PubMed

Comparative toxicity of chloro- and bromo-nitromethanes in mice based on a metabolomic method. Chemosphere. 2017 Jun 29;185:20-28 Authors: Yin J, Wu B, Zhang XX, Xian Q Abstract Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts have been widely found in drinking water. In vitro test found HNMs could induce higher cytotoxicity and genotoxicity than trihalomethanes and haloacetic acids. However, data on toxic effect from in vivo experiment is limited. In this study, bromonitromethane (BNM), bromochloronitromethane (BCNM) and trichloronitromethane (TCNM) were chosen as target HNMs, and exposed to mice for 30 d. Hepatic toxicity and serum metabolic profiles were determined to reveal toxic effects and mechanisms of the three HNMs. Results showed the three HNMs significantly decreased relative liver weight, indicating liver is one of the target organs. Further, the three HNMs exposure damaged hepatic antioxidant defense system, and increased oxidative DNA damage. Nuclear magnetic resonance based metabolomics analysis found amino acid metabolism and carbohydrate metabolism were disturbed by HNMs exposure. Some metabolites in these metabolisms are related to oxidative stress and damage. Combined with above results, BNM had the highest toxicity, followed by BCNM and TCNM, indicating bromo-HNMs had higher toxicity than chloro-HNMs. Induction of oxidative stress is one of the toxicity mechanisms of HNMs. This study firstly provides the insight into in vivo toxicity of HNMs and their underlying mechanisms based on metabolomics methods, which is very useful for their health risk assessment in drinking water. PMID: 28683333 [PubMed - as supplied by publisher]

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance. Cell Metab. 2017 Jul 05;26(1):212-229.e12 Authors: Martínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, Buqué X, Aurrekoetxea I, Delgado TC, Vázquez-Martínez R, González-García I, Roa J, Whittle AJ, Gomez-Santos B, Velagapudi V, Tung YCL, Morgan DA, Voshol PJ, Martínez de Morentin PB, López-González T, Liñares-Pose L, Gonzalez F, Chatterjee K, Sobrino T, Medina-Gómez G, Davis RJ, Casals N, Orešič M, Coll AP, Vidal-Puig A, Mittag J, Tena-Sempere M, Malagón MM, Diéguez C, Martínez-Chantar ML, Aspichueta P, Rahmouni K, Nogueiras R, Sabio G, Villarroya F, López M Abstract Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism. PMID: 28683288 [PubMed - in process]

Metabolomic Studies of Indonesian Jamu Medicines: Prediction of Jamu Efficacy and Identification of Important Metabolites. Mol Inform. 2017 Jul 06;: Authors: Wijaya SH, Batubara I, Nishioka T, Altaf-Ul-Amin M, Kanaya S Abstract In order to obtain a better understanding why some Jamu formulas can be used to treat a specific disease, we performed metabolomic studies of Jamu by taking into consideration the biologically active compounds existing in plants used as Jamu ingredients. A thorough integration of information from omics is expected to provide solid evidence-based scientific rationales for the development of modern phytomedicines. This study focused on prediction of Jamu efficacy based on its component metabolites and also identification of important metabolites related to each efficacy group. Initially, we compared the performance of Support Vector Machines and Random Forest to predict the Jamu efficacy with three different data pre-processing approaches, such as no filtering, Single Filtering algorithm, and a combination of Single Filtering algorithm and feature selection using Regularized Random Forest. Both classifiers performed very well and according to 5-fold cross-validation results, the mean accuracy of Support Vector Machine with linear kernel was slightly better than Random Forest. It can be concluded that machine learning methods can successfully relate Jamu efficacy with metabolites. In addition, we extended our analysis by identifying important metabolites from the Random Forest model. The inTrees framework was used to extract the rules and to select important metabolites for each efficacy group. Overall, we identified 94 significant metabolites associated to 12 efficacy groups and many of them were validated by published literature and KNApSAcK Metabolite Activity database. PMID: 28682479 [PubMed - as supplied by publisher]

Related Articles Assessment of the Therapeutic Potential of Persimmon Leaf Extract on Prediabetic Subjects. Mol Cells. 2017 Jul 06;: Authors: Khan MM, Tran BQ, Jang YJ, Park SH, Fondrie WE, Chowdhury K, Yoon SH, Goodlett DR, Chae SW, Chae HJ, Seo SY, Goo YA Abstract Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates. PMID: 28681595 [PubMed - as supplied by publisher]

Related Articles Untargeted metabolomics of neuronal cell culture: A model system for the toxicity testing of insecticide chemical exposure. J Appl Toxicol. 2017 Jul 06;: Authors: Hayton S, Maker GL, Mullaney I, Trengove RD Abstract Toxicity testing is essential for the protection of human health from exposure to toxic environmental chemicals. As traditional toxicity testing is carried out using animal models, mammalian cell culture models are becoming an increasingly attractive alternative to animal testing. Combining the use of mammalian cell culture models with screening-style molecular profiling technologies, such as metabolomics, can uncover previously unknown biochemical bases of toxicity. We have used a mass spectrometry-based untargeted metabolomics approach to characterize for the first time the changes in the metabolome of the B50 cell line, an immortalised rat neuronal cell line, following acute exposure to two known neurotoxic chemicals that are common environmental contaminants; the pyrethroid insecticide permethrin and the organophosphate insecticide malathion. B50 cells were exposed to either the dosing vehicle (methanol) or an acute dose of either permethrin or malathion for 6 and 24 hours. Intracellular metabolites were profiled by gas chromatography-mass spectrometry. Using principal components analysis, we selected the key metabolites whose abundance was altered by chemical exposure. By considering the major fold changes in abundance (>2.0 or <0.5 from control) across these metabolites, we were able to elucidate important cellular events associated with toxic exposure including disrupted energy metabolism and attempted protective mechanisms from excitotoxicity. Our findings illustrate the ability of mammalian cell culture metabolomics to detect finer metabolic effects of acute exposure to known toxic chemicals, and validate the need for further development of this process in the application of trace-level dose and chronic toxicity studies, and toxicity testing of unknown chemicals. PMID: 28681389 [PubMed - as supplied by publisher]

Related Articles Simultaneous production of intracellular triacylglycerols and extracellular polyol esters of fatty acids by Rhodotorula babjevae and Rhodotorula aff. paludigena. J Ind Microbiol Biotechnol. 2017 Jul 05;: Authors: Garay LA, Sitepu IR, Cajka T, Cathcart E, Fiehn O, German JB, Block DE, Boundy-Mills KL Abstract Microbial oils have been analyzed as alternatives to petroleum. However, just a handful of microbes have been successfully adapted to produce chemicals that can compete with their petroleum counterparts. One of the reasons behind the low success rate is the overall economic inefficiency of valorizing a single product. This study presents a lab-scale analysis of two yeast species that simultaneously produce multiple high-value bioproducts: intracellular triacylglycerols (TG) and extracellular polyol esters of fatty acids (PEFA), two lipid classes with immediate applications in the biofuels and surfactant industries. At harvest, the yeast strain Rhodotorula aff. paludigena UCDFST 81-84 secreted 20.9 ± 0.2 g L(-1) PEFA and produced 8.8 ± 1.0 g L(-1) TG, while the yeast strain Rhodotorula babjevae UCDFST 04-877 secreted 11.2 ± 1.6 g L(-1) PEFA and 18.5 ± 1.7 g L(-1) TG. The overall glucose conversion was 0.24 and 0.22 g(total lipid) g (glucose)(-1) , respectively. The results present a stable and scalable microbial growth platform yielding multiple co-products. PMID: 28681129 [PubMed - as supplied by publisher]

Related Articles Novel immune checkpoint blocker to treat Merkel cell carcinoma. Oncoimmunology. 2017;6(6):e1315496 Authors: Galluzzi L, Kroemer G PMID: 28680746 [PubMed - in process]

Related Articles Plasma acylcarnitines are associated with pulmonary hypertension. Pulm Circ. 2017 Mar;7(1):211-218 Authors: Luo N, Craig D, Ilkayeva O, Muehlbauer M, Kraus WE, Newgard CB, Shah SH, Rajagopal S Abstract Quantifying metabolic derangements in pulmonary hypertension (PH) by plasma metabolomics could identify biomarkers useful for diagnosis and treatment. The objective of this paper is to test the hypotheses that circulating metabolites are differentially expressed in PH patients compared with controls and among different hemodynamic subtypes of PH associated with left heart disease. We studied patients enrolled in the CATHGEN biorepository with PH (right heart catheterization mPAP ≥ 25 mmHg; n = 280). Of these, 133 met criteria for postcapillary PH, 82 for combined precapillary and postcapillary PH (CpcPH), and 65 for precapillary PH. Targeted profiling of 63 metabolites (acylcarnitines, amino acids, and ketones) was performed using tandem flow injection mass spectrometry. Multivariable linear regression was used to determine differences in metabolite factors derived from a principal components analysis between PH cases, PH subtypes, and non-PH controls. In adjusted models, the metabolite factor loaded with long-chain acylcarnitines was higher in all PH cases versus non-PH controls (P = 0.00008), but did not discriminate between CpcPH and postcapillary PH (P = 0.56). In analyses of subtypes, CpcPH patients had lower levels of factors loaded with urea cycle amino acids and short chain acylcarnitines as compared to controls (P = 0.002 and P = 0.01, respectively) and as compared to postcapillary PH (P = 0.04 and P = 0.02, respectively). Compared to controls, PH was strongly associated with greater concentrations of long-chain acylcarnitines. Postcapillary PH and CpcPH were weakly associated with distinct metabolomic profiles. These findings suggest the presence of unique metabolic abnormalities in subtypes of PH and may reflect underlying pathophysiology. PMID: 28680580 [PubMed - in process]

Related Articles The Induction of Noble Rot (Botrytis cinerea) Infection during Postharvest Withering Changes the Metabolome of Grapevine Berries (Vitis vinifera L., cv. Garganega). Front Plant Sci. 2017;8:1002 Authors: Negri S, Lovato A, Boscaini F, Salvetti E, Torriani S, Commisso M, Danzi R, Ugliano M, Polverari A, Tornielli GB, Guzzo F Abstract The natural or induced development of noble rot caused by the fungus Botrytis cinerea during the late stages of grapevine (Vitis vinifera L.) berry ripening is used in some traditional viticulture areas to produce high-quality wines such as Sauternes and Tokaji. In this research, we wanted to verify if by changing the environmental conditions during post-harvest withering we could induce the noble rot development on harvested berries in order to positively change the wine produced from withered Garganega berries. Therefore, we exposed the berries to postharvest withering under normal or artificially humid conditions, the latter to induce noble rot. The presence of noble rot symptoms was associated with the development of B. cinerea in the berries maintained under humid conditions. The composition of infected and non-infected berries was investigated by untargeted metabolomics using liquid chromatography/mass spectrometry. We also explored the effects of the two withering methods on the abundance of volatile organic compounds in wine by yeast-inoculated micro-fermentation followed by targeted gas chromatography/mass spectrometry. These experiments revealed significant metabolic differences between berries withered under normal and humid conditions, indicating that noble rot affects berry metabolism and composition. As well as well-known botrytization markers, we detected two novel lipids that have not been observed before in berries infected with noble rot. Unraveling the specific metabolic profile of berries infected with noble rot may help to determine the compounds responsible for the organoleptic quality traits of botrytized Garganega wines. PMID: 28680428 [PubMed - in process]

Related Articles IgA N- and O-glycosylation profiling reveals no association with the pregnancy-related improvement in rheumatoid arthritis. Arthritis Res Ther. 2017 Jul 05;19(1):160 Authors: Bondt A, Nicolardi S, Jansen BC, Kuijper TM, Hazes JMW, van der Burgt YEM, Wuhrer M, Dolhain RJEM Abstract BACKGROUND: The Fc glycosylation of immunoglobulin G (IgG) is well known to associate with rheumatoid arthritis (RA) disease activity. The same may be true for other classes of Igs. In the present study, we sought to determine whether the glycosylation of IgA was different between healthy subjects and patients with RA, as well as whether it was associated with RA disease activity, in particular with the pregnancy-associated improvement thereof or the flare after delivery. METHODS: A recently developed high-throughput method for glycoprofiling of IgA1 was applied to affinity-captured IgA from sera of patients with RA (n = 252) and healthy control subjects (n = 32) collected before, during and after pregnancy. RESULTS: IgA1 O-glycans bore more sialic acids in patients with RA than in control subjects. In addition, levels of bisecting N-acetylglucosamine of the N-glycans at asparagine 144 were higher in the patients with RA. The levels of several N-glycosylation traits were shown to change with pregnancy, similar to what has been shown before for IgG. However, the changes in IgA glycosylation were not associated with improvement or a flare of disease activity. CONCLUSIONS: The glycosylation of IgA differs between patients with RA and healthy control subjects. However, our data suggest only a minor, if any, association of IgA glycosylation with RA disease activity. PMID: 28679431 [PubMed - in process]

Non-occlusive Sweat Collection Combined with Chemical Isotope Labeling LC-MS for Human Sweat Metabolomics and Mapping the Sweat Metabolomes at Different Skin Locations. Anal Chem. 2017 Jul 05;: Authors: Hooton K, Li L Abstract Human sweat is an excellent biofluid candidate for metabolomics due to its non-invasive sample collection and relatively simple matrix. We report a simple and inexpensive method for sweat collection over a defined period (e.g., 24 hr) based on the use of a non-occlusive style sweat patch adhered to a skin. This method was combined with differential chemical isotope labeling (CIL) LC-MS for mapping the metabolome profiles of sweat samples collected from skins of left forearm, lower back, and neck of 20 healthy volunteers. Three 24-hr sweat samples were collected at three different days from each subject for examining day-to-day metabolome variations. A total of 342 LC-MS runs including replicate analyses were carried out (two runs were discarded due to instrumental issue), resulting in the detection and relative quantification of 3140 sweat metabolites with 84 metabolites identified and 2716 metabolites mass-matched to metabolome databases. Multivariate and univariate analyses of the metabolome data revealed a location-dependence characteristic of the sweat metabolome, offering a possibility of mapping the sweat metabolic differences according to skin locations. Significant differences in male and female sweat metabolomes could be detected, demonstrating the possibility of using sweat metabolome to reveal biological variations among different comparative groups. Thus the combination of non-invasive sweat collection and CIL LC-MS is a robust analytical tool for sweat metabolomics with potential applications including daily monitoring of the sweat metabolome as health indicators, discovering sweat-based disease biomarkers, and metabolomic mapping of sweat collected from different areas of skin with and without injuries or diseases. PMID: 28679039 [PubMed - as supplied by publisher]

21st Century Toolkit for Optimizing Population Health through Precision Nutrition. Crit Rev Food Sci Nutr. 2017 Jul 05;:0 Authors: O'Sullivan A, Henrick B, Dixon B, Barile D, Zivkovic A, Smilowitz J, Lemay D, Martin W, German JB, Schaefer SE Abstract Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of "big data" to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individual's unique phenotype, or the current state of health, as determined by the interactions among biology, environment and behavior. The tools of Precision Nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health. PMID: 28678528 [PubMed - as supplied by publisher]

Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. Int J Mol Sci. 2017 Jul 05;18(7): Authors: Sbirkov Y, Kwok C, Bhamra A, Thompson AJ, Gil V, Zelent A, Petrie K Abstract Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML. PMID: 28678185 [PubMed - in process]

Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints? Mar Drugs. 2017 Jul 04;15(7): Authors: Farag MA, Fekry MI, Al-Hammady MA, Khalil MN, El-Seedi HR, Meyer A, Porzel A, Westphal H, Wessjohann LA Abstract Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10-60 µg/mL. No obvious correlation between the extracts' IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels. PMID: 28677625 [PubMed - in process]

A Concise Review on Multi-Omics Data Integration for Terroir Analysis in Vitis vinifera. Front Plant Sci. 2017;8:1065 Authors: Fabres PJ, Collins C, Cavagnaro TR, Rodríguez López CM Abstract Vitis vinifera (grapevine) is one of the most important fruit crops, both for fresh consumption and wine and spirit production. The term terroir is frequently used in viticulture and the wine industry to relate wine sensory attributes to its geographic origin. Although, it can be cultivated in a wide range of environments, differences in growing conditions have a significant impact on fruit traits that ultimately affect wine quality. Understanding how fruit quality and yield are controlled at a molecular level in grapevine in response to environmental cues has been a major driver of research. Advances in the area of genomics, epigenomics, transcriptomics, proteomics and metabolomics, have significantly increased our knowledge on the abiotic regulation of yield and quality in many crop species, including V. vinifera. The integrated analysis of multiple 'omics' can give us the opportunity to better understand how plants modulate their response to different environments. However, 'omics' technologies provide a large amount of biological data and its interpretation is not always straightforward, especially when different 'omic' results are combined. Here we examine the current strategies used to integrate multi-omics, and how these have been used in V. vinifera. In addition, we also discuss the importance of including epigenomics data when integrating omics data as epigenetic mechanisms could play a major role as an intermediary between the environment and the genome. PMID: 28676813 [PubMed - in process]

Screening Specific Biomarkers of Herbs Using a Metabolomics Approach: A Case Study of Panax ginseng. Sci Rep. 2017 Jul 04;7(1):4609 Authors: Wang HP, Liu Y, Chen C, Xiao HB Abstract Medicinal herbs belonging to the same genus are always easily confused due to their extremely similar morphology and metabolites. Previously, to differentiate them, inherently specific biomarkers were screened out via intuitive comparison of their metabolite profiles. Unfortunately, the selected biomarkers have worked only partially. Most significant specific biomarkers have been neglected. Herein, a novel method for screening specific biomarkers of medicinal herbs using a metabolomics technique was developed. Firstly, the profiles of a group of easily confused herbs belonging to the same genus were analyzed by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry to detect all components, including low-response metabolites. Then, all components were compared between the different samples, and specific biomarkers were extracted by the metabolomics techniques of alignment, normalization, defining the sample sets, filtering by frequency and Venn diagram analysis with Mass Profiler Professional (MPP) software. Thirdly, the correlations of these biomarkers were investigated via partial correlational analysis to obtain the most representative specific biomarkers. As an example, selection of specific biomarkers for ginseng (Panax ginseng) was performed, and three specific biomarkers including chikusetsusaponin IVa, ginsenoside Rf and ginsenoside Rc were finally selected and verified as the most representative specific biomarkers of Panax ginseng. PMID: 28676690 [PubMed - in process]

Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition. BMC Med. 2017 Jul 05;15(1):122 Authors: Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, Gicquiau A, Gunter MJ, Ferrari P, Kaaks R, Kühn T, Floegel A, Boeing H, Trichopoulou A, Lagiou P, Anifantis E, Agnoli C, Palli D, Trevisan M, Tumino R, Bueno-de-Mesquita HB, Agudo A, Larrañaga N, Redondo-Sánchez D, Barricarte A, Huerta JM, Quirós JR, Wareham N, Khaw KT, Perez-Cornago A, Johansson M, Cross AJ, Tsilidis KK, Riboli E, Key TJ, Travis RC Abstract BACKGROUND: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62-0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40-0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4. CONCLUSIONS: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations. PMID: 28676103 [PubMed - in process]

Related Articles Acetate-mediated novel survival strategy against drought in plants. Nat Plants. 2017 Jun 26;3:17097 Authors: Kim JM, To TK, Matsui A, Tanoi K, Kobayashi NI, Matsuda F, Habu Y, Ogawa D, Sakamoto T, Matsunaga S, Bashir K, Rasheed S, Ando M, Takeda H, Kawaura K, Kusano M, Fukushima A, Endo TA, Kuromori T, Ishida J, Morosawa T, Tanaka M, Torii C, Takebayashi Y, Sakakibara H, Ogihara Y, Saito K, Shinozaki K, Devoto A, Seki M Abstract Water deficit caused by global climate changes seriously endangers the survival of organisms and crop productivity, and increases environmental deterioration(1,2). Plants' resistance to drought involves global reprogramming of transcription, cellular metabolism, hormone signalling and chromatin modification(3-8). However, how these regulatory responses are coordinated via the various pathways, and the underlying mechanisms, are largely unknown. Herein, we report an essential drought-responsive network in which plants trigger a dynamic metabolic flux conversion from glycolysis into acetate synthesis to stimulate the jasmonate (JA) signalling pathway to confer drought tolerance. In Arabidopsis, the ON/OFF switching of this whole network is directly dependent on histone deacetylase HDA6. In addition, exogenous acetic acid promotes de novo JA synthesis and enrichment of histone H4 acetylation, which influences the priming of the JA signalling pathway for plant drought tolerance. This novel acetate function is evolutionarily conserved as a survival strategy against environmental changes in plants. Furthermore, the external application of acetic acid successfully enhanced the drought tolerance in Arabidopsis, rapeseed, maize, rice and wheat plants. Our findings highlight a radically new survival strategy that exploits an epigenetic switch of metabolic flux conversion and hormone signalling by which plants adapt to drought. PMID: 28650429 [PubMed - indexed for MEDLINE]

Related Articles Infectious Agents and Neurodegenerative Diseases: Exploring the Links. Curr Top Med Chem. 2017;17(12):1390-1399 Authors: Alam MZ, Alam Q, Kamal MA, Jiman-Fatani AA, Azhar EI, Khan MA, Haque A Abstract Recent studies have shown that bacterial and viral infections are risk factors for various neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), Alzheimer's disease (AD), and Lyme disease (LD). However, it is still controversial how the infections play a role in neurological diseases progression. Infections in central nervous system may lead multiple damages in infected and neighboring cells. The infection leads to the activation of inflammatory processes and host immune responses, which acts as defense mechanism and also causes damage to the host neuronal functions and viability. Several bacterial and viral pathogens have been reported for neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in combination with other factors, like aging, metabolic diseases and the genetic makeup of the host. We will focus in this review on the possible link between neurodegeneration and infections particularly Chlamydophila pneumoniae, Borrelia burgdorferi, Mycoplasma etc. PMID: 28049398 [PubMed - indexed for MEDLINE]

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