PubMed

Related Articles Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation. Biomed Chromatogr. 2015 Jun;29(6):902-10 Authors: Zhang WQ, Hua YL, Zhang M, Ji P, Li JX, Zhang L, Li PL, Wei YM Abstract Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS. PMID: 25515821 [PubMed - indexed for MEDLINE]

Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 8;1014:17-23 Authors: Gao D, Wang Y, Xie W, Yang T, Jiang Y, Guo Y, Guan J, Liu H Abstract A marine natural compound flexibilide isolated from the soft coral Sinularia flexibilis has been found to have antitumor activity. However, its pharmacological mechanism on tumor cells has not been studied. Herein, an ultra-performance liquid chromatography coupled to quadrupole time of-flight mass spectrometry (UPLC/Q-TOF MS) based metabolomics approach was established to investigate the antitumor effect of flexibilide on HCT-116 cells and its action mechanism. Q-TOF MS and MS/MS were used to identify significantly different metabolites. Comparing flexibilide-treated HCT-116 cells group with control group (dimethyl sulfoxide), 19 distinct metabolites involved in sphingolipid metabolism, alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, glycerophospholipid metabolism, pyrimidine metabolism and others were discovered and identified. The significant decrease of phosphatidylcholine (PC) and phosphocholine levels and increase of lysophosphatidylcholine (LysoPC) levels in flexibilide treated cells suggested down-regulation of PC biosynthesis pathway. The decrease of sphingolipids reflected the lesions of cell membrane, and the up-regulation of sphingosine-1-phosphate indicated that TRAF2 and caspase-8 were likely to be activated by flexibilide and further caused cell apoptosis. Furthermore, TCA cycle was deemed to be down-regulated after flexibilide treatment, which might lead to an unsustainable of mitochondrial transmembrane potential MMP). The further measured descreased MMP with the increasing concentration of flexibilide treatment indiciated the dysfunction of mitochondrial which might finally lead to apoptosis. The UPLC/Q-TOF MS based metabolomics approach provides new insights into the mechanistic studies of flexibilide on tumor cells, which benefit its further improvement and application. PMID: 26859520 [PubMed - as supplied by publisher]

Impact of Freezing Delay Time on Tissue Samples for Metabolomic Studies. Front Oncol. 2016;6:17 Authors: Haukaas TH, Moestue SA, Vettukattil R, Sitter B, Lamichhane S, Segura R, Giskeødegård GF, Bathen TF Abstract INTRODUCTION: Metabolic profiling of intact tumor tissue by high-resolution magic angle spinning (HR MAS) MR spectroscopy (MRS) provides important biological information possibly useful for clinical diagnosis and development of novel treatment strategies. However, generation of high-quality data requires that sample handling from surgical resection until analysis is performed using systematically validated procedures. In this study, we investigated the effect of postsurgical freezing delay time on global metabolic profiles and stability of individual metabolites in intact tumor tissue. MATERIALS AND METHODS: Tumor tissue samples collected from two patient-derived breast cancer xenograft models (n = 3 for each model) were divided into pieces that were snap-frozen in liquid nitrogen at 0, 15, 30, 60, 90, and 120 min after surgical removal. In addition, one sample was analyzed immediately, representing the metabolic profile of fresh tissue exposed neither to liquid nitrogen nor to room temperature. We also evaluated the metabolic effect of prolonged spinning during the HR MAS experiments in biopsies from breast cancer patients (n = 14). All samples were analyzed by proton HR MAS MRS on a Bruker Avance DRX600 spectrometer, and changes in metabolic profiles were evaluated using multivariate analysis and linear mixed modeling. RESULTS: Multivariate analysis showed that the metabolic differences between the two breast cancer models were more prominent than variation caused by freezing delay time. No significant changes in levels of individual metabolites were observed in samples frozen within 30 min of resection. After this time point, levels of choline increased, whereas ascorbate, creatine, and glutathione (GS) levels decreased. Freezing had a significant effect on several metabolites but is an essential procedure for research and biobank purposes. Furthermore, four metabolites (glucose, glycine, glycerophosphocholine, and choline) were affected by prolonged HR MAS experiment time possibly caused by physical release of metabolites caused by spinning or due to structural degradation processes. CONCLUSION: The MR metabolic profiles of tumor samples are reproducible and robust to variation in postsurgical freezing delay up to 30 min. PMID: 26858940 [PubMed]

Central Role of Pyruvate Kinase in Carbon Co-Catabolism of Mycobacterium tuberculosis. J Biol Chem. 2016 Feb 8; Authors: Noy T, Vergnolle O, Hartman TE, Rhee KY, Jacobs WR, Berney M, Blanchard JS Abstract Mycobacterium tuberculosis (Mtb) displays a high degree of metabolic plasticity to adapt to challenging host environments. Genetic evidence suggests that Mtb relies mainly on fatty acid catabolism in the host. However, Mtb also maintains a functional glycolytic pathway and its role in the cellular metabolism of Mtb has yet to be understood. Pyruvate kinase catalyzes the last and rate-limiting step in glycolysis and the Mtb genome harbors one putative pyruvate kinase (pykA, Rv1617). Here we show that pykA encodes an active pyruvate kinase that is allosterically activated by glucose-6-phosphate (G6P) and adenosine monophosphate (AMP). Deletion of pykA prevents Mtb growth in the presence of fermentable carbon sources and has a cidal effect in the presence of glucose that correlates with elevated levels of the toxic catabolite methylglyoxal. Growth attenuation was also observed in media containing a combination of short chain fatty acids and glucose and surprisingly, in media containing odd- and even chain fatty acids alone. Untargeted high-sensitivity metabolomics revealed that inactivation of pyruvate kinase leads to accumulation of phosphoenolpyruvate (PEP), citrate and aconitate, which was consistent with allosteric inhibition of isocitrate dehydrogenase by PEP. This metabolic block could be relieved by addition of the alpha-ketoglutarate precursor glutamate. Taken together, our study identifies an essential role of pyruvate kinase in preventing metabolic block during carbon co-catabolism in Mtb. PMID: 26858255 [PubMed - as supplied by publisher]

Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted, High Resolution Metabolomics Study. J Pediatr. 2016 Feb 5; Authors: Jin R, Banton S, Tran VT, Konomi JV, Li S, Jones DP, Vos MB Abstract OBJECTIVE: To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. STUDY DESIGN: This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. RESULTS: The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. CONCLUSIONS: Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD. PMID: 26858195 [PubMed - as supplied by publisher]

European headache federation consensus on technical investigation for primary headache disorders. J Headache Pain. 2015 Dec;17(1):5 Authors: Mitsikostas DD, Ashina M, Craven A, Diener HC, Goadsby PJ, Ferrari MD, Lampl C, Paemeleire K, Pascual J, Siva A, Olesen J, Osipova V, Martelletti P, EHF committee Abstract The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect. PMID: 26857820 [PubMed - in process]

Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats. Biomed Chromatogr. 2016 Feb 8; Authors: Jiang H, Liu J, Wang T, Gao JR, Sun Y, Huang CB, Meng M, Qin XJ Abstract To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Spague-Dawley (SD) rats were randomly divided into control group (NC) and experimental group, with 8 in each. Rats in experimental group were induced by intracutaneous innoculation of 0.1mL Freund's complete adjuvant (FCA) to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, L-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. This article is protected by copyright. All rights reserved. PMID: 26856389 [PubMed - as supplied by publisher]

Related Articles Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses. J Exp Med. 2015 Oct 19;212(11):1921-30 Authors: Sawada Y, Honda T, Hanakawa S, Nakamizo S, Murata T, Ueharaguchi-Tanada Y, Ono S, Amano W, Nakajima S, Egawa G, Tanizaki H, Otsuka A, Kitoh A, Dainichi T, Ogawa N, Kobayashi Y, Yokomizo T, Arita M, Nakamura M, Miyachi Y, Kabashima K Abstract Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID: 26438363 [PubMed - indexed for MEDLINE]

Related Articles The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia. J Exp Med. 2015 Oct 19;212(11):1901-19 Authors: Yamamoto K, Miki Y, Sato M, Taketomi Y, Nishito Y, Taya C, Muramatsu K, Ikeda K, Nakanishi H, Taguchi R, Kambe N, Kabashima K, Lambeau G, Gelb MH, Murakami M Abstract Epidermal lipids are important for skin homeostasis. However, the entire picture of the roles of lipids, particularly nonceramide lipid species, in epidermal biology still remains obscure. Here, we report that PLA2G2F, a functionally orphan-secreted phospholipase A2 expressed in the suprabasal epidermis, regulates skin homeostasis and hyperplasic disorders. Pla2g2f(-/-) mice had a fragile stratum corneum and were strikingly protected from psoriasis, contact dermatitis, and skin cancer. Conversely, Pla2g2f-overexpressing transgenic mice displayed psoriasis-like epidermal hyperplasia. Primary keratinocytes from Pla2g2f(-) (/-) mice showed defective differentiation and activation. PLA2G2F was induced by calcium or IL-22 in keratinocytes and preferentially hydrolyzed ethanolamine plasmalogen-bearing docosahexaenoic acid secreted from keratinocytes to give rise to unique bioactive lipids (i.e., protectin D1 and 9S-hydroxyoctadecadienoic acid) that were distinct from canonical arachidonate metabolites (prostaglandins and leukotrienes). Ethanolamine lysoplasmalogen, a PLA2G2F-derived marker product, rescued defective activation of Pla2g2f(-/-) keratinocytes both in vitro and in vivo. Our results highlight PLA2G2F as a previously unrecognized regulator of skin pathophysiology and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases. PMID: 26438362 [PubMed - indexed for MEDLINE]

Related Articles Metabolic Effect Level Index Links Multivariate Metabolic Fingerprints to Ecotoxicological Effect Assessment. Environ Sci Technol. 2015 Jul 7;49(13):8096-104 Authors: Riedl J, Schreiber R, Otto M, Heilmeier H, Altenburger R, Schmitt-Jansen M Abstract A major goal of ecotoxicology is the prediction of adverse outcomes for populations from sensitive and early physiological responses. A snapshot of the physiological state of an organism can be provided by metabolic fingerprints. However, to inform chemical risk assessment, multivariate metabolic fingerprints need to be converted to readable end points suitable for effect estimation and comparison. The concentration- and time-dependent responsiveness of metabolic fingerprints to the PS-II inhibitor isoproturon was investigated by use of a Myriophyllum spicatum bioassay. Hydrophilic and lipophilic leaf extracts were analyzed with gas chromatography-mass spectrometry (GC-MS) and preprocessed with XCMS. Metabolic changes were aggregated in the quantitative metabolic effect level index (MELI), allowing effect estimation from Hill-based concentration-response models. Hereby, the most sensitive response on the concentration scale was revealed by the hydrophilic MELI, followed by photosynthetic efficiency and, 1 order of magnitude higher, by the lipophilic MELI and shoot length change. In the hydrophilic MELI, 50% change compares to 30% inhibition of photosynthetic efficiency and 10% inhibition of dry weight change, indicating effect development on different response levels. In conclusion, aggregated metabolic fingerprints provide quantitative estimates and span a broad response spectrum, potentially valuable for establishing adverse outcome pathways of chemicals in environmental risk assessment. PMID: 26020363 [PubMed - indexed for MEDLINE]

Related Articles Quantification of cellular viability by automated microscopy and flow cytometry. Oncotarget. 2015 Apr 20;6(11):9467-75 Authors: Sauvat A, Wang Y, Segura F, Spaggiari S, Müller K, Zhou H, Galluzzi L, Kepp O, Kroemer G Abstract Cellular viability is usually determined by measuring the capacity of cells to exclude vital dyes such as 4',6-diamidino-2-phenylindole (DAPI), or by assessing nuclear morphology with chromatinophilic plasma membrane-permeant dyes, such as Hoechst 33342. However, a fraction of cells that exclude DAPI or exhibit normal nuclear morphology have already lost mitochondrial functions and/or manifest massive activation of apoptotic caspases, and hence are irremediably committed to death. Here, we developed a protocol for the simultaneous detection of plasma membrane integrity (based on DAPI) or nuclear morphology (based on Hoechst 33342), mitochondrial functions (based on the mitochondrial transmembrane potential probe DiOC6(3)) and caspase activation (based on YO-PRO®-3, which can enter cells exclusively upon the caspase-mediated activation of pannexin 1 channels). This method, which allows for the precise quantification of dead, dying and healthy cells, can be implemented on epifluorescence microscopy or flow cytometry platforms and is compatible with a robotized, high-throughput workflow. PMID: 25816366 [PubMed - indexed for MEDLINE]

Related Articles Targeted Integration of RNA-Seq and Metabolite Data to Elucidate Curcuminoid Biosynthesis in Four Curcuma Species. Plant Cell Physiol. 2015 May;56(5):843-51 Authors: Li D, Ono N, Sato T, Sugiura T, Altaf-Ul-Amin M, Ohta D, Suzuki H, Arita M, Tanaka K, Ma Z, Kanaya S Abstract Curcuminoids, namely curcumin and its analogs, are secondary metabolites that act as the primary active constituents of turmeric (Curcuma longa). The contents of these curcuminoids vary among species in the genus Curcuma. For this reason, we compared two wild strains and two cultivars to understand the differences in the synthesis of curcuminoids. Because the fluxes of metabolic reactions depend on the amounts of their substrate and the activity of the catalysts, we analyzed the metabolite concentrations and gene expression of related enzymes. We developed a method based on RNA sequencing (RNA-Seq) analysis that focuses on a specific set of genes to detect expression differences between species in detail. We developed a 'selection-first' method for RNA-Seq analysis in which short reads are mapped to selected enzymes in the target biosynthetic pathways in order to reduce the effect of mapping errors. Using this method, we found that the difference in the contents of curcuminoids among the species, as measured by gas chromatography-mass spectrometry, could be explained by the changes in the expression of genes encoding diketide-CoA synthase, and curcumin synthase at the branching point of the curcuminoid biosynthesis pathway. PMID: 25637373 [PubMed - indexed for MEDLINE]

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016 Feb 6;7(1):41-50 Authors: Soubières AA, Poullis A Abstract There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use. PMID: 26855811 [PubMed - as supplied by publisher]

Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles. Environ Pollut. 2016 Feb 5;212:325-329 Authors: Taylor NS, Kirwan JA, Johnson C, Yan ND, Viant MR, Gunn JM, McGeer JC Abstract The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management. PMID: 26854702 [PubMed - as supplied by publisher]

Perturbation of pharmacologically relevant polyphenolic compounds in Moringa oleifera against photo-oxidative damages imposed by gamma radiation. J Photochem Photobiol B. 2016 Jan 26;156:79-86 Authors: Ramabulana T, Mavunda RD, Steenkamp PA, Piater LA, Dubery IA, Madala NE Abstract Oxidative stress is a physiological state associated with almost all biotic and abiotic stresses in plants. This phenomenon occurs due to imbalances which result from the overproduction of reactive oxygen species (ROS). Plants, however, have developed sophisticated mechanisms to mitigate the effect of ROS. In this regard, plant polyphenolic metabolites such as flavonoids are known to possess high antioxidant activities. In the current study, changes in the levels of phenolic compounds from Moringa oleifera after gamma radiation treatment were investigated with reverse phase liquid chromatography and mass spectrometric techniques in combination with multivariate data models such as principal component analysis and orthogonal projection to latent structures discriminant analysis. Our results revealed several polyphenolic compounds such as hydroxycinnamoyl derivatives and flavonoid molecules to be down-regulated post-radiation treatment. Interestingly, other flavonoid molecules were found to be up-regulated post-radiation treatment, thereby suggesting a possible compensatory phenomenon. The existence and involvement of structurally similar metabolites (such as regio-isomers of chlorogenic acids) in M. oleifera towards mitigating photo-oxidative damages are in support of the proposed evolutionary existence of a large pool of polyphenolics which contribute to the state of readiness, aptly described as a "better safe than sorry" phenomenon. Our study thus reaffirms the involvement of phenolic compounds as a first line of constitutive/preformed protection against oxidative stress. Furthermore, the obtained data supports M. oleifera as a source of versatile and pharmacologically relevant metabolites that may be exploited for ameliorating the oxidative damages imposed by several metabolic disorders in humans. PMID: 26854613 [PubMed - as supplied by publisher]

Integrating omics to unravel the stress response mechanisms in probiotic bacteria: approaches, challenges, and prospects. Crit Rev Food Sci Nutr. 2016 Feb 6;:0 Authors: Gandhi A, Shah NP Abstract Identifying the stress response mechanism of probiotic bacteria has always captivated the interest of the food producers. It is crucial to identify probiotic bacteria that have increased stress tolerance to survive during production, processing, and storage of food products. However, in order to achieve high resistance to environmental factors, there is a need to better understand the stress induced responses and adaptive mechanisms. With the advances in bacterial genomics, there has been an upsurge in application of other omics platforms such as transcriptomics, proteomics, metabolomics, and some more recent ones such as interactomics, fluxomics, and phenomics. These omics technologies have revolutionized the functional genomics and their application. There have been several studies implementing the various omics technologies to investigate the stress responses of probiotic bacteria. Integrated omics has the potential to provide in-depth information about the mechanisms of stress-induced responses in bacteria. However, there still remain challenges in integrating the information from different omics platforms. This review discusses the current omics techniques and the challenges faced in integrating various omics platforms with focus on their use in stress response studies. PMID: 26853094 [PubMed - as supplied by publisher]

An R package for the integrated analysis of metabolomics and spectral data. Comput Methods Programs Biomed. 2016 Jan 14; Authors: Costa C, Maraschin M, Rocha M Abstract Recently, there has been a growing interest in the field of metabolomics, materialized by a remarkable growth in experimental techniques, available data and related biological applications. Indeed, techniques as nuclear magnetic resonance, gas or liquid chromatography, mass spectrometry, infrared and UV-visible spectroscopies have provided extensive datasets that can help in tasks as biological and biomedical discovery, biotechnology and drug development. However, as it happens with other omics data, the analysis of metabolomics datasets provides multiple challenges, both in terms of methodologies and in the development of appropriate computational tools. Indeed, from the available software tools, none addresses the multiplicity of existing techniques and data analysis tasks. In this work, we make available a novel R package, named specmine, which provides a set of methods for metabolomics data analysis, including data loading in different formats, pre-processing, metabolite identification, univariate and multivariate data analysis, machine learning, and feature selection. Importantly, the implemented methods provide adequate support for the analysis of data from diverse experimental techniques, integrating a large set of functions from several R packages in a powerful, yet simple to use environment. The package, already available in CRAN, is accompanied by a web site where users can deposit datasets, scripts and analysis reports to be shared with the community, promoting the efficient sharing of metabolomics data analysis pipelines. PMID: 26853041 [PubMed - as supplied by publisher]

Related Articles Biomarkers in Pharmaceutical Research. Clin Chem. 2015 Nov;61(11):1343-53 Authors: Zhao X, Modur V, Carayannopoulos LN, Laterza OF Abstract BACKGROUND: Biomarkers are important tools in drug development and are used throughout pharmaceutical research. CONTENT: This review focuses on molecular biomarkers in drug development. It contains sections on how biomarkers are used to assess target engagement, pharmacodynamics, safety, and proof-of-concept. It also covers the use of biomarkers as surrogate end points and patient selection/companion diagnostics and provides insights into clinical biomarker discovery and biomarker development/validation with regulatory implications. To survey biomarkers used in drug development--acknowledging that many pharmaceutical development biomarkers are not published--we performed a focused PubMed search employing "biomarker" and the names of the largest pharmaceutical companies as keywords and filtering on clinical trials and publications in the last 10 years. This yielded almost 500 entries, the majority of which included disease-related (approximately 60%) or prognostic/predictive (approximately 20%) biomarkers. A notable portion (approximately 8%) included HER2 (human epidermal growth factor receptor 2) testing, highlighting the utility of biomarkers for patient selection. The remaining publications included target engagement, safety, and drug metabolism biomarkers. Oncology, cardiovascular disease, and osteoporosis were the areas with the most citations, followed by diabetes and Alzheimer disease. SUMMARY: Judicious biomarker use can improve pharmaceutical development efficiency by helping to select patients most appropriate for treatment using a given mechanism, optimize dose selection, and provide earlier confidence in accelerating or discontinuing compounds in clinical development. Optimal application of biomarker technology requires understanding of candidate drug pharmacology, detailed modeling of biomarker readouts relative to pharmacokinetics, rigorous validation and qualification of biomarker assays, and creative application of these elements to drug development problems. PMID: 26408531 [PubMed - indexed for MEDLINE]

Related Articles Outer membrane proteomics of kanamycin-resistant Escherichia coli identified MipA as a novel antibiotic resistance-related protein. FEMS Microbiol Lett. 2015 Jun;362(11) Authors: Li H, Zhang DF, Lin XM, Peng XX Abstract Antibiotic-resistant bacteria are a great threat to human health and food safety and there is an urgent need to understand the mechanisms of resistance for combating these bacteria. In the current study, comparative proteomic methodologies were applied to identify Escherichia coli K-12 outer membrane (OM) proteins related to kanamycin resistance. Mass spectrometry and western blotting results revealed that OM proteins TolC, Tsx and OstA were up-regulated, whereas MipA, OmpA, FadL and OmpW were down-regulated in kanamycin-resistant E. coli K-12 strain. Genetic deletion of tolC (ΔtolC-Km) led to a 2-fold decrease in the minimum inhibitory concentration (MIC) of kanamycin and deletion of mipA (ΔmipA-Km) resulted in a 4-fold increase in the MIC of kanamycin. Changes in the MICs for genetically modified strains could be completely recovered by gene complementation. Compared with the wild-type strain, the survival capability of ΔompA-Km was significantly increased and that of Δtsx-Km was significantly decreased. We further evaluated the role and expression of MipA in response to four other antibiotics including nalidixic acid, streptomycin, chloramphenicol and aureomycin, which suggested that MipA was a novel OM protein related to antibiotic resistance. PMID: 25940639 [PubMed - indexed for MEDLINE]

Related Articles Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test. PLoS One. 2015;10(3):e0119856 Authors: Saccenti E, van Duynhoven J, Jacobs DM, Smilde AK, Hoefsloot HC Abstract The ability to restore homeostasis upon environmental challenges has been proposed as a measure for health. Metabolic profiling of plasma samples during the challenge response phase should offer a profound view on the flexibility of a phenotype to cope with daily stressors. Current data modeling approaches, however, struggle to extract biological descriptors from time-resolved metabolite profiles that are able to discriminate between different phenotypes. Thus, for the case of oxylipin responses in plasma upon an oral glucose tolerance test we developed a modeling approach that incorporates a priori biological pathway knowledge. The degradation pathways of arachidonic and linoleic acids were modeled using a regression model based on a pseudo-steady-state approximated model, resulting in a parameter A that summarizes the relative enzymatic activity in these pathways. Analysis of the phenotypic parameters As suggests that different phenotypes can be discriminated according to preferred relative activity of the arachidonic and linoleic pathway. Correlation analysis shows that there is little or no competition between the arachidonic and linoleic acid pathways, although they share the same enzymes. PMID: 25786212 [PubMed - indexed for MEDLINE]