PubMed

Related Articles High resolution metabolomics to discriminate compounds in serum of male lung cancer patients in South Korea. Respir Res. 2016;17(1):100 Authors: Pamungkas AD, Park C, Lee S, Jee SH, Park YH Abstract BACKGROUND: The cancer death rate escalated during 20th century. In South Korea, lung cancer is expected to contribute 12,736 deaths in men, the highest amount among all cancers. Several risk factors may increase the chance to acquiring lung cancer, with mostly related to exogenous compounds found in cigarette smoke and synthetic manufacturing materials. As the mortality rate of lung cancer increases, deeper understanding is necessary to explore risk factors that may lead to this malignancy. In this regard, this study aims to apply high resolution metabolomics (HRM) using LC-MS to detect significant compounds that might contribute in inducing lung cancer and find the correlation of these compounds to the subjects' smoking habit. METHODS: The comparison was made between healthy control and lung cancer groups for metabolic differences. Further analyses to determine if these differences are related to tobacco-induced lung cancer (past-smoker control vs. past-smoker lung cancer patients (LCPs) and non-smoker control vs. current-smoker LCPs) were selected. The univariate analysis was performed, including a false discovery rate (FDR) of q = 0.05, to determine the significant metabolites between the analyses. Hierarchical clustering analysis (HCA) was done to discriminate metabolites between the control and case subjects. Selected compounds based on significant m/z features of human serum then experienced MS/MS examination, showing that for many m/z, the patterns of ion dissociation matched with standards. Then, the significant metabolites were identified using Metlin database and features were mapped on the human metabolic pathway mapping tool of the Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Using metabolomics-wide association studies, metabolic changes were observed among control group and lung cancer patients. Bisphenol A (211.11, [M + H-H2O](+)), retinol (287.23, [M + H](+)) and L-proline (116.07, [M + H](+)) were among the significant compounds found to have contributed in the discrimination between these groups, suggesting that these compounds might be related in the development of lung cancer. Retinol has been seen to have a correlation with smoking while both bisphenol A and L-proline were found to be unrelated. CONCLUSIONS: Two potential biomarkers, retinol and L-proline, were identified and these findings may create opportunities for the development of new lung cancer diagnostic tools. PMID: 27506545 [PubMed - in process]

Related Articles Software-assisted serum metabolite quantification using NMR. Anal Chim Acta. 2016 Aug 31;934:194-202 Authors: Jung YS, Hyeon JS, Hwang GS Abstract The goal of metabolomics is to analyze a whole metabolome under a given set of conditions, and accurate and reliable quantitation of metabolites is crucial. Absolute concentration is more valuable than relative concentration; however, the most commonly used method in NMR-based serum metabolic profiling, bin-based and full data point peak quantification, provides relative concentration levels of metabolites and are not reliable when metabolite peaks overlap in a spectrum. In this study, we present the software-assisted serum metabolite quantification (SASMeQ) method, which allows us to identify and quantify metabolites in NMR spectra using Chenomx software. This software uses the ERETIC2 utility from TopSpin to add a digitally synthesized peak to a spectrum. The SASMeQ method will advance NMR-based serum metabolic profiling by providing an accurate and reliable method for absolute quantification that is superior to bin-based quantification. PMID: 27506360 [PubMed - in process]

Related Articles Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening. Anal Chim Acta. 2016 Aug 31;934:186-93 Authors: Shao X, Gao D, Chen Y, Jin F, Hu G, Jiang Y, Liu H Abstract Since most of the central nervous system (CNS) drug candidates show poor permeability across the blood-brain barrier (BBB), development of a reliable platform for permeability assay will greatly accelerate drug discovery. Herein, we constructed a microfluidic BBB model to mimic drug delivery into the brain to induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties, human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured in a membrane-based microchannel. Sunitinib, a model drug, was then delivered into the microchannel and forced to permeate through the BBB model. The permeated amount was directly quantified by an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) after on-chip SPE (μSPE) pretreatment. Moreover, the permeated drug was incubated with glioma cells (U251) cultured inside agarose gel in the downstream to investigate drug-induced cytotoxicity. The resultant permeability of sunitinib was highly correlated with literature reported value, and it only required 30 min and 5 μL of sample solution for each permeation experiment. Moreover, after 48 h of treatment, the survival rate of U251 cells cultured in 3D scaffolds was nearly 6% higher than that in 2D, which was in accordance with the previously reported results. These results demonstrate that this platform provides a valid tool for drug permeability and cytotoxicity assays which have great value for the research and development of CNS drugs. PMID: 27506359 [PubMed - in process]

Related Articles cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells. PLoS Pathog. 2016 Apr;12(4):e1005546 Authors: Paijo J, Döring M, Spanier J, Grabski E, Nooruzzaman M, Schmidt T, Witte G, Messerle M, Hornung V, Kaever V, Kalinke U Abstract Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID: 27058035 [PubMed - indexed for MEDLINE]

Related Articles In vitro fermentation of lupin seeds (Lupinus albus) and broad beans (Vicia faba): dynamic modulation of the intestinal microbiota and metabolomic output. Food Funct. 2015 Oct;6(10):3316-22 Authors: Gullón P, Gullón B, Tavaria F, Vasconcelos M, Gomes AM Abstract Broad beans (Vicia faba) and lupin seeds (Lupinus albus) are legumes rich in a wide range of compounds, which may represent a useful dietary approach for modulating the human gut microbiome. In this work, after in vitro digestion, legume samples were used as carbon sources in anaerobic batch cultures to evaluate their impact on the intestinal microbiota composition and on their metabolic products. The fermentations were monitored by a decrease in pH, generation of short chain fatty acids (SCFA) and lactate and the changes in the dynamic bacterial populations by fluorescence in situ hybridization (FISH). The total SCFA at the end of fermentation was 81.52 mM for lupin seeds and 78.41 mM for broad beans accompanied by a decrease of the pH for both legumes. The microbial groups that increased significantly (P < 0.05) were Bifidobacterium spp., Lactobacillus-Enterococcus, Atopobium, Bacteroides-Pretovella, Clostridium coccoides-Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis. This impact on the intestinal microbiota suggests that lupin seeds and broad beans may be used in the development of novel functional foods, which can be included in dietary strategies for human health promotion. PMID: 26252418 [PubMed - indexed for MEDLINE]

Related Articles Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population. Sci Rep. 2015;5:11918 Authors: Yamakado M, Nagao K, Imaizumi A, Tani M, Toda A, Tanaka T, Jinzu H, Miyano H, Yamamoto H, Daimon T, Horimoto K, Ishizaka Y Abstract Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals' future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population. PMID: 26156880 [PubMed - indexed for MEDLINE]

Related Articles Use of NMR-Based Metabolomics to Chemically Characterize the Roasting Process of Chicory Root. J Agric Food Chem. 2016 Aug 9; Authors: Wei F, Furihata K, Zhang M, Miyakawa T, Tanokura M Abstract Roasted chicory root (Cichorium intybus) has been widely accepted as the most important coffee substitute. In this study, a nuclear magnetic resonance (NMR)-based comprehensive analysis was performed to monitor the substantial changes in the composition of chicory root during the roasting process. A detailed signal assignment of dried raw and roasted chicory roots was carried out using (1)H, (13)C, (1)H-(1)H DQF-COSY, (1)H-(13)C edited-HSQC, (1)H-(13)C CT-HMBC and (1)H-(13)C HSQC-TOCSY NMR spectra. On the basis of the signal assignments, 36 NMR-visible components were monitored simultaneously during roasting. Inulins, sucrose and most of the amino acids were largely degraded during the roasting process, while monosaccharides decreased at the beginning and then increased until the dark roasting stage. Acetamide, 5-hydroxymethylfurfural, di-D-fructose dianhydride and norfuraneol were newly formed during roasting. Furthermore, score plot of principal component analysis indicated that similar chemical composition profiles could be achieved by roasting the chicory root either at a higher firepower for a shorter time or at a lower firepower for a longer time. PMID: 27504711 [PubMed - as supplied by publisher]

Related Articles Metabolomics driven analysis of Erythrina lysistemon cell suspension culture in response to methyl jasmonate elicitation. J Adv Res. 2016 Sep;7(5):681-9 Authors: Farag MA, Mekky H, El-Masry S Abstract An MS-based metabolomic approach was used to profile the secondary metabolite of the ornamental plant Erythrina lysistemon via ultra-performance liquid chromatography coupled to photodiode array detection and high resolution q-TOF mass spectrometry (UPLC-PDA-MS). Cultures maintained the capacity to produce E. lysistemon flavonoid subclasses with pterocarpans amounting for the most abundant ones suggesting that it could provide a resource of such flavonoid subclass. In contrast, alkaloids, major constituents of Erythrina genus, were detected at trace levels in suspension cultures. Methyl jasmonate (MeJA), phytohormone, was further supplied to culture with the aim of increasing secondary metabolites production and with metabolite profiles subjected to multivariate data analysis to evaluate its effect. Results revealed that triterpene i.e. oleanolic acid and fatty acid i.e. hydroxy-octadecadienoic acid were elicited in response to methyl jasmonate, whereas pterocarpans i.e., isoneorautenol showed a decline in response to elicitation suggesting for the induction of terpenoid biosynthetic pathway and concurrent with a down regulation of pterocarpans. In conclusion, a total of 53 secondary metabolites including 3 flavones, 12 isoflavones, 4 isoflavanones, 4 alkaloids, 11 pterocarpans, and 5 phenolic acids were identified. PMID: 27504198 [PubMed]

Related Articles Epigenetics and nutrition-related epidemics of metabolic diseases: Current perspectives and challenges. Food Chem Toxicol. 2016 Aug 5; Authors: Hernández-Aguilera A, Fernández-Arroyo S, Cuyàs E, Luciano-Mateo F, Cabre N, Camps J, Lopez-Miranda J, Menendez JA, Joven J Abstract We live in a world fascinated by the relationship between disease and nutritional disequilibrium. The subtle and slow effects of chronic nutrient toxicity are a major public health concern. Since food is potentially important for the development of "metabolic memory", there is a need for more information on the type of nutrients causing adverse or toxic effects. We now know that metabolic alterations produced by excessive intake of some nutrients, drugs and chemicals directly impact epigenetic regulation. We envision that understanding how metabolic pathways are coordinated by environmental and genetic factors will provide novel insights for the treatment of metabolic diseases. New methods will enable the assembly and analysis of large sets of complex molecular and clinical data for understanding how inflammation and mitochondria affect bioenergetics, epigenetics and health. Collectively, the observations we highlight indicate that energy utilization and disease are intimately connected by epigenetics. The challenge is to incorporate metabolo-epigenetic data in better interpretations of disease, to expedite therapeutic targeting of key pathways linking nutritional toxicity and metabolism. An additional concern is that changes in the parental phenotype are detectable in the methylome of subsequent offspring. The effect might create a menace to future generations and preconceptional considerations. PMID: 27503834 [PubMed - as supplied by publisher]

Related Articles 1H NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease. J Proteome Res. 2016 Aug 9; Authors: Ruiz-Rodado V, Nicoli ER, Probert F, Smith DA, Morris L, Wassif CA, Platt FM, Grootveld M Abstract BACKGROUND/AIMS: Clinical manifestations of Niemann Pick type-C1 (NP-C1) disease include neonatal hepatosplenomegaly, and in some patients progressive liver dysfunction and failure. This study involved a 1H-NMR linked metabolomics analysis of liver samples collected from a NP-C1 disease mutant mouse model in order to explore time-dependent imbalances in metabolic pathways associated with NP-C1 liver dysfunction, including fibrosis. METHODS: NP-C1 mutant (Npc1-/-; NP-C1), control (Npc1+/+; WT) and NP-C1 heterozygous mice (Npc1+/-; HET) were generated from heterozygote matings. Aqueous extracts of these liver samples collected at time-points of 3, 6, 9 and 11 weeks were subjected to high-resolution NMR analysis, and multivariate (MV) metabolomics analyses of datasets acquired were performed. RESULTS: A MV random forests (RFs) model effectively discriminated between the NP-C1 and a combined HC/HET hepatic NMR profiles with very high predictive accuracy and reliability. Key distinguishing features included significant upregulations in the hepatic concentrations of phenylalanine, tyrosine, glutamate, lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate and 3-hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that imbalances in tyrosine biosynthesis, hepatic phenylalanine, tyrosine, glutamate/glutamine and nicotinate/niacinamide metabolism were involved in the pathogenesis of NP-C1 disease-associated liver dysfunction/damage. CONCLUSIONS: 1H NMR-linked metabolomics analysis provides valuable biomarker information regarding hepatic dysfunction or damage in NP-C1 disease. PMID: 27503774 [PubMed - as supplied by publisher]

Related Articles Multi-Color Fluorescence Detection-Based Microfluidic Device for Single-Cell Metabolomics: Simultaneous Quantitation of Multiple Small Molecules in Primary Liver Cells. Anal Chem. 2016 Aug 8; Authors: Li Q, Chen P, Fan Y, Wang X, Xu K, Li L, Tang B Abstract Single-cell metabolomics can be used to study cell diversity and how cells respond to environment. There is an urgent need to develop effective detection methods for single-cell metabolomics. Microchip electrophoresis with laser-induced fluorescence detection (MCE-LIFD) is a powerful tool to detect metabolites at the single-cell level. However, the existing one-laser excitation and one-color fluorescence collection in MCE-LIFD is not sufficient for the simultaneous detection of multiple small molecules with wide variations in their fluorescence excitation and emission spectra. In this manuscript, we describe a multi-color fluorescence detection-based microfluidic device (MFD-MD) for single-cell metabolomics research. We selected primary liver cells from acute ethanol-stimulated mice as the model cells and hydrogen peroxide (H2O2), glutathione (GSH) and cysteine (Cys) as representative small-molecule metabolites for single-cell analysis. The microfluidic chip enabled accurate single-cell manipulation and effective electrophoresis separation. The new multi-color fluorescence detection permitted simultaneous analysis of H2O2, GSH and Cys. Ethanol exposure induced an increase in H2O2 and a decrease in GSH and Cys. Obvious cell heterogeneity was observed. These results provide insights regarding the intracellular oxidative/antioxidative molecular mechanism in response to external stimuli. The MFD-MD provides a new opportunity for simultaneous single-cell analysis of multiple metabolites. PMID: 27503398 [PubMed - as supplied by publisher]

Related Articles Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA. BMC Pregnancy Childbirth. 2016;16(1):212 Authors: Cecatti JG, Souza RT, Sulek K, Costa ML, Kenny LC, McCowan LM, Pacagnella RC, Villas-Boas SG, Mayrink J, Passini R, Franchini KG, Baker PN, Preterm SAMBA and SCOPE study groups Abstract BACKGROUND: Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identify clinical and metabolite predictors for preterm birth. These innovative and unbiased techniques might be a strategic key to advance spontaneous preterm birth prediction. METHODS/DESIGN: Preterm SAMBA study consists of a discovery phase to identify biophysical and untargeted metabolomics from blood and hair samples associated with preterm birth, plus a validation phase to evaluate the performance of the predictive modelling. The first phase, a case-control study, will randomly select 100 women who had a spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an international consortium aimed to identify potential metabolomic predictors using biophysical data and blood samples collected at 20 weeks of gestation. The validation phase will recruit 1150 Brazilian pregnant women from five participant centres and will collect blood and hair samples at 20 weeks of gestation to evaluate the performance of the algorithm model (sensitivity, specificity, predictive values and likelihood ratios) in predicting spontaneous preterm birth (before 34 weeks, with a secondary analysis of delivery before 37 weeks). DISCUSSION: The Preterm SAMBA study intends to step forward on preterm birth prediction using metabolomics techniques, and accurate protocols for sample collection among multi-ethnic populations. The use of metabolomics in medical science research is innovative and promises to provide solutions for disorders with multiple complex underlying determinants such as spontaneous preterm birth. PMID: 27503110 [PubMed - in process]

Related Articles Changes of primary and secondary metabolites in barley plants exposed to CdO nanoparticles. Environ Pollut. 2016 Aug 6; Authors: Večeřová K, Večeřa Z, Dočekal B, Oravec M, Pompeiano A, Tříska J, Urban O Abstract The environmental fate of airborne nanoparticles and their toxicity to plants is not yet fully understood. Pot-grown barley plants with second leaves developed were therefore exposed to CdO nanoparticles (CdONPs) of ecologically relevant size (7-60 nm) and concentration (2.03 ± 0.45 × 10(5) particles cm(-3)) in air for 3 weeks. An experiment was designed to test the effects of different treatments when only leaves (T1); leaves and soil substrate (T2); and leaves, soil, and water supply were exposed to nanoparticles (T3). A fourth, control group of plants was left without treatment (T0). Although CdONPs were directly absorbed by leaves from the air, a part of leaf-allocated Cd was also transported from roots by transpiration flow. Chromatographic assays revealed that CdONPs had a significant effect on total content of primary metabolites (amino acids and saccharides) but no significant effect on total content of secondary metabolites (phenolic compounds, Krebs cycle acids, and fatty acids). In addition, the compositions of individual metabolite classes were affected by CdONP treatment. For example, tryptophan and phenylalanine were the most affected amino acids in both analysed organs, while ferulic acid and isovitexin constituted the polyphenols most affected in leaves. Even though CdONP treatment had no effect on total fatty acids content, there were significant changes in the composition of saturated and unsaturated fatty acids in both the roots and leaves of treated plants. Although the results indicate the most pronounced effect in T3 plants as compared to T1 and T2 plants, even just leaf exposure to CdONPs has the potential to induce changes in plant metabolism. PMID: 27503055 [PubMed - as supplied by publisher]

Related Articles In-Depth Characterization and Validation of Human Urine Metabolomes Reveal Novel Metabolic Signatures of Lower Urinary Tract Symptoms. Sci Rep. 2016;6:30869 Authors: Hao L, Greer T, Page D, Shi Y, Vezina CM, Macoska JA, Marker PC, Bjorling DE, Bushman W, Ricke WA, Li L Abstract Lower urinary tract symptoms (LUTS) are a range of irritative or obstructive symptoms that commonly afflict aging population. The diagnosis is mostly based on patient-reported symptoms, and current medication often fails to completely eliminate these symptoms. There is a pressing need for objective non-invasive approaches to measure symptoms and understand disease mechanisms. We developed an in-depth workflow combining urine metabolomics analysis and machine learning bioinformatics to characterize metabolic alterations and support objective diagnosis of LUTS. Machine learning feature selection and statistical tests were combined to identify candidate biomarkers, which were statistically validated with leave-one-patient-out cross-validation and absolutely quantified by selected reaction monitoring assay. Receiver operating characteristic analysis showed highly-accurate prediction power of candidate biomarkers to stratify patients into disease or non-diseased categories. The key metabolites and pathways may be possibly correlated with smooth muscle tone changes, increased collagen content, and inflammation, which have been identified as potential contributors to urinary dysfunction in humans and rodents. Periurethral tissue staining revealed a significant increase in collagen content and tissue stiffness in men with LUTS. Together, our study provides the first characterization and validation of LUTS urinary metabolites and pathways to support the future development of a urine-based diagnostic test for LUTS. PMID: 27502322 [PubMed - in process]

Related Articles Dehydroepiandrosterone-Induced Changes in Mitochondrial Proteins Contribute to Phenotypic Alterations in Hepatoma Cells. Biochem Pharmacol. 2016 Aug 5; Authors: Cheng ML, Chi LM, Wu PR, Ho HY Abstract Dehydroepiandrosterone (DHEA)-induced growth arrest of hepatoma cells is associated with metabolic disturbance. Our previous study has suggested that DHEA may cause cellular energy drain. It is possible that mitochondrial dysfunction may be mechanistically implicated in DHEA-induced changes in cellular phenotype. Treatment of SK-Hep-1 cells with DHEA caused significant reduction in proliferation, colony formation, and growth in semi-solid medium. Such changes in cellular phenotype were associated with mitochondrial depolarization, increase in mitochondrial mass, and decrease in respiratory activity. Level of reactive oxygen species (ROS) increased in DHEA-treated cells. To explore the mechanistic aspect of DHEA-induced mitochondrial dysfunction, we employed SILAC approach to study the changes in the mitoproteome of SK-Hep-1 cells after DHEA treatment. Respiratory chain complex proteins such as NDUFB8 and SDHB were differentially expressed. Of mitochondrial proteins with altered expression, FAST kinase domain-containing protein 2 (FASTKD2) showed significantly reduced expression. Exogenous expression of FASTKD2 in SK-Hep-1 cells increased their resistance to growth-inhibitory effect of DHEA, though it alone did not affect cell growth. FASTKD2 expression partially reversed the effect of DHEA on mitochondria, and reduced DHEA-induced ROS generation. Our results suggest that DHEA induces changes in mitochondrial proteins and respiratory activity, and contributes to growth arrest. FASTKD2 may be an important regulator of mitochondrial physiology, and represent a downstream target for DHEA. PMID: 27501919 [PubMed - as supplied by publisher]

Related Articles Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency. Eur J Endocrinol. 2016 May;174(5):601-9 Authors: Turcu AF, Nanba AT, Chomic R, Upadhyay SK, Giordano TJ, Shields JJ, Merke DP, Rainey WE, Auchus RJ Abstract OBJECTIVE: To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. DESIGN: Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. METHODS: We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. RESULTS: Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. CONCLUSIONS: All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess. PMID: 26865584 [PubMed - indexed for MEDLINE]

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Related Articles Tear biomarkers for keratoconus. Eye Vis (Lond). 2016;3:19 Authors: Nishtala K, Pahuja N, Shetty R, Nuijts RM, Ghosh A Abstract Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment. PMID: 27493978 [PubMed]

Related Articles Animal-Free Chemical Safety Assessment. Front Pharmacol. 2016;7:218 Authors: Loizou GD Abstract The exponential growth of the Internet of Things and the global popularity and remarkable decline in cost of the mobile phone is driving the digital transformation of medical practice. The rapidly maturing digital, non-medical world of mobile (wireless) devices, cloud computing and social networking is coalescing with the emerging digital medical world of omics data, biosensors and advanced imaging which offers the increasingly realistic prospect of personalized medicine. Described as a potential "seismic" shift from the current "healthcare" model to a "wellness" paradigm that is predictive, preventative, personalized and participatory, this change is based on the development of increasingly sophisticated biosensors which can track and measure key biochemical variables in people. Additional key drivers in this shift are metabolomic and proteomic signatures, which are increasingly being reported as pre-symptomatic, diagnostic and prognostic of toxicity and disease. These advancements also have profound implications for toxicological evaluation and safety assessment of pharmaceuticals and environmental chemicals. An approach based primarily on human in vivo and high-throughput in vitro human cell-line data is a distinct possibility. This would transform current chemical safety assessment practice which operates in a human "data poor" to a human "data rich" environment. This could also lead to a seismic shift from the current animal-based to an animal-free chemical safety assessment paradigm. PMID: 27493630 [PubMed]

Related Articles Tetanus toxin production is triggered by the transition from amino acid consumption to peptides. Anaerobe. 2016 Aug 1; Authors: Licona-Cassani C, Steen JA, Zaragoza NE, Moonen G, Moutafis G, Hodson MP, Power J, Nielsen LK, Marcellin E Abstract Bacteria produce some of the most potent molecules known, of which many cause serious diseases such as tetanus. For prevention, billions of people and countless animals are immunised with the highly effective vaccine, industrially produced by large-scale fermentation. However, toxin production is often hampered by low yields and batch-to-batch variability. Improved productivity has been constrained by a lack of understanding of the molecular mechanisms controlling toxin production. Here we have developed a reproducible experimental framework for screening phenotypic determinants in Clostridium tetani under a process that mimics an industrial setting. We show that amino acid depletion induces production of the toxin. Using time-course transcriptomics and extracellular metabolomics to generate a 'fermentation atlas' that ascribe growth behaviour, nutrient consumption and gene expression to the fermentation phases, we found a subset of preferred amino acids. Exponential growth is characterised by the consumption of those amino acids followed by a slower exponential growth phase where peptides are consumed, and toxin is produced. The results aim at assisting in fermentation medium design towards the improvement of vaccine production yields and reproducibility. In conclusion, our work not only provides deep fermentation dynamics but represents the foundation for bioprocess design based on C. tetani physiological behaviour under industrial settings. PMID: 27492724 [PubMed - as supplied by publisher]