PubMed

Related Articles Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery. Int J Cancer. 2018 Feb 16;: Authors: Liu X, Cheng X, Liu X, He L, Zhang W, Wang Y, Sun W, Ji Z Abstract Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In the present study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and bladder cancer patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations of urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC=0.924). A panel of indolylacryloylglycine, N2 -galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC=0.891).External sample(26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection.This study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery. This article is protected by copyright. All rights reserved. PMID: 29451296 [PubMed - as supplied by publisher]

Related Articles Access to the CNS: Biomarker Strategies for Dopaminergic Treatments. Pharm Res. 2018 Feb 15;35(3):64 Authors: van den Brink WJ, Palic S, Köhler I, de Lange ECM Abstract Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i.e., indicators of a pharmacological process) that reflect these effects. Dopaminergic treatments developed over the last decades were found to be associated with numerous biochemical pathways in the brain, including the norepinephrine and the kynurenine pathway. Additionally, they have shown to affect peripheral systems, for example the hypothalamus-pituitary-adrenal (HPA) axis. Dopaminergic agents thus have a complex and broad pharmacological profile, rendering drug development challenging. Considering the complex system-wide pharmacological profile of dopaminergic agents, this review underlines the needs for systems pharmacology studies that include: i) proteomics and metabolomics analysis; ii) longitudinal data evaluation and mathematical modeling; iii) pharmacokinetics-based interpretation of drug effects; iv) simultaneous biomarker evaluation in the brain, the cerebrospinal fluid (CSF) and plasma; and v) specific attention to condition-dependent (e.g., disease) pharmacology. Such approach is considered essential to increase our understanding of central nervous system (CNS) drug effects and substantially improve CNS drug development. PMID: 29450650 [PubMed - in process]

Related Articles Plant Genetics and Molecular Biology: An Introduction. Adv Biochem Eng Biotechnol. 2018 Feb 16;: Authors: Varshney RK, Pandey MK, Chitikineni A Abstract The rapidly evolving technologies can serve as a potential growth engine in agriculture as many of these technologies have revolutionized several industries in the recent past. The tremendous advancements in biotechnology methods, cost-effective sequencing technology, refinement of genomic tools, and standardization of modern genomics-assisted breeding methods hold great promise in taking the global agriculture to the next level through development of improved climate-smart seeds. These technologies can dramatically increase our capacity to understand the molecular basis of traits and utilize the available resources for accelerated development of stable high-yielding, nutritious, input-use efficient, and climate-smart crop varieties. This book aimed to document the monumental advances witnessed during the last decade in multiple fields of plant biotechnology such as genetics, structural and functional genomics, trait and gene discovery, transcriptomics, proteomics, metabolomics, epigenomics, nanotechnology, and analytical tools. This book will serve to update the scientific community, academicians, and other stakeholders in global agriculture on the rapid progress in various areas of agricultural biotechnology. This chapter provides a summary of the book, "Plant Genetics and Molecular Biology." Graphical Abstract. PMID: 29450572 [PubMed - as supplied by publisher]

Related Articles Calycosin Orchestrates Osteogenesis of Danggui Buxue Tang in Cultured Osteoblasts: Evaluating the Mechanism of Action by Omics and Chemical Knock-out Methodologies. Front Pharmacol. 2018;9:36 Authors: Gong AGW, Duan R, Wang HY, Dong TTX, Tsim KWK Abstract Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s) within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and ferulic acid have been reported to be the predominant chemicals found within DBT, and its roles in regulating osteoblastic differentiation have been proposed here. To probe the roles of calycosin and ferulic acid, these chemicals were specifically depleted from the DBT extracts. Here, calycosin-depleted DBT (DBTΔcal) and ferulic acid-depleted DBT (DBTΔfa), generated by semi-preparative HPLC, were coupled with RNA-seq and metabolomics analyses to reveal the synergistic functions of individual chemicals within a complex herbal mixture. The expressions of osteogenic differentiation markers were significantly increased under the treatments of DBT and DBTΔfa. The DBT-induced genes were markedly reduced in the absent of calycosin, i.e., DBTΔcal. In cultured osteoblasts, the DBT-activated Wnt/β-catenin and MAPK/Erk and signaling pathways were greatly affected when calycosin was depleted. By metabolomics analysis in DBT-treated osteoblasts, the profile of metabolites triggered by DBTΔcal showed distinction to that of DBT and/or DBTΔfa. Thus, our findings indicated that calycosin, rather than ferulic acid, could be an indispensable chemical in DBT to orchestrate multi-components of DBT in achieving maximal osteogenic properties. PMID: 29449812 [PubMed]

Related Articles Changes in grape polyphenols (V. vinifera L.) as a consequence of post-harvest withering by high-resolution mass spectrometry: Raboso Piave versus Corvina. J Mass Spectrom. 2016 Sep;51(9):750-60 Authors: Rosso MD, Soligo S, Panighel A, Carraro R, Vedova AD, Maoz I, Tomasi D, Flamini R Abstract Grape dehydration is an oenological process used for the production of high-quality reinforced and sweet wines. Corvina and Raboso Piave are two red grape varieties used for production of high-quality Italian wines, such as Recioto, Amarone di Valpolicella and Raboso Passito. Changes of polyphenolic composition of the grapes as a consequence of the withering were studied by ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC/QTOF); for identification of compounds a homemade HR-MS database of grape and wine metabolites, was used. Concomitant with trans-resveratrol and viniferins, relevant increases of other stilbenes (piceatannol, resveratrol trimers and tetramers) and antioxidant compounds (quercetin, syringetin and tamarixetin) were observed. These compounds are part of the induced metabolism occurring during the withering process and in general improve the nutraceutical properties of grapes and wines. On the other hand, longer processes showed to decrease flavan-3-ols and glycoside flavonols. Constant increase of E/Z ε-viniferin ratio was observed in all samples, and this parameter can be used to monitor the process. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27491020 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic study of wild and cultivated caper (Capparis spinosa L.) from different areas of Sardinia and their comparative evaluation. J Mass Spectrom. 2016 Sep;51(9):716-28 Authors: Maldini M, Foddai M, Natella F, Addis R, Chessa M, Petretto GL, Tuberoso CI, Pintore G Abstract Capparis spinosa L. (Capparidaceae), also known as caper, is widely known for its very aromatic flower buds (capers),that are largely employed as a flavouring in cooking. Capparis species are regarded as a potential source of important bioactive compounds, in fact, due to their botanical relationship with Brassica species; they contain glucosinolates, secondary plant metabolites, that have been studied for their potential anticarcinogenic properties. In addition, the presence of other numerous beneficial compounds such as polyphenols, alkaloids, lipids, vitamins and minerals have been reported. The aim of this study was to individuate and determinate the principal bioactive compounds occurring in different part (leaves, buds and flowers) of wild and cultivated C. spinosa collected from different area of Sardinia (Italy). Ultra-high performance liquid chromatography-triple quadrupole/linear ion trap tandem mass spectrometry methods were used for identification and simultaneous determination of 27 bioactive molecules. Analysis of different samples revealed qualitative and quantitative differences in the content of flavonoids, glucosinolates, anthocyanins and phenolic acids. In particular, glucocapparin resulted the most abundant with values ranging from 112 to 364 mg/100 g Fresh Weight (FW); followed by rutin with highest value of 126 mg/100 g FW, 4-hydroxyglucobrassicin with highest value of 42 mg/100 g FW and isorhamnetin 3-O-rutinoside with highest value of 24 mg/100 g FW. Based on this metabolomic targeted approach, quantitative results were treated by principal component analysis to explore and visualise correlation and discrimination among collections of C. spinosa samples. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27489055 [PubMed - indexed for MEDLINE]

6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates colon carcinogenesis via blockade of IL-6 mediated signals. Biomed Pharmacother. 2018 Feb 12;100:282-295 Authors: Mishra P, Raj V, Bhadauria AS, Singh AK, Rai A, Kumar P, Keshari AK, De A, Samanta A, Kumar U, Kumar D, Maity B, Nath S, Prakash A, Ansari KM, Saha S Abstract In this study, we investigated the in vivo antiproliferative activity of 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15 days. Various physiological, oxidative parameters, histopathology, ELISA, gene and protein expression studies were conducted to evaluate the anti-CRC potential of M1. The histopathology and biochemical tests indicated the protective action of M1 in DMH-induced colon cancer. ELISA confirms that M1 reduced the increased concentration of IL-6 more prominently than those of IL-2 and COX-2. Gene expression analysis revealed that M1 attenuated the increased mRNA over-expression of IL-6, JAK2 and STAT3. The result obtained from quantitative western blot analysis demonstrated that the CRC condition was produced by the IL-6 induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated with M1 treatment. This evidence was supported well with the application of data-based mathematical modeling. Applying the fitted model, we predicted the quantitative behavior of STAT3 populations not accessible to experimental measurement. Later, 1H NMR based serum metabolic profiling was carried out using rat sera to investigate the impact of M1 on CRC-induced metabolic alterations. M1 showed its ability to restore the perturbed metabolites in CRC condition. Altogether, our study provided the first time evidence that M1 exhibits anti-CRC potential through the blockade of IL-6/JAK2/STAT3 oncogenic signaling. PMID: 29448205 [PubMed - as supplied by publisher]

Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models. Biomaterials. 2018 Feb 08;162:144-153 Authors: Armiñán A, Palomino-Schätzlein M, Deladriere C, Arroyo-Crespo JJ, Vicente-Ruiz S, Vicent MJ, Pineda-Lucena A Abstract Metabolomics is becoming a relevant tool for understanding the molecular mechanisms involved in the response to new drug delivery systems. The applicability of this experimental approach to cell cultures and animal models makes metabolomics a useful tool for establishing direct connections between in vitro and in vivo data, thus providing a reliable platform for the characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression and flow cytometry studies to obtain a better coverage of the biochemical alterations associated with the administration of these compounds. The overall analysis revealed that polymer conjugation leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when compared to the free chemotherapeutic drug. Our results represent a first step in the application of integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems. PMID: 29448142 [PubMed - as supplied by publisher]

Advances in analytical tools for high throughput strain engineering. Curr Opin Biotechnol. 2018 Feb 12;54:33-40 Authors: Marcellin E, Nielsen LK Abstract The emergence of inexpensive, base-perfect genome editing is revolutionising biology. Modern industrial biotechnology exploits the advances in genome editing in combination with automation, analytics and data integration to build high-throughput automated strain engineering pipelines also known as biofoundries. Biofoundries replace the slow and inconsistent artisanal processes used to build microbial cell factories with an automated design-build-test cycle, considerably reducing the time needed to deliver commercially viable strains. Testing and hence learning remains relatively shallow, but recent advances in analytical chemistry promise to increase the depth of characterization possible. Analytics combined with models of cellular physiology in automated systems biology pipelines should enable deeper learning and hence a steeper pitch of the learning cycle. This review explores the progress, advances and remaining bottlenecks of analytical tools for high throughput strain engineering. PMID: 29448095 [PubMed - as supplied by publisher]

Salicin-7-sulfate: A new salicinoid from willow and implications for herbal medicine. Fitoterapia. 2018 Feb 12;: Authors: Noleto-Dias C, Ward JL, Bellisai A, Lomax C, Beale MH Abstract Willow (Salix sp.) is a historically well-known herbal medicine that provided the lead compound (salicin) for the discovery of aspirin, one of the most successful plant derived drugs in human medicine. During a metabolomics screen of 86 Salix species contained in the UK National Willow Collection, we have discovered, isolated and fully characterised a new natural salicinoid - salicin-7-sulfate. This molecule may have important human pharmacological actions that need to be considered in determining the efficacy and safety of willow herbal medicines. PMID: 29447984 [PubMed - as supplied by publisher]

Related Articles Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies. Front Immunol. 2018;9:129 Authors: Sonneveld ME, Koeleman CAM, Plomp HR, Wuhrer M, van der Schoot CE, Vidarsson G Abstract After albumin, immunoglobulin G (IgG) are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγR)IIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar. PMID: 29445378 [PubMed]

Related Articles Canagliflozin mediated dual inhibition of mitochondrial glutamate dehydrogenase and complex I: an off-target adverse effect. Cell Death Dis. 2018 Feb 14;9(2):226 Authors: Secker PF, Beneke S, Schlichenmaier N, Delp J, Gutbier S, Leist M, Dietrich DR Abstract Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin. Canagliflozin inhibited the glutamate dehydrogenase (GDH) and mitochondrial electron transport chain (ETC) complex I at clinically relevant concentrations. This dual inhibition specifically prevented replenishment of tricarboxylic acid cycle metabolites by glutamine (anaplerosis) and thus altered amino acid pools by increasing compensatory transamination reactions. Consequently, canagliflozin caused a characteristic intracellular accumulation of glutamine, glutamate and alanine in confluent, quiescent RPTEC/TERT1. Canagliflozin, but none of the classical ETC inhibitors, induced cytotoxicity at particularly low concentrations in proliferating RPTEC/TERT1, serving as model for proximal tubule regeneration in situ. This finding is testimony of the strong dependence of proliferating cells on glutamine anaplerosis via GDH. Our discovery of canagliflozin-mediated simultaneous inhibition of GDH and ETC complex I in renal cells at clinically relevant concentrations, and their particular susceptibility to necrotic cell death during proliferation, provides a mechanistic rationale for the adverse effects observed especially in patients with preexisting chronic kidney disease or previous kidney injury characterized by sustained regenerative tubular epithelial cell proliferation. PMID: 29445145 [PubMed - in process]

Related Articles Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue. J Lipid Res. 2018 Feb 14;: Authors: Gottschall H, Schmoecker C, Hartmann D, Rohwer N, Rund K, Kutzner L, Nolte F, Ostermann AI, Schebb NH, Weylandt KH Abstract Eicosanoids, including prostaglandins and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid - particularly prostaglandin E2 (PGE2) - formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n=27) had significantly lower tissue eicosanoid levels of most COX-derived metabolites than untreated individuals (n=31). In contrast, COX-derived lipid metabolites tended to be higher in patients with statin treatment (n=7) as compared to those not receiving statins (n=24). This effect was not discernible in subjects treated with ASA and statins (n=11): Individuals treated with both drugs showed a pronounced suppression of COX-derived eicosanoids in colon tissue even compared to subjects treated with ASA alone. Our data from a routine clinical setting support the hypothesis that ASA and statins could inhibit CRC development via lipid mediator modification. Further studies should directly investigate the effect of dual ASA and statin treatment on colon tumorigenesis in humans. PMID: 29444936 [PubMed - as supplied by publisher]

Related Articles Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite Profiles. Clin J Am Soc Nephrol. 2018 Feb 14;: Authors: Kalim S, Wald R, Yan AT, Goldstein MB, Kiaii M, Xu D, Berg AH, Clish C, Thadhani R, Rhee EP, Perl J Abstract BACKGROUND AND OBJECTIVES: In-center, extended duration nocturnal hemodialysis has been associated with variable clinical benefits, but the effect of extended duration hemodialysis on many established uremic solutes and other components of the metabolome is unknown. We determined the magnitude of change in metabolite profiles for patients on extended duration nocturnal hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 52-week prospective, observational study, we followed 33 patients receiving conventional thrice weekly hemodialysis who converted to nocturnal hemodialysis (7-8 hours per session, three times per week). A separate group of 20 patients who remained on conventional hemodialysis (3-4 hours per session, three times per week) served as a control group. For both groups, we applied liquid chromatography-mass spectrometry-based metabolite profiling on stored plasma samples collected from all participants at baseline and after 1 year. We examined longitudinal changes in 164 metabolites among those who remained on conventional hemodialysis and those who converted to nocturnal hemodialysis using Wilcoxon rank sum tests adjusted for multiple comparisons (false discovery rate <0.05). RESULTS: On average, the nocturnal group had 9.6 hours more dialysis per week than the conventional group. Among 164 metabolites, none changed significantly from baseline to study end in the conventional group. Twenty-nine metabolites changed in the nocturnal group, 21 of which increased from baseline to study end (including all branched-chain amino acids). Eight metabolites decreased after conversion to nocturnal dialysis, including l-carnitine and acetylcarnitine. By contrast, several established uremic retention solutes, including p-cresol sulfate, indoxyl sulfate, and trimethylamine N-oxide, did not change with extended dialysis. CONCLUSIONS: Across a wide array of metabolites examined, extended duration hemodialysis was associated with modest changes in the plasma metabolome, with most differences relating to metabolite increases, despite increased dialysis time. Few metabolites showed reduction with more dialysis, and no change in several established uremic toxins was observed. PMID: 29444900 [PubMed - as supplied by publisher]

Related Articles Qualitative and quantitative characterization of secondary metabolites and carbohydrates in Bai-Hu-Tang using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector. J Food Drug Anal. 2017 Oct;25(4):946-959 Authors: Zhong WF, Tong WS, Zhou SS, Yip KM, Li SL, Zhao ZZ, Xu J, Chen HB Abstract Bai-Hu-Tang (BHT), a classic traditional Chinese medicine (TCM) formula used for clearing heat and promoting body fluid, consists of four traditional Chinese medicines, i.e., Gypsum Fibrosum (Shigao), Anemarrhenae Rhizoma (Zhimu), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (Zhigancao), and nonglutinous rice (Jingmi). The chemical composition of BHT still remains largely elusive thus far. To qualitatively and quantitatively characterize secondary metabolites and carbohydrates in BHT, here a combination of analytical approaches using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultraperformance liquid chromatography coupled with photodiode array detector was developed and validated. A total of 42 secondary metabolites in BHT were tentatively or definitely identified, of which 10 major chemicals were quantified by the extracting ion mode of quadrupole time-of-flight mass spectrometry. Meanwhile, polysaccharides, oligosaccharides, and monosaccharides in BHT were also characterized via sample pretreatment followed by sugar composition analysis. The quantitative results indicated that the determined chemicals accounted for 35.76% of the total extract of BHT, which demonstrated that the study could be instrumental in chemical dissection and quality control of BHT. The research deliverables not only laid the root for further chemical and biological evaluation of BHT, but also provided a comprehensive analytical strategy for chemical characterization of secondary metabolites and carbohydrates in traditional Chinese medicine formulas. PMID: 28987372 [PubMed - indexed for MEDLINE]

Related Articles OLS Client and OLS Dialog: Open Source Tools to Annotate Public Omics Datasets. Proteomics. 2017 Oct;17(19): Authors: Perez-Riverol Y, Ternent T, Koch M, Barsnes H, Vrousgou O, Jupp S, Vizcaíno JA Abstract The availability of user-friendly software to annotate biological datasets and experimental details is becoming essential in data management practices, both in local storage systems and in public databases. The Ontology Lookup Service (OLS, http://www.ebi.ac.uk/ols) is a popular centralized service to query, browse and navigate biomedical ontologies and controlled vocabularies. Recently, the OLS framework has been completely redeveloped (version 3.0), including enhancements in the data model, like the added support for Web Ontology Language based ontologies, among many other improvements. However, the new OLS is not backwards compatible and new software tools are needed to enable access to this widely used framework now that the previous version is no longer available. We here present the OLS Client as a free, open-source Java library to retrieve information from the new version of the OLS. It enables rapid tool creation by providing a robust, pluggable programming interface and common data model to programmatically access the OLS. The library has already been integrated and is routinely used by several bioinformatics resources and related data annotation tools. Secondly, we also introduce an updated version of the OLS Dialog (version 2.0), a Java graphical user interface that can be easily plugged into Java desktop applications to access the OLS. The software and related documentation are freely available at https://github.com/PRIDE-Utilities/ols-client and https://github.com/PRIDE-Toolsuite/ols-dialog. PMID: 28792687 [PubMed - indexed for MEDLINE]

Related Articles Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces. Food Funct. 2016 Aug 10;7(8):3421-30 Authors: Dudonné S, Dal-Pan A, Dubé P, Varin TV, Calon F, Desjardins Y Abstract The low bioavailability of dietary phenolic compounds, resulting from poor absorption and high rates of metabolism and excretion, is a concern as it can limit their potential beneficial effects on health. Targeted metabolomic profiling in plasma and feces of mice supplemented for 15 days with a blueberry extract, a grape extract or their combination revealed significantly increased plasma concentrations (3-5 fold) of blueberry phenolic metabolites in the presence of a co-ingested grape extract, associated with an equivalent decrease in their appearance in feces. Additionally, the repeated daily administration of the blueberry-grape combination significantly increased plasma phenolic concentrations (2-3-fold) compared to animals receiving only a single acute dose, with no such increase being observed with individual extracts. These findings highlight a positive interaction between blueberry and grape constituents, in which the grape extract enhanced the absorption of blueberry phenolic compounds. This study provides for the first time in vivo evidence of such an interaction occurring between co-ingested phenolic compounds from fruit extracts leading to their improved bioavailability. PMID: 27443888 [PubMed - indexed for MEDLINE]

Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet. PLoS One. 2018;13(2):e0191909 Authors: Rutkowsky JM, Lee LL, Puchowicz M, Golub MS, Befroy DE, Wilson DW, Anderson S, Cline G, Bini J, Borkowski K, Knotts TA, Rutledge JC, Mouse Metabolic Phenotyping Center Imaging Working Group Abstract Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways. PMID: 29444171 [PubMed - in process]

Effect of Bulk MoS₂ on the Metabolic Profile of Yeast. J Nanosci Nanotechnol. 2018 Jun 01;18(6):3901-3907 Authors: Yu Y, Yang Q, Wu N, Tang H, Yi Y, Wang G, Ge Y, Zong J, Madzak C, Zhao Y, Jiang L, Huang H Abstract MoS2, a kind of two-dimensional material with unique performances, has been widely used in many fields. However, an in-depth understanding of its toxicity is still needed, let alone its effects on the environmental microorganism. Herein, we used different methods, including metabolomics technology, to investigate the influence of bulk MoS2 (BMS) on yeast cells. The results indicated that high concentrations (1 mg/L and more) of BMS could destroy cell membrane and induce ROS accumulation. When exposed to a low concentration of BMS (0.1 mg/L), the intracellular concentrations of many metabolites (e.g., fumaric acid, lysine) increased. However, most of their concentrations descended significantly as the yeast cells were treated with BMS of high concentrations (1 mg/L and more). Metabolomics analysis further revealed that exposure to high concentrations of BMS could significantly affect some metabolic pathways such as amino acid and citrate cycle related metabolism. These findings will be beneficial for MoS2 toxicity assessment and further applications. PMID: 29442725 [PubMed - in process]

LC-MS-based serum metabolomics reveals a distinctive signature in patients with rheumatoid arthritis. Clin Rheumatol. 2018 Feb 13;: Authors: Li J, Che N, Xu L, Zhang Q, Wang Q, Tan W, Zhang M Abstract Metabolomics has been applied to explore altered metabolite profiles in disease and identify unique metabolic signatures in recent years. We aim to characterize the metabolic profile of rheumatoid arthritis patients and explore its underlying pathological processes using metabolomics approach. Serum samples from 30 rheumatoid arthritis (RA) patients, 30 primary Sjogren's syndrome (pSS) patients, and 32 healthy controls (HC) were collected. The sample was analyzed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Potential biomarkers were screened from orthogonal projection to latent structure discriminate analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). Compared with HC and pSS patients, the RA patients had increased serum levels of 4-methoxyphenylacetic acid, glutamic acid, L-leucine, L-phenylalanine, L-tryptophan, L-proline, glyceraldehyde, fumaric acid, and cholesterol as well as decreased capric acid, argininosuccinic acid, and billirubin. A total of eight potential biomarkers were screened and tentatively identified for RA. A panel of three metabolites (4-methoxyphenylacetic acid, L-phenylalanine, and L-leucine) was identified as specific biomarkers of RA. ROC analysis showed that the panel had a sensitivity of 93.30% with a specificity of 95.20% in discrimination RA from other groups. UPLC-HRMS-based quantification of circulating metabolites was a useful tool for identifying RA patients from pSS patients and healthy controls. The potential biomarkers indicated that the RA metabolic disturbance might be associated with inflammation injury, amino acid metabolism, oxidative stress, and phospholipid metabolism. PMID: 29442259 [PubMed - as supplied by publisher]