions, homo and hetero-multimeric ions, fragment ions resulting from "prompt" in-source dissociations. As a joint reflection process within the French Infrastructure for Metabolomics and Fluxomics (MetaboHUB) and with the purpose of developing a robust and exchangeable annotated MS database made from pure reference compounds (chemical standards) analysis, it appeared to us that giving the metabolomics community some clues to standardize and unambiguously annotate each MS feature, was a prerequisite to data entry and further efficient querying of the database. The use of a harmonized notation is also mandatory for inter-laboratory MS data exchange. Additionally, thorough description of the variety of MS signals arising from the analysis of a unique metabolite might provide greater confidence on its annotation. PMID: 31083780 [PubMed - as supplied by publisher]

Related Articles The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites. Metabolites. 2019 May 12;9(5): Authors: Ismail H, Gillespie AL, Calderwood D, Iqbal H, Gallagher C, Chevallier OP, Elliott CT, Pan X, Mirza B, Green BD Abstract Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce (Lactuca sativa) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033-9777%, aminooxononanoic acid increased 1141-1803% and 2,3,5,4'tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272-48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites. PMID: 31083625 [PubMed]

Related Articles Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019 May 11;8(2): Authors: Wimalawansa SJ Abstract Recent advances in vitamin D research indicate that this vitamin, a secosteroid hormone, has beneficial effects on several body systems other than the musculoskeletal system. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D] are essential for human physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. Vitamin D is one of the key controllers of systemic inflammation, oxidative stress and mitochondrial respiratory function, and thus, the aging process in humans. In turn, molecular and cellular actions form 1,25(OH)2D slow down oxidative stress, cell and tissue damage, and the aging process. On the other hand, hypovitaminosis D impairs mitochondrial functions, and enhances oxidative stress and systemic inflammation. The interaction of 1,25(OH)2D with its intracellular receptors modulates vitamin D-dependent gene transcription and activation of vitamin D-responsive elements, which triggers multiple second messenger systems. Thus, it is not surprising that hypovitaminosis D increases the incidence and severity of several age-related common diseases, such as metabolic disorders that are linked to oxidative stress. These include obesity, insulin resistance, type 2 diabetes, hypertension, pregnancy complications, memory disorders, osteoporosis, autoimmune diseases, certain cancers, and systemic inflammatory diseases. Vitamin D adequacy leads to less oxidative stress and improves mitochondrial and endocrine functions, reducing the risks of disorders, such as autoimmunity, infections, metabolic derangements, and impairment of DNA repair; all of this aids a healthy, graceful aging process. Vitamin D is also a potent anti-oxidant that facilitates balanced mitochondrial activities, preventing oxidative stress-related protein oxidation, lipid peroxidation, and DNA damage. New understandings of vitamin D-related advances in metabolomics, transcriptomics, epigenetics, in relation to its ability to control oxidative stress in conjunction with micronutrients, vitamins, and antioxidants, following normalization of serum 25(OH)D and tissue 1,25(OH)2D concentrations, likely to promise cost-effective better clinical outcomes in humans. PMID: 31083546 [PubMed]

Related Articles Metabolomics Studies to Assess Biological Functions of Vitamin E Nicotinate. Antioxidants (Basel). 2019 May 11;8(5): Authors: Marcocci L, Suzuki YJ Abstract Vitamin E nicotinate (tocopherol nicotinate, tocopheryl nicotinate; TN) is an ester of two vitamins, tocopherol (vitamin E) and niacin (vitamin B3), in which niacin is linked to the hydroxyl group of active vitamin E. This vitamin E ester can be chemically synthesized and is used for supplementation. However, whether TN is formed in the biological system was unclear. Our laboratory previously detected TN in rat heart tissues, and its level was 30-fold lower in a failing heart (Wang et al., PLoS ONE 2017, 12, e0176887). The rat diet used in these experiments contained vitamin E acetate (tocopherol acetate; TA) and niacin separately, but not in the form of TN. Since only TN, but not other forms of vitamin E, was decreased in heart failure, the TN structure may elicit biologic functions independent of serving as a source of active vitamin E antioxidant. To test this hypothesis, the present study performed metabolomics to compare effects of TN on cultured cells to those of TA plus niacin added separately (TA + N). Human vascular smooth muscle cells were treated with TN or with TA + N (100 μM) for 10 min. Metabolite profiles showed that TN and TA + N influenced the cells differentially. TN effectively upregulated various primary fatty acid amides including arachidonoylethanoamine (anandamide/virodhamine) and palmitamide. TN also activated mitogen-activated protein kinases. These results suggest a new biological function of TN to elicit cell signaling. PMID: 31083512 [PubMed]