PubMed

Related Articles Novel Analytical Workflow for Comprehensive Non-targeted Phytochemical Metabolic Profiling. Chimia (Aarau). 2015;69(5):294-5 Authors: Hettich T, Schlotterbeck G Abstract The understanding and interpretation of pharmacological properties on a molecular level is of great importance for many different fields of research. Our study provides a novel model work-flow for comprehensive metabolic profiling by structural identification of relevant metabolites not limited to phytochemistry applications. High resolution liquid chromatography mass spectrometry LC-MS/MS data can be directly correlated with pharmacological test results on a molecular level. Thus the understanding and interpretation of pharmacological properties is supported by structural and chemical information. PMID: 26507349 [PubMed - indexed for MEDLINE]

Related Articles Combination of direct infusion mass spectrometry and gas chromatography mass spectrometry for toxicometabolomic study of red blood cells and serum of mice Mus musculus after mercury exposure. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Mar 15;985:75-84 Authors: García-Sevillano MA, García-Barrera T, Navarro F, Abril N, Pueyo C, López-Barea J, Gómez-Ariza JL Abstract Although mercury (Hg) is an important environmental and occupational pollutant, its toxicological effects, especially in serum and red blood cells (RBCs), have been scarcely studied. A toxicometabolomics workflow based on high resolution mass spectrometry approaches has been applied to investigate the toxicological effects of Hg in Mus musculus mice after subcutaneous injection for 10 days, which produced inflammation and vacuolization, steatosis and karyolysis in the hepatic tissue. To this end, direct infusion mass spectrometry (DIMS) of polar and lipophilic extracts from serum and RBCs, using positive and negative mode of acquisition (ESI+/ESI-), and gas chromatography-mass spectrometry were used. A quantitative analysis of reversible oxidized thiols in serum proteins demonstrated a strong oxidative stress induction in the liver of Hg-exposed mice. Endogenous metabolites alterations were identified by partial least squares-discriminant analysis (PLS-DA). Mercury-exposed mice show perturbations in energy metabolism, amino acid metabolism, membrane phospholipid breakdown and oxidative stress-related metabolites in serum along the exposure. This work reports for the first time the effects of Hg-exposure on RBCs metabolic pathways, and reveals disturbances in glycolysis, membrane turnover, glutathione and ascorbate metabolisms. PMID: 25660718 [PubMed - indexed for MEDLINE]

Related Articles Application of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify curcumin metabolites produced by human intestinal bacteria. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Mar 15;985:38-47 Authors: Lou Y, Zheng J, Hu H, Lee J, Zeng S Abstract Curcumin, a yellow pigment derived from the rhizomes of Curcuma longa Linn, is a natural antioxidant that exhibits a variety of pharmacological activities and therapeutic properties. However, as curcumin is generally conjugated when absorbed through the intestine, free curcumin is present at extremely low levels in the body. Thus, curcumin metabolites are presumed to be responsible for curcumin bioactivity. In this study, we describe a strategy using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS) with automated data analysis software (MetaboLynx(XS)) for rapid analysis of the metabolic profile of curcumin in human intestinal flora. The results show that curcumin undergoes extensive phase I and phase II metabolism. A total of 23 curcumin metabolites were detected and identified in vitro. Furthermore, we identified a number of novel metabolic pathways of curcumin in the human intestinal microflora system. PMID: 25658514 [PubMed - indexed for MEDLINE]

Related Articles Study on the pharmacokinetics profiles of polyphyllin I and its bioavailability enhancement through co-administration with P-glycoprotein inhibitors by LC-MS/MS method. J Pharm Biomed Anal. 2015 Mar 25;107:119-24 Authors: Zhu H, Zhu SC, Shakya S, Mao Q, Ding CH, Long MH, Li SL Abstract Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, is a promising natural anticancer candidate. Although the anticancer activity of PPI has been well demonstrated, information regarding the pharmacokinetics and bioavailability is limited. In this study, a series of reliable and rapid liquid chromatography-tandem mass spectrometry methods were developed and successfully applied to determinate PPI in rat plasma, cell incubation media and cell homogenate. Then the pharmacokinetics of PPI in rats was studied and the result revealed that PPI was slowly eliminated with low oral bioavailability (about 0.62%) at a dose of 50 mg/kg, and when co-administrated with verapamil (VPL) and cyclosporine A (CYA), the oral bioavailability of PPI could increase from 0.62% to 3.52% and 3.79% respectively. In addition, in vitro studies showed that with the presence of VPL and CYA in Caco-2 cells, the efflux ratio of PPI decreased from 12.5 to 2.96 and 2.22, and the intracellular concentrations increased 5.8- and 5.0-fold respectively. These results demonstrated that PPI, with poor oral bioavailability, is greatly impeded by P-gp efflux, and inhibition of P-gp can enhance its bioavailability. PMID: 25590941 [PubMed - indexed for MEDLINE]

Related Articles Metabolite profiling for the identification of altered metabolic pathways in Alzheimer's disease. J Pharm Biomed Anal. 2015 Mar 25;107:75-81 Authors: González-Domínguez R, García-Barrera T, Gómez-Ariza JL Abstract Gas chromatography coupled to mass spectrometry is the most frequent tool for metabolomic profiling of low molecular weight metabolites. Its suitability in health survey is beyond doubt, given that primary metabolites involved in central pathways of metabolism are usually altered in diseases. The objective of this work is to investigate metabolic differences in serum between Alzheimer's disease patients and healthy controls in order to elucidate pathological mechanisms underlying to disease. Alterations in levels of 23 metabolites were detected, including increased lactic acid, α-ketoglutarate, isocitric acid, glucose, oleic acid, adenosine and cholesterol, as well as decreased urea, valine, aspartic acid, pyroglutamate, glutamine, phenylalanine, asparagine, ornithine, pipecolic acid, histidine, tyrosine, palmitic and uric acid, tryptophan, stearic acid and cystine. Metabolic pathway analysis revealed the involvement of multiple affected pathways, such as energy deficiencies, oxidative stress, hyperammonemia, and others. Moreover, it is noteworthy that some of these compounds have not been previously described in AD research, such as α-ketoglutarate, isocitrate pipecolic acid, pyroglutamate and adenosine, confirming the potential of this metabolomic approach in the search of novel potential markers for early detection of Alzheimer's disease. PMID: 25575172 [PubMed - indexed for MEDLINE]

Related Articles Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol. 2014 Dec;28(11):607-18 Authors: Neuman MG, Cohen LB, Nanau RM Abstract BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers. AIM: To review the biomarkers used to diagnose and define the severity of NAFLD and NASH. METHODS: A comprehensive PubMed and Google Scholar literature search was performed using the terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed. RESULTS: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity. CONCLUSIONS: The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression. PMID: 25575111 [PubMed - indexed for MEDLINE]

Related Articles Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing. PLoS Genet. 2014 Sep;10(9):e1004620 Authors: Greaves LC, Nooteboom M, Elson JL, Tuppen HA, Taylor GA, Commane DM, Arasaradnam RP, Khrapko K, Taylor RW, Kirkwood TB, Mathers JC, Turnbull DM Abstract Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium. PMID: 25232829 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic and proteomic analysis of serum from preterm infants with necrotising entercolitis and late onset sepsis. Pediatr Res. 2015 Nov 16; Authors: Stewart CJ, Nelson A, Treumann A, Skeath T, Cummings SP, Embleton ND, Berrington JE Abstract BACKGROUND: Necrotising enterocolitis (NEC) and late onset sepsis (LOS) are the leading causes of death among preterm infants in the developed world. This study aimed to explore the serum proteome and metabolome longitudinally in preterm infants with NEC or LOS, matched to controls. METHODS: Nineteen patients (10 cases, 9 controls) were included. A sample 14 days prior to and following, as well as at disease diagnosis, was included for cases. Controls had serum matched at diagnosis for corresponding case. All samples (n=39) underwent shotgun proteomic analysis and 37 samples also underwent metabolomics analysis using ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). RESULTS: The proteomic and metabolomic profiles of serum were comparable between all infants. Eight proteins were associated with NEC and four proteins were associated with LOS. C-reactive protein (CRP) was increased in all NEC patients at diagnosisConclusion:No single protein or metabolite was detected in all NEC or LOS cases which was absent from controls, however, several proteins were identified which were associated with disease status. The differing expression of these proteins between diseased infants potentially relates to differing pathophysiology of disease. Thus, it is unlikely a single biomarker exists for NEC and/or LOS.Pediatric Research (2015); doi:10.1038/pr.2015.235. PMID: 26571220 [PubMed - as supplied by publisher]

Related Articles The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition. Nat Cell Biol. 2015 Nov 16; Authors: Sperber H, Mathieu J, Wang Y, Ferreccio A, Hesson J, Xu Z, Fischer KA, Devi A, Detraux D, Gu H, Battle SL, Showalter M, Valensisi C, Bielas JH, Ericson NG, Margaretha L, Robitaille AM, Margineantu D, Fiehn O, Hockenbery D, Blau CA, Raftery D, Margolin AA, Hawkins RD, Moon RT, Ware CB, Ruohola-Baker H Abstract For nearly a century developmental biologists have recognized that cells from embryos can differ in their potential to differentiate into distinct cell types. Recently, it has been recognized that embryonic stem cells derived from both mice and humans exhibit two stable yet epigenetically distinct states of pluripotency: naive and primed. We now show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in human embryonic stem cells (hESCs).  Specifically, in naive hESCs, NNMT and its enzymatic product 1-methylnicotinamide are highly upregulated, and NNMT is required for low S-adenosyl methionine (SAM) levels and the H3K27me3 repressive state. NNMT consumes SAM in naive cells, making it unavailable for histone methylation that represses Wnt and activates the HIF pathway in primed hESCs. These data support the hypothesis that the metabolome regulates the epigenetic landscape of the earliest steps in human development. PMID: 26571212 [PubMed - as supplied by publisher]

Related Articles Comparative Lipidomics of Caenorhabditis elegans Metabolic Disease Models by SWATH Non-Targeted Tandem Mass Spectrometry. Metabolites. 2015;5(4):677-696 Authors: Prasain JK, Wilson L, Hoang HD, Moore R, Miller MA Abstract Tandem mass spectrometry (MS/MS) with Sequential Window Acquisition of all Theoretical (SWATH) mass spectra generates a comprehensive archive of lipid species within an extract for retrospective, quantitative MS/MS analysis. Here we apply this new technology in Caenorhabditis elegans (C. elegans) to identify potential lipid mediators and pathways. The DAF-1 type I TGF-β and DAF-2 insulin receptors transmit endocrine signals that couple metabolic status to fertility and lifespan. Mutations in daf-1 and daf-2 reduce prostaglandin-endoperoxide synthase (i.e., Cox)-independent prostaglandin synthesis, increase triacylglyceride storage, and alter transcription of numerous lipid metabolism genes. However, the extent to which DAF-1 and DAF-2 signaling modulate lipid metabolism and the underlying mechanisms are not well understood. MS/MSALL with SWATH analysis across the groups identified significant changes in numerous lipids, including specific triacylglycerols, diacylglycerols, and phosphatidylinositols. Examples are provided, using retrospective neutral loss and precursor ion scans as well as MS/MS spectra, to help identify annotated lipids and search libraries for lipids of interest. As proof of principle, we used comparative lipidomics to investigate the prostaglandin metabolism pathway. SWATH data support an unanticipated model: Cox-independent prostaglandin synthesis may involve lysophosphatidylcholine and other lyso glycerophospholipids. This study showcases the power of comprehensive, retrospectively searchable lipid archives as a systems approach for biological discovery in genetic animal models. PMID: 26569325 [PubMed - as supplied by publisher]

Related Articles Global Profiling of Various Metabolites in Platycodon grandiflorum by UPLC-QTOF/MS. Int J Mol Sci. 2015;16(11):26786-26796 Authors: Lee JW, Ji SH, Kim GS, Song KS, Um Y, Kim OT, Lee Y, Hong CP, Shin DH, Kim CK, Lee SE, Ahn YS, Lee DY Abstract In this study, a method of metabolite profiling based on UPLC-QTOF/MS was developed to analyze Platycodon grandiflorum. In the optimal UPLC, various metabolites, including major platycosides, were separated well in 15 min. The metabolite extraction protocols were also optimized by selecting a solvent for use in the study, the ratio of solvent to sample and sonication time. This method was used to profile two different parts of P. grandiflorum, i.e., the roots of P. grandiflorum (PR) and the stems and leaves of P. grandiflorum (PS), in the positive and negative ion modes. As a result, PR and PS showed qualitatively and quantitatively different metabolite profiles. Furthermore, their metabolite compositions differed according to individual plant samples. These results indicate that the UPLC-QTOF/MS-based profiling method is a good tool to analyze various metabolites in P. grandiflorum. This metabolomics approach can also be applied to evaluate the overall quality of P. grandiflorum, as well as to discriminate the cultivars for the medicinal plant industry. PMID: 26569219 [PubMed - as supplied by publisher]

Related Articles The influence of gut microbiota on drug metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2015 Nov 16; Authors: Li H, He J, Jia W Abstract INTRODUCTION: Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences towards drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve the rational drug design. Areas covered: This review provides an overview on the microbiota-host co-metabolism on drug metabolism and summarizes 30 clinical drugs which are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation on some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are discussed. Expert opinion: The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota. Analytical technique innovation is urgently required to strengthen our capability in recognizing microbial functions, including metagenomics, metabolomics, and the integration of multi-disciplinary knowledge. PMID: 26569070 [PubMed - as supplied by publisher]

Related Articles High density lipoprotein efficiently accepts surface but not internal oxidised lipids from oxidised low density lipoprotein. Biochim Biophys Acta. 2015 Nov 10; Authors: Rasmiena AA, Barlow CK, Ng TW, Tull D, Meikle PJ Abstract OBJECTIVE: Oxidised low density lipoprotein (oxLDL) contributes to atherosclerosis, whereas high density lipoprotein (HDL) is known to be atheroprotective due, at least in part, to its ability to remove oxidised lipids from oxLDL. The molecular details of the lipid transfer process are not fully understood. We aimed to identify major oxidised lipid species of oxLDL and investigate their transfer upon co-incubation with HDL with varying levels of oxidation. APPROACH AND RESULTS: A total of 14 major species of oxidised phosphatidylcholine and oxidised cholesteryl ester from oxLDL were identified using an untargeted mass spectrometry approach. HDL obtained from pooled plasma of normolipidemic subjects (N=5) was oxidised under mild and heavy oxidative conditions. Non-oxidised (native) HDL and oxidised HDL were co-incubated with oxLDL, re-isolated and lipidomic analysis was performed. Lipoprotein surface lipids, oxidised phosphatidylcholines and oxidised cholesterols (7-ketocholesterol and 7β-hydroxycholesterol), but not internal oxidised cholesteryl esters, were effectively transferred to native HDL. Saturated and monounsaturated lyso-phosphatidylcholines were also transferred from the oxLDL to native HDL. These processes were attenuated when HDL was oxidised under mild and heavy oxidative conditions. The impaired capacities were accompanied by an increase in a ratio of sphingomyelin to phosphatidylcholine and a reduction in phosphatidylserine content in oxidised HDL, both of which are potentially important regulators of the oxidised lipid transfer capacity of HDL. CONCLUSIONS: Our study has revealed the differential transfer efficiency of surface and internal oxidised lipids from oxLDL and their acceptance onto HDL. These capacities were modulated when HDL was itself oxidised. PMID: 26569052 [PubMed - as supplied by publisher]

Related Articles Predictive associations between serum fatty acids and lipoproteins in healthy non-obese Norwegians: implications for cardiovascular health. Metabolomics. 2016;12(1):6 Authors: Lin C, Rajalahti T, Mjøs SA, Kvalheim OM Abstract A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patterns. Predictive FA patterns were revealed for lipoprotein features of importance for cardiovascular (CV) health. Thus, the subclasses of atherogenic small and very small low density lipoprotein (LDL) particles and the same subclasses of high density lipoprotein (HDL) particles were associated with a pattern of saturated FAs and mono-unsaturated C16-C18 FAs. Eicosapentaenoic acid (EPA) and the ratio of EPA to arachidonic acid (AA) had strongest associations to features that promotes CV health: (i) large average size of HDL and LDL particles, and, (ii) small average size of very low density lipoprotein (VLDL) particles. Total concentration of HDL in both genders correlated to EPA, but docosahexaenoic acid (DHA) correlated just as strongly for women. For men, docosapentaenoic acid (DPA) showed stronger association to HDL concentration than EPA. For both genders, concentration of large LDL particles showed associations to levels of EPA, but stronger to DHA and DPA. High values of EPA/AA seem to be the strongest single biomarker for good CV health in both men and women. PMID: 26568746 [PubMed - as supplied by publisher]

Related Articles Use of biomarkers for assessing radiation injury and efficacy of countermeasures. Expert Rev Mol Diagn. 2015 Nov 15; Authors: Singh VK, Newman VL, Romaine PL, Hauer-Jensen M, Pollard HB Abstract Several candidate drugs for Acute Radiation Syndrome have been identified which have low toxicity and significant radioprotective and radiomitigative efficacy. Inasmuch as exposing healthy human volunteers to injurious levels of radiation is unethical, development and approval of new radiation countermeasures for ARS are therefore presently based on animal studies and Phase I safety study in healthy volunteers. The Animal Efficacy Rule that underlies the Food and Drug Administration approval pathway requires a sound understanding of the mechanisms of injury, drug efficacy, and efficacy biomarkers. In this context, it is important to identify biomarkers for radiation injury and drug efficacy that can extrapolate animal efficacy results, and can be used to convert drug doses deduced from animal studies to those that can be efficacious when used in humans. Here, we summarize the progress of studies to identify candidate biomarkers for the extent of radiation injury and for evaluation of countermeasure efficacy. PMID: 26568096 [PubMed - as supplied by publisher]

Related Articles Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls. PLoS One. 2014;9(9):e108336 Authors: Kuzaj P, Kuhn J, Michalek RD, Karoly ED, Faust I, Dabisch-Ruthe M, Knabbe C, Hendig D Abstract Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization. PMID: 25265166 [PubMed - indexed for MEDLINE]

Related Articles Potential for Dietary ω-3 Fatty Acids to Prevent Nonalcoholic Fatty Liver Disease and Reduce the Risk of Primary Liver Cancer. Adv Nutr. 2015 Nov;6(6):694-702 Authors: Jump DB, Depner CM, Tripathy S, Lytle KA Abstract Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC. PMID: 26567194 [PubMed - in process]

Related Articles The oncolytic peptide LTX-315 triggers necrotic cell death. Cell Cycle. 2015 Nov 2;14(21):3506-12 Authors: Forveille S, Zhou H, Sauvat A, Bezu L, Müller K, Liu P, Zitvogel L, Pierron G, Rekdal Ø, Kepp O, Kroemer G Abstract The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects. PMID: 26566869 [PubMed - in process]

Related Articles Genomics-based strategies for the use of natural variation in the improvement of crop metabolism. Plant Sci. 2016 Jan;242:47-64 Authors: Scossa F, Brotman Y, de Abreu E Lima F, Willmitzer L, Nikoloski Z, Tohge T, Fernie AR Abstract Next-generation genomics holds great potential in the study of plant phenotypic variation. With several crop reference genomes now available, the affordable costs of de novo genome assembly or target resequencing offer the opportunity to mine the enormous amount of genetic diversity hidden in crop wild relatives. Wide introgressions from these wild ancestors species or land races represent a possible strategy to improve cultivated varieties. In this review, we discuss the mechanisms underlying metabolic diversity within plant species and the possible strategies (and barriers) to introgress novel metabolic traits into cultivated varieties. We show how deep genomic surveys uncover various types of structural variants from extended gene pools of major crops and highlight how this variation may be used for the improvement of crop metabolism. PMID: 26566824 [PubMed - in process]

Related Articles [Metabolic profiling analysis of amino metabolites in plant extract based on pre-column derivatization-ultra high performance liquid chromatography-mass spectrometry]. Se Pu. 2015 Jun;33(6):613-21 Authors: Ziang J, Zhao C, Zhao Y, Zhao J, Li L, Lu X, Xu G Abstract Amino metabolites are important compounds that play a key role in plant growth and development. A metabolic profiling analysis method of amino metabolites in plant extract was developed based on pre-column derivatization-ultra high performance liquid chromatography- mass spectrometry. Using the tobacco leaf as an example, a total of 87 amino metabolites, including amino acids, amines, peptides, alkaloids etc. were detected. The repeatability of the method was good with RSDs of 85 amino metabolites between 1. 5% and 18. 8%. Forty-three amino metabolites validated by standard samples showed good linearity with the correlation coefficients of 0.993-0.999, covered linear range of four orders of magnitude. The limits of detection were 0.03-6.58 ng/mL. The intra-day and inter-day precisions were 0.7%-15.6% and 0.8%-22.9%, respectively. The recoveries were 74.4%-122.7%. The influence of topping on metabolic profiling of amino metabolites in fresh tobacco was investigated using the developed method. The results showed that the amino metabolites in the upper tobacco leaves were most affected than those in the middle and lower leaves. Metabolism of amino metabolites in the upper leaves after topping was mainly towards the alkaloid synthesis. The method integrated the advantages of triple quadrupole mass spectrometry and high resolution quadrupole-time of flight mass spectrometry. It can be used for metabolic profiling analysis of amino metabolites in plant extract with high sensitivity and selectivity. PMID: 26536764 [PubMed - indexed for MEDLINE]