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22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Systematic mapping of protein-metabolite interactions with mass spectrometry-based techniques. Curr Opin Biotechnol. 2019 Oct 10;64:24-31 Authors: Li S, Shui W Abstract The recent rapid advance of systematic mapping of protein-metabolite interactions (PMIs) in both prokaryotic and eukaryotic cells has been catalyzed by development of innovative and effective proteomics or metabolomics strategies all based on large-scale mass spectrometry (MS) analysis of biomolecules. Both metabolite-centric and protein-centric approaches have been established to profile PMIs in the native cellular matrix treated by specific metabolites or proteins. Here we will review the development and application of versatile MS-based proteomics and metabolomics techniques for global PMI mapping in different species, which lead to the discovery of numerous uncharacterized PMIs that may reveal new interaction-derived functionality. We further discuss the strengths and limitations of different PMI mapping approaches as well as the key elements in MS quantification and data mining for reliable PMI identification. PMID: 31606719 [PubMed - as supplied by publisher]

Related Articles Allergic Disease and low ASQ Communication Score in Children. Brain Behav Immun. 2019 Oct 10;: Authors: Yadama AP, Kelly RS, Lee-Sarwar K, Mirzakhani H, Chu SH, Kachroo P, Litonjua AA, Lasky-Su J, Weiss ST Abstract Autism Spectrum Disorders (ASD) are complex and multifactorial. Previous investigations have revealed associations between allergic disease and ASD, which are characterized by impaired communication skills. In this study we observed an association between allergic disease and communication skills development as assessed by the Ages and Stages Questionnaire (ASQ) communication score, as a proxy for ASD, among children who participated in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). In particular, we observed significant associations between both a diagnosis of eczema at age 3 years (OR=1.87; confidence interval [CI]: 0.97-3.47; p=0.054) and a diagnosis of food allergy at age 6 years (OR=3.61; 95% CI: 1.18-9.85; p=0.015) with ASQ communication score. Plasma metabolomics analyses suggest that dysregulated tryptophan metabolism may contribute to the pathogenesis of these co-morbidities. PMID: 31606476 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis of lipid metabolizing enzyme activity. Methods Enzymol. 2019;626:407-428 Authors: Ware TB, Shin M, Hsu KL Abstract Lipids exert key structural, metabolic, and signaling functions in cells. Lipid diversity found in cells and tissues is regulated principally by metabolic enzymes whose activity is modulated posttranslationally to shape head group and fatty acyl composition of membrane lipids. Methodologies capable of monitoring in vivo changes in the lipidome are needed to assign substrate specificity of metabolic enzymes, which represents a key step toward understanding structure-function of lipids in living systems. The resulting lipid annotations also serve as important biomarkers for understanding mode of action for pharmacological agents targeting metabolic enzymes in cells and animal models. In this chapter, we describe a general metabolomics workflow to complement (chemo)proteomic efforts to modulate lipid pathways for basic science and translational applications. PMID: 31606084 [PubMed - in process]

Related Articles Metabolic profiling of seminal plasma from teratozoospermia patients. J Pharm Biomed Anal. 2019 Oct 03;178:112903 Authors: Mehrparvar B, Chashmniam S, Nobakht F, Amini M, Javidi A, Minai-Tehrani A, Arjmand B, Gilany K Abstract Teratozoospermia is one of conditions that can cause male infertility. The mechanism of teratozoospermia remains unclear. The knowledge of the metabolites in human seminal plasma (HSP) is meaningful for the pathological study of teratozoospermia. Analysis of changed metabolites in HSP can help understand the cellular mechanism, find the novel biomarkers and subsequently design a diagnosis test. In this study, the analysis of samples performed by proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) to identify the various metabolites, with the aim of finding metabolic profiles and biomarkers related to male infertility. Eighteen de-regulated metabolites were identified in fertile men compared to teratozoospermia patients. These changes illustrate the deficiencies in absorption or metabolism of these metabolites in teratozoospermia. Furthermore, metabolic profiling showed that it is not possible to classify teratozoospermia based on teratozoospermia index (TZI). To the best of our knowledge, this is the first metabolic profiling analysis of HSP described the metabolic features of teratozoospermia in a holistic view. PMID: 31605879 [PubMed - as supplied by publisher]

Related Articles Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis. Regul Toxicol Pharmacol. 2019 Oct 09;:104489 Authors: Kumar P, Agarwal A, Singh AK, Gautam AK, Chakraborti S, Kumar U, Kumar D, Bhattacharya B, Panda P, Saha B, Qidwai T, Maity B, Saha S Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the molecular mechanism associated with ZAF therapy for HCC. We found that HCC developed as a result of lower expression of caspases 3 and 9, but their levels returned to normal when the expression of eNOS, BAX, BAD, and Cyt C was decreased and when the expression of iNOS, Bcl-xl, and Bcl-2 was increased. Again, ZAF (80 mg/kg dose) treatment normalized the expression of caspase-mediated apoptotic factors, i.e. BAX and Bcl-2 proteins, as established through Western blot analysis. Later, 1H NMR-based serum metabolomics study revealed that levels of perturbed metabolites in DEN-induced rat serum returned to normal after ZAF administration. Altogether, the antineoplastic potential of ZAF was found to be comparable, and to some degree better, than the marketed chemotherapeutic 5-flurouracil, which may be beneficial for anti-HCC treatment from a future drug design perspective. PMID: 31605713 [PubMed - as supplied by publisher]

Related Articles Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism. Metabolomics. 2019 Oct 11;15(11):140 Authors: Kayser BD, Prifti E, Lhomme M, Belda E, Dao MC, Aron-Wisnewsky J, MICRO-Obes Consortium, Kontush A, Zucker JD, Rizkalla SW, Dugail I, Clément K Abstract INTRODUCTION: Low gut microbiome richness is associated with dyslipidemia and insulin resistance, and ceramides and other sphingolipids are implicated in the development of diabetes. OBJECTIVES: Determine whether circulating sphingolipids, particularly ceramides, are associated with alterations in the gut microbiome among obese patients with increased diabetes risk. METHODS: This was a cross-sectional and longitudinal retrospective analysis of a dietary/weight loss intervention. Fasted serum was collected from 49 participants (41 women) and analyzed by HPLC-MS/MS to quantify 45 sphingolipids. Shotgun metagenomic sequencing of stool was performed to profile the gut microbiome. RESULTS: Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and β-cell function. Significant associations with gut dysbiosis were demonstrated, with SM and ceramides being inversely correlated with gene richness. Ceramides with fatty acid chain lengths of 20-24 carbons were the most associated with low richness. Diet-induced weight loss, which improved gene richness, decreased most sphingolipids. Thirty-one MGS, mostly corresponding to unidentified bacteria species, were inversely correlated with ceramides, including a number of Bifidobacterium and Methanobrevibacter smithii. Higher ceramide levels were also associated with increased metagenomic modules for lipopolysaccharide synthesis and flagellan synthesis, two pathogen-associated molecular patterns, and decreased enrichment of genes involved in methanogenesis and bile acid metabolism. CONCLUSION: This study identifies an association between gut microbiota richness, ceramides, and diabetes risk in overweight/obese humans, and suggests that the gut microbiota may contribute to dysregulation of lipid metabolism in metabolic disorders. PMID: 31605240 [PubMed - in process]

Related Articles Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis. Sci Rep. 2019 Oct 11;9(1):14707 Authors: An JN, Hyeon JS, Jung Y, Choi YW, Kim JH, Yang SH, Oh S, Kwon S, Lee SH, Cho JH, Park SH, Ha H, Kim DK, Lee JP, Hwang GS Abstract Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients. PMID: 31605028 [PubMed - in process]

Related Articles TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes. Nat Commun. 2019 Oct 11;10(1):4671 Authors: Miklas JW, Clark E, Levy S, Detraux D, Leonard A, Beussman K, Showalter MR, Smith AT, Hofsteen P, Yang X, Macadangdang J, Manninen T, Raftery D, Madan A, Suomalainen A, Kim DH, Murry CE, Fiehn O, Sniadecki NJ, Wang Y, Ruohola-Baker H Abstract Mitochondrial trifunctional protein deficiency, due to mutations in hydratase subunit A (HADHA), results in sudden infant death syndrome with no cure. To reveal the disease etiology, we generated stem cell-derived cardiomyocytes from HADHA-deficient hiPSCs and accelerated their maturation via an engineered microRNA maturation cocktail that upregulated the epigenetic regulator, HOPX.  Here we report, matured HADHA mutant cardiomyocytes treated with an endogenous mixture of fatty acids manifest the disease phenotype: defective calcium dynamics and repolarization kinetics which results in a pro-arrhythmic state. Single cell RNA-seq reveals a cardiomyocyte developmental intermediate, based on metabolic gene expression. This intermediate gives rise to mature-like cardiomyocytes in control cells but, mutant cells transition to a pathological state with reduced fatty acid beta-oxidation, reduced mitochondrial proton gradient, disrupted cristae structure and defective cardiolipin remodeling. This study reveals that HADHA (tri-functional protein alpha), a monolysocardiolipin acyltransferase-like enzyme, is required for fatty acid beta-oxidation and cardiolipin remodeling, essential for functional mitochondria in human cardiomyocytes. PMID: 31604922 [PubMed - in process]

Related Articles RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nat Commun. 2019 Oct 11;10(1):4621 Authors: Cai D, Wang J, Gao B, Li J, Wu F, Zou JX, Xu J, Jiang Y, Zou H, Huang Z, Borowsky AD, Bold RJ, Lara PN, Li JJ, Chen X, Lam KS, To KF, Kung HJ, Fiehn O, Zhao R, Evans RM, Chen HW Abstract Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC. PMID: 31604910 [PubMed - in process]

Related Articles The missing indicator approach for censored covariates subject to limit of detection in logistic regression models. Ann Epidemiol. 2019 Aug 13;: Authors: Chiou SH, Betensky RA, Balasubramanian R Abstract PURPOSE: In several biomedical studies, one or more exposures of interest may be subject to nonrandom missingness because of the failure of the measurement assay at levels below its limit of detection. This issue is commonly encountered in studies of the metabolome using tandem mass spectrometry-based technologies. Owing to a large number of metabolites measured in these studies, preserving statistical power is of utmost interest. In this article, we evaluate the small sample properties of the missing indicator approach in logistic and conditional logistic regression models. METHODS: For nested case-control or matched case control study designs, we evaluate the bias, power, and type I error associated with the missing indicator method using simulation. We compare the missing indicator approach to complete case analysis and several imputation approaches. RESULTS: We show that under a variety of settings, the missing indicator approach outperforms complete case analysis and other imputation approaches with regard to bias, mean squared error, and power. CONCLUSIONS: For nested case-control and matched study designs of modest sample sizes, the missing indicator model minimizes loss of information and thus provides an attractive alternative to the oft-used complete case analysis and other imputation approaches. PMID: 31604610 [PubMed - as supplied by publisher]

Related Articles Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus. Parasit Vectors. 2019 Oct 11;12(1):470 Authors: van Gennip RGP, Drolet BS, Rozo Lopez P, Roost AJC, Boonstra J, van Rijn PA Abstract BACKGROUND: Transmission of vector-borne virus by insects is a complex mechanism consisting of many different processes; viremia in the host, uptake, infection and dissemination in the vector, and delivery of virus during blood-feeding leading to infection of the susceptible host. Bluetongue virus (BTV) is the prototype vector-borne orbivirus (family Reoviridae). BTV serotypes 1-24 (typical BTVs) are transmitted by competent biting Culicoides midges and replicate in mammalian (BSR) and midge (KC) cells. Previously, we showed that genome segment 10 (S10) encoding NS3/NS3a protein is required for virus propagation in midges. BTV serotypes 25-27 (atypical BTVs) do not replicate in KC cells. Several distinct BTV26 genome segments cause this so-called 'differential virus replication' in vitro. METHODS: Virus strains were generated using reverse genetics and their growth was examined in vitro. The midge feeding model has been developed to study infection, replication and disseminations of virus in vivo. A laboratory colony of C. sonorensis, a known competent BTV vector, was fed or injected with BTV variants and propagation in the midge was examined using PCR testing. Crossing of the midgut infection barrier was examined by separate testing of midge heads and bodies. RESULTS: A 100 nl blood meal containing ±105.3 TCID50/ml of BTV11 which corresponds to ±20 TCID50 infected 50% of fully engorged midges, and is named one Midge Alimentary Infective Dose (MAID50). BTV11 with a small in-frame deletion in S10 infected blood-fed midge midguts but virus release from the midgut into the haemolymph was blocked. BTV11 with S1[VP1] of BTV26 could be adapted to virus growth in KC cells, and contained mutations subdivided into 'corrections' of the chimeric genome constellation and mutations associated with adaptation to KC cells. In particular one amino acid mutation in outer shell protein VP2 overcomes differential virus replication in vitro and in vivo. CONCLUSION: Small changes in NS3/NS3a or in the outer shell protein VP2 strongly affect virus propagation in midges and thus vector competence. Therefore, spread of disease by competent Culicoides midges can strongly differ for very closely related viruses. PMID: 31604476 [PubMed - in process]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Hybrid Search: A Method for Identifying Metabolites Absent from Tandem Mass Spectrometry Libraries. Anal Chem. 2019 Oct 10;: Authors: Cooper BT, Yan X, Simón-Manso Y, Tchekhovskoi DV, Mirokhin YA, Stein SE Abstract Metabolomics has a critical need for better tools for mass spectral identification. Common metabolites may be identified by searching libraries of tandem mass spectra, which offers important advantages over other approaches to identification. But tandem libraries are not nearly complete enough to represent the full molecular diversity present in complex biological sam-ples. We present a novel hybrid search method that can help identify metabolites not in the library by similarity to com-pounds that are. We call it "hybrid" searching because it combines conventional, direct peak matching with the logical equivalent of neutral-loss matching. A successful hybrid search requires the library to contain "cognates" of the unknown: similar compounds with a structural difference confined to a single region of the molecule, that does not substantially alter its fragmentation behavior. We demonstrate that the hybrid search is highly likely to find similar compounds under such circumstances. PMID: 31600070 [PubMed - as supplied by publisher]

Related Articles Functional rare variants influence the clinical response to anti-TNF therapy in Crohn's disease. Therap Adv Gastroenterol. 2019;12:1756284819867848 Authors: Chaparro M, Aterido A, Guerra I, Iborra M, Cabriada JL, Bujanda L, Taxonera C, García-Sánchez V, Marín-Jiménez I, Barreiro-de Acosta M, Vera I, Martín-Arranz MD, Hernández-Breijo B, Mesonero F, Sempere L, Gomollón F, Hinojosa J, Bermejo F, Beltrán B, Rodríguez-Pescador A, Banales JM, Olivares D, Aguilar-Melero P, Menchén L, Ferreiro-Iglesias R, Blazquez Gómez I, Benitez García B, Guijarro LG, Marin AC, Bernardo D, Marsal S, Julia A, Gisbert JP Abstract Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn's disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. Methods: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn's Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic enrichment analyses. Results: A total of 41 consecutive CD patients were included; 3250 functional rare variants were identified (2682 damaging and 568 LoF variants). Two homozygous LoF mutations were found in HLA-B and HLA-DRB1 genes associated with lack of response and remission, respectively. Genome-wide LoF variants were enriched in epigenetic marks specific for the gastrointestinal tissue (colon, p = 4.11e-4; duodenum, p = 0.011). The burden of damaging variation in the TNF signaling pathway was associated with response to anti-TNF therapy (p = 0.016); damaging variants were enriched in epigenetic marks from CD8+ (p = 6.01e-4) and CD4+ (p = 0.032) T cells. Conclusions: Functional rare variants are involved in the response to anti-TNF therapy in CD. Cell-type enrichment analysis suggests that the gut mucosa and CD8+ T cells are the main mediators of this response. PMID: 31598133 [PubMed]

Related Articles Proceedings of the Ninth HDL (High-Density Lipoprotein) Workshop: Focus on Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2019 Oct 10;:ATVBAHA119313340 Authors: Rodriguez A, Trigatti BL, Mineo C, Knaack D, Wilkins JT, Sahoo D, Asztalos BF, Mora S, Cuchel M, Pownall HJ, Rosales C, Bernatchez P, Ribeiro Martins da Silva A, Getz GS, Barber JL, Shearer GC, Zivkovic AM, Tietge UJF, Sacks FM, Connelly MA, Oda MN, Davidson WS, Sorci-Thomas MG, Vaisar T, Ruotolo G, Vickers KC, Martel C Abstract The HDL (high-density lipoprotein) Workshop was established in 2009 as a forum for candid discussions among academic basic scientists, clinical investigators, and industry researchers about the role of HDL in cardiovascular disease. This ninth HDL Workshop was held on May 16 to 17, 2019 in Boston, MA, and included outstanding oral presentations from established and emerging investigators. The Workshop featured 5 sessions with topics that tackled the role of HDL in the vasculature, its structural complexity, its role in health and disease states, and its interaction with the intestinal microbiome. The highlight of the program was awarding the Jack Oram Award to the distinguished professor emeritus G.S. Getz from the University of Chicago. The tenth HDL Workshop will be held on May 2020 in Chicago and will continue the focus on intellectually stimulating presentations by established and emerging investigators on novel roles of HDL in cardiovascular and noncardiovascular health and disease states. PMID: 31597448 [PubMed - as supplied by publisher]

Related Articles Comprehensive Multi-Omics Analysis Reveals Aberrant Metabolism of Epstein-Barr-Virus-Associated Gastric Carcinoma. Cells. 2019 Oct 08;8(10): Authors: Yoon SJ, Kim JY, Long NP, Min JE, Kim HM, Yoon JH, Anh NH, Park MC, Kwon SW, Lee SK Abstract The metabolic landscape of Epstein-Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. In this study, we used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics using various mass spectrometry platforms. We found a significant downregulation of genes related to metabolic pathways, especially the metabolism of amino acids, lipids, and carbohydrates. The effect of dysregulated metabolic genes was confirmed in a survival analysis of 3951 gastric cancer patients. We found 57 upregulated metabolites and 31 metabolites that were downregulated in EBVaGC compared with EBV-negative gastric cancer. Sixty-nine lipids, mainly ether-linked phospholipids and triacylglycerols, were downregulated, whereas 45 lipids, mainly phospholipids, were upregulated. In total, 15 metabolisms related to polar metabolites and 15 lipid-associated pathways were involved in alteration of metabolites by EBV in gastric cancer. In this work, we have described the metabolic landscape of EBVaGC at the multi-omics level. These findings could help elucidate the mechanism of EBVaGC oncogenesis. PMID: 31597357 [PubMed - in process]

Related Articles Expanding the Reaction Space of Linkage-Specific Sialic Acid Derivatization. Molecules. 2019 Oct 08;24(19): Authors: Pongracz T, Wuhrer M, de Haan N Abstract The human glycome is characterized by a high degree of sialylation, affecting, amongst others, cell-cell interactions and protein half-life. An established method for the linkage isomer-specific characterization of N-glycan sialylation is based on the linkage-specific derivatization of sialylated glycoconjugates, inducing ethyl esterification of α2,6-linked sialic acids and lactonization of α2,3-linked sialic acids. While the carboxylic acid activator and nucleophile used in this reaction received extensive investigation, the role of the catalyst was never thoroughly explored. A frequently used catalyst for the linkage-specific esterification of sialic acids is 1-hydroxybenzotriazole (HOBt). Here, a systematic evaluation was performed of five HOBt alternatives in combination with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in ethanol for the linkage-specific derivatization of sialic acids. Derivatized glycans were analyzed by MALDI-TOF-MS and the catalyst performance was evaluated based on the completeness of the reactions and the linkage-specificity obtained. The use of both 6-Cl-HOBt and 6-CF3-HOBt resulted in high linkage-specificity and minimal byproduct formation, similar to the benchmark method using HOBt. Performing the reaction with these catalysts at neutral or acidic pH showed comparable efficiencies on both sialyllactose and complex-type N-glycans. The reported investigations resulted in an expansion of the reaction space for linkage-specific sialic acid derivatization. PMID: 31597281 [PubMed - in process]

Related Articles The Power of LC-MS Based Multiomics: Exploring Adipogenic Differentiation of Human Mesenchymal Stem/Stromal Cells. Molecules. 2019 Oct 08;24(19): Authors: Rampler E, Egger D, Schoeny H, Rusz M, Pacheco MP, Marino G, Kasper C, Naegele T, Koellensperger G Abstract The molecular study of fat cell development in the human body is essential for our understanding of obesity and related diseases. Mesenchymal stem/stromal cells (MSC) are the ideal source to study fat formation as they are the progenitors of adipocytes. In this work, we used human MSCs, received from surgery waste, and differentiated them into fat adipocytes. The combination of several layers of information coming from lipidomics, metabolomics and proteomics enabled network analysis of the biochemical pathways in adipogenesis. Simultaneous analysis of metabolites, lipids, and proteins in cell culture is challenging due to the compound's chemical difference, so most studies involve separate analysis with unimolecular strategies. In this study, we employed a multimolecular approach using a two-phase extraction to monitor the crosstalk between lipid metabolism and protein-based signaling in a single sample (~105 cells). We developed an innovative analytical workflow including standardization with in-house produced 13C isotopically labeled compounds, hyphenated high-end mass spectrometry (high-resolution Orbitrap MS), and chromatography (HILIC, RP) for simultaneous untargeted screening and targeted quantification. Metabolite and lipid concentrations ranged over three to four orders of magnitude and were detected down to the low fmol (absolute on column) level. Biological validation and data interpretation of the multiomics workflow was performed based on proteomics network reconstruction, metabolic modelling (MetaboAnalyst 4.0), and pathway analysis (OmicsNet). Comparing MSCs and adipocytes, we observed significant regulation of different metabolites and lipids such as triglycerides, gangliosides, and carnitine with 113 fully reprogrammed pathways. The observed changes are in accordance with literature findings dealing with adipogenic differentiation of MSC. These results are a proof of principle for the power of multimolecular extraction combined with orthogonal LC-MS assays and network construction. Considering the analytical and biological validation performed in this study, we conclude that the proposed multiomics workflow is ideally suited for comprehensive follow-up studies on adipogenesis and is fit for purpose for different applications with a high potential to understand the complex pathophysiology of diseases. PMID: 31597247 [PubMed - in process]