PubMed

Related Articles NMR metabolomic fingerprinting distinguishes milk from different farms. Food Res Int. 2018 Nov;113:131-139 Authors: Tenori L, Santucci C, Meoni G, Morrocchi V, Matteucci G, Luchinat C Abstract A fast and reproducible protocol for milk Nuclear Magnetic Resonance (NMR) metabolomic fingerprinting was developed, allowing for an accurate discrimination among milk samples from large-scale distribution, as well as among milk sample from different farms located in the same restricted geographical area. Seasonal variations in milk composition and correlations with cows' nutritional patterns are also assessed, underlining relationships between feeding and metabolites. The most important difference was related to the use of silage feeding. This finding is relevant to assess the suitability of milk for different dairy products. A prominent example is parmesan cheese, the preparation protocol of which excludes milk from silage-fed cows. PMID: 30195505 [PubMed - in process]

Related Articles Dysregulated serum metabolites in staging of hepatocellular carcinoma. Clin Biochem. 2018 Sep 06;: Authors: Wang W, Lv J, Chen N, Lou B, Mao W, Wang P, Chen Y Abstract BACKGROUND: Correct staging of hepatocellular carcinoma (HCC) could help physicians to precisely select treatments for patients, such as surgery, chemotherapy, or their combination. The objective of this study was to explore potential metabolic markers for staging of hepatocellular carcinoma. METHODS: By liquid chromatography with mass spectrometry (LC-MS), the serum metabolic profiles of 60 pathologically confirmed hepatocellular carcinoma (HCC) patients were analyzed using the TNM staging system and Chinese staging system. RESULTS: The serum levels of dihydrocortisol, lysophosphatidylcholine (LPC-18:0), lysophosphatidylethanolamine (LPE-16:0), taurine, uric acid, adipic acid, tetracosatetraenoic acid, and L-octanoylcarnitine differed significantly between staging I and non-stage I HCCs (p < 0.05) based on the HCC TNM staging system, and compared to stage I sera, non-stage I sera contained higher levels of dihydrocortisol, adipic acid, tetracosatetraenoic acid, and L-octanoylcarnitine. There are significant differences were observed in serum levels of LPC (22:6), alpha-linolenylcarnitine, estrone, LPE (16:0), LPE (18:2), and taurine between stage I and stage II HCCs (p < 0.05) based on the Chinese HCC staging system, and compared to stage I sera, stage II sera had a higher level of LPC (22:6). CONCLUSION: These dysregulated metabolites in sera of HCC patients potentially could be used as biomarkers for the clinical staging of HCC. PMID: 30195484 [PubMed - as supplied by publisher]

Metabolomics in chronic kidney disease: Strategies for extended metabolome coverage. J Pharm Biomed Anal. 2018 Aug 25;161:313-325 Authors: Yoric G, Julien B, Belén P, Serge R Abstract Chronic kidney disease (CKD) is becoming a major public health issue as prevalence is increasing worldwide. It also represents a major challenge for the identification of new early biomarkers, understanding of biochemical mechanisms, patient monitoring and prognosis. Each metabolite contained in a biofluid or tissue may play a role as a signal or as a driver in the development or progression of the pathology. Therefore, metabolomics is a highly valuable approach in this clinical context. It aims to provide a representative picture of a biological system, making exhaustive metabolite coverage crucial. Two aspects can be considered: analytical and biological coverage. From an analytical point of view, monitoring all metabolites within one run is currently impossible. Multiple analytical techniques providing orthogonal information should be carried out in parallel for coverage improvement. The biological aspect of metabolome coverage can be enhanced by using multiple biofluids or tissues for in-depth biological investigation, as the analysis of a single sample type is generally insufficient for whole organism extrapolation. Hence, recording of signals from multiple sample types and different analytical platforms generates massive and complex datasets so that chemometric tools, including data fusion approaches and multi-block analysis, are key tools for extracting biological information and for discovery of relevant biomarkers. This review presents the recent developments in the field of metabolomic analysis, from sampling and analytical strategies to chemometric tools, dedicated to the generation and handling of multiple complementary metabolomic datasets enabling extended metabolite coverage to improve our biological knowledge of CKD. PMID: 30195171 [PubMed - as supplied by publisher]

Using metabolome data for mathematical modeling of plant metabolic systems. Curr Opin Biotechnol. 2018 Sep 05;54:138-144 Authors: Hirai MY, Shiraishi F Abstract Plant metabolism is characterized by a wide diversity of metabolites, with systems far more complicated than those of microorganisms. Mathematical modeling is useful for understanding dynamic behaviors of plant metabolic systems for metabolic engineering. Time-series metabolome data has great potential for estimating kinetic model parameters to construct a genome-wide metabolic network model. However, data obtained by current metabolomics techniques does not meet the requirement for constructing accurate models. In this article, we highlight novel strategies and algorithms to handle the underlying difficulties and construct dynamic in vivo models for large-scale plant metabolic systems. The coarse but efficient modeling enables the prediction of unknown mechanisms regulating plant metabolism. PMID: 30195121 [PubMed - as supplied by publisher]

Postharvest metabolomic changes in Pyrus ussuriensis Maxim. wild accession 'Zaoshu Shanli'. J Sep Sci. 2018 Sep 08;: Authors: Xu J, Zhang Y, Qi D, Huo H, Dong X, Tian L, Zhang X, Liu C, Cao Y Abstract There are strong economic drivers for understanding the process of fruit postharvest softening. In this study, liquid chromatography-electrospray ionization-tandem mass spectrometry was used to analyze metabolite changes in 'Zaoshu Shanli' fruit after different storage periods; this wild accession of Pyrus ussuriensis presents good fruit quality and relatively low flesh firmness after fruit storage. The lipid metabolites in 'Zaoshu Shanli' fruit were significantly higher at 18 day of storage compared with those at 0 day of storage, and glycerophospholipid metabolism was different metabolic pathway. It was therefore speculated that lipid metabolism play an important role in pear fruit postharvest processes and softening. Furthermore, the abscisic acid and trans-zeatin contents in 'Zaoshu Shanli' fruit at 18 day of storage were significantly greater than those at 0 day of storage. Therefore, it was speculated that the abovementioned hormones play an important role in pear fruit postharvest softening. Together, these results provide fundamental insight into the reasonable control of pear fruit postharvest softening and lay a solid foundation for additional research. This article is protected by copyright. All rights reserved. PMID: 30194817 [PubMed - as supplied by publisher]

The role of human breast milk on biological metabolism in infants. Pediatr Int. 2018 Sep 08;: Authors: Shoji H, Shimizu T Abstract The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. Levels of a urinary marker of oxidative DNA damage (8-OHdG) were significantly lower in breast-fed term and preterm infants than those in formula-fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast-fed preterm infants than those who were mixed-fed infants at discharge. Urinary metabolomics analysis showed that the levels of choline, choline metabolites, and lactic acid were significantly lower in breast-fed term infants than those in formula-fed infants. Urinary PGD2 metabolite levels in breast-fed term infants were also significantly lower than those in formula-fed term infants. Our studies indicate that human breast milk affects various types of biological metabolism in early infancy. This article is protected by copyright. All rights reserved. PMID: 30194786 [PubMed - as supplied by publisher]

Related Articles Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the Resultant Mammalian Host Response. Immunity. 2018 Aug 31;: Authors: Uchimura Y, Fuhrer T, Li H, Lawson MA, Zimmermann M, Yilmaz B, Zindel J, Ronchi F, Sorribas M, Hapfelmeier S, Ganal-Vonarburg SC, Gomez de Agüero M, McCoy KD, Sauer U, Macpherson AJ Abstract Although the mammalian microbiota is well contained within the intestine, it profoundly shapes development and metabolism of almost every host organ. We questioned the range and depth of microbial metabolite penetration into the host, and how this is modulated by intestinal immunity. Chemically identical microbial and host metabolites were distinguished by stable isotope tracing from 13C-labeled live non-replicating Escherichia coli, differentiating 12C host isotopes with high-resolution mass spectrometry. Hundreds of endogenous microbial compounds penetrated 23 host tissues and fluids after intestinal exposure: subsequent 12C host metabolome signatures included lipidemia, reduced glycolysis, and inflammation. Penetrant bacterial metabolites from the small intestine were rapidly cleared into the urine, whereas induced antibodies curtailed microbial metabolite exposure by accelerating intestinal bacterial transit into the colon where metabolite transport mechanisms are limiting. Pervasive penetration of microbial molecules can cause extensive host tissue responses: these are limited by immune and non-immune intestinal mucosal adaptations to the microbiota. PMID: 30193848 [PubMed - as supplied by publisher]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/09/08PubMed 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.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/09/08PubMed 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.

Related Articles ZnO nanoparticles increase photosynthetic pigments and decrease lipid peroxidation in soil grown cilantro (Coriandrum sativum). Plant Physiol Biochem. 2018 Aug 29;132:120-127 Authors: Reddy Pullagurala VL, Adisa IO, Rawat S, Kalagara S, Hernandez-Viezcas JA, Peralta-Videa JR, Gardea-Torresdey JL Abstract The growth of the nanotechnology industry has raised concerns about its environmental impacts. In particular, the effect on terrestrial plants, which are the primary producers of the global food chain, is widely debated. In this study, cilantro plants (Coriandrum sativum) were cultivated for 35 days in soil amended with ZnO nanoparticles (N ZnO), bulk ZnO (B ZnO) and ZnCl2 (ionic/I Zn) at 0-400 mg/kg. Photosynthetic pigments, lipid peroxidation, 1NMR-based metabolic, and ICP-based metallomic profiles were evaluated. All Zn compounds increased the chlorophyll content by at least 50%, compared to control. Only N ZnO at 400 mg/kg decreased lipid peroxidation by 70%. 1NMR data showed that all compounds significantly changed the carbinolic-based compounds, compared with control. Highest root and shoot uptake of Zn was observed at B 400 and I 100, respectively. Results of this study corroborates that N ZnO at a concentration <400 mg/kg improved photosynthesis pigments and the defense response in cilantro plants cultivated in organic soil. PMID: 30189415 [PubMed - as supplied by publisher]

Related Articles Green tea polyphenols modify gut-microbiota dependent metabolisms of energy, bile constituents and micronutrients in female Sprague-Dawley rats. J Nutr Biochem. 2018 Aug 14;61:68-81 Authors: Zhou J, Tang L, Shen CL, Wang JS Abstract Our recent metagenomics analysis has uncovered remarkable modifying effects of green tea polyphenols (GTP) on gut-microbiota community structure and energy conversion related gene orthologs in rats. How these genomic changes could further influence host health is still unclear. In this work, the alterations of gut-microbiota dependent metabolites were studied in the GTP-treated rats. Six groups of female SD rats (n=12/group) were administered drinking water containing 0%, 0.5%, and 1.5% GTP (wt/vol). Their gut contents were collected at 3 and 6 months and were analyzed via high performance liquid chromatography (HPLC) and gas chromatography (GC)-mass spectrometry (MS). GC-MS based metabolomics analysis captured 2668 feature, and 57 metabolites were imputatively from top 200 differential features identified via NIST fragmentation database. A group of key metabolites were quantitated using standard calibration methods. Compared with control, the elevated components in the GTP-treated groups include niacin (8.61-fold), 3-phenyllactic acid (2.20-fold), galactose (3.13-fold), mannose (2.05-fold), pentadecanoic acid (2.15-fold), lactic acid (2.70-fold), and proline (2.15-fold); the reduced components include cholesterol (0.29-fold), cholic acid (0.62-fold), deoxycholic acid (0.41-fold), trehalose (0.14-fold), glucose (0.46-fold), fructose (0.12-fold), and alanine (0.61-fold). These results were in line with the genomic alterations of gut-microbiome previously discovered by metagenomics analysis. The alterations of these metabolites suggested the reduction of calorific carbohydrates, elevation of vitamin production, decreases of bile constituents, and modified metabolic pattern of amino acids in the GTP-treated animals. Changes in gut-microbiota associated metabolism may be a major contributor to the anti-obesity function of GTP. PMID: 30189365 [PubMed - as supplied by publisher]

Related Articles Data-driven rescoring of metabolite annotations significantly improves sensitivity. Anal Chem. 2018 Sep 06;: Authors: C Silva AS, Palmer A, Kovalev V, Tarasov A, Alexandrov T, Martens L, Degroeve S Abstract When analysing mass spectrometry imaging datasets, assigning a molecule to each of the thousands of generated images is a very complex task. Recent efforts have taken lessons from (tandem) mass spectrometry proteomics and applied them to imaging mass spectrometry metabolomics, with good results. Our goal is to go a step further in this direction and apply a well established, data-driven method to improve the results obtained from an annotation engine. By using a data-driven rescoring strategy, we are able to consistently improve the sensitivity of the annotation engine while maintaining control of statistics like estimated rate of false discoveries. All the code necessary to run a search and extract the additional features can be found at https://github.com/anasilviacs/sm-engine, and to rescore the results from a search in https://github.com/anasilviacs/rescore-metabolites. PMID: 30188119 [PubMed - as supplied by publisher]

Related Articles Effects of different levels of methionine on sow health and plasma metabolomics during late gestation. Food Funct. 2018 Sep 06;: Authors: Bin P, Azad MAK, Liu G, Zhu D, Kim SW, Yin Y Abstract Fetal growth, survival, and development are benchmarks for the production performance of sows, and methionine has been shown to impact fetal protein mass and the transport of nutrients through the uteroplacental vasculature. This study evaluated the effects of dietary methionine, administered during the late gestation period, on the production performance of sows. Specifically, it measured the effect of methionine on biochemical indicators in the plasma, plasma metabolites, and fecal bacterial communities. Thirty Landrace × Large White sows at day 90 of gestation were randomly assigned to three groups and fed the following diets: (1) a basal diet containing 0.36% methionine; (2) a basal diet + 0.12% methionine (0.48% methionine); and (3) a basal diet + 0.24% methionine (0.60% methionine). The results showed that the 0.48% methionine diet significantly (P < 0.05) increased piglets' birth weight, and the 0.60% methionine diet significantly (P < 0.05) improved the survival ratio. Dietary methionine lowered the triglyceride (TG) levels (P < 0.05), total bilirubin (BILT3) (P < 0.001) concentration, and gamma-glutamyl transferase (GGT) (P < 0.05) enzyme activity in the plasma at farrowing. In the plasma metabolomics, dietary methionine increased plasma pyroglutamic acid and decreased 2-pyrrolidinone, hypotaurine, and anyl-histidine in both the 0.48% methionine and 0.60% methionine groups. In addition, the bacteria richness (Chao1 and ACE) and diversity (Shannon) were reduced in the 0.48% methionine group. For the microbiota composition, at the family level, the 0.48% methionine group had a significant increase (P < 0.05) in the relative abundance of Methanobacteriaceae compared to the other two groups, but a decrease in the relative abundance of Enterobacteriaceae, Ruminococcaceae and Erysipelotrichaceae compared to the 0.60% methionine group. In conclusion, a diet consisting of 0.48% methionine administered during the late gestation period can improve the production performance of sows and maintain their health. PMID: 30187897 [PubMed - as supplied by publisher]

Related Articles Metabolomic analysis of obesity, metabolic syndrome, and type 2 diabetes: amino acid and acylcarnitine levels change along a spectrum of metabolic wellness. PeerJ. 2018;6:e5410 Authors: Libert DM, Nowacki AS, Natowicz MR Abstract Background: Metabolic syndrome (MS) is a construct used to separate "healthy" from "unhealthy" obese patients, and is a major risk factor for type 2 diabetes (T2D) and cardiovascular disease. There is controversy over whether obese "metabolically well" persons have a higher morbidity and mortality than lean counterparts, suggesting that MS criteria do not completely describe physiologic risk factors or consequences of obesity. We hypothesized that metabolomic analysis of plasma would distinguish obese individuals with and without MS and T2D along a spectrum of obesity-associated metabolic derangements, supporting metabolomic analysis as a tool for a more detailed assessment of metabolic wellness than currently used MS criteria. Methods: Fasting plasma samples from 90 adults were assigned to groups based on BMI and ATP III criteria for MS: (1) lean metabolically well (LMW; n = 24); (2) obese metabolically well (OBMW; n = 26); (3) obese metabolically unwell (OBMUW; n = 20); and (4) obese metabolically unwell with T2D (OBDM; n = 20). Forty-one amino acids/dipeptides, 33 acylcarnitines and 21 ratios were measured. Obesity and T2D effects were analyzed by Wilcoxon rank-sum tests comparing obese nondiabetics vs LMW, and OBDM vs nondiabetics, respectively. Metabolic unwellness was analyzed by Jonckheere-Terpstra trend tests, assuming worsening health from LMW → OBMW → OBMUW. To adjust for multiple comparisons, statistical significance was set at p < 0.005. K-means cluster analysis of aggregated amino acid and acylcarnitine data was also performed. Results: Analytes and ratios significantly increasing in obesity, T2D, and with worsening health include: branched-chain amino acids (BCAAs), cystine, alpha-aminoadipic acid, phenylalanine, leucine + lysine, and short-chain acylcarnitines/total carnitines. Tyrosine, alanine and propionylcarnitine increase with obesity and metabolic unwellness. Asparagine and the tryptophan/large neutral amino acid ratio decrease with T2D and metabolic unwellness. Malonylcarnitine decreases in obesity and 3-OHbutyrylcarnitine increases in T2D; neither correlates with unwellness. Cluster analysis did not separate subjects into discreet groups based on metabolic wellness. Discussion: Levels of 15 species and metabolite ratios trend significantly with worsening metabolic health; some are newly recognized. BCAAs, aromatic amino acids, lysine, and its metabolite, alpha-aminoadipate, increase with worsening health. The lysine pathway is distinct from BCAA metabolism, indicating that biochemical derangements associated with MS involve pathways besides those affected by BCAAs. Even those considered "obese, metabolically well" had metabolite levels which significantly trended towards those found in obese diabetics. Overall, this analysis yields a more granular view of metabolic wellness than the sole use of cardiometabolic MS parameters. This, in turn, suggests the possible utility of plasma metabolomic analysis for research and public health applications. PMID: 30186675 [PubMed]

Related Articles Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas aeruginosa by Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels. Front Microbiol. 2018;9:1952 Authors: Zhang Y, Sass A, Van Acker H, Wille J, Verhasselt B, Van Nieuwerburgh F, Kaever V, Crabbé A, Coenye T Abstract As one of the major pathogens in wound infections, Pseudomonas aeruginosa produces several virulence factors and forms biofilms; these processes are under the regulation of various quorum sensing (QS) systems. Therefore, QS has been regarded as a promising target to treat P. aeruginosa infections. In the present study, we evaluated the effect of the plant-derived QS inhibitor coumarin on P. aeruginosa biofilms and virulence. Coumarin inhibited QS in the P. aeruginosa QSIS2 biosensor strain, reduced protease and pyocyanin production, and inhibited biofilm formation in microtiter plates in different P. aeruginosa strains. The effects of coumarin in inhibiting biofilm formation in an in vitro wound model and reducing P. aeruginosa virulence in the Lucilia sericata infection model were strain-dependent. Transcriptome analysis revealed that several key genes involved in the las, rhl, Pseudomonas quinolone signal (PQS), and integrated QS (IQS) systems were downregulated in coumarin-treated biofilms of P. aeruginosa PAO1. Coumarin also changed the expression of genes related to type III secretion and cyclic diguanylate (c-di-GMP) metabolism. The cellular c-di-GMP level of P. aeruginosa PAO1 and recent clinical P. aeruginosa strains was significantly reduced by coumarin. These results provide new evidence for the possible application of coumarin as an anti-biofilm and anti-virulence agent against P. aeruginosa in wound infections. PMID: 30186266 [PubMed]

Related Articles A Metabolomics Study on the Bone Protective Effects of a Lignan-Rich Fraction From Sambucus Williamsii Ramulus in Aged Rats. Front Pharmacol. 2018;9:932 Authors: Xiao HH, Sham TT, Chan CO, Li MH, Chen X, Wu QC, Mok DK, Yao XS, Wong MS Abstract The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal medicine in China for treatment of bone diseases, has previously reported to exert protective effects on bone without exerting uterotrophic effects in ovariectomized (OVX) mice. The aim of the present study was to identify the potential metabolites and the associated metabolic pathways that contribute to the beneficial effects of SWR on bone in vivo. Aged female Sprague Dawley rats (9 months old) were either sham-operated or ovariectomized for 12 weeks, before receiving treatment for another 12 weeks with the following treatment groups (n = 12 each): vehicle (Sham), vehicle (OVX), Premarin (130 μg/kg) or low (57 mg/kg), medium (114 mg/kg), and high (228 mg/kg) doses of SWR. The results showed that SWRH significantly suppressed bone loss, improved bone micro-architecture and increased bone strength on tibia without stimulating uterus weight gain in OVX rats. Premarin exerted similar bone protective effects as SWRH but elicited uterotrophic effects in OVX rats. The metabolic profiles of serum samples were analyzed by using ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry and gas chromatography time-of flight mass spectrometry, and the metabolites that were significantly altered were identified by multivariate statistical analysis. Our study indicated that SWRH effectively restored the changes of 26 metabolites induced by estrogen-deficiency in OVX rats, which related to lipids, amino acids, tryptophan metabolisms, and anti-oxidative system. A subsequent validation showed that the serum level of superoxide dismutase and catalase were indeed up-regulated, while the serotonin level in a tryptophan hydroxylase 1 (TPH1) high expressing cells (rats RBL-2H3 cells) was down regulated after treatment with SWR. The results also suggested that the gut-microbiota may play an important role on the bone protective effects of SWR. The current study provides insight for understanding the unique mechanism of actions of SWR that might be involved in achieving bone protective effects in vivo. PMID: 30186170 [PubMed]

Related Articles Analysis of the Metabolic Characteristics of Serum Samples in Patients With Multiple Myeloma. Front Pharmacol. 2018;9:884 Authors: Du H, Wang L, Liu B, Wang J, Su H, Zhang T, Huang Z Abstract Aims: This study aimed to identify potential, non-invasive biomarkers for diagnosis and monitoring of the progress in multiple myeloma (MM) patients. Methods: MM patients and age-matched healthy controls (HC) were recruited in Discovery phase and Validation phase, respectively. MM patients were segregated into active group (AG) and responding group (RG). Serum samples were collected were conducted to non-targeted metabolomics analyses. Metabolites which were significantly changed (SCMs) among groups were identified in Discovery phase and was validated in Validation phase. The signaling pathways of these SCMs were enriched. The ability of SCMs to discriminate among groups in Validation phase was analyzed through receiver operating characteristic curve. The correlations between SCMs and clinical features, between SCMs and survival period of MM patients were analyzed. Results: Total of 23 SCMs were identified in AG compared with HC both in Discovery phase and Validation phase. Those SCMs were significantly enriched in arginine and proline metabolism and glycerophospholipid metabolism. 4 SCMs had the discriminatory ability between MM patients and healthy controls in Validation phase. Moreover, 12 SCMs had the ability to discriminate between the AG patients and RG patients in Validation phase. 10 out of 12 SCMs correlated with advanced features of MM. Moreover, 8 out of 12 SCMs had the negative impact on the survival of MM. 5'-Methylthioadenosine may be the only independent prognostic factor in survival period of MM. Conclusion: 10 SCMs identified in our study, which correlated with advanced features of MM, could be potential, novel, non-invasive biomarkers for active disease in MM. PMID: 30186161 [PubMed]

Related Articles Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances. J Expo Sci Environ Epidemiol. 2018 Sep 05;: Authors: Salihovic S, Fall T, Ganna A, Broeckling CD, Prenni JE, Hyötyläinen T, Kärrman A, Lind PM, Ingelsson E, Lind L Abstract Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans. PMID: 30185940 [PubMed - as supplied by publisher]

Related Articles Dormant Mycobacterium tuberculosis converts isoniazid to the active drug in a Wayne's model of dormancy. J Antibiot (Tokyo). 2018 Sep 05;: Authors: Raghunandanan S, Jose L, Kumar RA Abstract Isoniazid (INH) is one among the four first-line drugs used in the treatment of tuberculosis. The bactericidal activity of INH is due to its ability to inhibit mycolic acid synthesis, which is an integral component of the mycobacterial cell wall. Non-replicating Mycobacterium tuberculosis (MTB) is phenotypically resistant to INH. The exact mechanism of this resistance is not clear, although the inability of dormant MTB to convert the pro-drug into an active form is thought to be one of the possible reasons. Employing targeted metabolomics approach, we show that dormant MTB can metabolize INH into its active INH-NAD+ adduct form. Further we show that the dormant bacteria have unaltered gene expression levels of katG and inhA (INH metabolizing enzymes). Transcript levels of drug efflux pump proteins which were low during dormancy did not increase in response to INH treatment. These findings point to an alternative mechanism for INH resistance in dormant MTB, which needs to be further elucidated. PMID: 30185901 [PubMed - as supplied by publisher]

Related Articles Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants. Proc Natl Acad Sci U S A. 2018 Sep 05;: Authors: Kunduri G, Turner-Evans D, Konya Y, Izumi Y, Nagashima K, Lockett S, Holthuis J, Bamba T, Acharya U, Acharya JK Abstract Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype. PMID: 30185559 [PubMed - as supplied by publisher]