PubMed

Non-targeted LC-MS metabolomics approach for metabolic profiling of plasma and urine from pigs fed branched chain amino acids for maximum growth performance. J Proteome Res. 2016 Oct 5;: Authors: Soumeh EA, Hedemann MS, Poulsen HD, Corrent E, van Milgen J, Nørgaard JV Abstract The metabolic response to plasma and urine of pigs when feeding an optimum level of BCAA for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAA intake level that could be linked to the animal growth performance. Three dose-response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a non-targeted LC-MS approach to characterize the metabolic profile of bio-fluids when dietary BCAA is optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic acid, tauroursodeoxycholic acid, and taurocholic acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic acid and choline and relatively decreased excretion of 2-aminoadipic acid, acetyl-DL-valine, Ile, 2 methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic acid and taurocholic acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-aminoadipic acid and elevated urinary excretion of ascorbic acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA. PMID: 27704848 [PubMed - as supplied by publisher]

Metabolomic Analysis of Mouse Embryonic Fibroblast Cells in Response to Autophagy Induced by Acute Starvation. Sci Rep. 2016 Oct 05;6:34075 Authors: Shen S, Weng R, Li L, Xu X, Bai Y, Liu H Abstract Autophagy-related protein 7 (Atg7) is essential in the formation of the autophagophore and is indispensable for autophagy induction. Autophagy will exist in lower level or even be blocked in cells without Atg7. Even though the possible signaling pathways of Atg7 have been proposed, the metabolomic responses under acute starvation in cells with and without Atg7 have not been elucidated. This study therefore was designed and aimed to reveal the metabolomics of Atg7-dependent autophagy through metabolomic analysis of Atg7(-/-) mouse embryonic fibroblast cells (MEFs) and wild-type MEFs along with the starvation time. 30 significantly altered metabolites were identified in response to nutrient stress, which were mainly associated with amino acid, energy, carbohydrate, and lipid metabolism. For the wild-type MEFs, the induction of autophagy protected cell survival with some up-regulated lipids during the first two hours' starvation, while the subsequent apoptosis resulted in the decrease of cell viability after four hours' starvation. For the Atg7(-/-) MEFs, apoptosis perhaps led to the deactivation of tricarboxylic acid (TCA) cycle due to the lack of autophagy, which resulted in the immediate drop of cellular viability under starvation. These results contributed to the metabolomic study and provided new insights into the mechanism associated with Atg7-dependent autophagy. PMID: 27703171 [PubMed - in process]

Screening of Soluble Epoxide Hydrolase Inhibitory Ingredients from Traditional Chinese Medicines for Anti-inflammatory Use. J Ethnopharmacol. 2016 Oct 1;: Authors: Liu JY, Morisseau C, Huang H, Hammock BD Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. AIM OF THE STUDY: To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo. MATERIALS AND METHODS: In vitro inhibition assay of the sEH was conducted for the methanol and ethanol extracts of 27 anti-inflammatory TCMs. Two potent extracts were subject to further separation guided by bioassay to afford promising AI against sEH in vitro [Fr.5 of the crude ethanol extract of Rhizoma coptidis (FFCERC)]. Finally, the in vivo anti-inflammatory effect and sEH inhibitory potency of FFCERC was evaluated in a lipopolysacchride (LPS)-challenged murine model of acute systemic inflammation. The inflammatory status was characterized by the inflammatory cytokines TNF-α and interleukine-6 (IL-6) and sEH inhibitory function was evaluated by the plasma levels of epoxyeicosantrienoic acids (EETs) and dihydroxyeicosantrienoic acids (DHETs), which are the sEH mediated substrates and products, respectively. RESULTS: At the concentration of 25µg/mL, the crude ethanol extracts of 6 TCMs including Herba Asari, Radix Polygalae, Fructus Amomi, Radix Astragali, Radix Scutellariae, and Rhizoma Coptidis were potent against sEH. The crude extracts of Herba Asari and Rhizoma Coptidis were selected for further separation to afford FFCERC as the most promising AI for in vivo evaluation. Oral administration of FFCERC attenuated the significant increase in TNF-α and IL-6 caused by LPS challenge in a dose-dependent manner. In parallel, oral administration of FFCERC shifted the changes in plasma levels of EETs and DHETs caused by LPS-challenge like a synthetic sEH inhibitor. CONCLUSIONS: A sEH inhibitory AI from Rhizoma Coptidis is anti-inflammatory and the inhibition of sEH contributes to this biological effect, indicating that sEH may be at least one of multiple therapeutic targets for relevant TCMs. PMID: 27702689 [PubMed - as supplied by publisher]

Proteomic and metabolomic responses in D-shape larval mussels Mytilus galloprovincialis exposed to cadmium and arsenic. Fish Shellfish Immunol. 2016 Oct 1;: Authors: Wu H, Xu L, Ji C, Yu D Abstract Cadmium (Cd) and arsenic (As) are the main metal/metalloid contaminants in the coastal environments of the Bohai Sea, China. In this work, a combined proteomic and metabolomic approach was applied to investigate the biological effects of Cd and As (V) in the early life stage (D-shape larvae) of mussel Mytilus galloprovincialis. Results indicated that Cd was a potential immune toxicant to D-shape larval mussel because of the numerous proteomic responses related to immune system. Additionally, Cd induced oxidative stress, cellular injury and disturbance in nucleic acid metabolism in D-shape larval mussels. However, only two identified proteins were significantly altered in As (V)-treated group, suggesting that D-shape larval mussel was less sensitive to As (V) than to Cd at protein level. These two proteins in response to As (V) suggested that As (V) influenced anti-oxidative system and cell proliferation in D-shape larval mussels. Metabolic responses indicated that Cd and As (V) induced disturbances in osmotic regulation and energy metabolism in D-shape larval mussels via different metabolic pathways. In addition, Cd reduced lipid metabolism as well. This work demonstrated that a combination of proteomics and metabolomics could provide an insightful view in the biological effects of pollutants in mussel M. galloprovincialis at an early life stage. PMID: 27702675 [PubMed - as supplied by publisher]

Novel selective TOCSY method enables NMR spectral elucidation of metabolomic mixtures. J Magn Reson. 2016 Sep 16;272:147-157 Authors: MacKinnon N, While PT, Korvink JG Abstract Complex mixture analysis is routinely encountered in NMR-based investigations. With the aim of component identification, spectral complexity may be addressed chromatographically or spectroscopically, the latter being favored to reduce sample handling requirements. An attractive experiment is selective total correlation spectroscopy (sel-TOCSY), which is capable of providing tremendous spectral simplification and thereby enhancing assignment capability. Unfortunately, isolating a well resolved resonance is increasingly difficult as the complexity of the mixture increases and the assumption of single spin system excitation is no longer robust. We present TOCSY optimized mixture elucidation (TOOMIXED), a technique capable of performing spectral assignment particularly in the case where the assumption of single spin system excitation is relaxed. Key to the technique is the collection of a series of 1D sel-TOCSY experiments as a function of the isotropic mixing time (τm), resulting in a series of resonance intensities indicative of the underlying molecular structure. By comparing these τm-dependent intensity patterns with a library of pre-determined component spectra, one is able to regain assignment capability. After consideration of the technique's robustness, we tested TOOMIXED firstly on a model mixture. As a benchmark we were able to assign a molecule with high confidence in the case of selectively exciting an isolated resonance. Assignment confidence was not compromised when performing TOOMIXED on a resonance known to contain multiple overlapping signals, and in the worst case the method suggested a follow-up sel-TOCSY experiment to confirm an ambiguous assignment. TOOMIXED was then demonstrated on two realistic samples (whisky and urine), where under our conditions an approximate limit of detection of 0.6mM was determined. Taking into account literature reports for the sel-TOCSY limit of detection, the technique should reach on the order of 10μM sensitivity. We anticipate this technique will be highly attractive to various analytical fields facing mixture analysis, including metabolomics, foodstuff analysis, pharmaceutical analysis, and forensics. PMID: 27701031 [PubMed - as supplied by publisher]

Time is ripe: maturation of metabolomics in chronobiology. Curr Opin Biotechnol. 2016 Oct 1;43:70-76 Authors: Rhoades SD, Sengupta A, Weljie AM Abstract Sleep and circadian rhythms studies have recently benefited from metabolomics analyses, uncovering new connections between chronobiology and metabolism. From untargeted mass spectrometry to quantitative nuclear magnetic resonance spectroscopy, a diversity of analytical approaches has been applied for biomarker discovery in the field. In this review we consider advances in the application of metabolomics technologies which have uncovered significant effects of sleep and circadian cycles on several metabolites, namely phosphatidylcholine species, medium-chain carnitines, and aromatic amino acids. Study design and data processing measures essential for detecting rhythmicity in metabolomics data are also discussed. Future developments in these technologies are anticipated vis-à-vis validating early findings, given metabolomics has only recently entered the ring with other systems biology assessments in chronometabolism studies. PMID: 27701007 [PubMed - as supplied by publisher]

Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications. JCI Insight. 2016 Sep 22;1(15):e86976 Authors: Sas KM, Kayampilly P, Byun J, Nair V, Hinder LM, Hur J, Zhang H, Lin C, Qi NR, Michailidis G, Groop PH, Nelson RG, Darshi M, Sharma K, Schelling JR, Sedor JR, Pop-Busui R, Weinberg JM, Soleimanpour SA, Abcouwer SF, Gardner TW, Burant CF, Feldman EL, Kretzler M, Brosius FC, Pennathur S Abstract Diabetes is associated with altered cellular metabolism, but how altered metabolism contributes to the development of diabetic complications is unknown. We used the BKS db/db diabetic mouse model to investigate changes in carbohydrate and lipid metabolism in kidney cortex, peripheral nerve, and retina. A systems approach using transcriptomics, metabolomics, and metabolic flux analysis identified tissue-specific differences, with increased glucose and fatty acid metabolism in the kidney, a moderate increase in the retina, and a decrease in the nerve. In the kidney, increased metabolism was associated with enhanced protein acetylation and mitochondrial dysfunction. To confirm these findings in human disease, we analyzed diabetic kidney transcriptomic data and urinary metabolites from a cohort of Southwestern American Indians. The urinary findings were replicated in 2 independent patient cohorts, the Finnish Diabetic Nephropathy and the Family Investigation of Nephropathy and Diabetes studies. Increased concentrations of TCA cycle metabolites in urine, but not in plasma, predicted progression of diabetic kidney disease, and there was an enrichment of pathways involved in glycolysis and fatty acid and amino acid metabolism. Our findings highlight tissue-specific changes in metabolism in complication-prone tissues in diabetes and suggest that urinary TCA cycle intermediates are potential prognostic biomarkers of diabetic kidney disease progression. PMID: 27699244 [PubMed - in process]

Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney. JCI Insight. 2016 Jul 21;1(11):e87680 Authors: Sato Y, Mii A, Hamazaki Y, Fujita H, Nakata H, Masuda K, Nishiyama S, Shibuya S, Haga H, Ogawa O, Shimizu A, Narumiya S, Kaisho T, Arita M, Yanagisawa M, Miyasaka M, Sharma K, Minato N, Kawamoto H, Yanagita M Abstract Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor(+) (p75NTR(+)) fibroblasts and homeostatic chemokine-producing fibroblasts inside TLTs, and retinoic acid-producing fibroblasts around TLTs. Deletion of CD4(+) cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly. PMID: 27699223 [PubMed - in process]

Comparative and parallel genome-wide association studies for metabolic and agronomic traits in cereals. Nat Commun. 2016 Oct 04;7:12767 Authors: Chen W, Wang W, Peng M, Gong L, Gao Y, Wan J, Wang S, Shi L, Zhou B, Li Z, Peng X, Yang C, Qu L, Liu X, Luo J Abstract The plant metabolome is characterized by extensive diversity and is often regarded as a bridge between genome and phenome. Here we report metabolic and phenotypic genome-wide studies (mGWAS and pGWAS) in rice grain that, in addition to previous metabolic GWAS in rice leaf and maize kernel, show both distinct and overlapping aspects of genetic control of metabolism within and between species. We identify new candidate genes potentially influencing important metabolic and/or morphological traits. We show that the differential genetic architecture of rice metabolism between different tissues is in part determined by tissue specific expression. Using parallel mGWAS and pGWAS we identify new candidate genes potentially responsible for variation in traits such as grain colour and size, and provide evidence of metabotype-phenotype linkage. Our study demonstrates a powerful strategy for interactive functional genomics and metabolomics in plants, especially the cloning of minor QTLs for complex phenotypic traits. PMID: 27698483 [PubMed - in process]

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing. Sci Rep. 2016 Oct 04;6:34692 Authors: Su T, Tan Y, Tsui MS, Yi H, Fu XQ, Li T, Chan CL, Guo H, Li YX, Zhu PL, Tse AK, Cao H, Lu AP, Yu ZL Abstract Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR. PMID: 27698376 [PubMed - in process]

Omics-based approaches reveal phospholipids remodeling of Rhizopus oryzae responding to furfural stress for fumaric acid-production from xylose. Bioresour Technol. 2016 Sep 30;222:24-32 Authors: Pan X, Liu H, Liu J, Wang C, Wen J Abstract In order to relieve the toxicity of furfural on Rhizopus oryzae fermentation, the molecular mechanism of R. oryzae responding to furfural stress for fumaric acid-production was investigated by omics-based approaches. In metabolomics analysis, 29 metabolites including amino acid, sugars, polyols and fatty acids showed significant changes for maintaining the basic cell metabolism at the cost of lowering fumaric acid production. To further uncover the survival mechanism, lipidomics was carried out, revealing that phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and polyunsaturated acyl chains might be closely correlated with R. oryzae's adapting to furfural stress. Based on the above omics analysis, lecithin, inositol and soybean oil were exogenously supplemented separately with an optimized concentration in the presence of furfural, which increased fumaric acid titer from 5.78g/L to 10.03g/L, 10.05g/L and 12.13g/L (increased by 73.5%, 73.8% and 110%, respectively). These findings provide a methodological guidance for hemicellulose-fumaric acid development. PMID: 27697734 [PubMed - as supplied by publisher]

Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease. J Pharm Biomed Anal. 2016 Sep 26;132:103-108 Authors: Singh B, Jana SK, Ghosh N, Das SK, Joshi M, Bhattacharyya P, Chaudhury K Abstract Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. (1)H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising. PMID: 27697570 [PubMed - as supplied by publisher]

DNA shuffling approach for recombinant polyvalent OmpAs against V. alginolyticus and E. tarda infections. Fish Shellfish Immunol. 2016 Sep 30;: Authors: Li H, Chu X, Peng B, Peng XX Abstract Molecular breeding via DNA shuffling directs the evolution of vaccines with desired traits. In the present study, polyvalent OmpA vaccines were generated by DNA shuffling of five ompA genes from four species of bacteria Vibrio parahaemolyticus, V. alginolyticus, Edwardsiella tarda and Escherichia coli. First, a new hybrid OmpA was constructed using VA0764 primers and used for construction of a prokaryotic expressing library PompAs-FV containing 84 ompAs, which were validated by PCR and SDS/PAGE. Then, the 84 ompAs were used to construct a eukaryotic expressing library EompAs-FV for preparing DNA vaccines. Third, extracellular bacterium V. alginolyticus challenge post active immunization using these DNA vaccines was carried out to identify genes with high immunoprotection. Among the 84 ompAs, 17 showed higher or equal immune protection against infection caused by V. alginolyticus than control VA0764. Finally, immune protection against infection caused by intracellular bacterium Edwardsiella tarda was assessed further using the top seven out of the 17 ompAs. This led to identification of three efficient polyvalent vaccines against infections caused by the extracellular bacterium V. alginolyticus and intracellular bacterium E. tarda. In addition, we sequenced genes for understanding mechanisms of the polyvalent vaccines, but association of immune protection with mutation of gene and amino acids is not determined. These results indicate that DNA shuffling is an efficient way to develop polyvalent vaccines against microbial infections. PMID: 27697557 [PubMed - as supplied by publisher]

Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity. Biochim Biophys Acta. 2016 Sep 30;: Authors: Klingler C, Zhao X, Adhikary T, Li J, Xu G, Häring HU, Schleicher E, Lehmann R, Weigert C Abstract Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10μM LPC for 24h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A. The increase in both PDK4 and ANGPTL4 RNA expression was abolished in the presence of either PPARδ antagonist GSK0660 or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD. The activation of PPARδ transcriptional activity by LPC was shown as PPARδ-dependent luciferase reporter gene expression and enhanced DNA binding of the PPARδ/RXR dimer. On a functional level, further results show that the LPC-mediated activation of PPARδ can reduce fatty acid-induced inflammation and ER stress in human skeletal muscle cells. The protective effect of LPC was prevented in the presence of the PPARδ antagonist GSK0660. Taking together, LPCs can activate PPARδ, which is consistent with the association of high plasma LPC levels and PPARδ-dependent anti-diabetic and anti-inflammatory effects. PMID: 27697477 [PubMed - as supplied by publisher]

Advances in the genomics and metabolomics of dairy lactobacilli: A review. Food Microbiol. 2017 Feb;61:33-49 Authors: Stefanovic E, Fitzgerald G, McAuliffe O Abstract The Lactobacillus genus represents the largest and most diverse genera of all the lactic acid bacteria (LAB), encompassing species with applications in industrial, biotechnological and medical fields. The increasing number of available Lactobacillus genome sequences has allowed understanding of genetic and metabolic potential of this LAB group. Pangenome and core genome studies are available for numerous species, demonstrating the plasticity of the Lactobacillus genomes and providing the evidence of niche adaptability. Advancements in the application of lactobacilli in the dairy industry lie in exploring the genetic background of their commercially important characteristics, such as flavour development potential or resistance to the phage attack. The integration of available genomic and metabolomic data through the generation of genome scale metabolic models has enabled the development of computational models that predict the behaviour of organisms under specific conditions and present a route to metabolic engineering. Lactobacilli are recognised as potential cell factories, confirmed by the successful production of many compounds. In this review, we discuss the current knowledge of genomics, metabolomics and metabolic engineering of the prevalent Lactobacillus species associated with the production of fermented dairy foods. In-depth understanding of their characteristics opens the possibilities for their future knowledge-based applications. PMID: 27697167 [PubMed - in process]

Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine. J Appl Toxicol. 2016 Oct 3;: Authors: Fennell TR, Mortensen NP, Black SR, Snyder RW, Levine KE, Poitras E, Harrington JM, Wingard CJ, Holland NA, Pathmasiri W, Sumner SC Abstract Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg(-1) ) or by gavage (p.o.) (10 mg kg(-1) ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (μg Ag g(-1) tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27696470 [PubMed - as supplied by publisher]

Toluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signalling. J Neurochem. 2016 Oct 1;: Authors: Furlong TM, Duncan JR, Corbit LH, Rae CD, Rowlands BD, Maher AD, Nasrallah FA, Milligan CJ, Petrou S, Lawrence AJ, Balleine BW Abstract Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long-term impact remains limited. Here we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes found that acute toluene exposure reduced NMDA receptor signalling. Finally, in an adolescent rodent model of chronic intermittent exposure to toluene (10,000 ppm), we found that, while toluene exposure did not affect initial learning, it induced a deficit in updating that learning when response-outcome relationships were reversed or degraded in an instrumental conditioning paradigm. There were also group differences when more effort was required to obtain the reward; toluene exposed animals were less sensitive to progressive ratio schedules and to delayed discounting. These behavioural deficits were accompanied by changes in subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks after the final exposure to toluene in the hippocampus, prefrontal cortex and ventromedial striatum; regions with recognised roles in behavioural flexibility and decision-making. Collectively our data suggest that exposure to toluene is sufficient to induce adaptive changes in glutamatergic and GABAergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug-use. This article is protected by copyright. All rights reserved. PMID: 27696399 [PubMed - as supplied by publisher]

Ocean acidification influences host DNA methylation and phenotypic plasticity in environmentally susceptible corals. Evol Appl. 2016 Oct;9(9):1165-1178 Authors: Putnam HM, Davidson JM, Gates RD Abstract As climate change challenges organismal fitness by creating a phenotype-environment mismatch, phenotypic plasticity generated by epigenetic mechanisms (e.g., DNA methylation) can provide a temporal buffer for genetic adaptation. Epigenetic mechanisms may be crucial for sessile benthic marine organisms, such as reef-building corals, where ocean acidification (OA) and warming reflect in strong negative responses. We tested the potential for scleractinian corals to exhibit phenotypic plasticity associated with a change in DNA methylation in response to OA. Clonal coral fragments of the environmentally sensitive Pocillopora damicornis and more environmentally robust Montipora capitata were exposed to fluctuating ambient pH (7.9-7.65) and low pH (7.6-7.35) conditions in common garden tanks for ~6 weeks. M. capitata responded weakly, or acclimated more quickly, to OA, with no difference in calcification, minimal separation of metabolomic profiles, and no change in DNA methylation between treatments. Conversely, P. damicornis exhibited diminished calcification at low pH, stronger separation in metabolomic profiles, and responsiveness of DNA methylation to treatment. Our data suggest corals differ in their temporal dynamics and sensitivity for environmentally triggered real-time epigenetic reprogramming. The generation of potentially heritable plasticity via environmental induction of DNA methylation provides an avenue for assisted evolution applications in corals under rapid climate change. PMID: 27695524 [PubMed - in process]

Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR. Front Pharmacol. 2016;7:307 Authors: Li Z, Li A, Gao J, Li H, Qin X Abstract Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF. PMID: 27695416 [PubMed - in process]

The metabolome 18 years on: a concept comes of age. Metabolomics. 2016;12(9):148 Authors: Kell DB, Oliver SG Abstract BACKGROUND: The term 'metabolome' was introduced to the scientific literature in September 1998. AIM AND KEY SCIENTIFIC CONCEPTS OF THE REVIEW: To mark its 18-year-old 'coming of age', two of the co-authors of that paper review the genesis of metabolomics, whence it has come and where it may be going. PMID: 27695392 [PubMed - in process]