PubMed

Related Articles UPLC-MSE profiling of Phytoplankton metabolites: application to the identification of pigments and structural analysis of metabolites in Porphyridium purpureum. Mar Drugs. 2015 Apr;13(4):2541-58 Authors: Juin C, Bonnet A, Nicolau E, Bérard JB, Devillers R, Thiéry V, Cadoret JP, Picot L Abstract A fast and high-resolution UPLC-MSE analysis was used to identify phytoplankton pigments in an ethanol extract of Porphyridium purpureum (Pp) devoid of phycobiliproteins. In a first step, 22 standard pigments were analyzed by UPLC-MSE to build a database including retention time and accurate masses of parent and fragment ions. Using this database, seven pigments or derivatives previously reported in Pp were unequivocally identified: β,β-carotene, chlorophyll a, zeaxanthin, chlorophyllide a, pheophorbide a, pheophytin a, and cryptoxanthin. Minor amounts of Divinyl chlorophyll a, a chemotaxonomic pigment marker for prochlorophytes, were also unequivocally identified using the database. Additional analysis of ionization and fragmentation patterns indicated the presence of ions that could correspond to hydroxylated derivatives of chlorophyll a and pheophytin a, produced during the ethanolic extraction, as well as previously described galactosyldiacylglycerols, the thylakoid coenzyme plastoquinone, and gracilamide B, a molecule previously reported in the red seaweed Gracillaria asiatica. These data point to UPLC-MSE as an efficient technique to identify phytoplankton pigments for which standards are available, and demonstrate its major interest as a complementary method for the structural elucidation of ionizable marine molecules. PMID: 25913708 [PubMed - indexed for MEDLINE]

Related Articles Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry. Nitric Oxide. 2015 Apr 30;46:102-13 Authors: Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H, Suematsu M Abstract CD44 expressed in cancer cells was shown to stabilize cystine transporter (xCT) that uptakes cystine and excretes glutamate to supply cysteine as a substrate for reduced glutathione (GSH) for survival. While targeting CD44 serves as a potentially therapeutic stratagem to attack cancer growth and chemoresistance, the impact of CD44 targeting in cancer cells on metabolic systems of tumors and host tissues in vivo remains to be fully determined. This study aimed to reveal effects of CD44 silencing on alterations in energy metabolism and sulfur-containing metabolites in vitro and in vivo using capillary electrophoresis-mass spectrometry and quantitative imaging mass spectrometry (Q-IMS), respectively. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by Q-IMS. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines, GSH and energy charges not only in metastatic tumors but also in the host liver. In culture, HCT116 cells treated with shCD44 decreased total amounts of methionine-pool metabolites including spermidine and spermine, and reactive cysteine persulfides, suggesting roles of these metabolites for cancer growth. Collectively, these results suggest that CD44 expressed in cancer accounts for a key regulator of metabolic interplay between tumor and the host tissue. PMID: 25461272 [PubMed - indexed for MEDLINE]

Oxidative-stress detoxification and signaling in cyanobacteria: The crucial glutathione synthesis pathway supports the production of ergothioneine and ophthalmate. Mol Microbiol. 2015 Dec 29; Authors: Narainsamy K, Farci S, Braun E, Junot C, Cassier-Chauvat C, Chauvat F Abstract Using genetics and metabolomics we investigated the synthesis (gshA and gshB genes) and catabolism (ggt) of the conserved antioxidant glutathione in the model cyanobacterium Synechocystis PCC6803. These three genes are crucial to Synechocystis, in agreement with the proposed invention of glutathione by ancient cyanobacteria to protect themselves against the toxicity of oxygen they produced through photosynthesis. Consistent with their indispensability, gshA and gshB also operate in the production of another antioxidant, ergothioneine, as well as of the glutathione analogues ophthalmate and norophthalmate. Furthermore, we show that glutathione, ophthalmate and norophthalmate are accumulated in cells stressed by glucose, and that the two glutathione-dependent glyoxalase enzymes operate in the protection against glucose and its catabolite methylglyoxal. These findings are interesting because ophthalmate and norophthalmate were observed only in mammals so far, where ophthalmate is regarded as a biomarker of glutathione depletion. Instead, our data suggest that ophthalmate and norophthalmate are stress-induced markers of cysteine depletion triggered by its accelerated incorporation into glutathione, to face its increased demand for detoxification purposes. Hence, Synechocystis is an attractive model for the analysis of the role of glutathione, ergothioneine, ophthalmate and norophthalmate, in signalling and detoxification of oxidants and metabolic by-products. This article is protected by copyright. All rights reserved. PMID: 26713511 [PubMed - as supplied by publisher]

Personalizing Protein Nourishment. Crit Rev Food Sci Nutr. 2015 Dec 29;:0 Authors: Dallas DC, Sanctuary MR, Qu Y, Khajavi SH, Van Zandt AE, Dyandra M, Frese SA, Barile D, German JB Abstract Proteins are not equally digestible-their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources and processing methods must be tailored to the consumer's digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiological conditions alter digestive capacity. Possible solutions to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermentation are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein analysis of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health. PMID: 26713355 [PubMed - as supplied by publisher]

Chemical Characterization and in Vitro Cytotoxicity on Squamous Cell Carcinoma Cells of Carica Papaya Leaf Extracts. Toxins (Basel). 2015;8(1) Authors: Nguyen TT, Parat MO, Hodson MP, Pan J, Shaw PN, Hewavitharana AK Abstract In traditional medicine, Carica papaya leaf has been used for a wide range of therapeutic applications including skin diseases and cancer. In this study, we investigated the in vitro cytotoxicity of aqueous and ethanolic extracts of Carica papaya leaves on the human oral squamous cell carcinoma SCC25 cell line in parallel with non-cancerous human keratinocyte HaCaT cells. Two out of four extracts showed a significantly selective effect towards the cancer cells and were found to contain high levels of phenolic and flavonoid compounds. The chromatographic and mass spectrometric profiles of the extracts obtained with Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds identified were flavonoids or flavonoid glycosides, particularly compounds from the kaempferol and quercetin families, of which several have previously been reported to possess anticancer activities. These results confirm that papaya leaf is a potential source of anticancer compounds and warrant further scientific investigation to validate the traditional use of papaya leaf to treat cancer. PMID: 26712788 [PubMed - in process]

p300 is not required for metabolic adaptation to endurance exercise training. FASEB J. 2015 Dec 28; Authors: LaBarge SA, Migdal CW, Buckner EH, Okuno H, Gertsman I, Stocks B, Barshop BA, Nalbandian SR, Philp A, McCurdy CE, Schenk S Abstract The acetyltransferase, E1a-binding protein (p300), is proposed to regulate various aspects of skeletal muscle development, metabolism, and mitochondrial function, via its interaction with numerous transcriptional regulators and other proteins. Remarkably, however, the contribution of p300 to skeletal muscle function and metabolism, in vivo, is poorly understood. To address this, we used Cre-LoxP methodology to generate mice with skeletal muscle-specific knockout of E1a-binding protein (mKO). mKO mice were indistinguishable from their wild-type/floxed littermates, with no differences in lean mass, skeletal muscle structure, fiber type, respirometry flux, or metabolites of fatty acid and amino acid metabolism. Ex vivo muscle function in extensor digitorum longus and soleus muscles, including peak stress and time to fatigue, as well as in vivo running capacity were also comparable. Moreover, expected adaptations to a 20 d voluntary wheel running regime were not compromised in mKO mice. Taken together, these findings demonstrate that p300 is not required for the normal development or functioning of adult skeletal muscle, nor is it required for endurance exercise-mediated mitochondrial adaptations.-LaBarge, S. A., Migdal, C. W., Buckner, E. H., Okuno, H., Gertsman, I., Stocks, B., Barshop, B. A., Nalbandian, S. R., Philp, A., McCurdy, C. E., Schenk, S. p300 is not required for metabolic adaptation to endurance exercise training. PMID: 26712218 [PubMed - as supplied by publisher]

New findings on the in vivo antioxidant activity of Curcuma longa extract by an integrated (1)H-NMR and HPLC-MS metabolomic approach. Fitoterapia. 2015 Dec 19; Authors: Dall'Acqua S, Stocchero M, Boschiero I, Schiavon M, Golob S, Uddin J, Voinovich D, Mammi S, Schievano E Abstract Curcuminoids possess powerful antioxidant activity as demonstrated in many chemical in vitro tests and in several in vivo trials. Nevertheless, the mechanism of this activity is not completely elucidated and studies on the in vivo antioxidant effects are still needed. Metabolomics may be used as an attractive approach for such studies and in this paper, we describe the effects of oral administration of a Curcuma longa L. extract (150mg/kg of total curcuminoids) to 12 healthy rats with particular attention to urinary markers of oxidative stress. The experiment was carried out over 33days and changes in the 24-h urine samples metabolome were evaluated by (1)H-NMR and HPLC-MS. Both techniques produced similar representations for the collected samples confirming our previous study. Modifications of the urinary metabolome lead to the observation of different variables proving the complementarity of (1)H-NMR and HPLC-MS for metabolomic purposes. The urinary levels of allantoin, m-tyrosine, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine were decreased in the treated group thus supporting an in vivo antioxidant effect of the oral administration of Curcuma extract to healthy rats. On the other hand, urinary TMAO levels were higher in the treated compared to the control group suggesting a role of curcumin supplementation on microbiota or on TMAO urinary excretion. Furthermore, the urinary levels of the sulfur containing compounds taurine and cystine were also changed suggesting a role for such constituents in the biochemical pathways involved in Curcuma extract bioactivity and indicating the need for further investigation on the complex role of antioxidant curcumin effects. PMID: 26712080 [PubMed - as supplied by publisher]

Comprehensive proteomic and metabolomic signatures of nontypeable Haemophilus influenzae-induced acute otitis media reveal bacterial aerobic respiration in an immunosuppressed environment. Mol Cell Proteomics. 2015 Dec 28; Authors: Harrison A, Dubois LG, St John-Williams L, Moseley MA, Hardison RL, Heimlich DR, Stoddard A, Kerschner JE, Justice SS, Thompson JW, Mason KM Abstract A thorough understanding of the molecular details of the interactions between bacteria and host are critical to ultimately prevent disease. Recent technological advances allow simultaneous analysis of host and bacterial protein and metabolic profiles from a single small tissue sample to provide insight into pathogenesis. We used the chinchilla model of human otitis media (OM) to determine, for the first time, the most expansive delineation of global changes in protein and metabolite profiles during an experimentally induced disease. After 48 hours of infection with nontypeable Haemophilus influenzae (NTHI), middle ear tissue lysates were analyzed by high-resolution quantitative two-dimensional liquid chromatography-tandem mass spectrometry. Dynamic changes in 105 chinchilla proteins and 66 metabolites define the early proteomic and metabolomic signature of OM. Our studies indicate that establishment of disease coincides with actin morphogenesis, suppression of inflammatory mediators and bacterial aerobic respiration. We validated the observed increase in the actin-remodeling complex, Arp2/3 and experimentally demonstrated a role for Arp2/3 in NTHI invasion. Direct inhibition of actin branch morphology altered bacterial invasion into host epithelial cells, and is supportive of our efforts to utilize the information gathered to modify outcomes of disease. The twenty-eight NTHI proteins identified participate in carbohydrate and amino acid metabolism, redox homeostasis and include cell wall-associated metabolic proteins. Quantitative characterization of the molecular signatures of infection will redefine our understanding of host response driven developmental changes during pathogenesis. These data represent the first comprehensive study of host protein and metabolite profiles in vivo in response to infection and show the feasibility of extensive characterization of host protein profiles during disease. Identification of novel protein targets and metabolic biomarkers will advance development of therapeutic and diagnostic options for treatment of disease. PMID: 26711468 [PubMed - as supplied by publisher]

Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell Rep. 2015 Dec 16; Authors: Bjørge MD, Hildrestrand GA, Scheffler K, Suganthan R, Rolseth V, Kuśnierczyk A, Rowe AD, Vågbø CB, Vetlesen S, Eide L, Slupphaug G, Nakabeppu Y, Bredy TW, Klungland A, Bjørås M Abstract Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic DNA lesion associated with cognitive decline. We have examined behavior and cognitive function in mice deficient of these glycosylases. Ogg1(-/-)Mutyh(-/-) mice were more active and less anxious, with impaired learning ability. In contrast, Mutyh(-/-) mice showed moderately improved memory. We observed no apparent change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutants belong to pathways known to be involved in anxiety and cognition. Esr1 targets were upregulated, suggesting a role of Ogg1 and Mutyh in repression of Esr1 signaling. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh regulate hippocampal gene expression related to cognition and behavior, suggesting a role for the glycosylases in regulating adaptive behavior. PMID: 26711335 [PubMed - as supplied by publisher]

Related Articles Urinary prostaglandin E2 metabolite and pancreatic cancer risk: case-control study in urban Shanghai. PLoS One. 2015;10(2):e0118004 Authors: Zhao J, Wang J, Du J, Xu H, Zhang W, Ni QX, Yu H, Risch HA, Gao YT, Gao Y Abstract Pancreatic cancer has been increasing in importance in Shanghai over the last four decades. The etiology of the disease is still unclear. Evidence suggests that the COX-2 pathway, an important component of inflammation, may be involved in the disease. We aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) level and risk of pancreatic cancer. From a recent population-based case-control study in Shanghai, 200 pancreatic ductal adenocarcinoma cases and 200 gender- and age- frequency matched controls were selected for the present analysis. Urinary PGE-M was measured with a liquid chromatography/mass spectrometric assay. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A positive association was observed between PGE-M leve and pancreatic cancer risk: OR = 1.63 (95% CI 1.01-2.63) for the third tertile compared to the first. Though the interactions were not statistically significant, the associations tended to be stronger among subjects with diabetes history (OR = 3.32; 95% CI 1.20-9.19) and higher meat intake (OR = 2.12; 95% CI 1.10-4.06). The result suggests that higher urinary PGE-M level may be associated with increased risk of pancreatic ductal adenocarcinoma. PMID: 25679523 [PubMed - indexed for MEDLINE]

Related Articles Autophagy in stress and disease. Cell Death Differ. 2015 Mar;22(3):365-6 Authors: Maiuri MC, Kroemer G PMID: 25661524 [PubMed - indexed for MEDLINE]

Related Articles Phosphatidylethanolamine positively regulates autophagy and longevity. Cell Death Differ. 2015 Mar;22(3):499-508 Authors: Rockenfeller P, Koska M, Pietrocola F, Minois N, Knittelfelder O, Sica V, Franz J, Carmona-Gutierrez D, Kroemer G, Madeo F Abstract Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death. Conversely, the artificial increase of intracellular PE levels, by provision of its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1, significantly increased autophagic flux, both in yeast and in mammalian cell culture. Importantly administration of ethanolamine was sufficient to extend the lifespan of yeast (Saccharomyces cerevisiae), mammalian cells (U2OS, H4) and flies (Drosophila melanogaster). We thus postulate that the availability of PE may constitute a bottleneck for functional autophagy and that organismal life or healthspan could be positively influenced by the consumption of ethanolamine-rich food. PMID: 25571976 [PubMed - indexed for MEDLINE]

Related Articles Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015 Mar;22(3):509-16 Authors: Pietrocola F, Lachkar S, Enot DP, Niso-Santano M, Bravo-San Pedro JM, Sica V, Izzo V, Maiuri MC, Madeo F, Mariño G, Kroemer G Abstract Several natural compounds found in health-related food items can inhibit acetyltransferases as they induce autophagy. Here we show that this applies to anacardic acid, curcumin, garcinol and spermidine, all of which reduce the acetylation level of cultured human cells as they induce signs of increased autophagic flux (such as the formation of green fluorescent protein-microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta and the depletion of sequestosome-1, p62/SQSTM1) coupled to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). We performed a screen to identify the acetyltransferases whose depletion would activate autophagy and simultaneously inhibit mTORC1. The knockdown of only two acetyltransferases (among 43 candidates) had such effects: EP300 (E1A-binding protein p300), which is a lysine acetyltranferase, and NAA20 (N(α)-acetyltransferase 20, also known as NAT5), which catalyzes the N-terminal acetylation of methionine residues. Subsequent studies validated the capacity of a pharmacological EP300 inhibitor, C646, to induce autophagy in both normal and enucleated cells (cytoplasts), underscoring the capacity of EP300 to repress autophagy by cytoplasmic (non-nuclear) effects. Notably, anacardic acid, curcumin, garcinol and spermidine all inhibited the acetyltransferase activity of recombinant EP300 protein in vitro. Altogether, these results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent autophagy inducers including spermidine de facto act as EP300 inhibitors. PMID: 25526088 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of isomeric aglycones central-icaritin (c-IT) and icaritin (IT) in osteoporotic rats by UPLC-QTOF-MS. Drug Test Anal. 2015 Apr;7(4):309-19 Authors: Jiang J, Feng L, Sun E, Li H, Cui L, Jia X Abstract The isomers, although of similarly chemical structures, have different pharmacological activities due to their metabolic processes in vivo. Central-icaritin (c-IT) and icaritin (IT) are isomers and major bioactive aglycones of the Herba Epimedii. In this study, we found that the anti-osteoporotic effect of c-IT was stronger than IT on bone structural changes in osteoporotic rats evaluated by Micro-μCT with the parameters of bone mineral density (BMD), bone mineral content (BMC), tissue mineral content (TMC), and tissue mineral density (TMD). c-IT treatment significantly increased the bone microarchitecture, compared with IT (p < 0.05). In order to explain their differences in anti-osteoporosis, the metabolic profiling and pathways of c-IT and IT in the plasma, bile, urine, and faeces of ovariectomized (OVX) rats were investigated by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) after oral administration of c-IT or IT (80 mg/kg). Finally, 59 metabolites of c-IT and 43 metabolites of IT were identified by elucidating their corresponding quasimolecular ions and fragment ions. IT could be quickly absorbed into blood and reached a maximum plasma concentration, and then be rapidly conversed to its glucuronidation metabolites, most of which were excreted out by urine. Interestingly, the absorbed and conjugated speeds of c-IT were slower than IT. The metabolic processes of c-IT existed enterohepatic circulation, which decreased the metabolism and excretion rate of c-IT, and prolonged the anti-osteoporosis effect. Our findings provided evidence on the difference on metabolic profiles of c-IT and IT in osteoporotic rats, which might shed new lights on improving anti-osteoporotic effects of IT and c-IT. PMID: 24934976 [PubMed - indexed for MEDLINE]

Related Articles Comparative study on intestinal metabolism and absorption in vivo of ginsenosides in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid chromatography quadruple time-of-flight mass spectrometry based chemical profiling approach. Drug Test Anal. 2015 Apr;7(4):320-30 Authors: Zhu H, Shen H, Xu J, Xu JD, Zhu LY, Wu J, Chen HB, Li SL Abstract Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated. PMID: 24853104 [PubMed - indexed for MEDLINE]

Related Articles Lipidomics reveals associations of phospholipids with obesity and insulin resistance in young adults. J Clin Endocrinol Metab. 2015 Dec 28;:jc20153525 Authors: Rauschert S, Uhl O, Koletzko B, Kirchberg F, Mori TA, Huang RC, Beilin LJ, Hellmuth C, Oddy WH Abstract CONTEXT: Obesity and related diseases have become a global public health burden. Identifying biomarkers will lead to a better understanding of the underlying mechanisms associated with obesity and the pathways leading to insulin resistance (IR) and diabetes. OBJECTIVE: This study aimed to identify lipidomic biomarkers associated with obesity and IR using plasma samples from a population-based cohort of young adults. DESIGN AND SETTING: The Western Australian Pregnancy Cohort (Raine) Study enrolled 2900 pregnant women from 1989 to 1991. The 20yr follow-up was conducted between March 2010 and April 2012. PARTICIPANTS: and Samples: Plasma samples from 1176 subjects aged 20 years were analysed using mass spectrometry based metabolomics. MAIN OUTCOME MEASURES: Associations of analytes with markers of obesity and IR including BMI, waist circumference (WC), homeostasis model assessment (HOMA-IR) and insulin, were examined. Analyses were stratified by BMI and adjusted for lifestyle and other factors. RESULTS: WC was positively associated with seven sphingomyelins and five diacyl-phosphatidylcholines and negatively associated with two lyso-phosphatidylcholines. HOMA-IR was negatively associated with two diacyl-phosphatidylcholines and positively with one lyso-phosphatidylcholine and one diacyl-phosphatidylcholine. No significant association was found in the obese/overweight group of the HOMA-IR model. In the normal weight group, one lyso-phosphatidylcholine was increased. CONCLUSION: A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lyso-phosphatidylcholines was identified between subjects with normal weight and obesity independent of LDL-C and HDL-C concentrations. Our results suggest weight status dependent mechanisms for the development of IR with lyso-phosphatidylcholine C14:0 as a key metabolite in non-obese IR. PMID: 26709969 [PubMed - as supplied by publisher]

Related Articles Dansylation isotope labeling liquid chromatography mass spectrometry for parallel profiling of human urinary and fecal submetabolomes. Anal Chim Acta. 2016 Jan 15;903:100-9 Authors: Su X, Wang N, Chen D, Li Y, Lu Y, Huan T, Xu W, Li L, Li L Abstract Human urine and feces can be non-invasively collected for metabolomics-based disease biomarker discovery research. Because urinary and fecal metabolomes are thought to be different, analysis of both biospecimens may generate a more comprehensive metabolomic profile that can be better related to the health state of an individual. Herein we describe a method of using differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) for parallel metabolomic profiling of urine and feces. Dansylation labeling was used to quantify the amine/phenol submetabolome changes among different samples based on (12)C-labeling of individual samples and (13)C-labeling of a pooled urine or pooled feces and subsequent analysis of the (13)C-/(12)C-labeled mixture by LC-MS. The pooled urine and pooled feces are further differentially labeled, mixed and then analyzed by LC-MS in order to relate the metabolite concentrations of the common metabolites found in both biospecimens. This method offers a means of direct comparison of urinary and fecal submetabolomes. We evaluated the analytical performance and demonstrated the utility of this method in the analysis of urine and feces collected daily from three healthy individuals for 7 days. On average, 2534 ± 113 (n = 126) peak pairs or metabolites could be detected from a urine sample, while 2507 ± 77 (n = 63) peak pairs were detected from a fecal sample. In total, 5372 unique peak pairs were detected from all the samples combined; 3089 and 3012 pairs were found in urine and feces, respectively. These results reveal that the urine and fecal metabolomes are very different, thereby justifying the consideration of using both biospecimens to increase the probability of finding specific biomarkers of diseases. Furthermore, the CIL LC-MS method described can be used to perform parallel quantitative analysis of urine and feces, resulting in more complete coverage of the human metabolome. PMID: 26709303 [PubMed - in process]

Related Articles Wine metabolomics reveals new sulfonated products in bottled white wines, promoted by small amounts of oxygen. J Chromatogr A. 2015 Dec 8; Authors: Arapitsas P, Ugliano M, Perenzoni D, Angeli A, Pangrazzi P, Mattivi F Abstract The impact of minute amounts of oxygen in the headspace on the post-bottling development of wine is generally considered to be very important, since oxygen can either damage or improve the quality of wine. This project aimed to gain new experimental evidence about the chemistry of the interaction between wine and oxygen. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC-MS method. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, glutathione and pantetheine; and sulfonated indole-3-lactic acid hexoside and tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottling. PMID: 26709023 [PubMed - as supplied by publisher]

Related Articles Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients. Osteoarthritis Cartilage. 2015 Dec 18; Authors: Zhang W, Sun G, Likhodii S, Liu M, Aref-Eshghi E, Harper PE, Martin G, Furey A, Green R, Randell E, Rahman P, Zhai G Abstract OBJECTIVE: To identify novel biomarker(s) for knee osteoarthritis (OA) using a metabolomics approach. METHOD: We utilized a two-stage case-control study design. Plasma samples were collected from knee OA patients and healthy controls after 8-hour fasting and metabolically profiled using a targeted metabolomics assay kit. Linear regression was used to identify novel metabolic markers for OA. Receiver operating characteristic (ROC) analysis was used to examine diagnostic values. Gene expression analysis was performed on human cartilage to explore the potential mechanism for the novel OA marker(s). RESULTS: 64 knee OA patients and 45 controls were included in the discovery stage and 72 knee OA patients and 76 age and sex matched controls were included in the validation stage. We identified and confirmed six metabolites that were significantly associated with knee OA, of which arginine was the most significant metabolite (p < 3.5×10(-13)) with knee OA patients having on average 69 μM lower than that in controls. ROC analysis showed that arginine had the greatest diagnostic value with AUC of 0.984. The optimal cutoff of arginine concentration was 57 μM with 98.3% sensitivity and 89% specificity. The depletion of arginine in OA patients was most likely due to the over activity of arginine to ornithine pathway, leading to imbalance between cartilage repair and degradation. CONCLUSION: Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes. PMID: 26708258 [PubMed - as supplied by publisher]

Related Articles Construction and immune protection evaluation of recombinant polyvalent OmpAs derived from genetically divergent ompA by DNA shuffling. Fish Shellfish Immunol. 2015 Dec 17; Authors: Li H, Chu X, Li D, Zeng ZH, Peng XX Abstract A wide variety of bacterial infections is a major challenge in aquaculture. Development of polyvalent vaccines that can fight against as many pathogens as possible is especially necessary. The present study uses DNA shuffling to create a new hybrid OmpA with improved cross-protection against V. alginolyticus and E. tarda through the recombination of six OmpA genes from V. parahaemolyticus, V. alginolyticus, E. tarda and E. coli. Out of the 43 recombinant chimeras genes constructed using VA0764 primers, EompAs-19 was demonstrated as an ideal polyvalent vaccine against infections caused V. alginolyticus and E. tarda. Compared with VA0764, OmpAs-19 had three mutations, which may be a molecular basis of EompAs-19 as an efficient polyvalent vaccine against both V. alginolyticus and E. tarda infections. These results develop a polyvalent vaccine that prevents the infections caused by extracellular and intracellular bacteria. Thus, the present study highlights the way to develop polyvalent vaccines against microbial infections by DNA shuffling. PMID: 26707781 [PubMed - as supplied by publisher]