PubMed

Related Articles Metabolic mechanism for L-leucine-induced metabolome to eliminate Streptococcus iniae. J Proteome Res. 2017 Mar 07;: Authors: Du CC, Yang M, Li MY, Yang J, Peng B, Li H, Peng XX Abstract Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for L-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS based metabolomics was used to investigate tilapia liver metabolic profile in the presence of exogenous L-leucine. Thirty-seven metabolites of differential abundance were determined, and eleven metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting the two metabolites play crucial roles in L-leucine-induced elimination of the pathogen by the host. Exogenous L-serine reduces mortality of tilapias infected by S. iniae, providing a robust proof for supporting the conclusion. Furthermore, exogenous serine elevates expression of genes Il-1β and Il-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that L-leucine promotes macrophages to kill both Gram-positive and negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous L-leucine is partly attributed to elevation of serine. These results demonstrate a metabolic mechanism by which exogenous L-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens. PMID: 28266220 [PubMed - as supplied by publisher]

Related Articles Quality control of Hypericum perforatum L. analytical challenges and recent progress. J Pharm Pharmacol. 2017 Mar 07;: Authors: Agapouda A, Booker A, Kiss T, Hohmann J, Heinrich M, Csupor D Abstract OBJECTIVES: The most widely applied qualitative and quantitative analytical methods in the quality control of Hypericum perforatum extracts will be reviewed, including routine analytical tools and most modern approaches. KEY FINDINGS: Biologically active components of H. perforatum are chemically diverse; therefore, different chromatographic and detection methods are required for the comprehensive analysis of St. John's wort extracts. Naphthodianthrones, phloroglucinols and flavonoids are the most widely analysed metabolites of this plant. For routine quality control, detection of major compounds belonging to these groups seems to be sufficient; however, closer characterization requires the detection of minor compounds as well. CONCLUSIONS: TLC and HPTLC are basic methods in the routine analysis, whereas HPLC-DAD is the most widely applied method for quantitative analysis due to its versatility. LC-MS is gaining importance in pharmacokinetic studies due to its sensitivity. Modern approaches, such as DNA barcoding, NIRS and NMR metabolomics, may offer new possibilities for the more detailed characterization of secondary metabolite profile of H. perforatum extracts. PMID: 28266019 [PubMed - as supplied by publisher]

Related Articles Expanding Lipidome Coverage Using LC-MS/MS Data-Dependent Acquisition with Automated Exclusion List Generation. J Am Soc Mass Spectrom. 2017 Mar 06;: Authors: Koelmel JP, Kroeger NM, Gill EL, Ulmer CZ, Bowden JA, Patterson RE, Yost RA, Garrett TJ Abstract Untargeted omics analyses aim to comprehensively characterize biomolecules within a biological system. Changes in the presence or quantity of these biomolecules can indicate important biological perturbations, such as those caused by disease. With current technological advancements, the entire genome can now be sequenced; however, in the burgeoning fields of lipidomics, only a subset of lipids can be identified. The recent emergence of high resolution tandem mass spectrometry (HR-MS/MS), in combination with ultra-high performance liquid chromatography, has resulted in an increased coverage of the lipidome. Nevertheless, identifications from MS/MS are generally limited by the number of precursors that can be selected for fragmentation during chromatographic elution. Therefore, we developed the software IE-Omics to automate iterative exclusion (IE), where selected precursors using data-dependent topN analyses are excluded in sequential injections. In each sequential injection, unique precursors are fragmented until HR-MS/MS spectra of all ions above a user-defined intensity threshold are acquired. IE-Omics was applied to lipidomic analyses in Red Cross plasma and substantia nigra tissue. Coverage of the lipidome was drastically improved using IE. When applying IE-Omics to Red Cross plasma and substantia nigra lipid extracts in positive ion mode, 69% and 40% more molecular identifications were obtained, respectively. In addition, applying IE-Omics to a lipidomics workflow increased the coverage of trace species, including odd-chained and short-chained diacylglycerides and oxidized lipid species. By increasing the coverage of the lipidome, applying IE to a lipidomics workflow increases the probability of finding biomarkers and provides additional information for determining etiology of disease. Graphical Abstract ᅟ. PMID: 28265968 [PubMed - as supplied by publisher]

Related Articles Metabolic profiling study of shikonin's cytotoxic activity in the Huh7 human hepatoma cell line. Mol Biosyst. 2017 Mar 07;: Authors: Spyrelli ED, Kyriazou AV, Virgiliou C, Nakas A, Deda O, Papageorgiou VP, Assimopoulou AN, Gika HG Abstract Shikonin and its enantiomer alkannin, which are natural products, have been extensively studied in vitro and in vivo for, among others, their antitumor activity. The investigation of the molecular pathways involved in their action is of interest, since they are not yet clearly defined. Metabolic profiling in cells can provide a picture of a cell's phenotype upon intervention, assisting in the elucidation of the mechanism of action. In this study, the cytotoxic effect of shikonin on a human hepatocarcinoma cell line was studied. Huh7 cells were treated with shikonin at 5 μM, and it was found that shikonin markedly inhibited cell growth. Metabolic profiling indicated alterations in the metabolic content of the cells and the culture media upon treatment, detecting the metabolic response of the cells. This study demonstrates the potential of metabolomics to improve knowledge on the mechanisms involved in shikonin's antitumor action. PMID: 28265634 [PubMed - as supplied by publisher]

Related Articles Perspective on precision medicine in paediatric heart failure. Clin Sci (Lond). 2017 Mar 01;131(6):439-448 Authors: Fridman MD, Mital S Abstract In 2015, President Obama launched the Precision Medicine Initiative (PMI), which introduced new funding to a method of research with the potential to study rare and complex diseases. Paediatric heart failure, a heterogeneous syndrome affecting approximately 1 in 100000 children, is one such condition in which precision medicine techniques may be applied with great benefit. Current heart failure therapies target downstream effects of heart failure rather than the underlying cause of heart failure. As such, they are often ineffective in paediatric heart failure, which is typically of primary (e.g. genetic) rather than secondary (e.g. acquired) aetiology. It is, therefore, important to develop therapies that can target the causes of heart failure in children with greater specificity thereby decreasing morbidity, mortality and burden of illness on both patients and their families. The benefits of co-ordinated research in genomics, proteomics, metabolomics, transcriptomics and phenomics along with dietary, lifestyle and social factors have led to novel therapeutic and prognostic applications in other fields such as oncology. Applying such co-ordinated research efforts to heart failure constitutes an important step in advancing care and improving the lives of those affected. PMID: 28265035 [PubMed - in process]

Related Articles Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. FASEB J. 2017 Mar 06;: Authors: Vorrink SU, Ullah S, Schmidt S, Nandania J, Velagapudi V, Beck O, Ingelman-Sundberg M, Lauschke VM Abstract Adverse reactions or lack of response to medications are important concerns for drug development programs. However, faithful predictions of drug metabolism and toxicity are difficult because animal models show only limited translatability to humans. Furthermore, current in vitro systems, such as hepatic cell lines or primary human hepatocyte (PHH) 2-dimensional (2D) monolayer cultures, can be used only for acute toxicity tests because of their immature phenotypes and inherent instability. Therefore, the migration to novel phenotypically stable models is of prime importance for the pharmaceutical industry. Novel 3-dimensional (3D) culture systems have been shown to accurately mimic in vivo hepatic phenotypes on transcriptomic and proteomic level, but information about their metabolic stability is lacking. Using a combination of targeted and untargeted high-resolution mass spectrometry, we found that PHHs in 3D spheroid cultures remained metabolically stable for multiple weeks, whereas metabolic patterns of PHHs from the same donors cultured as conventional 2D monolayers rapidly deteriorated. Furthermore, pharmacokinetic differences between donors were maintained in 3D spheroid cultures, enabling studies of interindividual variability in drug metabolism and toxicity. We conclude that the 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long-term drug metabolism and pharmacokinetics.-Vorrink, S. U., Ullah, S., Schmid, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman-Sundberg, M., Lauschke, V. M. Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. PMID: 28264975 [PubMed - as supplied by publisher]

Related Articles Genomics and Biochemistry of Saccharomyces cerevisiae Wine Yeast Strains. Biochemistry (Mosc). 2016 Dec;81(13):1650-1668 Authors: Eldarov MA, Kishkovskaia SA, Tanaschuk TN, Mardanov AV Abstract Saccharomyces yeasts have been used for millennia for the production of beer, wine, bread, and other fermented products. Long-term "unconscious" selection and domestication led to the selection of hundreds of strains with desired production traits having significant phenotypic and genetic differences from their wild ancestors. This review summarizes the results of recent research in deciphering the genomes of wine Saccharomyces strains, the use of comparative genomics methods to study the mechanisms of yeast genome evolution under conditions of artificial selection, and the use of genomic and postgenomic approaches to identify the molecular nature of the important characteristics of commercial wine strains of Saccharomyces. Succinctly, data concerning metagenomics of microbial communities of grapes and wine and the dynamics of yeast and bacterial flora in the course of winemaking is provided. A separate section is devoted to an overview of the physiological, genetic, and biochemical features of sherry yeast strains used to produce biologically aged wines. The goal of the review is to convince the reader of the efficacy of new genomic and postgenomic technologies as tools for developing strategies for targeted selection and creation of new strains using "classical" and modern techniques for improving winemaking technology. PMID: 28260488 [PubMed - indexed for MEDLINE]

Related Articles (1)H NMR-based metabonomic study on the effects of Epimedium on glucocorticoid-induced osteoporosis. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Dec 01;1038:118-126 Authors: Pan S, Chen A, Han Z, Wang Y, Lu X, Yang Y Abstract Glucocorticoids are widely used in clinical practice for the treatment of many immune-mediated and inflammatory diseases, and glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. Epimedium is one of the most commonly used traditional Chinese medicines for treating osteoporosis. In the present study, we systematically analysed the metabonomic characteristics of GIO model rats and elucidated the therapeutic effect of Epimedium by using a (1)H NMR-based metabonomic approach in conjunction with multivariate data analysis. Rats in treatment and model groups were injected with dexamethasone (0.1mg/kg/day) for 5 weeks. Simultaneously, two treatment groups were orally administered Epimedium (10g/kg/day) or Alendronate (1.2mg/kg/day) for 5 weeks. In GIO model rats, lipid and lactate levels in serum were increased, while creatine/creatinine, PC/GPC, taurine, glycine and β-glucose levels were decreased. In urine, GIO rats had higher levels of phenylacetylglycine but lower levels of 2-oxoglutarate, citrate, creatine/creatinine, taurine, PC/GPC and hippurate than controls. Epimedium reversed the aforementioned metabolic alterations in multiple metabolic pathways involved in energy, lipid, amino acid and phospholipid metabolism and gut microbiota derangement. Our results indicated that Epimedium had significant effects in the prevention and treatment of osteoporosis. It is concluded that (1)H NMR metabonomics is a useful method for studying the metabolic effects of traditional Chinese medicine from a systematic and holistic view. PMID: 27810280 [PubMed - indexed for MEDLINE]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/03/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Endometriosis is associated with aberrant metabolite profiles in plasma. Fertil Steril. 2017 Mar;107(3):699-706.e6 Authors: Letsiou S, Peterse DP, Fassbender A, Hendriks MM, van den Broek NJ, Berger R, O DF, Vanhie A, Vodolazkaia A, Van Langendonckt A, Donnez J, Harms AC, Vreeken RJ, Groothuis PG, Dolmans MM, Brenkman AB, D'Hooghe TM Abstract OBJECTIVE: To identify metabolites that are associated with and predict the presence of endometriosis. DESIGN: Metabolomics study using state-of-the-art mass spectrometry approaches. SETTING: University hospital and universities. PATIENT(S): Twenty-five women with laparoscopically confirmed endometriosis (cases) and 19 women with laparoscopically documented absence of endometriosis (controls). None of the women included in this study had received oral contraception or GnRH agonists for a minimum of 1 month before blood collection. INTERVENTION(S): Plasma collection. MAIN OUTCOME MEASURE(S): Metabolite profiles were generated and interrogated using multiple mass spectrometry methods, that is, high performance liquid chromatography coupled with negative mode electrospray ionization tandem mass spectrometry, UPLC-MS/MS, and ultra performance liquid chromatography-electroSpray ionization-quadrupole time-of-flight (UPLC-ESI-Q-TOF). Metabolite groups investigated included phospholipids, glycerophospholipids, ether-phospholipids, cholesterol-esters, triacylglycerol, sphingolipids, free fatty acids, steroids, eicosanoids, and acylcarnitines. RESULT(S): A panel of acylcarnitines predicted the presence of endometriosis with 88.9% specificity and 81.5% sensitivity in human plasma, with a positive predictive value of 75%. However, due to data limitations the outcome of the receiver operating characteristic curve analysis was not significant. CONCLUSION(S): A diagnostic model based on acylcarnitines has the potential to predict the presence and stage of endometriosis. PMID: 28259259 [PubMed - in process]

Effects of boiling duration in processing of White Paeony Root on its overall quality evaluated by ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry based metabolomics analysis and high performance liquid chromatography quantification. Chin J Nat Med. 2017 Jan;15(1):62-70 Authors: Ming K, Xu J, Liu HH, Xu JD, Li XY, Lu M, Wang CR, Chen HB, Li SL Abstract Boiling processing is commonly used in post-harvest handling of White Paeony Root (WPR), in order to whiten the herbal materials and preserve the bright color, since such WPR is empirically considered to possess a higher quality. The present study was designed to investigate whether and how the boiling processing affects overall quality of WPR. First, an ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry-based metabolomics approach coupled with multivariate statistical analysis was developed to compare the holistic quality of boiled and un-boiled WPR samples. Second, ten major components in WPR samples boiled for different durations were quantitatively determined using high performance liquid chromatography to further explore the effects of boiling time on the holistic quality of WPR, meanwhile the appearance of the processed herbal materials was observed. The results suggested that the boiling processing conspicuously affected the holistic quality of WPR by simultaneously and inconsistently altering the chemical compositions and that short-time boiling processing between 2 and 10 min could both make the WPR bright-colored and improve the contents of major bioactive components, which were not achieved either without boiling or with prolonged boiling. In conclusion, short-term boiling (2-10 min) is recommended for post-harvest handling of WPR. PMID: 28259254 [PubMed - in process]

Probiotic treatment reduces depressive-like behaviour in rats independently of diet. Psychoneuroendocrinology. 2017 Feb 16;79:40-48 Authors: Abildgaard A, Elfving B, Hokland M, Wegener G, Lund S Abstract The gut microbiota has recently emerged as an important regulator of brain physiology and behaviour in animals, and ingestion of certain bacteria (probiotics) therefore appear to be a potential treatment for major depressive disorder (MDD). However, some conceptual and mechanistical aspects need further elucidation. We therefore aimed at investigating whether the habitual diet may interact with the effect of probiotics on depression-related behaviour and further examined some potentially involved mechanisms underlying the microbe-mediated behavioural effects. Forty male Sprague-Dawley rats were fed a control (CON) or high-fat diet (HFD) for ten weeks and treated with either a multi-species probiotic formulation or vehicle for the last five weeks. Independently of diet, probiotic treatment markedly reduced depressive-like behaviour in the forced swim test by 34% (95% CI: 22-44%). Furthermore, probiotic treatment skewed the cytokine production by stimulated blood mononuclear cells towards IFNγ, IL2 and IL4 at the expense of TNFα and IL6. In addition, probiotics lowered hippocampal transcript levels of factors involved in HPA axis regulation (Crh-r1, Crh-r2 and Mr), whereas HFD increased these levels. A non-targeted plasma metabolomics analysis revealed that probiotics raised the level of indole-3-propionic acid, a potential neuroprotective agent. Our findings clearly support probiotics as a potential treatment strategy in MDD. Importantly, the efficacy was not attenuated by intake of a "Western pattern" diet associated with MDD. Mechanistically, the HPA axis, immune system and microbial tryptophan metabolism could be important in this context. Importantly, our study lend inspiration to clinical trials on probiotics in depressed patients. PMID: 28259042 [PubMed - as supplied by publisher]

Gas chromatography-mass spectrometry profiles of urinary organic acids in healthy captive cheetahs (Acinonyx jubatus). J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 16;1049-1050:8-15 Authors: Tordiffe AS, van Reenen M, Reyers F, Mienie LJ Abstract In captivity, cheetahs (Acinonyx jubatus) frequently suffer from several unusual chronic diseases that rarely occur in their free-ranging counterparts. In order to develop a better understanding of their metabolism and health we documented the urine organic acids of 41 apparently healthy captive cheetahs, in an untargeted metabolomic study, using gas chromatography-mass spectrometry. A total of 339 organic acids were detected and annotated. Phenolic compounds, thought to be produced by the anaerobic fermentation of aromatic amino acids in the distal colon, as well as their corresponding glycine conjugates, were present in high concentrations. The most abundant organic acids in the cheetahs' urine were an as yet unidentified compound and a novel cadaverine metabolite, tentatively identified as N(1),N(5)-dimethylpentane-1,5-diamine. Pantothenic acid and citramalic acid concentrations correlated negatively with age, while glutaric acid concentrations correlated positively with age, suggesting possible dysregulation of coenzyme A metabolism in older cheetahs. This study provides a baseline of urine organic acid reference values in captive cheetahs and suggests important avenues for future research in this species. PMID: 28259021 [PubMed - as supplied by publisher]

Related Articles NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells. Mol Oncol. 2017 Mar 04;: Authors: Bernacchioni C, Ghini V, Cencetti F, Japtok L, Donati C, Bruni P, Turano P Abstract Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase (SK) 1 in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR-based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction of CO2 production. Additionally, SK1-expressing cells displayed a significant increase of glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies. PMID: 28258651 [PubMed - as supplied by publisher]

Related Articles Profiling of ARDS Pulmonary Edema Fluid Identifies a Metabolically Distinct Subset. Am J Physiol Lung Cell Mol Physiol. 2017 Mar 03;:ajplung.00438.2016 Authors: Rogers AJ, Contrepois K, Wu M, Zheng M, Peltz G, Ware LB, Matthay MA Abstract There is considerable biologic and physiologic heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a sub-group of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Non-targeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal components analysis (PCA) and partial least squares discriminant analysis (PLSDA) were conducted to find discriminant metabolites. 760 unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared to edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus, metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biologic heterogeneity among ARDS patients who meet standard clinical and physiologic criteria for ARDS. PMID: 28258106 [PubMed - as supplied by publisher]

Related Articles Cadmium-induced changes in vacuolar aspects of Arabidopsis thaliana. Plant Physiol Biochem. 2017 Feb 23;114:29-37 Authors: Sharma SS, Yamamoto K, Hamaji K, Ohnishi M, Anegawa A, Sharma S, Thakur S, Kumar V, Uemura T, Nakano A, Mimura T Abstract We have examined the changes due to Cd treatment in the vacuolar form in root tip cortical cells in Arabidopsis thaliana employing a transformant with GFP fused to a tonoplast protein. A Cd-induced enhancement in complexity with general expansion of vacuolar system within 24 h was evident. The changes in the vacuolar form were dependent on the applied Cd concentrations. Concomitantly, as revealed through dithizone staining, Cd accumulated in the seedling roots exhibiting abundance of Cd-dithizone complexes in root tip, root hairs and vasculature. To get insight into the involvement of SNARE protein-mediated vesicle fusion in Cd detoxification, the magnitude of Cd toxicity in a couple of knock out mutants of the vacuolar Qa-SNARE protein VAM3/SYP22 was compared with that in the wild type. The Cd toxicity appeared to be comparable in the mutants and the wild type. In order to analyze the Cd effects at cellular level, we treated the Arabidopsis suspension-cultured cells with Cd. Cd, however, did not induce a change in the vacuolar form in suspension-cultured cells although Cd measured with ICP-MS was obviously taken up into the cell. The V-ATPase activity in the microsomal fractions from vacuoles isolated from A. thaliana suspension cultured cells remained unaffected by Cd. Changes in the levels of certain metabolites of Cd-treated cells were also not so distinct except for those of glutathione. The significance of findings is discussed. PMID: 28257948 [PubMed - as supplied by publisher]

Related Articles Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism. PLoS Pathog. 2017 Mar 03;13(3):e1006256 Authors: Sychev ZE, Hu A, DiMaio TA, Gitter A, Camp ND, Noble WS, Wolf-Yadlin A, Lagunoff M Abstract Kaposi's Sarcoma associated Herpesvirus (KSHV), an oncogenic, human gamma-herpesvirus, is the etiological agent of Kaposi's Sarcoma the most common tumor of AIDS patients world-wide. KSHV is predominantly latent in the main KS tumor cell, the spindle cell, a cell of endothelial origin. KSHV modulates numerous host cell-signaling pathways to activate endothelial cells including major metabolic pathways involved in lipid metabolism. To identify the underlying cellular mechanisms of KSHV alteration of host signaling and endothelial cell activation, we identified changes in the host proteome, phosphoproteome and transcriptome landscape following KSHV infection of endothelial cells. A Steiner forest algorithm was used to integrate the global data sets and, together with transcriptome based predicted transcription factor activity, cellular networks altered by latent KSHV were predicted. Several interesting pathways were identified, including peroxisome biogenesis. To validate the predictions, we showed that KSHV latent infection increases the number of peroxisomes per cell. Additionally, proteins involved in peroxisomal lipid metabolism of very long chain fatty acids, including ABCD3 and ACOX1, are required for the survival of latently infected cells. In summary, novel cellular pathways altered during herpesvirus latency that could not be predicted by a single systems biology platform, were identified by integrated proteomics and transcriptomics data analysis and when correlated with our metabolomics data revealed that peroxisome lipid metabolism is essential for KSHV latent infection of endothelial cells. PMID: 28257516 [PubMed - as supplied by publisher]

Related Articles Antioxidant Activity of the Lignins Derived from Fluidized-Bed Fast Pyrolysis. Molecules. 2017 Mar 01;22(3): Authors: Qazi SS, Li D, Briens C, Berruti F, Abou-Zaid MM Abstract A challenge in recent years has been the rational use of forest and agriculture residues for the production of bio-fuel, biochemical, and other bioproducts. In this study, potentially useful compounds from pyrolytic lignins were identified by HPLC-MS/MS and untargeted metabolomics. The metabolites identified were 2-(4-allyl-2-methoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-1-propanol, benzyl benzoate, fisetinidol, phenyllactic acid, 2-phenylpropionic acid, 6,3'-dimethoxyflavone, and vanillin. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH), trolox equivalent antioxidant capacity (TEAC), and total phenolics content (TPC) per gram of pyrolytic lignin ranged from 14 to 503 mg ascorbic acid equivalents, 35 to 277 mg trolox equivalents, and 0.42 to 50 mg gallic acid equivalents, respectively. A very significant correlation was observed between the DPPH and TPC (r = 0.8663, p ≤ 0.0001), TEAC and TPC (r = 0.8044, p ≤ 0.0001), and DPPH and TEAC (r = 0.8851, p ≤ 0.0001). The polyphenolic compounds in the pyrolytic lignins which are responsible for radical scavenging activity and antioxidant properties can be readily profiled with HPLC-MS/MS combined with untargeted metabolomics. The results also suggest that DPPH, TEAC, and TPC assays are suitable methods for the measurement of antioxidant activity in a variety of pyrolytic lignins. These data show that the pyrolytic lignins can be considered as promising sources of natural antioxidants and value-added chemicals. PMID: 28257062 [PubMed - in process]

Related Articles Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics. Theranostics. 2017;7(3):624-633 Authors: Buckle T, van der Wal S, van Malderen SJ, Müller L, Kuil J, van Unen V, Peters RJ, van Bemmel ME, McDonnell LA, Velders AH, Koning F, Vanhaeke F, van Leeuwen FW Abstract BACKGROUND: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. METHODS: A hybrid label that contained both a DTPA chelate (that was coordinated with either (165)Ho or (111)In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of ((165)Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging ((165)Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS ((165)Ho) and radiodetection ((111)In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging ((165)Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). RESULTS: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging ((165)Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the intracellular distribution. In vivo biodistribution patterns obtained with ICP-MS ((165)Ho) and radiodetection ((111)In) of the hybrid peptide were shown to be similar. Assessment of tracer distribution in excised tissues revealed the location of tracer uptake with both LA-ICP-MS-imaging and fluorescence imaging. CONCLUSION: Lanthanide-isotope chelation expands the scope of fluorescent/radioactive hybrid tracers to include MS-based analytical tools such as mass-cytometry, ICP-MS and LA-ICP-MS imaging in molecular pathology. In contradiction to common expectations, MS detection using a single chelate imaging agent was shown to be feasible, enabling a direct link between nuclear medicine-based imaging and theranostic methods. PMID: 28255355 [PubMed - in process]

Related Articles Multilevel pharmacokinetics-driven modeling of metabolomics data. Metabolomics. 2017;13(3):31 Authors: Daghir-Wojtkowiak E, Wiczling P, Waszczuk-Jankowska M, Kaliszan R, Markuszewski MJ Abstract INTRODUCTION: Multilevel modeling is a quantitative statistical method to investigate variability and relationships between variables of interest, taking into account population structure and dependencies. It can be used for prediction, data reduction and causal inference from experiments and observational studies allowing for more efficient elucidation of knowledge. OBJECTIVES: In this study we introduced the concept of multilevel pharmacokinetics (PK)-driven modelling for large-sample, unbalanced and unadjusted metabolomics data comprising nucleoside and creatinine concentration measurements in urine of healthy and cancer patients. METHODS: A Bayesian multilevel model was proposed to describe the nucleoside and creatinine concentration ratio considering age, sex and health status as covariates. The predictive performance of the proposed model was summarized via area under the ROC, sensitivity and specificity using external validation. RESULTS: Cancer was associated with an increase in methylthioadenosine/creatinine excretion rate by a factor of 1.42 (1.09-2.03) which constituted the highest increase among all nucleosides. Age influenced nucleosides/creatinine excretion rates for all nucleosides in the same direction which was likely caused by a decrease in creatinine clearance with age. There was a small evidence of sex-related differences for methylthioadenosine. The individual a posteriori prediction of patient classification as area under the ROC with 5th and 95th percentile was 0.57(0.5-0.67) with sensitivity and specificity of 0.59(0.42-0.76) and 0.57(0.45-0.7), respectively suggesting limited usefulness of 13 nucleosides/creatinine urine concentration measurements in predicting disease in this population. CONCLUSION: Bayesian multilevel pharmacokinetics-driven modeling in metabolomics may be useful in understanding the data and may constitute a new tool for searching towards potential candidates of disease indicators. PMID: 28255294 [PubMed - in process]