PubMed

Related Articles Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts. PLoS One. 2017;12(3):e0173078 Authors: Friedrich N, Pietzner M, Cannet C, Thuesen BH, Hansen T, Wallaschofski H, Grarup N, Skaaby T, Budde K, Pedersen O, Nauck M, Linneberg A Abstract BACKGROUND: Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH). METHODS: Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function. RESULTS: Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values. CONCLUSION: The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research. PMID: 28253303 [PubMed - in process]

Related Articles Chronic effects of copper in oysters Crassostrea hongkongensis under different exposure regimes by NMR-based metabolomics. Environ Toxicol Chem. 2017 Mar 02;: Authors: Cao C, Wang WX Abstract Traditional metal toxicity tests on organisms mainly focused on the continuous exposure at a fixed concentration. However, organisms are more likely exposed to pollutants intermittently in estuarine environments which are significantly impacted by the anthropogenic activity. This study examined whether different copper (Cu) exposure regimes at an equivalent dose can induce different metabolomics effects on the oysters. An estuarine oyster Crassostrea hongkongensis was exposed to Cu continuously or intermittently at an equal dose (time × concentration) for six weeks. Continuous exposure regimes included two doses of 3.3 µg/L-24 h and 20 µg/L-24 h, with the corresponding equal doses of two intermittent exposure regimes of 20 µg/L-4 h, 120 µg/L-4 h, respectively. Time-course measurements suggested that Cu bioaccumulation was comparable at equal low dose between continuous regime (3.3 µg/L-24h) and intermittent regime (20 µg/L-4h), but there was considerable difference for the high dose at different regimes. NMR-based metabolomics suggested that continuous and intermittent Cu exposures led to much similar metabolite variation pattern in gills at an equal high dose, including decreased amino acids (e.g., aspartate, glycine, isoleucine, leucine, lysine, phenylalanine, threonine and valine), lower energy related compounds (e.g., ATP/ADP, acetate, citrate and glycogen) and altered osmolytes (e.g., homarine and taurine). These biomarkers indicated the disturbance of osmotic regulation and energy metabolism induced by Cu exposure regardless of regimes. Besides, the 4-h intermittent Cu exposure resulted in slightly less adverse effects when compared with the corresponding equal-dose continuous exposure. Oysters appeared to recover during the intervals of Cu exposure. Our results indicated that metabolomics effects induced by Cu were more dose-dependent than the Cu exposure regime. This article is protected by copyright. All rights reserved. PMID: 28252223 [PubMed - as supplied by publisher]

Related Articles Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia. Sci Rep. 2016 Apr 14;6:24383 Authors: JianXin C, Xue X, ZhongFeng L, Kuo G, FeiLong Z, ZhiHong L, Xian W, HongCai S Abstract Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. (1)H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID: 27075394 [PubMed - indexed for MEDLINE]

Related Articles Global metabolic profiling for the study of Rhizoma Paridis saponins-induced hepatotoxicity in rats. Environ Toxicol. 2017 Jan;32(1):99-108 Authors: Man S, Qiu P, Li J, Zhang L, Gao W Abstract Rhizoma Paridis saponins (RPS) is a traditional Chinese medicine (TCM) from the plant Paris polyphylla var. yunnanensis (Fr.) Hand.-Mazz. Despite its potentially clinical utility such as anticancer and anti-inflammation, it has slight side effects and toxicity as previous report. In this work, 90-day administration of RPS induced liver injury. (1) H-NMR- and GC/MS-based metabonomic analyses in conjunction with histopathological examinations, blood biochemistry and hepatic phase I and II enzymes assays were performed to evaluate the toxic mechanisms of RPS induced in rats. As a result, oral administration of RPS possessed certain liver toxicity in SD rats. (1) H-NMR and GC/MS data indicated that RPS inhibited the oxidation of fatty acids, glycolysis, and TCA cycle pathway, and disturbed glycine, serine, and threonine metabolism. Low expression of TG, T-CHO, and LDL-C and high levels of ALT and AST indicated that chronic exposure to RPS caused hepatocyte damage, synthesis dysfunction, and transportation failure of lipoproteins. In addition, RPS downregulated the mRNA levels of CYP1A2, CYP2E1, and UGTs. In conclusion, we used metabonomics approach to study the toxicity of RPS for the first time. This research demonstrated that metabonomics method was a promising tool to study and diagnose TCM-induced toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 99-108, 2017. PMID: 26590097 [PubMed - indexed for MEDLINE]

Related Articles Simultaneous quantification of estrogens, their precursors and conjugated metabolites in human breast cancer cells by LC-HRMS without derivatization. J Pharm Biomed Anal. 2017 Feb 22;138:344-350 Authors: Poschner S, Zehl M, Maier-Salamon A, Jäger W Abstract Liquid chromatography-mass spectrometry (LC-MS) is the state of the art technique for quantification of steroid hormones. Currently used methods are typically limited by the need of pre-column derivatization to increase ionization efficiency; however, this causes hydrolysis of conjugated metabolites. Our newly established LC-HRMS method is able to simultaneously quantify conjugated and unconjugated steroids without prior derivatization using deuterated internal standards and solid-phase extraction. This assay was validated according to ICH Q2(R1) guidelines for the analysis of the 10 main steroids of the estrogenic pathway, namely 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA), DHEA-3-sulfate, estrone, 17β-estradiol, estriol (16α-OH-17β-estradiol), estrone-3-sulfate, 17β-estradiol-3-(β-d-glucuronide), 17β-estradiol-3-sulfate and testosterone. Assay performance characteristics were excellent with results for accuracy (98.8-101.2%), precision (mean: 2.05%, all ≤2.80%), stability over five freeze-thaw-cycles (95.7-100.4%) and SPE accuracy (96.9-102.0%), as well as suitable lower and upper limits of quantification for cell culture experiments (LLOQ 0.005-2ng/ml, ULOQ 3-2000ng/ml). Furthermore, we demonstrated the functionality of our method for the monitoring of steroid levels in the human breast cancer cell line MCF-7. This sensitive assay allows for the first time detailed investigations on estrogen metabolomics in breast cancer cells and may also apply to other estrogen-dependent tumor entities. PMID: 28249239 [PubMed - as supplied by publisher]

Related Articles PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis. Nat Commun. 2017 Mar 01;8:14609 Authors: Hirabayashi T, Anjo T, Kaneko A, Senoo Y, Shibata A, Takama H, Yokoyama K, Nishito Y, Ono T, Taya C, Muramatsu K, Fukami K, Muñoz-Garcia A, Brash AR, Ikeda K, Arita M, Akiyama M, Murakami M Abstract Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1(-/-) epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1(-/-) keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects. PMID: 28248300 [PubMed - in process]

Related Articles The Proteome of the Red Blood Cell: An Auspicious Source of New Insights into Membrane-Centered Regulation of Homeostasis. Proteomes. 2016 Nov 25;4(4): Authors: Bosman GJ Abstract During the past decade, the hand-in-hand development of biotechnology and bioinformatics has enabled a view of the function of the red blood cell that surpasses the supply of oxygen and removal of carbon dioxide. Comparative proteomic inventories have yielded new clues to the processes that regulate membrane-cytoskeleton interactions in health and disease, and to the ways by which red blood cells communicate with their environment. In addition, proteomic data have revealed the possibility that many, hitherto unsuspected, metabolic processes are active in the red blood cell cytoplasm. Recent metabolomic studies have confirmed and expanded this notion. Taken together, the presently available data point towards the red blood cell membrane as the hub at which all regulatory processes come together. Thus, alterations in the association of regulatory proteins with the cell membrane may be a sine qua non for the functional relevance of any postulated molecular mechanism. From this perspective, comparative proteomics centered on the red blood cell membrane constitute a powerful tool for the identification and elucidation of the physiologically and pathologically relevant pathways that regulate red blood cell homeostasis. Additionally, this perspective provides a focus for the interpretation of metabolomic studies, especially in the development of biomarkers in the blood. PMID: 28248245 [PubMed - in process]

Related Articles "Omics"-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives. Proteomes. 2016 Sep 12;4(3): Authors: Matthews H, Hanison J, Nirmalan N Abstract The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the "data-heavy" outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences-genomics, transcriptomics, proteomics and metabolomics-have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process. PMID: 28248238 [PubMed - in process]

Related Articles Omics Approaches for the Study of Adaptive Immunity to Staphylococcus aureus and the Selection of Vaccine Candidates. Proteomes. 2016 Mar 07;4(1): Authors: Holtfreter S, Kolata J, Stentzel S, Bauerfeind S, Schmidt F, Sundaramoorthy N, Bröker BM Abstract Staphylococcus aureus is a dangerous pathogen both in hospitals and in the community. Due to the crisis of antibiotic resistance, there is an urgent need for new strategies to combat S. aureus infections, such as vaccination. Increasing our knowledge about the mechanisms of protection will be key for the successful prevention or treatment of S. aureus invasion. Omics technologies generate a comprehensive picture of the physiological and pathophysiological processes within cells, tissues, organs, organisms and even populations. This review provides an overview of the contribution of genomics, transcriptomics, proteomics, metabolomics and immunoproteomics to the current understanding of S. aureus‑host interaction, with a focus on the adaptive immune response to the microorganism. While antibody responses during colonization and infection have been analyzed in detail using immunoproteomics, the full potential of omics technologies has not been tapped yet in terms of T-cells. Omics technologies promise to speed up vaccine development by enabling reverse vaccinology approaches. In consequence, omics technologies are powerful tools for deepening our understanding of the "superbug" S. aureus and for improving its control. PMID: 28248221 [PubMed - in process]

Related Articles Fradiamine A, a new siderophore from the deep-sea actinomycete Streptomyces fradiae MM456M-mF7. J Antibiot (Tokyo). 2017 Mar 01;: Authors: Takehana Y, Umekita M, Hatano M, Kato C, Sawa R, Igarashi M Abstract New bioactive substances were identified from several marine actinomycetes strains by LC-HRESI-MS based non-targeted metabolomics. A new siderophore and its derivative, named fradiamines A and B, were isolated from the extract of the deep-sea actinomycetes Streptomyces fradiae MM456M-mF7 by Diaion CHP-20P, Sephadex LH-20 column chromatography and HPLC. Fradiamine A was a new compound, but fradiamine B was previously patented as a sweetness enhancer. Their structures were determined by NMR and LC-HRESI-MS/MS analysis. Fradiamines A and B contained two alkyl amines asymmetrically bonded to citrate, a type of structure derived from actinomycetes and other bacteria and rarely observed in siderophores. Fradiamines A and B showed moderate antibiotic activity against Clostridium difficile with IC50 values of 32 and 8 μg ml(-1), respectively.The Journal of Antibiotics advance online publication, 1 March 2017; doi:10.1038/ja.2017.26. PMID: 28246378 [PubMed - as supplied by publisher]

Related Articles Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis. Am J Physiol Endocrinol Metab. 2017 Feb 28;:ajpendo.00464.2016 Authors: Ferrannini E, Iervasi G, Cobb J, Ndreu R, Nannipieri M Abstract While hyper/hypothyroidism causes dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) followed up for 3 years, we measured insulin sensitivity (by the insulin clamp technique) and a panel of 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) there emerged most features of IR (male sex, higher BMI, waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides levels, reduced insulin-mediated glucose disposal and ß-cell glucose sensitivity). In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity and, in a subset of 303 subjects, directly related to endogenous glucose production. In multiple regression models adjusting for sex, age, BMI and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of the decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, ß-cell glucose sensitivity and baseline glycemia. Serum tyrosine levels were higher in IR and were directly associated with fT3; higher α-hydroxybutyrate levels signaled enhanced oxidative stress impairing tyrosine degradation. In 25 morbidly obese patients, surgery-induced weight loss improved IR and consensually lowered fT3 High-normal fT3 levels are associated with IR both cross-sectionally and longitudinally, and predict deterioration of glucose tolerance. This association is supported by a metabolite pattern that points at increased oxidative stress as part of the IR syndrome. PMID: 28246105 [PubMed - as supplied by publisher]

Related Articles Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice. PLoS One. 2017;12(2):e0172912 Authors: den Hartigh LJ, Wang S, Goodspeed L, Wietecha T, Houston B, Omer M, Ogimoto K, Subramanian S, Gowda GA, O'Brien KD, Kaiyala KJ, Morton GJ, Chait A Abstract BACKGROUND: Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. OBJECTIVE: We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. METHODS: Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss. Metabolic endpoints such as energy expenditure, glucose and insulin tolerance testing, and trunk fat distribution were measured. RESULTS: By design, 10,12 CLA and CR caused equivalent weight loss, with greater fat loss by 10,12 CLA accompanied by increased energy expenditure, reduced respiratory quotient, increased fat oxidation, accumulation of alternatively activated macrophages, and browning of subcutaneous white adipose tissue (WAT). Moreover, 10,12 CLA-supplemented mice better defended their body temperature against a cold challenge. However, 10,12 CLA concurrently induced the detrimental loss of subcutaneous WAT without reducing visceral WAT, promoted reduced plasma and WAT adipokine levels, worsened hepatic steatosis, and failed to improve glucose metabolism. Obese mice undergoing CR were protected from subcutaneous-specific fat loss, had improved hepatic steatosis, and subsequently showed the expected improvements in WAT adipokines, glucose metabolism and WAT inflammation. CONCLUSIONS: These results suggest that 10,12 CLA mediates the preferential loss of subcutaneous fat that likely contributes to hepatic steatosis and maintained insulin resistance, despite significant weight loss and WAT browning in mice. Collectively, we have shown that weight loss due to 10,12 CLA supplementation or CR results in dramatically different metabolic phenotypes, with the latter promoting a healthier form of weight loss. PMID: 28245284 [PubMed - in process]

Related Articles Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses. PLoS One. 2017;12(2):e0173069 Authors: Benevenuto RF, Agapito-Tenfen SZ, Vilperte V, Wikmark OG, van Rensburg PJ, Nodari RO Abstract Some genetically modified (GM) plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA) analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses. PMID: 28245233 [PubMed - in process]

Related Articles Impact of the Pd2Spermine chelate on osteosarcoma metabolism: an NMR metabolomics study. J Proteome Res. 2017 Feb 28;: Authors: Lamego I, Marques MP, Duarte IF, Martins AS, Oliveira H, Gil AM Abstract A metabolomics study of Pd2Spermine(Spm) on osteosarcoma MG-63 and osteoblastic HOb cells is presented, to assess the impact of the potential palladium drug on cell metabolism compared to cisplatin (cDDP). In spite of its higher cytotoxicity, Pd2Spm induced lower (and reversible) metabolic impact in MG-63 cells and absence of apoptosis; conversely, it induced significant deviations in osteoblastic amino acid metabolism. However, when in combination with doxorubicin and methotrexate, Pd2Spm induced strong metabolic deviations on lipids, choline compounds, amino acids, nucleotides and compounds related to antioxidative mechanisms (e.g. glutathione, inositol, hypoxanthine), similarly to the cDDP cocktail. Synergetic effects included triggering of lipid biosynthesis by Pd2Spm in the presence of doxorubicin (and reinforced by methotrexate) and changes in the glycosylation substrate uridine diphosphate acetylgalactosamine and methionine and serine metabolisms. This work provides promising results relating to the impact of Pd2Spm on osteosarcoma cellular metabolism, particularly in drug combination protocols. Lipid metabolism, glycosylation and amino acid metabolisms emerge as relevant features for targeted studies to further understand a potential anti-cancer mechanism of combined Pd2Spm. PMID: 28244322 [PubMed - as supplied by publisher]

Related Articles Early Effect of Amyloid β-Peptide on Hippocampal and Serum Metabolism in Rats Studied by an Integrated Method of NMR-Based Metabolomics and ANOVA-Simultaneous Component Analysis. Biomed Res Int. 2017;2017:3262495 Authors: Du Y, Zheng H, Xia H, Zhao L, Hu W, Bai G, Yan Z, Gao H Abstract Amyloid β (Aβ) deposition has been implicated in the pathogenesis of Alzheimer's disease. However, the early effect of Aβ deposition on metabolism remains unclear. In the present study, thus, we explored the metabolic changes in the hippocampus and serum during first 2 weeks of Aβ25-35 injection in rats by using an integrated method of NMR-based metabolomics and ANOVA-simultaneous component analysis (ASCA). Our results show that Aβ25-35 injection, time, and their interaction had statistically significant effects on the hippocampus and serum metabolome. Furthermore, we identified key metabolites that mainly contributed to these effects. After Aβ25-35 injection from 1 to 2 weeks, the levels of lactate, N-acetylaspartate, creatine, and taurine were decreased in rat hippocampus, while an increase in lactate and decreases in LDL/VLDL and glucose were observed in rat serum. Therefore, we suggest that the reduction in energy and lipid metabolism as well as an increase in anaerobic glycolysis may occur at the early stage of Aβ25-35 deposition. PMID: 28243597 [PubMed - in process]

Related Articles Metabolomic analysis of human oral cancer cells with adenylate kinase 2 or phosphorylate glycerol kinase 1 inhibition. J Cancer. 2017;8(2):298-304 Authors: Ji EH, Cui L, Yuan X, Cheng S, Messadi D, Yan X, Hu S Abstract The purpose of this study was to use liquid chromatography-mass spectrometry (LC-MS) with XCMS for a quantitative metabolomic analysis of UM1 and UM2 oral cancer cells after knockdown of metabolic enzyme adenylate kinase 2 (AK2) or phosphorylate glycerol kinase 1 (PGK1). UM1 and UM2 cells were initially transfected with AK2 siRNA, PGK1 siRNA or scrambled control siRNA, and then analyzed with LC-MS for metabolic profiles. XCMS analysis of the untargeted metabolomics data revealed a total of 3200-4700 metabolite features from the transfected UM1 or UM2 cancer cells and 369-585 significantly changed metabolites due to AK2 or PGK1 suppression. In addition, cluster analysis showed that a common group of metabolites were altered by AK2 knockdown or by PGK1 knockdown between the UM1 and UM2 cells. However, the set of significantly changed metabolites due to AK2 knockdown was found to be distinct from those significantly changed by PGK1 knockdown. Our study has demonstrated that LC-MS with XCMS is an efficient tool for metabolomic analysis of oral cancer cells, and knockdown of different genes results in distinct changes in metabolic phenotypes in oral cancer cells. PMID: 28243334 [PubMed - in process]

Related Articles The Role of Sarcosine, Uracil, and Kynurenic Acid Metabolism in Urine for Diagnosis and Progression Monitoring of Prostate Cancer. Metabolites. 2017 Feb 23;7(1): Authors: Gkotsos G, Virgiliou C, Lagoudaki I, Sardeli C, Raikos N, Theodoridis G, Dimitriadis G Abstract The aim of this pilot study is to evaluate sarcosine, uracil, and kynurenic acid in urine as potential biomarkers in prostate cancer detection and progression monitoring. Sarcosine, uracil, and kynurenic acid were measured in urine samples of 32 prostate cancer patients prior to radical prostatectomy, 101 patients with increased prostate-specific antigen prior to ultrasonographically-guided prostatic biopsy collected before and after prostatic massage, and 15 healthy volunteers (controls). The results were related to histopathologic data, Gleason score, and PSA (Prostate Specific Antigen). Metabolites were measured after analysis of urine samples with Ultra-High Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) instrumentation. Multivariate, nonparametric statistical tests including receiver operating characteristics analyses, one-way analysis of variance (Kruskal-Wallis test), parametric statistical analysis, and Pearson correlation, were performed to evaluate diagnostic performance. Decreased median sarcosine and kynurenic acid and increased uracil concentrations were observed for patients with prostate cancer compared to participants without malignancy. Results showed that there was no correlation between the concentration of the studied metabolites and the cancer grade (Gleason score <7 vs. ≥7) and the age of the patients. Evaluation of biomarkers by ROC (Receiving Operating Characteristics) curve analysis showed that differentiation of prostate cancer patients from participants without malignancy was not enhanced by sarcosine or uracil levels in urine. In contrast to total PSA values, kynurenic acid was found a promising biomarker for the detection of prostate cancer particularly in cases where collection of urine samples was performed after prostatic massage. Sarcosine and uracil in urine samples of patients with prostate cancer were not found as significant biomarkers for the diagnosis of prostate cancer. None of the three metabolites can be used reliably for monitoring the progress of the disease. PMID: 28241496 [PubMed - in process]

Related Articles Impact of Exercise and Aging on Rat Urine and Blood Metabolome. An LC-MS Based Metabolomics Longitudinal Study. Metabolites. 2017 Feb 23;7(1): Authors: Deda O, Gika HG, Taitzoglou I, Raikos Ν, Theodoridis G Abstract Aging is an inevitable condition leading to health deterioration and death. Regular physical exercise can moderate the metabolic phenotype changes of aging. However, only a small number of metabolomics-based studies provide data on the effect of exercise along with aging. Here, urine and whole blood samples from Wistar rats were analyzed in a longitudinal study to explore metabolic alterations due to exercise and aging. The study comprised three different programs of exercises, including a life-long protocol which started at the age of 5 months and ended at the age of 21 months. An acute exercise session was also evaluated. Urine and whole blood samples were collected at different time points and were analyzed by LC-MS/MS (Liquid Chromatography-tandem Mass Spectrometry). Based on their metabolic profiles, samples from trained and sedentary rats were differentiated. The impact on the metabolome was found to depend on the length of exercise period with acute exercise also showing significant changes. Metabolic alterations due to aging were equally pronounced in sedentary and trained rats in both urine and blood analyzed samples. PMID: 28241477 [PubMed - in process]

Related Articles Metabolic Profiling as a Screening Tool for Cytotoxic Compounds: Identification of 3-Alkyl Pyridine Alkaloids from Sponges Collected at a Shallow Water Hydrothermal Vent Site North of Iceland. Mar Drugs. 2017 Feb 22;15(2): Authors: Einarsdottir E, Magnusdottir M, Astarita G, Köck M, Ögmundsdottir HM, Thorsteinsdottir M, Rapp HT, Omarsdottir S, Paglia G Abstract Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens. PMID: 28241423 [PubMed - in process]

Related Articles Bioprospecting of Turbinaria Macroalgae as a Potential Source of Health Protective Compounds. Chem Biodivers. 2017 Feb;14(2): Authors: Stranska-Zachariasova M, Kurniatanty I, Gbelcova H, Jiru M, Rubert J, Nindhia TG, D'Acunto CW, Sumarsono SH, Tan MI, Hajslova J, Ruml T Abstract The present study aims to focus on the bioprospecting of marine macroalgae of Turbinaria species, plenteous biomass of the world ocean. Three types of solvents, i.e., H2 O, MeOH/H2 O (80:20, v/v) and hexane/i-PrOH (50:50, v/v), were used for extraction. Both the biological activity and the pattern of present chemicals were characterized. For the cell proliferation assay, the human embryonic kidney 293 cells, cervix/breast/pancreatic adenocarcinoma, and osteosarcoma cells were used. For the antioxidant activity determination, both intracellular assay with human embryonic kidney and cervix adenocarcinoma cells, as well as the biochemical DPPH test, were employed. To complete the information about macroalgae composition, organic compounds were characterized by the liquid chromatography coupled with high resolution tandem mass spectrometry. Attention was concentrated mainly on the lipidomic profile characterization. In spite the fact that any significant antiproliferative effect was not observed for cancer cells, both the Turbinaria species were shown to be good protectors against the oxidative stress of the non-cancer cells. Most of the antioxidants were determined in the hexane/i-PrOH extract. As regards the lipids identified, most of them belonged to the triacylglycerols followed by sphingomyelins, diacylglycerols, and polar (lyso)phospholipids. Additionally to fatty acids with 14, 16 and 18 carbons, also those with odd carbon numbers were frequently present. PMID: 27936316 [PubMed - indexed for MEDLINE]