Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 2 min ago

Impact of primary carbon sources on microbiome shaping and biotransformation of pharmaceuticals and personal care products.

Sat, 02/03/2019 - 13:14
Related Articles Impact of primary carbon sources on microbiome shaping and biotransformation of pharmaceuticals and personal care products. Biodegradation. 2019 Feb 28;: Authors: Rossmassler K, Kim S, Broeckling CD, Galloway S, Prenni J, De Long SK Abstract Knowledge of the conditions that promote the growth and activity of pharmaceutical and personal care product (PPCP)-degrading microorganisms within mixed microbial systems are needed to shape microbiomes in biotreatment reactors and manage process performance. Available carbon sources influence microbial community structure, and specific carbon sources could potentially be added to end-of-treatment train biotreatment systems (e.g., soil aquifer treatment [SAT]) to select for the growth and activity of a range of microbial phylotypes that collectively degrade target PPCPs. Herein, the impacts of primary carbon sources on PPCP biodegradation and microbial community structure were explored to identify promising carbon sources for PPCP biotreatment application. Six types of primary carbon sources were investigated: casamino acids, two humic acid and peptone mixtures (high and low amounts of humic acid), molasses, an organic acids mixture, and phenol. Biodegradation was tracked for five PPCPs (diclofenac, 5-fluorouracil, gemfibrozil, ibuprofen, and triclosan). Primary carbon sources were found to differentially impact microbial community structures and rates and efficiencies of PPCP biotransformation. Of the primary carbon sources tested, casamino acids, organic acids, and phenol showed the fastest biotransformation; however, on a biomass-normalized basis, both humic acid-peptone mixtures showed comparable or superior biotransformation. By comparing microbial communities for the different primary carbon sources, abundances of unclassified Beijerinckiaceae, Beijerinckia, Sphingomonas, unclassified Sphingomonadaceae, Flavobacterium, unclassified Rhizobiales, and Nevskia were statistically linked with biotransformation of specific PPCPs. PMID: 30820709 [PubMed - as supplied by publisher]

Identification of potential human urinary biomarkers for tomato juice intake by mass spectrometry-based metabolomics.

Sat, 02/03/2019 - 13:14
Related Articles Identification of potential human urinary biomarkers for tomato juice intake by mass spectrometry-based metabolomics. Eur J Nutr. 2019 Feb 28;: Authors: Hövelmann Y, Jagels A, Schmid R, Hübner F, Humpf HU Abstract PURPOSE: Dietary biomarkers allow the accurate and objective determination of the dietary intake of humans and can thus be valuable for investigating the relation between consumption of foods and biochemical as well as physiological responses. The objective of this study was the identification of potential urinary biomarkers for consumption of tomato juice. METHODS: In the course of a dietary intervention study, the human urine metabolome of a study cohort was compared between a tomato-free diet and after intake of tomato juice by application of an LC-HRMS-based metabolomics approach. The data acquisition was achieved using an orbitrap mass spectrometer, followed by multistage data processing and univariate as well as multivariate statistical analysis to identify discriminating features. RESULTS: Statistical analysis revealed several unique features detectable after tomato juice intake. The most discriminating markers were putatively identified as hydroxylated and sulfonated metabolites of esculeogenin B, aglycone of the steroidal glycoalkaloid esculeoside B recently found in tomato juice. Furthermore, the β-carboline alkaloids tangutorid E and F and glucuronidated derivatives thereof were identified in urine. CONCLUSIONS: Steroidal glycoalkaloids in tomato juice are cleaved after ingestion, and hydroxylated and sulfonated metabolites of their aglycones might serve as urinary biomarkers for tomato juice intake. Similarly, β-carboline alkaloids and glucuronidated derivatives were identified as potential urinary biomarkers. Both the aglycones of the steroidal alkaloids and the β-carboline alkaloids might exhibit biological activities worth investigating. PMID: 30820652 [PubMed - as supplied by publisher]

Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy.

Sat, 02/03/2019 - 13:14
Related Articles Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy. Cancer Cell Int. 2019;19:37 Authors: Chen Y, Chen Z, Su Y, Lin D, Chen M, Feng S, Zou C Abstract Background: The staging system of nasopharyngeal carcinoma (NPC) has close relationship with the degree of cell differentiation, but most NPC patients remain undiagnosed until advanced phases. Novel metabolic markers need to be characterized to support diagnose at an early stage. Methods: Metabolic characteristics of nasopharyngeal normal cell NP69 and two types of NPC cells, including CNE1 and CNE2 associated with high and low differentiation degrees were studied by combining 1H NMR spectroscopy with Raman spectroscopy. Statistical methods were also utilized to determine potential characteristic metabolites for monitoring differentiation progression. Results: Metabolic profiles of NPC cells were significantly different according to differentiation degrees. Various characteristic metabolites responsible for different differentiated NPC cells were identified, and then disordered metabolic pathways were combed according to these metabolites. We found disordered pathways mainly included amino acids metabolisms like essential amino acids metabolisms, as well as altered lipid metabolism and TCA cycle, and abnormal energy metabolism. Thus our results provide evidence about close relationship between differentiation degrees of NPC cells and the levels of intracellular metabolites. Moreover, Raman spectrum analysis also provided complementary and confirmatory information about intracellular components in single living cells. Eight pathways were verified to that in NMR analysis, including amino acids metabolisms, inositol phosphate metabolism, and purine metabolism. Conclusions: Methodology of NMR-based metabolomics combining with Raman spectroscopy could be powerful and straightforward to reveal cell differentiation development and meanwhile lay the basis for experimental and clinical practice to monitor disease progression and therapeutic evaluation. PMID: 30820190 [PubMed]

compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets.

Sat, 02/03/2019 - 13:14
Related Articles compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets. Anal Chem. 2017 04 04;89(7):3919-3928 Authors: Edmands WM, Petrick L, Barupal DK, Scalbert A, Wilson MJ, Wickliffe JK, Rappaport SM Abstract A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS2Miner (Comprehensive MS2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS2 data files as inputs. The number of MS2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS2Miner integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS2 data with a Web application GUI compMS2Explorer (Comprehensive MS2 Explorer) that also facilitates data-sharing and transparency. The automatable compMS2Miner workflow consists of the following steps: (i) matching unknown MS1 features to precursor MS2 scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the compMS2Explorer application. Metabolite identities and comments can also be recorded using an interactive table within compMS2Explorer. The utility of the package is illustrated with a data set of blood serum samples from 7 diet induced obese (DIO) and 7 nonobese (NO) C57BL/6J mice, which were also treated with an antibiotic (streptomycin) to knockdown the gut microbiota. The results of fully autonomous and objective usage of compMS2Miner are presented here. All automatically annotated spectra output by the workflow are provided in the Supporting Information and can alternatively be explored as publically available compMS2Explorer applications for both positive and negative modes ( https://wmbedmands.shinyapps.io/compMS2_mouseSera_POS and https://wmbedmands.shinyapps.io/compMS2_mouseSera_NEG ). The workflow provided rapid annotation of a diversity of endogenous and gut microbially derived metabolites affected by both diet and antibiotic treatment, which conformed to previously published reports. Composite spectra (n = 173) were autonomously matched to entries of the Massbank of North America (MoNA) spectral repository. These experimental and virtual (lipidBlast) spectra corresponded to 29 common endogenous compound classes (e.g., 51 lysophosphatidylcholines spectra) and were then used to calculate the ranking capability of 7 individual scoring metrics. It was found that an average of the 7 individual scoring metrics provided the most effective weighted average ranking ability of 3 for the MoNA matched spectra in spite of potential risk of false positive annotations emerging from automation. Minor structural differences such as relative carbon-carbon double bond positions were found in several cases to affect the correct rank of the MoNA annotated metabolite. The latest release and an example workflow is available in the package vignette ( https://github.com/WMBEdmands/compMS2Miner ) and a version of the published application is available on the shinyapps.io site ( https://wmbedmands.shinyapps.io/compMS2Example ). PMID: 28225587 [PubMed - indexed for MEDLINE]

metabolomics; +22 new citations

Fri, 01/03/2019 - 15:58
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 2019/03/01PubMed 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.

metabolomics; +22 new citations

Fri, 01/03/2019 - 12:56
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 2019/03/01PubMed 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.

metabolomics; +18 new citations

Thu, 28/02/2019 - 15:41
18 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 2019/02/28PubMed 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.

metabolomics; +18 new citations

Thu, 28/02/2019 - 12:38
18 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 2019/02/28PubMed 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.

Targeted metabolomics for the quantitative measurement of 9 gut microbiota-host co-metabolites in rat serum, urine and feces by liquid chromatography-tandem mass spectrometry.

Wed, 27/02/2019 - 12:33
Targeted metabolomics for the quantitative measurement of 9 gut microbiota-host co-metabolites in rat serum, urine and feces by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Feb 19;1110-1111:133-143 Authors: Zeng Y, Lin Y, Li L, Li Y, Zhang X, Wang M, Chen Y, Luo L, Lu B, Xie Z, Liao Q Abstract Gut microbiota-host co-metabolites play an essential role in maintaining homeostasis, and their concentration changes are closely related to a variety of diseases. Developing a targeted metabolomics analytical platform for these co-metabolites will help to elucidate the relationship between intestinal flora and host. Here we present a simple and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of nine gut microbiota-host co-metabolites in rat serum, urine and feces. The compounds were separated on a reversed-phase C18 column using gradient elution with a solvent system consisting of methanol and water (containing 0.05% formic acid) and a 7-min run time. All of the calibration curves exhibited good linear relationships (R2 ≥ 0.9984, Percent Residual Accuracy ≥93.27%). The intra- and interday precision, expressed as relative standard deviation (RSD), was ≤ 14.84%. The accuracy was within 100 ± 13.16% for all analytes. The recovery of the nine compounds in biological samples was ≥ 85.80% with an appropriate RSD (≤12.04%). The validated method was successfully applied to monitor the global changes of these metabolites in obesity. Taken together, these results demonstrate that the method can simultaneously determine the nine co-metabolites in multiple biological matrices and is an essential part of the targeted metabolomics analytical platform, which may become an approach to evaluate the occurrence, development and therapeutic effects of metabolic diseases. PMID: 30807966 [PubMed - as supplied by publisher]

A comparative study of UHPLC/Orbitrap MS metabolomics profiles and biological properties of Asphodeline taurica from Bulgaria and Turkey.

Wed, 27/02/2019 - 12:33
A comparative study of UHPLC/Orbitrap MS metabolomics profiles and biological properties of Asphodeline taurica from Bulgaria and Turkey. J Pharm Biomed Anal. 2019 Feb 07;168:174-180 Authors: Lazarova I, Zengin G, Gevrenova R, Nedialkov P, Aneva I, Aumeeruddy MZ, Mahomoodally MF Abstract The present investigation attempts to compare the pharmacological properties and phytochemical profile of four extracts (ethyl acetate, dichloromethane, methanol, and water) of Asphodeline taurica (Pall.) Endl. roots from Bulgaria and Turkey. The Bulgarian ethyl acetate extract displayed the highest antioxidant activity in the DPPH, CUPRAC, and phosphomolybdenum assay, and strongest inhibition against α-amylase and α-glucosidase. The Turkish aqueous extract exhibited the strongest ABTS scavenging and ferric reducing power while its methanol extract was the most effective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitor. On the other hand, the Turkish dichloromethane extract showed the highest lipase inhibition. UHPLC/Orbitrap MS analysis showed a wide array of individual phenolics; six free anthraquinones, two bianthraquinones, three bianthracenes, three anthraquinone glycosides and one bianthracen glycoside were identified. The present data suggest that A. taurica roots can be considered as a valuable source of biologically active phytocompounds with functional properties for the cosmetic and pharmaceutical industries. PMID: 30807922 [PubMed - as supplied by publisher]

Metabolomic study reveals the acute hypotensive effect of S-1-propenylcysteine accompanied by alteration of the plasma histidine level in spontaneously hypertensive rats.

Wed, 27/02/2019 - 12:33
Metabolomic study reveals the acute hypotensive effect of S-1-propenylcysteine accompanied by alteration of the plasma histidine level in spontaneously hypertensive rats. J Pharm Biomed Anal. 2019 Feb 12;168:148-154 Authors: Matsutomo T, Ushijima M, Kunimura K, Ohtani M Abstract Our previous study has shown that a single dose of S-1-propenylcysteine (S1PC) exerted an antihypertensive effect in spontaneously hypertensive rats (SHR), while its mode of action remained to be further investigated. The aim of this study was to explore the potential mechanism of the antihypertensive effect of S1PC in SHR using a liquid chromatography-mass spectrometry (LC-MS)-based metabolomic approach. Blood samples were serially collected from SHR after a single oral administration of S1PC (6.5 mg/kg body weight). The metabolomics data acquired from the LC-MS analysis of plasma samples were processed using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). In addition, the SHR were treated with S1PC or histidine (10 mg/kg body weight) with and without intravenous preinjection of thioperamide, a histamine H3 receptor antagonist. The blood pressure of SHR was measured by the tail-cuff method at different times after administration. In the PLS-DA score plots, the clusters of the S1PC groups were clearly or partly separated from those of the control groups at 1.5 and 3 h after administration, indicating the metabolic profiles were substantially altered by the S1PC treatment at these time points. Comparative analysis based on variable importance in the projection (VIP) values obtained from PLS-DA led to the identification of 14 and 15 metabolites differing between the two groups at 1.5 and 3 h, respectively, which included various amino acids. Among the metabolites identified, the plasma histidine level in the S1PC group significantly increased at 1.5 and 3 h, and decreased to that in the control group at 6 h. Moreover, pretreatment with thioperamide inhibited the blood pressure lowering effect of S1PC as well as that of histidine. These results suggested that S1PC alters histidine metabolism and consequently exerts the antihypertensive effect via the central histamine H3 receptor. PMID: 30807919 [PubMed - as supplied by publisher]

1H NMR-based metabolomics profiling of citrus juices produced in Veracruz, México.

Wed, 27/02/2019 - 12:33
1H NMR-based metabolomics profiling of citrus juices produced in Veracruz, México. Chem Biodivers. 2019 Feb 26;: Authors: Villa-Ruano N, Pérez-Hernández N, Zepeda-Vallejo LG, Quiroz-Acosta T, Mendieta-Moctezuma A, Montoya-García CO, García-Nava ML, Becerra Martínez E Abstract This study describes the 1H NMR-based metabolomics profiling of juices from citrus fruits harvested in the state of Veracruz, México. The hydrophilic profile of commercial lemons (Agrio and Persian), tangerines (Fremont and Mónica), oranges (Valencia and Washington Navel), and grapefruits (Red Ruby and Rio Red) was determined. According to our results, 35 metabolites were identified in the 1H NMR profiling. The statistical differences obtained by PCA and OPLS-DA revealed that specific amino acids, sugars, and organic acids were differential metabolites in the species and cultivars studied. High endogenous levels of sucrose (10-190 mM), α-glucose, β-glucose (α,β isomers, 40-205 mM), and fructose (36-170 mM) were detected in the juices of grapefruits, oranges, and tangerines, whereas citric acid (40-530 mM) was the principal organic acid in the juices of lemons. To calculate the specific amounts of metabolites from these species and their cultivars, the results were finely analyzed using the qNMR method. According to these calculations, Valencia oranges had the highest concentration of ascorbic acid (>2 mM). The described 1H NMR method is highly reproducible, inexpensive, and highly robust in comparison to other analytical methods used to determine the hydrophilic profile of citrus juices. PMID: 30807682 [PubMed - as supplied by publisher]

Metabolomics analysis in acute paraquat poisoning patients based on UPLC-Q-TOF-MS and machine learning approach.

Wed, 27/02/2019 - 12:33
Metabolomics analysis in acute paraquat poisoning patients based on UPLC-Q-TOF-MS and machine learning approach. Chem Res Toxicol. 2019 Feb 26;: Authors: Wen C, Lin F, Huang B, Zhang Z, Wang X, Ma J, Lin G, Chen H, Hu L Abstract Most of paraquat (PQ) poisoned patients died for acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. The initial PQ plasma concentrations of PQ poisoned patients were > 1000 ng/mL, and the blood samples were collected at before first hemoperfusion (HP), after first HP, and after last HP. The results showed that PQ poisoned patients all differed from healthy subjects, whatever they were before or after first HP or after last HP. The efficient machine learning approaches selected key metabolites from three UPLC/Q-TOF-MS datasets which had highest classification performance in terms of classification accuracy, Matthews Correlation Coefficients, sensitivity and specificity, respectively. The mass identification revealed that the most important metabolite was adenosine, which sustained in low level, regardless of whether PQ poisoned patients received HP treatment. In conclusion, decreased adenosine was the most important metabolite in PQ poisoned patients. The metabolic disturbance caused by PQ poisoning can't be improved by HP treatment even the PQ was cleared from the blood. PMID: 30807114 [PubMed - as supplied by publisher]

Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry.

Wed, 27/02/2019 - 12:33
Related Articles Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry. Biochimie. 2019 Feb;157:111-122 Authors: Callejón-Leblic B, Pereira-Vega A, Vázquez-Gandullo E, Sánchez-Ramos JL, Gómez-Ariza JL, García-Barrera T Abstract The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC. PMID: 30439409 [PubMed - indexed for MEDLINE]

Rapid, field-deployable method for collecting and preserving plant metabolome for biochemical and functional characterization.

Wed, 27/02/2019 - 12:33
Related Articles Rapid, field-deployable method for collecting and preserving plant metabolome for biochemical and functional characterization. PLoS One. 2018;13(9):e0203569 Authors: Skubel SA, Dushenkov V, Graf BL, Niu Q, Poulev A, Kalariya HM, Foxcroft LC, Raskin I Abstract Study of plant metabolome is a growing field of science that catalogs vast biochemical and functional diversity of phytochemicals. However, collecting and storing samples of plant metabolome, sharing these samples across the scientific community and making them compatible with bioactivity assays presents significant challenges to the advancement of metabolome research. We have developed a RApid Metabolome Extraction and Storage (RAMES) technology that allows efficient, highly compact, field-deployable collection and storage of libraries of plant metabolome. RAMES technology combines rapid extraction with immobilization of extracts on glass microfiber filter discs. Two grams of plant tissue extracted in ethanol, using a specially adapted Dremel® rotary tool, produces 25-35 replicas of 10 mm glass fiber discs impregnated with phytochemicals. These discs can be either eluted with solvents (such as 70% ethanol) to study the metabolomic profiles or used directly in a variety of functional assays. We have developed simple, non-sterile, anti-fungal, anti-bacterial, and anti-oxidant assays formatted for 24-multiwell plates directly compatible with RAMES discs placed inside the wells. Using these methods we confirmed activity in 30 out of 32 randomly selected anti-microbial medicinal plants and spices. Seven species scored the highest activity (total kill) in the anti-bacterial (bacteria from human saliva) and two anti-fungal screens (Fusarium spp. and Saccharomyces cerevisiae), providing functional validation of RAMES technology. RAMES libraries showed limited degradation of compounds after 12 months of storage at -20°C, while others remained stable. Fifty-eight percent of structures characterized in the extracts loaded onto RAMES discs could be eluted from the discs without significant losses. Miniaturized RAMES technology, as described and validated in this manuscript offers a labor, cost, and time-effective alternative to conventional collection of phytochemicals. RAMES technology enables creation of comprehensive metabolomic libraries from various ecosystems and geographical regions in a format compatible with further biochemical and functional studies. PMID: 30188945 [PubMed - indexed for MEDLINE]

Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma.

Wed, 27/02/2019 - 12:33
Related Articles Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma. Endocrinology. 2018 08 01;159(8):2836-2849 Authors: Chortis V, Taylor AE, Doig CL, Walsh MD, Meimaridou E, Jenkinson C, Rodriguez-Blanco G, Ronchi CL, Jafri A, Metherell LA, Hebenstreit D, Dunn WB, Arlt W, Foster PA Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry-based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress. PMID: 29850793 [PubMed - indexed for MEDLINE]

Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes.

Wed, 27/02/2019 - 12:33
Related Articles Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes. Trends Plant Sci. 2018 07;23(7):638-647 Authors: Zager JJ, Lange BM Abstract Many aromatic plants accumulate mixtures of secondary (or specialized) metabolites in anatomical structures called glandular trichomes (GTs). Different GT types may also synthesize different mixtures of secreted metabolites, and this contributes to the enormous chemical diversity reported to occur across species. Over the past two decades, significant progress has been made in characterizing the genes and enzymes that are responsible for the unique metabolic capabilities of GTs in different lineages of flowering plants. Less is known about the processes that regulate flux distribution through precursor pathways toward metabolic end-products. We discuss here the results from a meta-analysis of genome-scale models that were developed to capture the unique metabolic capabilities of different GT types. PMID: 29735428 [PubMed - indexed for MEDLINE]

Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth.

Wed, 27/02/2019 - 12:33
Related Articles Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth. J Pediatr. 2018 06;197:280-285.e3 Authors: Stone C, Qiu Y, Kurland IJ, Slaughter JC, Moore P, Cook-Mills J, Hartert T, Aschner JL Abstract We examined the effect of maternal smoking on plasma and urinary levels of vitamin E isoforms in preterm infants. Maternal smoking during pregnancy decreased infant plasma alpha- and gamma-tocopherol concentrations at 1 week and 4 weeks, with 45% of infants of smokers deficient in alpha-tocopherol at 1 month after birth. PMID: 29398053 [PubMed - indexed for MEDLINE]

Rice SUB1A constrains remodelling of the transcriptome and metabolome during submergence to facilitate post-submergence recovery.

Wed, 27/02/2019 - 12:33
Related Articles Rice SUB1A constrains remodelling of the transcriptome and metabolome during submergence to facilitate post-submergence recovery. Plant Cell Environ. 2018 04;41(4):721-736 Authors: Locke AM, Barding GA, Sathnur S, Larive CK, Bailey-Serres J Abstract The rice (Oryza sativa L.) ethylene-responsive transcription factor gene SUB1A-1 confers tolerance to prolonged, complete submergence by limiting underwater elongation growth. Upon desubmergence, SUB1A-1 genotypes rapidly recover photosynthetic function and recommence development towards flowering. The underpinnings of the transition from stress amelioration to the return to homeostasis are not well known. Here, transcriptomic and metabolomic analyses were conducted to identify mechanisms by which SUB1A improves physiological function over the 24 hr following a sublethal submergence event. Evaluation of near-isogenic genotypes after submergence and over a day of reaeration demonstrated that SUB1A transiently constrains the remodelling of cellular activities associated with growth. SUB1A influenced the abundance of ca. 1,400 transcripts and had a continued impact on metabolite content, particularly free amino acids, glucose, and sucrose, throughout the recovery period. SUB1A promoted recovery of metabolic homeostasis but had limited influence on mRNAs associated with growth processes and photosynthesis. The involvement of low energy sensing during submergence and recovery was supported by dynamics in trehalose-6-phosphate and mRNAs encoding key enzymes and signalling proteins, which were modulated by SUB1A. This study provides new evidence of convergent signalling pathways critical to the rapidly reversible management of carbon and nitrogen metabolism in submergence resilient rice. PMID: 29094353 [PubMed - indexed for MEDLINE]

Dietary copper-fructose interactions alter gut microbial activity in male rats.

Wed, 27/02/2019 - 12:33
Related Articles Dietary copper-fructose interactions alter gut microbial activity in male rats. Am J Physiol Gastrointest Liver Physiol. 2018 01 01;314(1):G119-G130 Authors: Song M, Li X, Zhang X, Shi H, Vos MB, Wei X, Wang Y, Gao H, Rouchka EC, Yin X, Zhou Z, Prough RA, Cave MC, McClain CJ Abstract Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes. PMID: 29025734 [PubMed - indexed for MEDLINE]

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