PubMed

Related Articles Simultaneous untargeted and targeted metabolomics profiling of underivatized primary metabolites in sulfur-deficient barley by ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Plant Methods. 2018;14:62 Authors: Ghosson H, Schwarzenberg A, Jamois F, Yvin JC Abstract Background: Metabolomics based on mass spectrometry analysis are increasingly applied in diverse scientific domains, notably agronomy and plant biology, in order to understand plants' behaviors under different stress conditions. In fact, these stress conditions are able to disrupt many biosynthetic pathways that include mainly primary metabolites. Profiling and quantifying primary metabolites remain a challenging task because they are poorly retained in reverse phase columns, due to their high polarity and acid-base properties. The aim of this work is to develop a simultaneous untargeted/targeted profiling of amino acids, organic acids, sulfur metabolites, and other several metabolites. This method will be applied on sulfur depleted barley, in order to study this type of stress, which is difficult to detect at early stage. Also, this method aims to explore the impact of this stress on barley's metabolome. Results: Ultra-high performance liquid chromatography-high resolution mass spectrometry-based method was successfully applied to real samples allowing to discriminate, detect, and quantify primary metabolites in short-runs without any additional sampling step such as derivatization or ion pairing. The retention of polar metabolites was successfully achieved using modified C18 columns with high reproducibility (relative standard deviation below 10%). The quantification method showed a high sensitivity and robustness. Furthermore, high resolution mass spectrometry detection provided reliable quantification based on exact mass, eliminating potential interferences, and allowing the simultaneous untargeted metabolomics analysis. The untargeted data analysis was conducted using Progenesis QI software, performing alignment, peak picking, normalization and multivariate analysis. The simultaneous analysis provided cumulative information allowing to discriminate between two plant batches. Thus, discriminant biomarkers were identified and validated. Simultaneously, quantification confirmed coherently the relative abundance of these biomarkers. Conclusions: A fast and innovated simultaneous untargeted/targeted method has successfully been developed and applied to sulfur deficiency on barley. This work opens interesting perspectives in both fundamental and applied research. Biomarker discovery give precious indication to understand plant behavior during a nutritional deficiency. Thus, direct or indirect measurement of these compounds allows a real time fertilization management and encounter the challenges of sustainable agriculture. PMID: 30061918 [PubMed]

Related Articles Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart. Proc Natl Acad Sci U S A. 2018 Jul 30;: Authors: Warren JS, Tracy CM, Miller MR, Makaju A, Szulik MW, Oka SI, Yuzyuk TN, Cox JE, Kumar A, Lozier BK, Wang L, Llana JG, Sabry AD, Cawley KM, Barton DW, Han YH, Boudina S, Fiehn O, Tucker HO, Zaitsev AV, Franklin S Abstract Smyd1, a muscle-specific histone methyltransferase, has established roles in skeletal and cardiac muscle development, but its role in the adult heart remains poorly understood. Our prior work demonstrated that cardiac-specific deletion of Smyd1 in adult mice (Smyd1-KO) leads to hypertrophy and heart failure. Here we show that down-regulation of mitochondrial energetics is an early event in these Smyd1-KO mice preceding the onset of structural abnormalities. This early impairment of mitochondrial energetics in Smyd1-KO mice is associated with a significant reduction in gene and protein expression of PGC-1α, PPARα, and RXRα, the master regulators of cardiac energetics. The effect of Smyd1 on PGC-1α was recapitulated in primary cultured rat ventricular myocytes, in which acute siRNA-mediated silencing of Smyd1 resulted in a greater than twofold decrease in PGC-1α expression without affecting that of PPARα or RXRα. In addition, enrichment of histone H3 lysine 4 trimethylation (a mark of gene activation) at the PGC-1α locus was markedly reduced in Smyd1-KO mice, and Smyd1-induced transcriptional activation of PGC-1α was confirmed by luciferase reporter assays. Functional confirmation of Smyd1's involvement showed an increase in mitochondrial respiration capacity induced by overexpression of Smyd1, which was abolished by siRNA-mediated PGC-1α knockdown. Conversely, overexpression of PGC-1α rescued transcript expression and mitochondrial respiration caused by silencing Smyd1 in cardiomyocytes. These findings provide functional evidence for a role of Smyd1, or any member of the Smyd family, in regulating cardiac energetics in the adult heart, which is mediated, at least in part, via modulating PGC-1α. PMID: 30061404 [PubMed - as supplied by publisher]

Related Articles Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review. Cancers (Basel). 2018 Jul 27;10(8): Authors: Erben V, Bhardwaj M, Schrotz-King P, Brenner H Abstract BACKGROUND: Several approaches have been suggested to be useful in the early detection of colorectal neoplasms. Since metabolites are closely related to the phenotype and are available from different human bio-fluids, metabolomics are candidates for non-invasive early detection of colorectal neoplasms. OBJECTIVES: We aimed to summarize current knowledge on performance characteristics of metabolomics biomarkers that are potentially applicable in a screening setting for the early detection of colorectal neoplasms. DESIGN: We conducted a systematic literature search in PubMed and Web of Science and searched for biomarkers for the early detection of colorectal neoplasms in easy-to-collect human bio-fluids. Information on study design and performance characteristics for diagnostic accuracy was extracted. RESULTS: Finally, we included 41 studies in our analysis investigating biomarkers in different bio-fluids (blood, urine, and feces). Although single metabolites mostly had limited ability to distinguish people with and without colorectal neoplasms, promising results were reported for metabolite panels, especially amino acid panels in blood samples, as well as nucleosides in urine samples in several studies. However, validation of the results is limited. CONCLUSIONS: Panels of metabolites consisting of amino acids in blood and nucleosides in urinary samples might be useful biomarkers for early detection of advanced colorectal neoplasms. However, to make metabolomic biomarkers clinically applicable, future research in larger studies and external validation of the results is required. PMID: 30060469 [PubMed]

Related Articles 1H-NMR metabolomic profiling reveals a distinct metabolic recovery response in shoots and roots of temporarily drought-stressed sugar beets. PLoS One. 2018;13(5):e0196102 Authors: Wedeking R, Maucourt M, Deborde C, Moing A, Gibon Y, Goldbach HE, Wimmer MA Abstract Yield formation in regions with intermittent drought periods depends on the plant's ability to recover after cessation of the stress. The present work assessed differences in metabolic recovery of leaves and roots of drought-stressed sugar beets with high temporal resolution. Plants were subjected to drought for 13 days, and rewatered for 12 days. At one to two-day intervals, plant material was harvested for untargeted 1H-NMR metabolomic profiling, targeted analyses of hexose-phosphates, starch, amino acids, nitrate and proteins, and physiological measurements including relative water content, osmotic potential, electrolyte leakage and malondialdehyde concentrations. Drought triggered changes in primary metabolism, especially increases in amino acids in both organs, but leaves and roots responded with different dynamics to rewatering. After a transient normalization of most metabolites within 8 days, a second accumulation of amino acids in leaves might indicate a stress imprint beneficial in upcoming drought events. Repair mechanisms seemed important during initial recovery and occurred at the expense of growth for at least 12 days. These results indicate that organ specific metabolic recovery responses might be related to distinct functions and concomitant disparate stress levels in above- and belowground organs. With respect to metabolism, recovery was not simply a reversal of the stress responses. PMID: 29738573 [PubMed - indexed for MEDLINE]

Related Articles Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls. PLoS One. 2018;13(4):e0195318 Authors: Fiandaca MS, Mapstone M, Mahmoodi A, Gross T, Macciardi F, Cheema AK, Merchant-Borna K, Bazarian J, Federoff HJ Abstract Past and recent attempts at devising objective biomarkers for traumatic brain injury (TBI) in both blood and cerebrospinal fluid have focused on abundance measures of time-dependent proteins. Similar independent determinants would be most welcome in diagnosing the most common form of TBI, mild TBI (mTBI), which remains difficult to define and confirm based solely on clinical criteria. There are currently no consensus diagnostic measures that objectively define individuals as having sustained an acute mTBI. Plasma metabolomic analyses have recently evolved to offer an alternative to proteomic analyses, offering an orthogonal diagnostic measure to what is currently available. The purpose of this study was to determine whether a developed set of metabolomic biomarkers is able to objectively classify college athletes sustaining mTBI from non-injured teammates, within 6 hours of trauma and whether such a biomarker panel could be effectively applied to an independent cohort of TBI and control subjects. A 6-metabolite panel was developed from biomarkers that had their identities confirmed using tandem mass spectrometry (MS/MS) in our Athlete cohort. These biomarkers were defined at ≤6 hours following mTBI and objectively classified mTBI athletes from teammate controls, and provided similar classification of these groups at the 2, 3, and 7 days post-mTBI. The same 6-metabolite panel, when applied to a separate, independent cohort provided statistically similar results despite major differences between the two cohorts. Our confirmed plasma biomarker panel objectively classifies acute mTBI cases from controls within 6 hours of injury in our two independent cohorts. While encouraged by our initial results, we expect future studies to expand on these initial observations. PMID: 29677216 [PubMed - indexed for MEDLINE]

Related Articles Productivity, Physicochemical Changes, and Antioxidant Activity of Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Cultivated on Lignocellulosic Residues. Int J Med Mushrooms. 2017;19(11):1041-1052 Authors: Gaitán-Hernández R, Zavaleta MAB, Aquino-Bolaños EN Abstract The effects of substrate and strain on productivity, physicochemical characteristics, and compounds with antioxidant activity were evaluated in basidiomes of the shiitake mushroom, Lentinus edodes. Strains IE-245 and IE-256 and the substrates oak wood shavings (OW), sorghum stubble (SS), and sugar cane bagasse (SC) were used. Productivity was evaluated by measuring biological efficiency (BE), production rate (PR), and yield. Total sugars, total soluble solids, pH, titratable acidity, color parameters, total phenolics, flavonoids, ascorbic acid, and antioxidant activity of the basidiomes were measured. BE, PR and yield were higher with the combination IE-256/SS, at 103.71%, 1.32%, and 34.57%, respectively. The largest amount of total sugars (17.61 mg glucose · g-1 dry weight) was found with combination IE-256/SS. Variation was observed in basidiome color; the lowest luminosity (L*) value (darkest color) was found in the IE-256 strain on the OW substrate (L* = 30.45), whereas that of the IE-245 strain on the SC substrate was the lightest in color (L* = 57.00). The largest amounts of total phenolics were recorded in the IE-256 strain on the OW (6.50 mg gallic acid equivalents [GAE] · g-1 dry weight) and the SS substrates (5.85 mg GAE · g-1 dry weight). The best antioxidant activity was obtained with IE-256-0.80, 0.65, and 0.59 μmol Trolox equivalents · g dry weight-1-on the OW, SC, and SS substrates, respectively. Based on the values of BE, PR, and yield, IE-256/SS was the most productive. Substrate and strain, and their interactions, influenced the physicochemical characteristics of the basidiomes and the amounts of compounds with antioxidant activity they contained. PMID: 29345566 [PubMed - indexed for MEDLINE]

Related Articles Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis. Transl Res. 2018 05;195:25-47 Authors: Mindikoglu AL, Opekun AR, Putluri N, Devaraj S, Sheikh-Hamad D, Vierling JM, Goss JA, Rana A, Sood GK, Jalal PK, Inker LA, Mohney RP, Tighiouart H, Christenson RH, Dowling TC, Weir MR, Seliger SL, Hutson WR, Howell CD, Raufman JP, Magder LS, Coarfa C Abstract The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultrahigh performance liquid chromatography-tandem mass spectrometry to identify preliminary metabolomic biomarker candidates. Among the 1028 metabolites identified, 34 were significantly increased in subjects with high liver and kidney disease severity compared with those with low liver and kidney disease severity. The highest average fold-change (2.39) was for 4-acetamidobutanoate. Metabolite-based enriched pathways were significantly associated with the identified metabolomic signature (P values ranged from 2.07E-06 to 0.02919). Ascorbate and aldarate metabolism, methylation, and glucuronidation were among the most significant protein-based enriched pathways associated with this metabolomic signature (P values ranged from 1.09E-18 to 7.61E-05). Erythronate had the highest association with measured GFR (R-square = 0.571, P <0.0001). Erythronate (R = 0.594, P <0.0001) and N6-carbamoylthreonyladenosine (R = 0.591, P <0.0001) showed stronger associations with measured GFR compared with creatinine (R = 0.588, P <0.0001) even after controlling for age, gender, and race. The 5 most significant metabolites that predicted mortality independent of kidney disease and demographics were S-adenosylhomocysteine (P = 0.0003), glucuronate (P = 0.0006), trans-aconitate (P = 0.0018), 3-ureidopropionate (P = 0.0021), and 3-(4-hydroxyphenyl)lactate (P = 0.0047). A unique metabolomic signature associated with hepatorenal dysfunction in cirrhosis was identified for further investigations that provide potentially important mechanistic insights into cirrhosis-altered metabolism. PMID: 29291380 [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 2018/07/31PubMed 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.

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 2018/07/31PubMed 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.

Metabolite changes behind faster growth and less reproduction of Daphnia similis exposed to low-dose silver nanoparticles. Ecotoxicol Environ Saf. 2018 Jul 26;163:266-273 Authors: Wang P, Ng QX, Zhang H, Zhang B, Ong CN, He Y Abstract With increasing presence of silver nanoparticles (AgNPs) into the environment, the chronic and low-dose effects of AgNPs are of vital concern. This study evaluated chronic physiological effects of AgNPs on Daphnia similis, which were exposed to two ambient encountered concentrations (0.02 and 1 ppb) of AgNPs for 21 days. It was observed that the low-dose AgNPs stimulated a significant increase in average length/dry mass, but inhibited reproduction compared to control specimens. Non-targeted metabolomics based on liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOFMS-MS) and gas chromatograph-quadrupole time of flight mass spectrometry (GC-QTOF-MS) were utilized to elucidate the underlying molecular mechanisms of these responses. Forty one metabolites were identified, including 18 significantly-changed metabolites, suggesting up regulation in protein digestion and absorption (amino acids, such as isoleucine, tryptophan, lysine, leucine, valine, aspartic acid, threonine, tyrosine) and down regulation of lipid related metabolism (fatty acids, such as arachidonic acid, stearidonic acid, linoelaidic acid and eicosapentaenoic acid) were key events in these responses. The increase in these amino acid contents explains the accelerated growth of D. similis from the metabolic pathway of aminoacyl-tRNA biosynthesis. Down regulation of fatty acid contents corresponds to the observed drop in the reproduction rate considering the fatty acid biological enzymatic reaction pathways. Significant changes in metabolites provided a renewed mechanistic understanding of low concentration chronic toxicity of AgNP toxicity on D. similis. PMID: 30056340 [PubMed - as supplied by publisher]

Metabolic profiling of the anti-tumor drug regorafenib in mice. J Pharm Biomed Anal. 2018 Jul 20;159:524-535 Authors: Wang YK, Xiao XR, Xu KP, Li F Abstract Regorafenib is a novel tyrosine kinase inhibitor, which has been approved by the United States Food and Drug Administration for the treatment of various tumors. The purpose of the present study was to describe the metabolic map of regorafenib, and investigate its effect on liver function. Mass spectrometry-based metabolomics approach integrated with multiple mass defect filter was used to determine the metabolites of regorafenib in vitro incubation mixtures (human liver microsomes and mouse liver microsomes), serum, urine and feces samples from mice treated with 80 mg/kg regorafenib. Eleven metabolites including four novel metabolites were identified in the present investigation. As halogen substituted drug, reductive defluorination and oxidative dechlorination metabolites of regorafenib were firstly report in present study. By screening using recombinant cytochrome P450 s (CYPs), CYP3A4 was found to be the principal isoforms involved in regorafenib metabolism. The predication with a molecular docking model confirmed that regorafenib had potential to interact with the active sites of CYP3A4, CYP3A5 and CYP2D6. Serum chemistry analysis revealed no evidence of hepatic damage from regorafenib exposure. This study provided a global view of regorafenib metabolism and its potential side-effects. PMID: 30055476 [PubMed - as supplied by publisher]

Impact of tart cherries polyphenols on the human gut microbiota and phenolic metabolites in vitro and in vivo. J Nutr Biochem. 2018 Apr 07;59:160-172 Authors: Mayta-Apaza AC, Pottgen E, De Bodt J, Papp N, Marasini D, Howard L, Abranko L, Van de Wiele T, Lee SO, Carbonero F Abstract Tart cherries have been reported to exert potential health benefits attributed to their specific and abundant polyphenol content. However, there is a need to study the impact and fate of tart cherries polyphenols in the gut microbiota. Here, tart cherries, pure polyphenols (and apricots) were submitted to in vitro bacterial fermentation assays and assessed through 16S rRNA gene sequence sequencing and metabolomics. A short-term (5 days, 8 oz. daily) human dietary intervention study was also conducted for microbiota analyses. Tart cherry concentrate juices were found to contain expected abundances of anthocyanins (cyanidin-glycosylrutinoside) and flavonoids (quercetin-rutinoside) and high amounts of chlorogenic and neochlorogenic acids. Targeted metabolomics confirmed that gut microbes were able to degrade those polyphenols mainly to 4-hydroxyphenylpropionic acids and to lower amounts of epicatechin and 4-hydroxybenzoic acids. Tart cherries were found to induce a large increase of Bacteroides in vitro, likely due to the input of polysaccharides, but prebiotic effect was also suggested by Bifidobacterium increase from chlorogenic acid. In the human study, two distinct and inverse responses to tart cherry consumption were associated with initial levels of Bacteroides. High-Bacteroides individuals responded with a decrease in Bacteroides and Bifidobacterium, and an increase of Lachnospiraceae, Ruminococcus and Collinsella. Low-Bacteroides individuals responded with an increase in Bacteroides or Prevotella and Bifidobacterium, and a decrease of Lachnospiraceae, Ruminococcus and Collinsella. These data confirm that gut microbiota metabolism, in particular the potential existence of different metabotypes, needs to be considered in studies attempting to link tart cherries consumption and health. PMID: 30055451 [PubMed - as supplied by publisher]

Related Articles Integrating -Omics Approaches into Human Population-Based Studies of Prenatal and Early-Life Exposures. Curr Environ Health Rep. 2018 Jul 27;: Authors: Everson TM, Marsit CJ Abstract PURPOSE OF REVIEW: We present the study design and methodological suggestions for population-based studies that integrate molecular -omics data and highlight recent studies that have used such data to examine the potential impacts of prenatal environmental exposures on fetal health. RECENT FINDINGS: Epidemiologic studies have observed numerous relationships between prenatal exposures (smoking, toxic metals, endocrine disruptors) and fetal and early-life molecular profiles, though such investigations have so far been dominated by epigenomic association studies. However, recent transcriptomic, proteomic, and metabolomic studies have demonstrated their promise for the identification of exposure and response biomarkers. Molecular -omics have opened new avenues of research in environmental health that can improve our understanding of disease etiology and contribute to the development of exposure and response biomarkers. Studies that incorporate multiple -omics data from different molecular domains in longitudinally collected samples hold particular promise. PMID: 30054820 [PubMed - as supplied by publisher]

Related Articles Comprehensive organic profiling of biological particles derived from blood. Sci Rep. 2018 Jul 27;8(1):11310 Authors: Wu CY, Martel J, Young JD Abstract Mineral nanoparticles form in physiological and pathological processes occurring in the human body. The calcium phosphate mineral phase of the particles has affinity for proteins and lipids, but the complete profiling of the organic molecules that bind to the particles has not been described in detail. We report here a comprehensive analysis of organic components found in mineralo-organic particles derived from body fluids. Based on biological staining, fluorescent tagging, proteomics and metabolomics, our results indicate that the mineral particles bind to proteins, amino acids, carbohydrates, polysaccharides, phospholipids, fatty acids, DNA and low molecular weight metabolites. These results can be used to study the formation and effects of mineralo-organic particles in biological fluids. PMID: 30054526 [PubMed - in process]

Related Articles Complementary intestinal mucosa and microbiota responses to caloric restriction. Sci Rep. 2018 Jul 27;8(1):11338 Authors: Duszka K, Ellero-Simatos S, Ow GS, Defernez M, Paramalingam E, Tett A, Ying S, König J, Narbad A, Kuznetsov VA, Guillou H, Wahli W Abstract The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR. PMID: 30054525 [PubMed - in process]

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 2018/07/28PubMed 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.

Impact of pulsed UV-B stress exposure on plant performance: How recovery periods stimulate secondary metabolism while reducing adaptive growth attenuation. Plant Cell Environ. 2018 Jul 26;: Authors: Höll J, Lindner S, Walter H, Joshi D, Poschet G, Pfleger S, Ziegler T, Hell R, Bogs J, Rausch T Abstract Upon continuous stress exposure plants display attenuated metabolic stress responses due to regulatory feedback loops. Here we have tested the hypothesis that pulsed stress exposure with intervening recovery periods should affect these feedback loops, thereby causing increased accumulation of stress-induced metabolites. The response of Arabidopsis plantlets to continuous UV-B exposure (Cuv ) was compared to that of pulsed UV-B exposure (Puv ). The differential responses to Puv versus Cuv were monitored at the level of gene expression and metabolite accumulation, using wild type (WT) and different mutant lines. In comparison to Cuv , Puv increased sinapyl and flavonol (S+F) content, whereas adaptive growth attenuation was reduced. Furthermore, in a myb4 mutant (AtMYB4, repressor-type R2R3-MYB transcription factor) the S+F content was increased only for Cuv , but not beyond the level for Puv observed in WT. These observations and the ability of AtMYB4 to repress AtMYB12/AtMYB111-mediated activation of target gene promoters (pCHS, pFLS) indicate that the increase of S+F content after Puv observed in WT plants results from reduced feedback inhibition by AtMYB4. The results support the notion that stress-induced metabolic changes not necessarily cause a growth penalty. Furthermore, the observed Puv -induced increase in flavonol accumulation may stimulate reevaluation of commercial plant production practices. PMID: 30049021 [PubMed - as supplied by publisher]

1H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds. J Ethnopharmacol. 2018 Jul 23;: Authors: Bapela MJ, Heyman H, Senejoux F, Meyer JJM Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The Vha-Venda people living in rural areas of Limpopo Province of South Africa regularly use traditional plant-based medicines to treat malaria. In our earlier publication, twenty indigenous plant species used to treat malaria or its symptoms by Vha-Venda people were evaluated for antiplasmodial activity. The main objective of the current study was to assess the robustness of NMR-based metabolomics in discriminating classes of secondary compounds that are responsible for the observed antimalarial activity and the isolation of antiplasmodial compounds. MATERIALS AND METHODS: Twenty dichloromethane extracts were reconstituted in CDCl3, subjected to 1H NMR-based metabolomic analysis on a Varian 600MHz spectrometer and the acquired 1H NMR spectra were then evaluated collectively using multivariate data analysis (MDA). Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) were used to 'globally' discern antiplasmodial profiles. A contribution plot was then generated from the OPLS-DA scoring plot in an attempt to determine the classes of compounds that are responsible for the observed grouping. Further phytochemical analyses were conducted on the lipophilic extracts of Tabernaemontana elegans and Vangueria infausta subsp. infausta. These best candidates were fractionated, purified and their isolated compounds identified based on conventional chromatographic and spectroscopic techniques. RESULTS: The PCA did not separate the acquired profiles according to the detected antiplasmodial bioactivity. Application of a supervised OPLS-DA on the 1H NMR profiles resulted in a discrimination pattern that could be correlated to the observed antimalarial bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Prominent peaks were observed in the aromatic, sugar-based/N-containing and aliphatic spectral regions of the contribution plot. Two known indole alkaloids were isolated from T. elegans, and identified as tabernaemontanine (IC50 = 12.0±0.8µM) and dregamine (IC50 = 62.0±2.4µM). Friedelin (IC50 = 7.20±0.5µM) and morindolide (IC50 = 107.1±0.6µM) were isolated from V. infausta subsp. infausta. This is the first report of the rare iridoid lactone, morindolide's antimalarial activity. While these two compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria. CONCLUSION: The study illustrated the potential of NMR-based metabolomics in discriminating classes of compounds that may be attributed to antiplasmodial activity. Additionally, the study demonstrated the potential of discovering novel antiplasmodial scaffolds from medicinal plants and the rationale for the bioprospecting antimalarial plant species used by Vha-Venda people. PMID: 30048730 [PubMed - as supplied by publisher]

Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential. Pharmacol Ther. 2018 Jul 23;: Authors: Xiang AS, Meikle PJ, Carey AL, Kingwell BA Abstract Development of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrates in mediating the primary heat-producing functions of BAT, and to date thought to be principally sourced from stored intracellular lipid droplets. While this prior understanding is not disputed, recent evidence has demonstrated the importance of lipids derived from the circulation, including those from dietary sources and from tissue lipolysis, especially white adipose tissue lipolysis. Moreover, recent studies have shed further light on a potential role for BAT as an autocrine, paracrine and endocrine organ, with lipids as key signaling molecules. Advances in metabolomics have enabled high-resolution exploration of biomolecules that may be associated with various physiological processes and potentially pathological states. Such approaches have led to several novel lipid species recently being associated with BAT function and dysfunction. Further exploration of the circulating lipidome will likely reveal additional novel BAT biomarkers that can inform development of BAT-directed therapies. This review will address current progress and new strategies to identify and characterize BAT-associated lipids which may represent both novel activators and/or activity biomarkers with both research and clinical utility. PMID: 30048608 [PubMed - as supplied by publisher]

NMR-Based Metabolomics Approach To Study the Influence of Different Conditions of Water Irrigation and Greenhouse Ventilation on Zucchini Crops. J Agric Food Chem. 2018 Jul 26;: Authors: Abreu AC, Aguilera-Sáez LM, Peña A, García-Valverde M, Marín P, Valera DL, Fernández I Abstract This study describes the approach of 1H NMR metabolomic profiling for the differentiation of zucchini produced under different conditions of water irrigation (desalinated seawater -0.397 dS/m, 0.52 €/m3 vs groundwater -2.36 dS/m, 0.29 €/m3) and ventilation (surface area of the vent openings/greenhouse area was 15.0% for one sector and 9.8% for the other). Overall, 72 extracts of zucchini ( Cucubirta pepo L. cv Victoria) under four different conditions were regularly analyzed during the spring-summer cycle from April to July 2017. We have found that zucchini plants irrigated with desalinated seawater increased the zucchini production yield, presented fruits with higher concentration of glucose, fructose, and vitamin B3, and displayed an increased antioxidant activity. On the contrary, plant groundwater irrigation produced the increment of sucrose level that could rise the sweetness perception of the fruits. Finally, the ventilation variable produced a higher concentration of trigonelline, histidine, and phenylalanine but only on those zucchinis irrigated with groundwater. PMID: 30047728 [PubMed - as supplied by publisher]