PubMed

Metabolic analysis of the response of Pseudomonas putida DOT-T1E strains to toluene using Fourier transform infrared spectroscopy and gas chromatography mass spectrometry. Metabolomics. 2016;12:112 Authors: Sayqal A, Xu Y, Trivedi DK, AlMasoud N, Ellis DI, Muhamadali H, Rattray NJ, Webb C, Goodacre R Abstract INTRODUCTION: An exceptionally interesting stress response of Pseudomonas putida strains to toxic substances is the induction of efflux pumps that remove toxic chemical substances from the bacterial cell out to the external environment. To exploit these microorganisms to their full potential a deeper understanding of the interactions between the bacteria and organic solvents is required. Thus, this study focuses on investigation of metabolic changes in P. putida upon exposure to toluene. OBJECTIVE: Investigate observable metabolic alterations during interactions of three strains of P. putida (DOT-T1E, and its mutants DOT-T1E-PS28 and DOT-T1E-18) with the aromatic hydrocarbon toluene. METHODS: The growth profiles were measured by taking optical density (OD) measurement at 660 nm (OD660) at various time points during incubation. For fingerprinting analysis, Fourier-transform infrared (FT-IR) spectroscopy was used to investigate any phenotypic changes resulting from exposure to toluene. Metabolic profiling analysis was performed using gas chromatography-mass spectrometry (GC-MS). Principal component-discriminant function analysis (PC-DFA) was applied to the FT-IR data while multiblock principal component analysis (MB-PCA) and N-way analysis of variance (N-way ANOVA) were applied to the GC-MS data. RESULTS: The growth profiles demonstrated the effect of toluene on bacterial cultures and the results suggest that the mutant P. putida DOT-T1E-18 was more sensitive (significantly affected) to toluene compared to the other two strains. PC-DFA on FT-IR data demonstrated the differentiation between different conditions of toluene on bacterial cells, which indicated phenotypic changes associated with the presence of the solvent within the cell. Fifteen metabolites associated with this phenotypic change, in P. putida due to exposure to solvent, were from central metabolic pathways. Investigation of MB-PCA loading plots and N-way ANOVA for condition | strain × time blocking (dosage of toluene) suggested ornithine as the most significant compound that increased upon solvent exposure. CONCLUSION: The combination of metabolic fingerprinting and profiling with suitable multivariate analysis revealed some interesting leads for understanding the mechanism of Pseudomonas strains response to organic solvent exposure. PMID: 27398079 [PubMed - as supplied by publisher]

Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells. Immunity. 2016 Jul 1; Authors: Lam WY, Becker AM, Kennerly KM, Wong R, Curtis JD, Llufrio EM, McCommis KS, Fahrmann J, Pizzato HA, Nunley RM, Lee J, Wolfgang MJ, Patti GJ, Finck BN, Pearce EL, Bhattacharya D Abstract Durable antibody production after vaccination or infection is mediated by long-lived plasma cells (LLPCs). Pathways that specifically allow LLPCs to persist remain unknown. Through bioenergetic profiling, we found that human and mouse LLPCs could robustly engage pyruvate-dependent respiration, whereas their short-lived counterparts could not. LLPCs took up more glucose than did short-lived plasma cells (SLPCs) in vivo, and this glucose was essential for the generation of pyruvate. Glucose was primarily used to glycosylate antibodies, but glycolysis could be promoted by stimuli such as low ATP levels and the resultant pyruvate used for respiration by LLPCs. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, led to a progressive loss of LLPCs and of vaccine-specific antibodies in vivo. Thus, glucose uptake and mitochondrial pyruvate import prevent bioenergetic crises and allow LLPCs to persist. Immunizations that maximize these plasma cell metabolic properties might thus provide enduring antibody-mediated immunity. PMID: 27396958 [PubMed - as supplied by publisher]

Related Articles Omics in Chlamydomonas for Biofuel Production. Subcell Biochem. 2016;86:447-69 Authors: Aucoin HR, Gardner J, Boyle NR Abstract In response to demands for sustainable domestic fuel sources, research into biofuels has become increasingly important. Many challenges face biofuels in their effort to replace petroleum fuels, but rational strain engineering of algae and photosynthetic organisms offers a great deal of promise. For decades, mutations and stress responses in photosynthetic microbiota were seen to result in production of exciting high-energy fuel molecules, giving hope but minor capability for design. However, '-omics' techniques for visualizing entire cell processing has clarified biosynthesis and regulatory networks. Investigation into the promising production behaviors of the model organism C. reinhardtii and its mutants with these powerful techniques has improved predictability and understanding of the diverse, complex interactions within photosynthetic organisms. This new equipment has created an exciting new frontier for high-throughput, predictable engineering of photosynthetically produced carbon-neutral biofuels. PMID: 27023246 [PubMed - indexed for MEDLINE]

Related Articles Reconstruction of Tissue-Specific Metabolic Networks Using CORDA. PLoS Comput Biol. 2016 Mar;12(3):e1004808 Authors: Schultz A, Qutub AA Abstract Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation. PMID: 26942765 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic, enzymatic, and histochemical analyzes of cassava roots during postharvest physiological deterioration. BMC Res Notes. 2015;8:648 Authors: Uarrota VG, Maraschin M Abstract BACKGROUND: Under postharvest physiological deterioration cassava root tubers alter the expression of biosynthetic pathways of certain primary and secondary metabolites, as well as the activity of some scavenging enzymes. Therefore, in this study we hypothesized that cassava cultivars differ as to their physiological responses to deterioration and their biochemical profiles can be an indicative of the tolerance or susceptibility to deterioration. RESULTS: The results corroborate the working hypothesis, revealing that high Levels of phenolic acids, scopoletin, carotenoids, proteins, and augmented activities of guaiacol peroxidase and hydrogen peroxide in non-stored cassava roots can be used as potential biomarkers of cassava deterioration. CONCLUSIONS: Cassava physiological deterioration depends on cultivar and many compounds are up and downregulated during storage time. Secondary metabolites, enzymes, scopoletin, scavenging reactive oxygen species, and acidic polysaccharides are activated as responses to the physiological stress induced in root tubers. PMID: 26541143 [PubMed - indexed for MEDLINE]

Related Articles Risk factors for mortality in severe multiply injury patients with acute hypoxemic respiratory failure. Eur Rev Med Pharmacol Sci. 2015 Oct;19(19):3693-700 Authors: Chen YD, Feng XL, Deng L, Zhou P, Wang JD, Cai B, Jiang H, Dong Y, Zhang XH Abstract OBJECTIVE: To investigate the risk factors related to mortality in severe polytrauma patients with acute hypoxemic respiratory failure (AHRF). PATIENTS AND METHODS: From December 2011 to December 2014, we identified and intubated 524 traumatic AHRF patients in a level 1 trauma centers. Amongst those, we enrolled seventy-six severe traumatic AHRF patients with an injury severity score (ISS) over 16 and need for over 24 hour intra-tracheal mechanical ventilation for our study. Patients were followed daily to collect data about demographics, injury characteristic, diagnostic, treatment, respiratory parameters, major complications, duration of mechanical ventilation, length of stay, prevalence of major complications and 28-days mortality. RESULTS: Of the 76 patients in our study, 61 patients were male. Patients' ages were from 15 to 78 years old (43±17) and the predominant source of trauma was road traffic accidents. Before ventilation, patients had a mean PaO2/FiO2 ratio of 108±63, pH of 7.1±0.3, PaCO2 of 54±24 mmHg, respectively. The PaO2/FiO22 ratios were significantly improved by ventilation and the average duration of ventilation was 9.63±8.74 days. There were two peak dying times and the 28-days ICU mortality rate was 28.9%. Logistic regression analysis revealed the mortality rate to be significantly higher in patients with higher APACHE II scores (odds ratio: 1.60, p=0.002), shorter intervals between injury and admission (odds ratio: -0.91, p=0.03) and between admission and ventilation (odds ratio: -1.85, p=0.012), and lower pH (odds ratio: -0.692, p=0.044). The receiver operating characteristic (ROC) curves showed that best cut off points for mortality predictors were APACHE II scores greater than 25, time interval between injury and admission less than 2h, time interval between admission and ventilation less than 0.5h, and pH <7.16. CONCLUSIONS: Traumatic AHRF patients requiring ventilation support show a high rate of early mortality. Greater vigilance for high APACHE II score, short time interval between injury and ventilation, low pH in traumatic AHRF patients is required. PMID: 26502860 [PubMed - indexed for MEDLINE]

Related Articles Modulation of Glucokinase Regulatory Protein: A Double-Edged Sword? Trends Mol Med. 2015 Oct;21(10):583-94 Authors: Brouwers MC, Jacobs C, Bast A, Stehouwer CD, Schaper NC Abstract The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be introduced to T2DM patients. Recently, genome-wide association studies (GWASs) have shown that variants in the gene encoding GKRP protect against T2DM and kidney disease but predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These genetic data, together with previous experience with systemic and hepatospecific glucokinase activators, provide insight into the anticipated efficacy and safety of small-molecule disruptors in humans. Interestingly, they suggest that the opposite--enhanced GKRP-glucokinase binding--could be beneficial in selected patients. PMID: 26432016 [PubMed - indexed for MEDLINE]

Related Articles Epileptogenesis. Cold Spring Harb Perspect Med. 2015 Oct;5(10) Authors: Pitkänen A, Lukasiuk K, Dudek FE, Staley KJ Abstract Epileptogenesis is a chronic process that can be triggered by genetic or acquired factors, and that can continue long after epilepsy diagnosis. In 2015, epileptogenesis is not a treatment indication, and there are no therapies available in clinic to treat individuals at risk of epileptogenesis. However, thanks to active research, a large number of animal models have become available for search of molecular mechanisms of epileptogenesis. The first glimpses of treatment targets and biomarkers that could be developed to become useful in clinic are in sight. However, the heterogeneity of the epilepsy condition, and the dynamics of molecular changes over the course of epileptogenesis remain as challenges to overcome. PMID: 26385090 [PubMed - indexed for MEDLINE]

Related Articles LC-MS-based serum metabolomic analysis reveals dysregulation of phosphatidylcholines in esophageal squamous cell carcinoma. J Proteomics. 2015 Sep 8;127(Pt A):96-102 Authors: Mir SA, Rajagopalan P, Jain AP, Khan AA, Datta KK, Mohan SV, Lateef SS, Sahasrabuddhe N, Somani BL, Keshava Prasad TS, Chatterjee A, Veerendra Kumar KV, VijayaKumar M, Kumar RV, Gundimeda S, Pandey A, Gowda H Abstract UNLABELLED: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers with poor prognosis. Here, we carried out liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based untargeted metabolomic analysis of ESCC serum samples. Statistical analysis resulted in the identification of 652 significantly dysregulated molecular features in serum from ESCC patients as compared to the healthy subjects. Phosphatidylcholines were identified as a major class of dysregulated metabolites in this study suggesting potential perturbation of phosphocholine metabolism in ESCC. By using a targeted MS/MS approach both in positive and negative mode, we were able to characterize and confirm the structure of seven metabolites. Our study describes a quantitative LC-MS approach for characterizing dysregulated lipid metabolism in ESCC. BIOLOGICAL SIGNIFICANCE: Altered metabolism is a hallmark of cancer. We carried out (LC-MS)-based untargeted metabolomic profiling of serum from esophageal squamous cell carcinoma (ESCC) patients to characterize dysregulated metabolites. Phosphatidylcholine metabolism was found to be significantly altered in ESCC. Our study illustrates the use of mass spectrometry-based metabolomic analysis to characterize molecular alterations associated with ESCC. This article is part of a Special Issue entitled: Proteomics in India. PMID: 25982385 [PubMed - indexed for MEDLINE]

Metabolomic profile for the early detection of coronary artery disease by using UPLC-QTOF/MS. J Pharm Biomed Anal. 2016 Jun 25;129:34-42 Authors: Xu X, Gao B, Guan Q, Zhang D, Ye X, Zhou L, Tong G, Li H, Zhang L, Tian J, Huang J Abstract Traditional risk factors cannot promote prediction capacity for the patients with coronary artery disease (CAD), who usually do not show apparent symptoms until they develop acute myocardial infarction (AMI). As such, novel predictive diagnostic strategies are essential to accurately define patients at risk of acute coronary syndrome. In this study, non-targeted metabolomic profiling using ultra-performance liquid chromatography coupled to time of flight mass spectrometry (UPLC-QTOF/MS) was performed in combination with multivariate statistical model to analyze the serum samples of patients with stable angina (n=38), acute myocardial infarction (AMI) (n=34) and healthy age- and gender-matched controls (n=71). Results showed a clear distinction in metabolomic profiles between stable angina and AMI when using OPLS-DA with both positive and negative models. Internal cross-validation methods were used to confirm model validity with an area under the curve (AUROC)=0.983. We identified various classes of altered metabolites including phospholipids, fatty acids, sphingolipids, glycerolipids and steroids. We then demonstrated the differential roles of these metabolites using multivariate statistical model. Phospholipids previously associated with CAD were shown to have lower predictive capacity to discriminate AMI patients from stable angina patients. Interestingly, ceramides, bile acid and steroids hormone such as Cer(t18:0/16:0), Cer(d18:0/12:0), dehydroepiandrosterone sulfate (VIP scores of 1.99, 1.97, 1.64, respectively), were found to be associated with the progression of CAD. These results suggest that metabolomic approaches may facilitate the development of more stringent and predictive patient criteria in the diagnosis and treatment of CAD. PMID: 27394176 [PubMed - as supplied by publisher]

Pleiotropic effects of 4-hydroxynonenal on oxidative burst and phagocytosis in neutrophils. Redox Biol. 2016 Jun 23;9:57-66 Authors: Chacko BK, Wall SB, Kramer PA, Ravi S, Mitchell T, Johnson MS, Wilson L, Barnes S, Landar A, Darley-Usmar VM Abstract Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume large quantities of oxygen to rapidly generate ROS, a process that is referred to as the oxidative burst. These ROS are required for the efficient removal of phagocytized cellular debris and pathogens. In chronic inflammatory diseases, neutrophils are exposed to increased levels of oxidants and pro-inflammatory cytokines that can further prime oxidative burst responses and generate lipid oxidation products such as 4-hydroxynonenal (4-HNE). In this study we hypothesized that since 4-HNE can target glycolysis then this could modify the oxidative burst. To address this the oxidative burst was determined in freshly isolated healthy subject neutrophils using 13-phorbol myristate acetate (PMA) and the extracellular flux analyzer. Neutrophils pretreated with 4-HNE exhibited a significant decrease in the oxidative burst response and phagocytosis. Mass spectrometric analysis of alkyne-HNE treated neutrophils followed by click chemistry detected modification of a number of cytoskeletal, metabolic, redox and signaling proteins that are critical for the NADPH oxidase mediated oxidative burst. These modifications were confirmed using a candidate immunoblot approach for critical proteins of the active NADPH oxidase enzyme complex (Nox2 gp91phox subunit and Rac1 of the NADPH oxidase) and glyceraldehyde phosphate dehydrogenase, a critical enzyme in the metabolic regulation of oxidative burst. Taken together, these data suggest that 4-HNE-induces a pleiotropic mechanism to inhibit neutrophil function. These mechanisms may contribute to the immune dysregulation associated with chronic pathological conditions where 4-HNE is generated. PMID: 27393890 [PubMed - as supplied by publisher]

Performance evaluation of tile-based Fisher Ratio analysis using a benchmark yeast metabolome dataset. J Chromatogr A. 2016 Jun 22; Authors: Watson NE, Parsons BA, Synovec RE Abstract Performance of tile-based Fisher Ratio (F-ratio) data analysis, recently developed for discovery-based studies using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS), is evaluated with a metabolomics dataset that had been previously analyzed in great detail, but while taking a brute force approach. The previously analyzed data (referred to herein as the benchmark dataset) were intracellular extracts from Saccharomyces cerevisiae (yeast), either metabolizing glucose (repressed) or ethanol (derepressed), which define the two classes in the discovery-based analysis to find metabolites that are statistically different in concentration between the two classes. Beneficially, this previously analyzed dataset provides a concrete means to validate the tile-based F-ratio software. Herein, we demonstrate and validate the significant benefits of applying tile-based F-ratio analysis. The yeast metabolomics data are analyzed more rapidly in about one week versus one year for the prior studies with this dataset. Furthermore, a null distribution analysis is implemented to statistically determine an adequate F-ratio threshold, whereby the variables with F-ratio values below the threshold can be ignored as not class distinguishing, which provides the analyst with confidence when analyzing the hit table. Forty-six of the fifty-four benchmarked changing metabolites were discovered by the new methodology while consistently excluding all but one of the benchmarked nineteen false positive metabolites previously identified. PMID: 27393630 [PubMed - as supplied by publisher]

Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry. J Am Soc Mass Spectrom. 2016 Jul 8; Authors: Chen Z, Coy SL, Pannkuk EL, Laiakis EC, Hall AB, Fornace AJ, Vouros P Abstract Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure. Graphical Abstract ᅟ. PMID: 27392730 [PubMed - as supplied by publisher]

Strategies for Comparing Metabolic Profiles: Implications for the Inference of Biochemical Mechanisms from Metabolomics Data. IEEE/ACM Trans Comput Biol Bioinform. 2016 Jul 7; Authors: Qi Z, Voit E Abstract Large amounts of metabolomics data have been accumulated in recent years and await analysis. Previously we had developed a systems biological approach to infer biochemical mechanisms underlying metabolic alterations observed in cancers and other diseases. The method utilized the typical Euclidean distance for comparing metabolic profiles. Here we ask whether any of the numerous alternative metrics might serve this purpose better. METHODS AND FINDINGS: We used enzymatic alterations in purine metabolism that were measured in human renal cell carcinoma to test various metrics with the goal of identifying the best metrics for discerning metabolic profiles of healthy and diseased individuals. The results showed that several metrics have similarly good performance, but that some are unsuited for comparisons of metabolic profiles. Furthermore, the results suggest that relative changes in metabolite levels, which reduce bias toward large metabolite concentrations, are better suited for comparisons of metabolic profiles than absolute changes. Finally, we demonstrate that a sequential search for enzymatic alterations, ranked by importance, is not always valid. CONCLUSIONS: We identified metrics that are appropriate for comparisons of metabolic profiles. In addition, we constructed strategic guidelines for the algorithmic identification of biochemical mechanisms from metabolomics data. PMID: 27392364 [PubMed - as supplied by publisher]

Metabolic Characteristics of 16HBE and A549 Cells Exposed to Different Surface Modified Gold Nanorods. Adv Healthc Mater. 2016 Jul 8; Authors: Liu Z, Wang L, Zhang L, Wu X, Nie G, Chen C, Tang H, Wang Y Abstract Gold nanorods (AuNRs) have shown their great potential in cancer treatment due to their special physiochemical and optical properties, and the ease of surface modification. However, the molecular mechanism of biological effects induced by different surface modified AuNRs remains largely undetermined. Herein, this study for the first time systematically analyzed metabolic impacts of three surface modified AuNRs in cancer and noncancer cells detected by NMR and GC-FID/MS metabolomics and validated by molecular biological approach. It is found that positively and negatively charged AuNRs induce different metabolic consequences. Most importantly, it is found that the PEI-AuNRs display specific cytotoxicity to A549 cells while posing little impact on 16HBE cells. The cytotoxicity of PEI-AuNRs to A549 cells is manifested in large disruptions to the cell metabolisms, which affects energy metabolism, choline metabolism, the hexosamine biosynthesis pathway, and oxidative stress to cells. The results of this study provide comprehensive molecular information on the distinct biological effects of different surface modified AuNRs, and can be valuable in designing purpose-driven nanomaterials. Most importantly, this work highlights the potential of metabolomics coupled with molecular biological techniques in screening antitumor nanodrugs and revealing the molecular mechanism of their biological effects. PMID: 27391541 [PubMed - as supplied by publisher]

Integrated omics-analysis reveals Wnt-mediated NAD+ metabolic reprogramming in cancer stem-like cells. Oncotarget. 2016 Jul 6; Authors: Lee J, Kee HJ, Min S, Park KC, Park S, Hwang TH, Ryu DH, Hwang GS, Cheong JH Abstract Abnormal tumor cell metabolism is a consequence of alterations in signaling pathways that provide critical selective advantage to cancer cells. However, a systematic characterization of the metabolic and signaling pathways altered in cancer stem-like cells (CSCs) is currently lacking. Using nuclear magnetic resonance and mass spectrometry, we profiled the whole-cell metabolites of a pair of parental (P-231) and stem-like cancer cells (S-231), and then integrated with whole transcriptome profiles. We identified elevated NAAD+ in S-231 along with a coordinated increased expression of genes in Wnt/calcium signaling pathway, reflecting the correlation between metabolic reprogramming and altered signaling pathways. The expression of CD38 and ALP, upstream NAAD+ regulatory enzymes, was oppositely regulated between P- and S-231; high CD38 strongly correlated with NAADP in P-231 while high ALP with NAAD+ levels in S-231. Antagonizing Wnt activity by dnTCF4 transfection reversed the levels of NAAD+ and ALP expression in S-231. Of note, elevated NAAD+ caused a decrease of cytosolic Ca2+ levels preventing calcium-induced apoptosis in nutrient-deprived conditions. Reprograming of NAD+ metabolic pathway instigated by Wnt signaling prevented cytosolic Ca2+ overload thereby inhibiting calcium-induced apoptosis in S-231. These results suggest that "oncometabolites" resulting from cross talk between the deranged core cancer signaling pathway and metabolic network provide a selective advantage to CSCs. PMID: 27391070 [PubMed - as supplied by publisher]

Use of Plasma Metabolomics to Identify Diagnostic Biomarkers for Early Stage Epithelial Ovarian Cancer. J Cancer. 2016;7(10):1265-72 Authors: Fan L, Yin M, Ke C, Ge T, Zhang G, Zhang W, Zhou X, Lou G, Li K Abstract The early detection of ovarian carcinoma is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. The currently available biomarkers (such as CA125 and HE4) are insufficiently reliable to distinguish early stage (I/II) epithelial ovarian cancer (EOC) patients from normal individuals because they possess a relatively poor sensitivity and specificity. To evaluate the application of metabolomics to biomarker discovery in the early stages of epithelial ovarian cancer (EOC), plasma samples from 21 early stage EOC patients and 31 healthy controls were analyzed with ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof/MS) in conjunction with multivariate statistical analysis. Eighteen metabolites, including lysophospholipids, 2-piperidone and MG (18:2), were found to be disturbed in early stage EOC with satisfactory diagnostic accuracy (AUC=0.920). These biomarkers were specifically validated in the EOC nude mouse model, and five of the biomarkers (lysophospholipids, adrenoyl ethanolamide et al.) were highly suspected of being associated with EOC because they were differentially expressed with the same tendency in the EOC nude mice versus normal controls. In conclusion, the selected metabolic biomarkers have considerable utility and significant potential for diagnosing early ovarian cancer and investigating its underlying mechanisms. PMID: 27390602 [PubMed]

Review on proteomics for food authentication. J Proteomics. 2016 Jul 4; Authors: Ortea I, O'Connor G, Maquet A Abstract Consumers have the right to know what is in the food they are eating. Accordingly, European and global food regulations require that the provenance of the food can be guaranteed from farm to fork. Many different instrumental techniques have been proposed for food authentication. Although traditional methods are still being used, new approaches such as genomics, proteomics, and metabolomics are helping to complement existing methodologies for verifying the claims made about certain food products. During the last decade, proteomics (the large-scale analysis of proteins in a particular biological system at a particular time) has been applied to different research areas within food technology. Since proteins can be used as markers for many properties of a food, even indicating processes to which the food has been subjected, they can provide further evidence of the foods labeling claim. This review is a comprehensive and updated overview of the applications, drawbacks, advantages, and challenges of proteomics for food authentication in the assessment of the foods compliance with labeling regulations and policies. SIGNIFICANCE: This review paper provides a comprehensive and critical overview of the application of proteomics approaches to determine the authenticity of several food products updating the performances and current limitations of the applied techniques in both laboratory and industrial environments. PMID: 27389853 [PubMed - as supplied by publisher]

Untargeted Metabolomics of Tomato Plants after Root-knot Nematode Infestation. J Agric Food Chem. 2016 Jul 7; Authors: Eloh K, Sasanelli N, Maxia A, Caboni P Abstract After two months from the infestation of tomato plants with the root-knot nematode (RKN) Meloidogyne incognita, we performed a GC-MS untargeted fingerprint analysis for the identification of characteristic metabolites and biomarkers. Principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) suggested dramatic local changes of the plant metabolome. In the case of tomato leaves, β-alanine, phenylalanine, melibiose were induced in response to root-knot nematode stimuli, while ribose, glycerol, myristic acid and palmitic acid were reduced. For tomato stems, upregulated metabolites were: ribose, sucrose, fructose, and glucose while fumaric acid and glycine were downregulated. The variation in molecular strategies to the infestation of root-knot nematodes may play an important role in how Solanum lycopersicum and other plants adapt to nematode parasitic stress. PMID: 27389052 [PubMed - as supplied by publisher]

The metabolic signature of biomass formation in barley. Plant Cell Physiol. 2016 Jul 7; Authors: Ghaffari MR, Shahinnia F, Usadel B, Junker B, Schreiber F, Sreenivasulu N, Hajirezaei MR Abstract The network analysis of genome wide transcriptome responses, metabolic signatures and enzymes' relationship to biomass formation has been studied in a diverse panel of 12 barley accessions during vegetative and reproductive stages. The primary metabolites and enzymes involved in central metabolism that determine the accumulation of shoot biomass at the vegetative stage of barley development are primarily being linked to sucrose accumulation and sucrose synthase activity. Interestingly, the metabolic and enzyme links which are strongly associated with biomass accumulation during reproductive stages are related to the starch accumulation and TCA cycle intermediates citrate, malate, trans-aconitate and isocitrate. Additional significant associations were also found for UDP glucose, adenosine triphosphate and the amino acids isoleucine, valine, glutamate and histidine during the reproductive stage. A network analysis resulted in a combined identification of metabolite and enzyme signatures indicative for grain weight accumulation that was correlated with AGPase activity, a rate limiting enzyme involved in starch biosynthesis and with alanine amino transferase activity involved in the synthesis of storage proteins. We propose that the mechanism related to vegetative and reproductive biomass formation versus seed biomass formation is being linked to distinct fluxes regulating sucrose, starch, sugars and amino acids as central resources. These distinct biomarkers can be used to engineer biomass production and grain weight in barley. PMID: 27388338 [PubMed - as supplied by publisher]