PubMed

Related Articles Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment: A Scientific Statement From the American Heart Association. Circ Cardiovasc Genet. 2016 Apr 19; Authors: Ferguson JF, Allayee H, Gerszten RE, Ideraabdullah F, Kris-Etherton PM, Ordovás JM, Rimm EB, Wang TJ, Bennett BJ Abstract Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. PMID: 27095829 [PubMed - as supplied by publisher]

Related Articles Cytokinin metabolism in maize: Novel evidence of cytokinin abundance, interconversions and formation of a new trans-zeatin metabolic product with a weak anticytokinin activity. Plant Sci. 2016 Jun;247:127-37 Authors: Hluska T, Dobrev PI, Tarkowská D, Frébortová J, Zalabák D, Kopečný D, Plíhal O, Kokáš F, Briozzo P, Zatloukal M, Motyka V, Galuszka P Abstract Cytokinins (CKs) are an important group of phytohormones. Their tightly regulated and balanced levels are essential for proper cell division and plant organ development. Here we report precise quantification of CK metabolites and other phytohormones in maize reproductive organs in the course of pollination and kernel maturation. A novel enzymatic activity dependent on NADP(+) converting trans-zeatin (tZ) to 6-(3-methylpyrrol-1-yl)purine (MPP) was detected. MPP shows weak anticytokinin properties and inhibition of CK dehydrogenases due to their ability to bind to an active site in the opposite orientation than substrates. Although the physiological significance of tZ side-chain cyclization is not anticipated as the MPP occurrence in maize tissue is very low, properties of the novel CK metabolite indicate its potential for utilization in plant in vitro tissue culture. Furthermore, feeding experiments with different isoprenoid CKs revealed distinct preferences in glycosylation of tZ and cis-zeatin (cZ). While tZ is preferentially glucosylated at the N9 position, cZ forms mainly O-glucosides. Since O-glucosides, in contrast to N9-glucosides, are resistant to irreversible cleavage catalyzed by CK dehydrogenases, the observed preference of maize CK glycosyltransferases to O-glycosylate zeatin in the cis-position might be a reason why cZ derivatives are over-accumulated in different maize tissues and organs. PMID: 27095406 [PubMed - in process]

Related Articles Drug target identification using network analysis: Taking active components in Sini decoction as an example. Sci Rep. 2016;6:24245 Authors: Chen S, Jiang H, Cao Y, Wang Y, Hu Z, Zhu Z, Chai Y Abstract Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound. PMID: 27095146 [PubMed - in process]

Related Articles Glucose 6-phosphate dehydrogenase deficient subjects may be better "storers" than donors of red blood cells. Free Radic Biol Med. 2016 Apr 14; Authors: Tzounakas VL, Kriebardis AG, Georgatzakou HT, Foudoulaki-Paparizos LE, Dzieciatkowska M, Wither MJ, Nemkov T, Hansen KC, Papassideri IS, D'Alessandro A, Antonelou MH Abstract Storage of packed red blood cells (RBCs) is associated with progressive accumulation of lesions, mostly triggered by energy and oxidative stresses, which potentially compromise the effectiveness of the transfusion therapy. Concerns arise as to whether glucose 6-phosphate dehydrogenase deficient subjects (G6PD(-)), ~5% of the population in the Mediterranean area, should be accepted as routine donors in the light of the increased oxidative stress their RBCs suffer from. To address this question, we first performed morphology (scanning electron microscopy), physiology and omics (proteomics and metabolomics) analyses on stored RBCs from healthy or G6PD(-) donors. We then used an in vitro model of transfusion to simulate transfusion outcomes involving G6PD(-) donors or recipients, by reconstituting G6PD(-) stored or fresh blood with fresh or stored blood from healthy volunteers, respectively, at body temperature. We found that G6PD(-) cells store well in relation to energy, calcium and morphology related parameters, though at the expenses of a compromised anti-oxidant system. Additional stimuli, mimicking post-transfusion conditions (37°C, reconstitution with fresh healthy blood, incubation with oxidants) promoted hemolysis and oxidative lesions in stored G6PD(-)cells in comparison to controls. On the other hand, stored healthy RBC units showed better oxidative parameters and lower removal signaling when reconstituted with G6PD(-)fresh blood compared to control. Although the measured parameters of stored RBCs from the G6PD deficient donors appeared to be acceptable, the results from the in vitro model of transfusion suggest that G6PD(-)RBCs could be more susceptible to hemolysis and oxidative stresses post-transfusion. On the other hand, their chronic exposure to oxidative stress might make them good recipients, as they better tolerate exposure to oxidatively damaged long stored healthy RBCs. PMID: 27094493 [PubMed - as supplied by publisher]

Related Articles Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM Rat model of type 2 diabetes. Am J Physiol Endocrinol Metab. 2016 Apr 19;:ajpendo.00052.2016 Authors: Piccolo BD, Graham JL, Stanhope KL, Fiehn O, Havel PJ, Adams SH Abstract Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM Rat model: i.e., pre-diabetic (PD), 2-weeks (D2W), 3-months (D3M) and 6-months (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28%, 29%, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-beta-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 months post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, that the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. PMID: 27094034 [PubMed - as supplied by publisher]

Related Articles Temporal and organ-specific detection of cNMPs including cUMP in the zebrafish. Biochem Biophys Res Commun. 2015 Dec 25;468(4):708-12 Authors: Dittmar F, Abdelilah-Seyfried S, Tschirner SK, Kaever V, Seifert R Abstract The cyclic pyrimidine nucleotides cCMP and cUMP occur in mammalian cell lines. Recently, cCMP was also identified in mouse organs. Due to technical difficulties, it has not been possible to detect cUMP in organs or tissues yet. Here, we have generated a temporal profile of the occurrence of nucleoside 3',5'-cyclic monophosphates during different developmental stages of embryogenesis and in different organs of the adult zebrafish Danio rerio. Cyclic nucleotides were quantified by high performance liquid chromatography quadrupole tandem mass spectrometry. The identity of cCMP and cUMP in the zebrafish was confirmed by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. We show for the first time that cUMP can be detected during embryogenesis and in adult organs of this vertebrate model system. PMID: 26551461 [PubMed - indexed for MEDLINE]

Related Articles Secondary electrospray ionization-mass spectrometry and a novel statistical bioinformatic approach identifies a cancer-related profile in exhaled breath of breast cancer patients: a pilot study. J Breath Res. 2015 Sep;9(3):031001 Authors: Martinez-Lozano Sinues P, Landoni E, Miceli R, Dibari VF, Dugo M, Agresti R, Tagliabue E, Cristoni S, Orlandi R Abstract Breath analysis represents a new frontier in medical diagnosis and a powerful tool for cancer biomarker discovery due to the recent development of analytical platforms for the detection and identification of human exhaled volatile compounds. Statistical and bioinformatic tools may represent an effective complement to the technical and instrumental enhancements needed to fully exploit clinical applications of breath analysis. Our exploratory study in a cohort of 14 breast cancer patients and 11 healthy volunteers used secondary electrospray ionization-mass spectrometry (SESI-MS) to detect a cancer-related volatile profile. SESI-MS full-scan spectra were acquired in a range of 40-350 mass-to-charge ratio (m/z), converted to matrix data and analyzed using a procedure integrating data pre-processing for quality control, and a two-step class prediction based on machine-learning techniques, including a robust feature selection, and a classifier development with internal validation. MS spectra from exhaled breath showed an individual-specific breath profile and high reciprocal homogeneity among samples, with strong agreement among technical replicates, suggesting a robust responsiveness of SESI-MS. Supervised analysis of breath data identified a support vector machine (SVM) model including 8 features corresponding to m/z 106, 126, 147, 78, 148, 52, 128, 315 and able to discriminate exhaled breath from breast cancer patients from that of healthy individuals, with sensitivity and specificity above 0.9.Our data highlight the significance of SESI-MS as an analytical technique for clinical studies of breath analysis and provide evidence that our noninvasive strategy detects volatile signatures that may support existing technologies to diagnose breast cancer. PMID: 26390050 [PubMed - indexed for MEDLINE]

Related Articles Heart-Specific Knockout of the Mitochondrial Thioredoxin Reductase (Txnrd2) Induces Metabolic and Contractile Dysfunction in the Aging Myocardium. J Am Heart Assoc. 2015 Jul;4(7) Authors: Kiermayer C, Northrup E, Schrewe A, Walch A, de Angelis MH, Schoensiegel F, Zischka H, Prehn C, Adamski J, Bekeredjian R, Ivandic B, Kupatt C, Brielmeier M Abstract BACKGROUND: Ubiquitous deletion of thioredoxin reductase 2 (Txnrd2) in mice is embryonically lethal and associated with abnormal heart development, while constitutive, heart-specific Txnrd2 inactivation leads to dilated cardiomyopathy and perinatal death. The significance of Txnrd2 in aging cardiomyocytes, however, has not yet been examined. METHODS AND RESULTS: The tamoxifen-inducible heart-specific αMHC-MerCreMer transgene was used to inactivate loxP-flanked Txnrd2 alleles in adult mice. Hearts and isolated mitochondria from aged knockout mice were morphologically and functionally analyzed. Echocardiography revealed a significant increase in left ventricular end-systolic diameters in knockouts. Fractional shortening and ejection fraction were decreased compared with controls. Ultrastructural analysis of cardiomyocytes of aged mice showed mitochondrial degeneration and accumulation of autophagic bodies. A dysregulated autophagic activity was supported by higher levels of lysosome-associated membrane protein 1 (LAMP1), microtubule-associated protein 1A/1B-light chain 3-I (LC3-I), and p62 in knockout hearts. Isolated Txnrd2-deficient mitochondria used less oxygen and tended to produce more reactive oxygen species. Chronic hypoxia inducible factor 1, α subunit stabilization and altered transcriptional and metabolic signatures indicated that energy metabolism is deregulated. CONCLUSIONS: These results imply a novel role of Txnrd2 in sustaining heart function during aging and suggest that Txnrd2 may be a modifier of heart failure. PMID: 26199228 [PubMed - indexed for MEDLINE]

Non-targeted Metabolite Profiling and Scavenging Activity Unveil the Nutraceutical Potential of Psyllium (Plantago ovata Forsk). Front Plant Sci. 2016;7:431 Authors: Patel MK, Mishra A, Jha B Abstract Non-targeted metabolomics implies that psyllium (Plantago ovata) is a rich source of natural antioxidants, PUFAs (ω-3 and ω-6 fatty acids) and essential and sulfur-rich amino acids, as recommended by the FAO for human health. Psyllium contains phenolics and flavonoids that possess reducing capacity and reactive oxygen species (ROS) scavenging activities. In leaves, seeds, and husks, about 76, 78, 58% polyunsaturated, 21, 15, 20% saturated, and 3, 7, 22% monounsaturated fatty acids were found, respectively. A range of FAs (C12 to C24) was detected in psyllium and among different plant parts, a high content of the nutritive indicators ω-3 alpha-linolenic acid CPS (57%) and ω-6 linoleic acid CPS (18%) was detected in leaves. Similarly, total content of phenolics and the essential amino acid valine were also detected utmost in leaves followed by sulfur-rich amino acids and flavonoids. In total, 36 different metabolites were identified in psyllium, out of which 26 (13 each) metabolites were detected in leaves and seeds, whereas the remaining 10 were found in the husk. Most of the metabolites are natural antioxidants, phenolics, flavonoids, or alkaloids and can be used as nutrient supplements. Moreover, these metabolites have been reported to have several pharmaceutical applications, including anti-cancer activity. Natural plant ROS scavengers, saponins, were also detected. Based on metabolomic data, the probable presence of a flavonoid biosynthesis pathway was inferred, which provides useful insight for metabolic engineering in the future. Non-targeted metabolomics, antioxidants and scavenging activities reveal the nutraceutical potential of the plant and also suggest that psyllium leaves can be used as a green salad as a dietary supplement to daily food. PMID: 27092153 [PubMed]

Exploiting Genomics Resources to Identify Candidate Genes Underlying Antioxidants Content in Tomato Fruit. Front Plant Sci. 2016;7:397 Authors: Calafiore R, Ruggieri V, Raiola A, Rigano MM, Sacco A, Hassan MI, Frusciante L, Barone A Abstract The tomato is a model species for fleshy fruit development and ripening, as well as for genomics studies of others Solanaceae. Many genetic and genomics resources, including databases for sequencing, transcriptomics and metabolomics data, have been developed and are today available. The purpose of the present work was to uncover new genes and/or alleles that determine ascorbic acid and carotenoids accumulation, by exploiting one Solanum pennellii introgression lines (IL7-3) harboring quantitative trait loci (QTL) that increase the content of these metabolites in the fruit. The higher ascorbic acid and carotenoids content in IL7-3 was confirmed at three fruit developmental stages. The tomato genome reference sequence and the recently released S. pennellii genome sequence were investigated to identify candidate genes (CGs) that might control ascorbic acid and carotenoids accumulation. First of all, a refinement of the wild region borders in the IL7-3 was achieved by analyzing CAPS markers designed in our laboratory. Afterward, six CGs associated to ascorbic acid and one with carotenoids metabolism were identified exploring the annotation and the Gene Ontology terms of genes included in the region. Variants between the sequence of the wild and the cultivated alleles of these genes were investigated for their functional relevance and their potential effects on the protein sequences were predicted. Transcriptional levels of CGs in the introgression region were extracted from RNA-Seq data available for the entire S. pennellii introgression lines collection and verified by Real-Time qPCR. Finally, seven IL7-3 sub-lines were genotyped using 28 species-specific markers and then were evaluated for metabolites content. These analyses evidenced a significant decrease in transcript abundance for one 9-cis-epoxycarotenoid dioxygenase and one L-ascorbate oxidase homolog, whose role in the accumulation of carotenoids and ascorbic acid is discussed. Comprehensively, the reported results demonstrated that combining genetic and genomic resources in tomato, including bioinformatics tools, was a successful strategy to dissect one QTL for the increase of ascorbic acid and carotenoids in tomato fruit. PMID: 27092148 [PubMed]

A MALDI-MS-based quantitative analytical method for endogenous estrone in human breast cancer cells. Sci Rep. 2016;6:24489 Authors: Kim KJ, Kim HJ, Park HG, Hwang CH, Sung C, Jang KS, Park SH, Kim BG, Lee YK, Yang YH, Jeong JH, Kim YG Abstract The level of endogenous estrone, one of the three major naturally occurring estrogens, has a significant correlation with the incidence of post-menopausal breast cancer. However, it is challenging to quantitatively monitor it owing to its low abundance. Here, we develop a robust and highly sensitive mass-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based quantitative platform to identify the absolute quantities of endogenous estrones in a variety of clinical specimens. The one-step modification of endogenous estrone provided good linearity (R(2) > 0.99) and significantly increased the sensitivity of the platform (limit of quantitation: 11 fmol). In addition, we could identify the absolute amount of endogenous estrones in cells of the breast cancer cell line MCF-7 (34 fmol/10(6) cells) by using a deuterated estrone as an internal standard. Finally, by applying the MALDI-MS-based quantitative method to endogenous estrones, we successfully monitored changes in the metabolic expression level of estrones (17.7 fmol/10(6) letrozole-treated cells) in MCF-7 cells resulting from treatment with an aromatase inhibitor. Taken together, these results suggest that this MALDI-MS-based quantitative approach may be a general method for the targeted metabolomics of ketone-containing metabolites, which can reflect clinical conditions and pathogenic mechanisms. PMID: 27091422 [PubMed - in process]

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows. Sci Rep. 2016;6:24642 Authors: Huber K, Dänicke S, Rehage J, Sauerwein H, Otto W, Rolle-Kampczyk U, von Bergen M Abstract The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life. PMID: 27089826 [PubMed - in process]

Related Articles Spatial distribution of metabolites in the human lens. Exp Eye Res. 2016 Feb;143:68-74 Authors: Tamara SO, Yanshole LV, Yanshole VV, Fursova AZh, Stepakov DA, Novoselov VP, Tsentalovich YP Abstract Spatial distribution of 34 metabolites along the optical and equatorial axes of the human lens has been determined. For the majority of metabolites, the homogeneous distribution has been observed. That suggests that the rate of the metabolite transformation in the lens is low due to the general metabolic passivity of the lens fiber cells. However, the redox processes are active in the lens; as a result, some metabolites, including antioxidants, demonstrate the "nucleus-depleted" type of distribution, whereas secondary UV filters show the "nucleus-enriched" type. The metabolite concentrations at the lens poles and equator are similar for all metabolites under study. The concentric pattern of the "nucleus-depleted" and "nucleus-enriched" distributions testifies that the metabolite distribution inside the lens is mostly governed by a passive diffusion, relatively free along the fiber cells and retarded in the radial direction across the cells. No significant difference in the metabolite distribution between the normal and cataractous human lenses was found. PMID: 26500196 [PubMed - indexed for MEDLINE]

Related Articles RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway. Nat Commun. 2015;6:7367 Authors: Murakawa Y, Hinz M, Mothes J, Schuetz A, Uhl M, Wyler E, Yasuda T, Mastrobuoni G, Friedel CC, Dölken L, Kempa S, Schmidt-Supprian M, Blüthgen N, Backofen R, Heinemann U, Wolf J, Scheidereit C, Landthaler M Abstract The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFα mRNA decay via a 3'UTR constitutive decay element (CDE). Here we applied PAR-CLIP to human RC3H1 to identify ∼ 3,800 mRNA targets with >16,000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage-induced mRNAs, indicating a role of this RNA-binding protein in the post-transcriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of the NF-κB pathway regulators such as IκBα and A20. RC3H1 uses ROQ and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IκB kinase and NF-κB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κB pathway. PMID: 26170170 [PubMed - indexed for MEDLINE]

Related Articles The pervasiveness and plasticity of circadian oscillations: the coupled circadian-oscillators framework. Bioinformatics. 2015 Oct 1;31(19):3181-8 Authors: Patel VR, Ceglia N, Zeller M, Eckel-Mahan K, Sassone-Corsi P, Baldi P Abstract MOTIVATION: Circadian oscillations have been observed in animals, plants, fungi and cyanobacteria and play a fundamental role in coordinating the homeostasis and behavior of biological systems. Genetically encoded molecular clocks found in nearly every cell, based on negative transcription/translation feedback loops and involving only a dozen genes, play a central role in maintaining these oscillations. However, high-throughput gene expression experiments reveal that in a typical tissue, a much larger fraction ([Formula: see text]) of all transcripts oscillate with the day-night cycle and the oscillating species vary with tissue type suggesting that perhaps a much larger fraction of all transcripts, and perhaps also other molecular species, may bear the potential for circadian oscillations. RESULTS: To better quantify the pervasiveness and plasticity of circadian oscillations, we conduct the first large-scale analysis aggregating the results of 18 circadian transcriptomic studies and 10 circadian metabolomic studies conducted in mice using different tissues and under different conditions. We find that over half of protein coding genes in the cell can produce transcripts that are circadian in at least one set of conditions and similarly for measured metabolites. Genetic or environmental perturbations can disrupt existing oscillations by changing their amplitudes and phases, suppressing them or giving rise to novel circadian oscillations. The oscillating species and their oscillations provide a characteristic signature of the physiological state of the corresponding cell/tissue. Molecular networks comprise many oscillator loops that have been sculpted by evolution over two trillion day-night cycles to have intrinsic circadian frequency. These oscillating loops are coupled by shared nodes in a large network of coupled circadian oscillators where the clock genes form a major hub. Cells can program and re-program their circadian repertoire through epigenetic and other mechanisms. AVAILABILITY AND IMPLEMENTATION: High-resolution and tissue/condition specific circadian data and networks available at http://circadiomics.igb.uci.edu. CONTACT: pfbaldi@ics.uci.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID: 26049162 [PubMed - indexed for MEDLINE]

Related Articles Recent advances in omic technologies for meat quality management. Meat Sci. 2015 Nov;109:18-26 Authors: Picard B, Lebret B, Cassar-Malek I, Liaubet L, Berri C, Le Bihan-Duval E, Hocquette JF, Renand G Abstract The knowledge of the molecular organization of living organisms evolved considerably during the last years. The methodologies associated also progressed with the development of the high-throughput sequencing (SNP array, RNAseq, etc.) and of genomic tools allowing the simultaneous analysis of hundreds or thousands of genes, proteins or metabolites. In farm animals, some proteins, mRNAs or metabolites whose abundance has been associated with meat quality traits have been detected in pig, cattle, chicken. They constitute biomarkers for the assessment and prediction of qualities of interest in each species, with potential biomarkers across species. The ongoing development of rapid methods will allow their use for decision-making and management tools in slaughterhouses, to better allocate carcasses or cuts to the appropriate markets. Besides, their application on living animals will help to improve genetic selection and to adapt a breeding system to fulfill expected quality level. The ultimate goal is to propose effective molecular tools for the management of product quality in meat production chains. PMID: 26002117 [PubMed - indexed for MEDLINE]

Related Articles Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget. 2015 May 30;6(15):13416-33 Authors: Schumann T, Adhikary T, Wortmann A, Finkernagel F, Lieber S, Schnitzer E, Legrand N, Schober Y, Nockher WA, Toth PM, Diederich WE, Nist A, Stiewe T, Wagner U, Reinartz S, Müller-Brüsselbach S, Müller R Abstract The nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor associated with macrophage polarization. However, its function in tumor-associated macrophages (TAMs) has not been investigated to date. Here, we report the PPARβ/δ-regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients. Comparison with monocyte-derived macrophages shows that the vast majority of direct PPARβ/δ target genes are upregulated in TAMs and largely refractory to synthetic agonists, but repressible by inverse agonists. Besides genes with metabolic functions, these include cell type-selective genes associated with immune regulation and tumor progression, e.g., LRP5, CD300A, MAP3K8 and ANGPTL4. This deregulation is not due to increased expression of PPARβ/δ or its enhanced recruitment to target genes. Instead, lipidomic analysis of malignancy-associated ascites revealed high concentrations of polyunsaturated fatty acids, in particular linoleic acid, acting as potent PPARβ/δ agonists in macrophages. These fatty acid ligands accumulate in lipid droplets in TAMs, thereby providing a reservoir of PPARβ/δ ligands. These observations suggest that the deregulation of PPARβ/δ target genes by ligands of the tumor microenvironment contributes to the pro-tumorigenic polarization of ovarian carcinoma TAMs. This conclusion is supported by the association of high ANGPTL4 expression with a shorter relapse-free survival in serous ovarian carcinoma. PMID: 25968567 [PubMed - indexed for MEDLINE]

Related Articles Metabolism and disposition of a potent and selective JNK inhibitor [14C]tanzisertib following oral administration to rats, dogs and humans. Xenobiotica. 2015 May;45(5):428-41 Authors: Atsriku C, Hoffmann M, Ye Y, Kumar G, Surapaneni S Abstract 1. The disposition of tanzisertib [(1S,4R)-4-(9-((S)tetrahydrofuran-3-yl)-8-(2,4,6-trifluorophenylamino)-9H-purin-2-ylamino) cyclohexanol], a potent, orally active c-Jun amino-terminal kinase inhibitor intended for treatment of fibrotic diseases was studied in rats, dogs and humans following a single oral dose of [(14)C]tanzisertib (Independent Investigational Review Board Inc., Plantation, FL). 2. Administered dose was quantitatively recovered in all species and feces/bile was the major route of elimination. Tanzisertib was rapidly absorbed (Tmax: 1-2 h) across all species with unchanged tanzisertib representing >83% of plasma radioactivity in dogs and humans, whereas <34% was observed in rats. Variable amounts of unchanged tanzisertib (1.5-32% of dose) was recovered in urine/feces across all species, the highest in human feces. 3. Metabolic profiling revealed that tanzisertib was primarily metabolized via oxidation and conjugation pathways, but extensively metabolized in rats relative to dogs/humans. CC-418424 (S-cis isomer of tanzisertib) was the major plasma metabolite in rats (38.4-46.4% of plasma radioactivity), while the predominant plasma metabolite in humans and dogs was M18 (tanzisertib-/CC-418424 glucuronide), representing 7.7 and 3.2% of plasma radioactivity, respectively. Prevalent biliary metabolite in rats and dogs, M18 represented 16.8 and 17.1% of dose, respectively. 4. In vitro studies using liver subcellular fractions and expressed enzymes characterized involvement of novel human aldo-keto reductases for oxido-reduction and UDP-glucuronosyltransferases for conjugation pathways. PMID: 25482583 [PubMed - indexed for MEDLINE]

Related Articles An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol. Xenobiotica. 2015 May;45(5):396-405 Authors: Bushee JL, Dunne CE, Argikar UA Abstract 1. Topical glaucoma treatments have often been limited by poor absorption and bioavailability. Betaxolol, a selective β1-blocker, has been well studied for its pharmacokinetics and disposition. Limited ocular, betaxolol metabolism data is available despite a growing number of novel ocular treatments. 2. In vitro ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver. 3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human in vitro ocular data. M1 was specific to human and only captured by the liver data. 4. Liver S9 over predicted the extent of ocular metabolism compared to ocular fractions. Rabbit liver S9 fractions demonstrated extensive glucuronidation and higher parent turn-over in 1 h as compared to other matrices. 5. This research assesses in vitro species and organ differences across preclinical species and human. The complex data set highlights the need for an in vitro ocular system to explore poorly documented ocular metabolism. PMID: 25475994 [PubMed - indexed for MEDLINE]

Metabolomics by (1)H-HRMAS-NMR of Tomato Plants Treated with two Secondary Metabolites Isolated from Trichoderma. J Agric Food Chem. 2016 Apr 18; Authors: Mazzei P, Vinale F, Woo SL, Pascale A, Lorito M, Piccolo A Abstract Trichoderma fungi release 6-pentyl-2H-pyran-2-one, 1, and, harzianic acid, 2, secondary metabolites to improve plant growth and health protection. We isolated 1 and 2 from Trichoderma strains, whose different concentrations were used to treat seeds of Solanum lycopersicum. The metabolic profile in the resulting 15 d old tomato leaves was studied by high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy directly on the whole samples without any preliminary extraction. PCA of HRMAS-NMR showed significantly enhanced acetylcholine and GABA content accompanied by variable amount of amino-acids in samples treated with both Trichoderma secondary metabolites. Seed germination rates, seedling fresh weight and the metabolome of tomato leaves were also dependent on doses of 1 and 2 treatments. HRMAS-NMR spectroscopy was proved to represent a rapid and reliable technique for evaluating specific changes in the metabolome of plant leaves and calibrating the best concentration of bioactive compounds required to stimulate plant growth. PMID: 27088924 [PubMed - as supplied by publisher]