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

A novel strategy for rapid screening of the complex triterpene saponin mixture present in the methanolic extract of blackberry leaves (Rubus cv. Loch Ness) by UHPLC/QTOF-MS.

Mon, 22/10/2018 - 14:56
Related Articles A novel strategy for rapid screening of the complex triterpene saponin mixture present in the methanolic extract of blackberry leaves (Rubus cv. Loch Ness) by UHPLC/QTOF-MS. J Pharm Biomed Anal. 2018 Oct 07;164:47-56 Authors: Gradillas A, Martínez-Alcázar MP, Gutiérrez E, Ramos-Solano B, García A Abstract Triterpene saponins are important chemical constituents in blackberry leaves and have significant antimicrobial activity, among other healthful properties. In this study, a new UHPLC-MS method was optimized with outstanding efficiency for a non-targeted metabolic approach and comprehensive analysis of bioactive compounds in blackberry leaves (Rubus cv. Loch Ness). With minimum sample treatment, phenols and triterpene saponins, among others, were separated according to their elution times. Once separated, the major triterpene saponins were classified by their aglycone moieties and their structures tentatively identified based on their accurate mass spectra in positive and negative ESI mode. By the use of UHPLC coupled to a TOF, a high-resolution and accuracy mass analyzer, reliable molecular formulas of the detected compounds were predicted, and along with the generated MS spectra in full scan mode, allowed the tentative identification and classification of the most abundant triterpene saponins presented the samples analyzed. A rapid and comprehensive strategy to study the complex saponin profile is presented. Unlike other LC-MS/MS methods, the proposed method requires just one mass analyzer, and to our knowledge, this is the first systematic study on triterpene saponins in blackberry leaves. PMID: 30343243 [PubMed - as supplied by publisher]

Metabolomic alterations and oxidative stress are associated with environmental pollution in Procambarus clarkii.

Mon, 22/10/2018 - 14:56
Related Articles Metabolomic alterations and oxidative stress are associated with environmental pollution in Procambarus clarkii. Aquat Toxicol. 2018 Oct 13;205:76-88 Authors: Fernández-Cisnal R, García-Sevillano MA, García-Barrera T, Gómez-Ariza JL, Abril N Abstract Soils contaminated by toxic metallic elements from agricultural activities raise grave concern about their potential risk to human health through direct intake, bioaccumulation through the food chain, and their impacts on ecological systems. We have measured here the lipid and protein oxidation status and used metabolomic methodologies to identify and characterize the changes caused by metal pollution exposure in the digestive glands and gills of Procambarus clarkii, the red swamp crayfish. Specimens captured at two sites with intensive agriculture practices using diverse types of agrochemicals, located in the borders of Doñana Natural Park, were compared to ones caught in the core of the Park, a proven non-polluted place. As a highly metabolically active organ, the digestive gland accumulated more metallic elements than the gills and was consequently more affected at the metabolic level. Results also indicate that chronic pollution exposure generates oxidative stress and mitochondrial dysfunction that imposes a metabolic shift to enhanced aerobic glycolysis and lipid metabolism alteration. The integration of metabolomics with previous proteomic data gives a comprehensive vision of the metabolic disorders caused by chronic metal exposure to P. clarkii and identifies potential biomarkers useful for routine risk assessment of the aquatic ecosystems health. PMID: 30343212 [PubMed - as supplied by publisher]

Inhibition of ATP citrate lyase (ACLY) protects airway epithelia from PM2.5-induced epithelial-mesenchymal transition.

Mon, 22/10/2018 - 14:56
Related Articles Inhibition of ATP citrate lyase (ACLY) protects airway epithelia from PM2.5-induced epithelial-mesenchymal transition. Ecotoxicol Environ Saf. 2018 Oct 18;167:309-316 Authors: Fu Y, Lu R, Cui J, Sun H, Yang H, Meng Q, Wu S, Aschner M, Li X, Chen R Abstract Epidemiological studies have associated ambient fine particulate matter (PM2.5) exposure with lung cancer, in which epithelial-mesenchymal transition (EMT) is an initial process. Thus, it is important to identify the key molecule or pathway involved in the PM2.5 induced EMT. Human bronchial epithelial (HBE) cells were exposed to PM2.5 (100 or 500 μg/ml) for 30 passages and analyzed by metabolomics to identify the alteration of metabolites related to PM2.5 exposure. The expression levels of EMT markers were evaluated by qRT-PCR and Western blot assays in HBE cells and murine lung tissues. Reduced epithelial markers, increased mesenchymal markers expression levels and increased capacity of metastasis were observed in PM2.5-exposed HBE cells. Metabolomics analysis suggested upregulation of citrate acid with fold change (FC) of 2.89 or 4.18 in 100 or 500 μg/ml PM2.5 treated HBE cells. For both of the in vitro and in vivo study, the up-regulation of ATP citrate lyase (ACLY) was confirmed following PM2.5 exposure. Importantly, ACLY knockdown in HBE cells reversed EMT, migration and invasion capacities in HBE cells induced by PM2.5. Taken together, our data suggest that inhibition of ACLY demonstrates a protection against PM2.5-induced EMT, providing a concern on the molecular mechanisms of PM2.5-associated pulmonary disorders. PMID: 30343145 [PubMed - as supplied by publisher]

Microbiome and diabetes: Where are we now?

Sun, 21/10/2018 - 14:34
Related Articles Microbiome and diabetes: Where are we now? Diabetes Res Clin Pract. 2018 Oct 17;: Authors: Vallianou NG, Stratigou T, Tsagarakis S Abstract Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review. PMID: 30342053 [PubMed - as supplied by publisher]

Advances in metabolic flux analysis toward genome-scale profiling of higher organisms.

Sun, 21/10/2018 - 14:34
Related Articles Advances in metabolic flux analysis toward genome-scale profiling of higher organisms. Biosci Rep. 2018 Oct 19;: Authors: Basler G, Fernie AR, Nikoloski Z Abstract Methodological and technological advances have recently paved the way for metabolic flux profiling in higher organisms, like plants. However, in comparison to omics technologies, flux profiling has yet to provide comprehensive differential flux maps at a genome-scale and in different cell types, tissues, and organs. Here we highlight the recent advances in technologies to gather metabolic labeling patterns and flux profiling approaches. We provide an opinion of how recent local flux profiling approaches can be used in conjunction with the constraint-based modelling framework to arrive at genome-scale flux maps. In addition, we point at approaches which use metabolomics data without introduction of label to predict either non-steady state fluxes in a time-series experiment or flux changes in different experimental scenarios. The combination of these developments allows an experimentally feasible approach for flux-based large-scale systems biology studies. PMID: 30341247 [PubMed - as supplied by publisher]

High-throughput chinmedomics strategy for discovering the quality-markers and potential targets for Yinchenhao decoction.

Sun, 21/10/2018 - 14:34
Related Articles High-throughput chinmedomics strategy for discovering the quality-markers and potential targets for Yinchenhao decoction. Phytomedicine. 2018 Apr 10;: Authors: Sun H, Zhang AH, Yang L, Li MX, Fang H, Xie J, Wang XJ Abstract BACKGROUND: Yinchenhao decoction (YCHD) has been widely applied in the clinic for various kinds of liver disease, especially for the therapy of dampness-heat jaundice syndrome (DHJS). Some studies have investigated the pharmacological activity and compositions of YCHD. However, its Q-markers and the action targets are still unrevealed. PURPOSE: This work aims to clarify the therapeutic effect of YCHD against DHJS and discover the quality-markers (Q-markers) of YCHD based on the high-throughput chinmedomics strategy and then predict the potential targets and action mechanism of YCHD against DHJS. METHODS: Ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS) combined with pattern recognition method was utilized to analyze serum samples and urine samples. Multivariate data analysis and network pharmacology technology were used to identify the effective components and biomarkers associated with therapeutic effects. RESULTS: With the high sensitivity UPLC-MS technology, a total of 69 compounds from YCHD were identified and 41 of them were absorbed in blood. Besides, 34 urine biomarkers from DHJS were identified. Of note, we utilized chinmedomics technology on the correlation analysis of urine biomarkers and absorbed components to determine 9 core-compounds as the Q-markers responsible for the efficacy of YCHD. Finally, a total of 12 potential targets were discovered. CONCLUSION: This work provides a powerful method for clarifying the efficacy of TCM and discovering the effective ingredients as Q-markers. PMID: 30340940 [PubMed - as supplied by publisher]

Untargeted lipidomic features associated with colorectal cancer in a prospective cohort.

Sun, 21/10/2018 - 14:34
Related Articles Untargeted lipidomic features associated with colorectal cancer in a prospective cohort. BMC Cancer. 2018 Oct 19;18(1):996 Authors: Perttula K, Schiffman C, Edmands WMB, Petrick L, Grigoryan H, Cai X, Gunter MJ, Naccarati A, Polidoro S, Dudoit S, Vineis P, Rappaport SM Abstract BACKGROUND: Epidemiologists are beginning to employ metabolomics and lipidomics with archived blood from incident cases and controls to discover causes of cancer. Although several such studies have focused on colorectal cancer (CRC), they all followed targeted or semi-targeted designs that limited their ability to find discriminating molecules and pathways related to the causes of CRC. METHODS: Using an untargeted design, we measured lipophilic metabolites in prediagnostic serum from 66 CRC patients and 66 matched controls from the European Prospective Investigation into Cancer and Nutrition (Turin, Italy). Samples were analyzed by liquid chromatography-high-resolution mass spectrometry (LC-MS), resulting in 8690 features for statistical analysis. RESULTS: Rather than the usual multiple-hypothesis-testing approach, we based variable selection on an ensemble of regression methods, which found nine features to be associated with case-control status. We then regressed each selected feature on time-to-diagnosis to determine whether the feature was likely to be either a potentially causal biomarker or a reactive product of disease progression (reverse causality). CONCLUSIONS: Of the nine selected LC-MS features, four appear to be involved in CRC etiology and merit further investigation in prospective studies of CRC. Four other features appear to be related to progression of the disease (reverse causality), and may represent biomarkers of value for early detection of CRC. PMID: 30340609 [PubMed - in process]

¹H NMR Spectroscopy and MVA to Evaluate the Effects of Caulerpin-Based Diet on Diplodus sargus Lipid Profiles.

Sun, 21/10/2018 - 14:34
Related Articles ¹H NMR Spectroscopy and MVA to Evaluate the Effects of Caulerpin-Based Diet on Diplodus sargus Lipid Profiles. Mar Drugs. 2018 Oct 18;16(10): Authors: Del Coco L, Felline S, Girelli CR, Angilè F, Magliozzi L, Almada F, D'Aniello B, Mollo E, Terlizzi A, Fanizzi FP Abstract The biological invasion of the green algae Caulerpa cylindracea represents a serious scientific and public issue in the Mediterranean Sea, essentially due to strong modifications both to habitat structure and native benthic communities. Although alterations in health status and changes in flesh quality of some marine species (dietary exposed to C. cylindracea) have been observed, no studies on cause-effect relationships have been carried out. Here, for the first time, through a controlled feeding experiment followed by ¹H NMR Spectroscopy and multivariate analysis (PCA, OPLS-DA), we showed that caulerpin taken with diet is directly responsible of changes observed in metabolic profile of fish flesh, including alteration of lipid metabolism, in particular with a reduction of ω3 PUFA content. The potential of caulerpin to directly modulate lipid metabolism opens up new questions about causal mechanism triggered by algal metabolite also in view of a possible exploitation in the nutraceutical/medical field. PMID: 30340347 [PubMed - in process]

Probiotics in Autoimmune and Inflammatory Disorders.

Sun, 21/10/2018 - 14:34
Related Articles Probiotics in Autoimmune and Inflammatory Disorders. Nutrients. 2018 Oct 18;10(10): Authors: Liu Y, Alookaran JJ, Rhoads JM Abstract Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial⁻immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes. PMID: 30340338 [PubMed - in process]

metabolomics; +37 new citations

Sat, 20/10/2018 - 14:07
37 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 2018/10/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +29 new citations

Sat, 20/10/2018 - 01:58
29 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 2018/10/19PubMed 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.

PRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation.

Thu, 18/10/2018 - 13:23
PRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation. Cell Rep. 2018 Oct 16;25(3):690-701.e8 Authors: Chan LH, Zhou L, Ng KY, Wong TL, Lee TK, Sharma R, Loong JH, Ching YP, Yuan YF, Xie D, Lo CM, Man K, Artegiani B, Clevers H, Yan HH, Leung SY, Richard S, Guan XY, Huen MSY, Ma S Abstract Arginine methylation is a post-translational modification that plays pivotal roles in signal transduction and gene transcription during cell fate determination. We found protein methyltransferase 6 (PRMT6) to be frequently downregulated in hepatocellular carcinoma (HCC) and its expression to negatively correlate with aggressive cancer features in HCC patients. Silencing of PRMT6 promoted the tumor-initiating, metastasis, and therapy resistance potential of HCC cell lines and patient-derived organoids. Consistently, loss of PRMT6 expression aggravated liver tumorigenesis in a chemical-induced HCC PRMT6 knockout (PRMT6-/-) mouse model. Integrated transcriptome and protein-protein interaction studies revealed an enrichment of genes implicated in RAS signaling and showed that PRMT6 interacted with CRAF on arginine 100, which decreased its RAS binding potential and altered its downstream MEK/ERK signaling. Our work describes a critical repressive function for PRMT6 in maintenance of HCC cells by regulating RAS binding and MEK/ERK signaling via methylation of CRAF on arginine 100. PMID: 30332648 [PubMed - in process]

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension.

Thu, 18/10/2018 - 13:23
Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension. Cell Rep. 2018 Oct 16;25(3):677-689.e4 Authors: Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B Abstract Dietary salt reduction and exercise are lifestyle modifications for salt-sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. An untargeted metabolomic approach demonstrates lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB), in high salt-fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut-microbiotal and Th17-mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt-sensitive hypertension as exercise. PMID: 30332647 [PubMed - in process]

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans.

Thu, 18/10/2018 - 13:23
Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. Cell Rep. 2018 Oct 16;25(3):663-676.e6 Authors: Walters RO, Arias E, Diaz A, Burgos ES, Guan F, Tiano S, Mao K, Green CL, Qiu Y, Shah H, Wang D, Hudgins AD, Tabrizian T, Tosti V, Shechter D, Fontana L, Kurland IJ, Barzilai N, Cuervo AM, Promislow DEL, Huffman DM Abstract A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis. PMID: 30332646 [PubMed - in process]

GeneLab: Omics database for spaceflight experiments.

Thu, 18/10/2018 - 13:23
GeneLab: Omics database for spaceflight experiments. Bioinformatics. 2018 Oct 17;: Authors: Ray S, Gebre S, Fogle H, Berrios DC, Tran PB, Galazka JM, Costes SV Abstract Motivation: - To curate and organize expensive spaceflight experiments conducted aboard space stations and maximize the scientific return of investment, while democratizing access to vast amounts of spaceflight related omics data generated from several model organisms. Results: - The GeneLab Data System (GLDS) is an open access database containing fully coordinated and curated "omics" (genomics, transcriptomics, proteomics, metabolomics) data, detailed metadata and radiation dosimetry for a variety of model organisms. GLDS is supported by an integrated data system allowing federated search across several public bioinformatics repositories. Archived datasets can be queried using full-text search (e.g., keywords, Boolean and wildcards) and results can be sorted in multifactorial manner using assistive filters. GLDS also provides a collaborative platform built on GenomeSpace for sharing files and analyses with collaborators. It currently houses 172 datasets and supports standard guidelines for submission of datasets, MIAME (for microarray), ENCODE Consortium Guidelines (for RNA-seq) and MIAPE Guidelines (for proteomics). Availability and Implementation: - https://genelab.nasa.gov/. PMID: 30329036 [PubMed - as supplied by publisher]

Plasma Energy-Balance Metabolites Discriminate Asymptomatic Patients with Peripheral Artery Disease.

Thu, 18/10/2018 - 13:23
Related Articles Plasma Energy-Balance Metabolites Discriminate Asymptomatic Patients with Peripheral Artery Disease. Mediators Inflamm. 2018;2018:2760272 Authors: Hernández-Aguilera A, Fernández-Arroyo S, Cabre N, Luciano-Mateo F, Baiges-Gaya G, Fibla M, Martín-Paredero V, Menendez JA, Camps J, Joven J Abstract Peripheral artery disease (PAD) is a common disease affecting 20-25% of population over 60 years old. Early diagnosis is difficult because symptoms only become evident in advanced stages of the disease. Inflammation, impaired metabolism, and mitochondrial dysfunction predispose to PAD, which is normally associated with other highly prevalent and related conditions, such as diabetes, dyslipidemia, and hypertension. We have measured energy-balance-associated metabolite concentrations in the plasma of PAD patients segregated by the severity of the disease and in plasma of healthy volunteers using a quantitative and targeted metabolomic approach. We found relevant associations between several metabolites (3-hydroxybutirate, aconitate, (iso)citrate, glutamate, and serine) with markers of oxidative stress and inflammation. Metabolomic profiling also revealed that (iso)citrate and glutamate are metabolites with high ability to discriminate between healthy participants and PAD patients without symptoms. Collectively, our data suggest that metabolomics provide significant information on the pathogenesis of PAD and useful biomarkers for the diagnosis and assessment of progression. PMID: 30327580 [PubMed - in process]

Opportunities for green microextractions in comprehensive two-dimensional gas chromatography / mass spectrometry-based metabolomics - A review.

Thu, 18/10/2018 - 13:23
Related Articles Opportunities for green microextractions in comprehensive two-dimensional gas chromatography / mass spectrometry-based metabolomics - A review. Anal Chim Acta. 2018 Dec 21;1040:1-18 Authors: de Souza JRB, Dias FFG, Caliman JD, Augusto F, Hantao LW Abstract Microextractions have become an attractive class of techniques for metabolomics. The most popular technique is solid-phase microextraction that revolutionized the field of modern sample preparation in the early nineties. Ever since this milestone, microextractions have taken on many principles and formats comprising droplets, fibers, membranes, needles, and blades. Sampling devices may be customized to impart exhaustive or equilibrium-based characteristics to the extraction method. Equilibrium-based approaches may rely on additional methods for calibration, such as diffusion-based or on-fiber kinetic calibration to improve bioanalysis. In addition, microextraction-based methods may enable minimally invasive sampling protocols and measure the average free concentration of analytes in heterogeneous multiphasic biological systems. On-fiber derivatization has evidenced new opportunities for targeted and untargeted analysis in metabolomics. All these advantages have highlighted the potential of microextraction techniques for in vivo and on-site sampling and sample preparation, while many opportunities are still available for laboratory protocols. In this review, we outline and discuss some of the most recent applications using microextractions techniques for comprehensive two-dimensional gas chromatography-based metabolomics, including potential research opportunities. PMID: 30327098 [PubMed - in process]

Supplementation of a clay mineral-based product modulates plasma metabolomic profile and liver enzymes in cattle fed grain-rich diets.

Thu, 18/10/2018 - 13:23
Related Articles Supplementation of a clay mineral-based product modulates plasma metabolomic profile and liver enzymes in cattle fed grain-rich diets. Animal. 2018 Oct 17;:1-10 Authors: Humer E, Kröger I, Neubauer V, Reisinger N, Zebeli Q Abstract Grain-rich diets often lead to subacute ruminal acidosis (SARA) impairing rumen and systemic cattle health. Recent data suggest beneficial effects of a clay mineral (CM)- based product on the rumen microbiome of cattle during SARA. This study sought to investigate whether the CM supplementation can counteract SARA-induced perturbations of the bovine systemic health. The study used an intermittent diet-induced SARA-model with eight dry Holstein cows receiving either no additive as control or CM via concentrates (n=8 per treatment). Cows received first a forage diet (Baseline) for 1 week, followed by a 1-week SARA-challenge (SARA 1), a 1-week recovery phase (Recovery) and finally a second SARA-challenge for 2 weeks (SARA 2). Cows were monitored for feed intake, reticular pH and chewing behavior. Blood samples were taken and analyzed for metabolites related to glucose and lipid metabolism as well as liver health biomarkers. In addition, a targeted electrospray ionization-liquid chromatography-MS-based metabolomics approach was carried out on the plasma samples obtained at the end of the Baseline and SARA 1 phase. Data showed that supplementing the cows' diet with CM improved ruminating chews per regurgitated bolus by 16% in SARA 1 (P=0.01) and enhanced the dry matter intake during the Recovery phase (P=0.05). Moreover, the SARA-induced decreases in several amino acids and phosphatidylcholines were less pronounced in cows receiving CM (P≤0.10). The CM-supplemented cows also had lower concentrations of lactate (P=0.03) and biogenic amines such as histamine and spermine (P<0.01) in the blood. In contrast, the concentration of acylcarnitines with key metabolic functions was increased in the blood of treated cows (P≤0.05). In SARA 2, the CM-cows had lower concentrations of the liver enzymes aspartate aminotransferase and γ-glutamyltransferase (P<0.05). In conclusion, the data suggest that supplementation of CM holds the potential to alleviate the negative effects of high-grain feeding in cattle by counteracting multiple SARA-induced perturbations in the systemic metabolism and liver health. PMID: 30326981 [PubMed - as supplied by publisher]

Identification of redox imbalance as a prominent metabolic response elicited by rapeseed feeding in swine metabolome.

Thu, 18/10/2018 - 13:23
Related Articles Identification of redox imbalance as a prominent metabolic response elicited by rapeseed feeding in swine metabolome. J Anim Sci. 2018 May 04;96(5):1757-1768 Authors: Chen C, Pérez de Nanclares M, Kurtz JF, Trudeau MP, Wang L, Yao D, Saqui-Salces M, Urriola PE, Mydland LT, Shurson GC, Overland M Abstract Rapeseed (RS) is an abundant and inexpensive source of energy and AA in diets for monogastrics and a sustainable alternative to soybean meal. It also contains diverse bioactive phytochemicals that could have antinutritional effects at high dose. When the RS-derived feed ingredients (RSF) are used in swine diets, the uptake of these nutrients and phytochemicals is expected to affect the metabolic system. In this study, 2 groups of young pigs (17.8 ± 2.7 kg initial BW) were equally fed a soybean meal-based control diet and an RSF-based diet, respectively, for 3 wk. Digesta, liver, and serum samples from these pigs were examined by liquid chromatography-mass spectrometry-based metabolomic analysis to determine the metabolic effects of the 2 diets. Analyses of digesta samples revealed that sinapine, sinapic acid, and gluconapin were robust exposure markers of RS. The distribution of free AA along the intestine of RSF pigs was consistent with the reduced apparent ileal digestibility of AA observed in these pigs. Despite its higher fiber content, the RSF diet did not affect microbial metabolites in the digesta, including short-chain fatty acids and secondary bile acids. Analyses of the liver and serum samples revealed that RSF altered the levels of AA metabolites involved in the urea cycle and 1-carbon metabolism. More importantly, RSF increased the levels of multiple oxidized metabolites and aldehydes while decreased the levels of ascorbic acid and docosahexaenoic acid-containing lipids in the liver and serum, suggesting that RSF could disrupt redox balance in young pigs. Overall, the results indicated that RSF elicited diverse metabolic events in young pigs through its influences on nutrient and antioxidant metabolism, which might affect the performance and health in long-term feeding and also provide the venues for nutritional and processing interventions to improve the utilization of RSF in pigs. PMID: 29518202 [PubMed - indexed for MEDLINE]

An experimental study on investigating the postmortem interval in dichlorvos poisoned rats by GC/MS-based metabolomics.

Wed, 17/10/2018 - 12:58
An experimental study on investigating the postmortem interval in dichlorvos poisoned rats by GC/MS-based metabolomics. Leg Med (Tokyo). 2018 Oct 11;36:28-36 Authors: Dai X, Fan F, Ye Y, Lu X, Chen F, Wu Z, Liao L Abstract The estimation of the postmortem interval (PMI) is always a key issue in forensic science. Although many attempts based on metabolomics approaches have been proven to be feasible and accurate for PMI estimation, there have been no reports regarding the determination of the PMI in acute dichlorvos (DDVP) poisoning. In this study, all rats were killed by acute DDVP poisoning at a dose three fold the oral LD50 (240 mg/kg). Gas chromatography-mass spectrometry (GC/MS) was applied to investigate the metabolic profiling of blood samples at various times after death up to 72 h. A total of 39 metabolites were found to be associated with PMI, and the combinations of various numbers of metabolites were used to establish support vector regression (SVR) models to investigate the PMI. The SVR model constructed by 23 metabolites had a minimum mean squared error (MSE) of 5.49 h for the training set. Then, the SVR model was validated by prediction set with an MSE of 10.33 h, suggesting good predictive ability of the model for investigating the PMI. The findings demonstrated the great potential of GC/MS-based metabolomics combined with the SVR model in determining the PMI of DDVP poisoned rats and provided an experimental basis for the application of this approach in investigating the PMI of other toxicants. PMID: 30326392 [PubMed - as supplied by publisher]

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