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Line Engelbrechtsen Eva Pers Winning Iepsen Ehm A. Andersson Yuvaraj Mahendran Julie Lundgren Anna Elisabet Jonsson Sten Madsbad Jens Juul Holst Henrik Vestergaard Torben Hansen Signe Sørensen Torekov 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):181
Introduction
Increased levels of circulating branched chain amino acids (BCAAs), as well as phenylalanine, and tyrosine have been suggested to be involved in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unknown how these metabolites are affected by weight loss, and during weight-maintaining treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RA).Objective
We aimed to characterize changes in metabolites related to protein turnover and glycolysis after a weight loss intervention followed by long term weight maintenance with/without GLP-1 RA.Methods
Fifty-eight obese individuals underwent a diet-induced 12 % body weight loss during 8 weeks. Participants were randomized to weight maintenance with or without administration of the GLP-1 RA liraglutide (1.2 mg/day) for 52 weeks. Metabolomic profiling by high-throughput proton nuclear magnetic resonance spectroscopy was used for quantification of metabolites.Results
The weight loss was maintained in both groups and was associated with 9–20 % decreases in plasma concentrations of alanine, phenylalanine, histidine, tyrosine and the BCAAs leucine, isoleucine and valine (p < 0.05). Plasma citrate levels increased during weight loss (p = 5.2 × 10?15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = ?0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005).Conclusion
Weight loss is associated with marked changes in plasma concentrations of eight amino acids and glycolysis-related metabolites. Levels of the suggested type 2 diabetes risk markers (BCAAs) remain low during long-term weight maintenance.3.
Background
The Eph family of receptor tyrosine kinases plays important roles in neural development. Previous studies have implicated Eph receptors and their ligands, the ephrins, in neuronal migration, axon bundling and guidance to specific targets, dendritic spine formation and neural plasticity. However, specific contributions of EphA5 and EphA6 receptors to the regulation of neuronal cell morphology have not been well studied.Results
Here we show that deletion of EphA5 and EphA6 results in abnormal Golgi staining patterns of cells in the brain, and abnormal spine morphology.Conclusion
These observations suggest novel functions of these Eph receptors in the regulation of neuronal and spine structure in brain development and function.4.
Gajanan Sathe Chan Hyun Na Santosh Renuse Anil Madugundu Marilyn Albert Abhay Moghekar Akhilesh Pandey 《Clinical proteomics》2018,15(1):29
Background
Cerebrospinal fluid (CSF) is an important source of potential biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are needed to assist in diagnosis, monitoring disease progression and evaluating efficacy of therapies. Recent studies have demonstrated the involvement of tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is related to altered tyrosine phosphorylation of proteins in the brain and identification of abnormally phosphorylated tyrosine peptides in CSF has the potential to ascertain candidate biomarkers for neurodegenerative disorders.Methods
In this study, we used an antibody-based tyrosine phosphopeptide enrichment method coupled with high resolution Orbitrap Fusion Tribrid Lumos Fourier transform mass spectrometer to catalog tyrosine phosphorylated peptides from cerebrospinal fluid. The subset of identified tyrosine phosphorylated peptides was also validated using parallel reaction monitoring (PRM)-based targeted approach.Results
To date, there are no published studies on global profiling of phosphotyrosine modifications of CSF proteins. We carried out phosphotyrosine profiling of CSF using an anti-phosphotyrosine antibody-based enrichment and analysis using high resolution Orbitrap Fusion Lumos mass spectrometer. We identified 111 phosphotyrosine peptides mapping to 66 proteins, which included 24 proteins which have not been identified in CSF previously. We then validated a set of 5 tyrosine phosphorylated peptides in an independent set of CSF samples from cognitively normal subjects, using a PRM-based targeted approach.Conclusions
The findings from this deep phosphotyrosine profiling of CSF samples have the potential to identify novel disease-related phosphotyrosine-containing peptides in CSF.5.
Lamya Rezig Adele Servadio Liborio Torregrossa Paolo Miccoli Fulvio Basolo Laetitia Shintu Stefano Caldarelli 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):141
Introduction
Ultrasound examination coupled with fine-needle aspiration (FNA) cytology is the gold standard for the diagnosis of thyroid cancer. However, about 10–40% of these analyses cannot be conclusive on the malignancy of the lesions and lead to surgery. The cytological indeterminate FNA biopsies are mainly constituted of follicular—patterned lesions, which are benign in 80% of the cases.Objectives
The development of a FNAB classification approach based on the metabolic phenotype of the lesions, complementary to cytology and other molecular tests in order to limit the number of patients undergoing unnecessary thyroidectomy.Methods
We explored the potential of a NMR-based metabolomics approach to improve the quality of the diagnosis from FNABs, using thyroid tissues collected post-surgically.Results
The NMR-detected metabolites were used to produce a robust OPLSDA model to discriminate between benign and malignant tumours. Malignancy was correlated with amino acids such as tyrosine, serine, alanine, leucine and phenylalanine and anti-correlated with myo-inositol, scyllo-inositol and citrate. Diagnosis accuracy was of 84.8% when only indeterminate lesions were considered.Conclusion
These results on model FNAB indicate that there is a clear interest in exploring the possibility to export NMR metabolomics to pre-surgical diagnostics.6.
Dorothea Lesche Roland Geyer Daniel Lienhard Christos T. Nakas Gaëlle Diserens Peter Vermathen Alexander B. Leichtle 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):159
Background
Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.Aim
Determine whether routinely used plasma centrifugation protocols (1500×g 10 min; 3000×g 5 min) influence non-targeted metabolomic analyses.Methods
Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.Results
Besides significant differences in platelet count, we identified substantial alterations in NMR and HRMS data related to the different centrifugation protocols.Conclusion
Already minor differences in plasma centrifugation can significantly influence metabolomic patterns and potentially bias metabolomics studies.7.
Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains 总被引:1,自引:0,他引:1
Etheresia Pretorius Martin J. Page Lize Engelbrecht Graham C. Ellis Douglas B. Kell 《Cardiovascular diabetology》2017,16(1):141
Background
We have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of ‘dense matted deposits’. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can be induced to form such clots by the addition of tiny amounts of bacterial lipopolysaccharide or lipoteichoic acid. Type 2 diabetes (T2D) is also accompanied by raised levels of LPS.Methods
We use superresolution and confocal microscopies to investigate the amyloid nature of clots from healthy and T2D individuals.Results
We show here, with the established stain thioflavin T and the novel stains Amytracker? 480 and 680, that the clotting of plasma from type 2 diabetics is also amyloid in nature, and that this may be prevented by the addition of suitable concentrations of LPS-binding protein.Conclusion
This implies strongly that there is indeed a microbial component to the development of type 2 diabetes, and suggests that LBP might be used as treatment for it and its sequelae.8.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.9.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.10.
John M. Wentworth Naiara G. Bediaga Megan A. S. Penno Esther Bandala-Sanchez Komal N. Kanojia Konstantinos A. Kouremenos Jennifer J. Couper Leonard C. Harrison ENDIA Study Group 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):130
Background
Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.Method
Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.Results
Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.Conclusion
Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.11.
Background
Tks5/FISH is a scaffold protein comprising of five SH3 domains and one PX domain. Tks5 is a substrate of the tyrosine kinase Src and is required for the organization of podosomes/invadopodia implicated in invasion of tumor cells. Recent data have suggested that a close homologue of Tks5, Tks4, is implicated in the EGF signaling.Results
Here, we report that Tks5 is a component of the EGF signaling pathway. In EGF-treated cells, Tks5 is tyrosine phosphorylated within minutes and the level of phosphorylation is sustained for at least 2 hours. Using specific kinase inhibitors, we demonstrate that tyrosine phosphorylation of Tks5 is catalyzed by Src tyrosine kinase. We show that treatment of cells with EGF results in plasma membrane translocation of Tks5. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutation of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks5.Conclusions
Our results identify Tks5 as a novel component of the EGF signaling pathway.12.
Manuja Kaluarachchi Claire L. Boulangé Ibrahim Karaman John C. Lindon Timothy M. D. Ebbels Paul Elliott Russell P. Tracy Nels C. Olson 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):32
Introduction
Differences in the metabolite profiles between serum and plasma are incompletely understood.Objectives
To evaluate metabolic profile differences between serum and plasma and among plasma sample subtypes.Methods
We analyzed serum, platelet rich plasma (PRP), platelet poor plasma (PPP), and platelet free plasma (PFP), collected from 8 non-fasting apparently healthy women, using untargeted standard 1D and CPMG 1H NMR and reverse phase and hydrophilic (HILIC) UPLC-MS. Differences between metabolic profiles were evaluated using validated principal component and orthogonal partial least squares discriminant analysis.Results
Explorative analysis showed the main source of variation among samples was due to inter-individual differences with no grouping by sample type. After correcting for inter-individual differences, lipoproteins, lipids in VLDL/LDL, lactate, glutamine, and glucose were found to discriminate serum from plasma in NMR analyses. In UPLC-MS analyses, lysophosphatidylethanolamine (lysoPE)(18:0) and lysophosphatidic acid(20:0) were higher in serum, and phosphatidylcholines (PC)(16:1/18:2, 20:3/18:0, O-20:0/22:4), lysoPC(16:0), PE(O-18:2/20:4), sphingomyelin(18:0/22:0), and linoleic acid were lower. In plasma subtype analyses, isoleucine, leucine, valine, phenylalanine, glutamate, and pyruvate were higher among PRP samples compared with PPP and PFP by NMR while lipids in VLDL/LDL, citrate, and glutamine were lower. By UPLC-MS, PE(18:0/18:2) and PC(P-16:0/20:4) were higher in PRP compared with PFP samples.Conclusions
Correction for inter-individual variation was required to detect metabolite differences between serum and plasma. Our results suggest the potential importance of inter-individual effects and sample type on the results from serum and plasma metabolic phenotyping studies.13.
Antonio Murgia Christine Hinz Sonia Liggi Jùlìa Denes Zoe Hall James West Maria Laura Santoru Cristina Piras Cristina Manis Paolo Usai Luigi Atzori Julian L. Griffin Pierluigi Caboni 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):140
Background
Inflammatory bowel disease is a group of pathologies characterised by chronic inflammation of the intestine and an unclear aetiology. Its main manifestations are Crohn’s disease and ulcerative colitis. Currently, biopsies are the most used diagnostic tests for these diseases and metabolomics could represent a less invasive approach to identify biomarkers of disease presence and progression.Objectives
The lipid and the polar metabolite profile of plasma samples of patients affected by inflammatory bowel disease have been compared with healthy individuals with the aim to find their metabolomic differences. Also, a selected sub-set of samples was analysed following solid phase extraction to further characterise differences between pathological samples.Methods
A total of 200 plasma samples were analysed using drift tube ion mobility coupled with time of flight mass spectrometry and liquid chromatography for the lipid metabolite profile analysis, while liquid chromatography coupled with triple quadrupole mass spectrometry was used for the polar metabolite profile analysis.Results
Variations in the lipid profile between inflammatory bowel disease and healthy individuals were highlighted. Phosphatidylcholines, lyso-phosphatidylcholines and fatty acids were significantly changed among pathological samples suggesting changes in phospholipase A2 and arachidonic acid metabolic pathways. Variations in the levels of cholesteryl esters and glycerophospholipids were also found. Furthermore, a decrease in amino acids levels suggests mucosal damage in inflammatory bowel disease.Conclusions
Given good statistical results and predictive power of the model produced in our study, metabolomics can be considered as a valid tool to investigate inflammatory bowel disease.14.
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N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.16.
Caroline Ivanne Le Roy Luke John Mappley Roberto Marcello La Ragione Martin John Woodward Sandrine Paule Claus 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):157
Introduction
Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments.Objectives
As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus).Methods
Metabolic extractions were performed prior to 1H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized.Results
Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice.Conclusion
This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health.17.
Amir Abdoli 《生物学前沿》2017,12(6):387-391
Background
Inflammatory conditions are involved in the pathophysiology of cancer. Recent findings have revealed that excessive salt and fat intake is involved in the development of severe inflammatory reactions.Methods
literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of high salt and fat intake in the induction of inflammatory reactions and their roles in the etiopathogenesis of cancer.Results
The results indicate that high salt and fat intake can induce severe inflammatory conditions. However, various inflammatory conditions have been strongly linked to the development of cancer. Hence, high salt and fat intake might be involved in the pathogenesis of cancer progression via putative mechanisms related to inflammatory reactions.Conclusion
Reducing salt and fat intake may decrease the risk of cancer.18.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.19.
Shiwei Zhang Qiding Zhong Daobing Wang Zhanbin Huang Guohui Li 《Biotechnology letters》2017,39(12):1853-1857
Objectives
To determine the origin of 15N-labeled phenylalanine in microbial metabolic flux analysis using 15N as a tracer, a method for measuring phenylalanine δ15N using HPLC coupled with elemental analysis-isotope ratio mass spectrometry (EA-IRMS) was developed.Results
The original source of the 15N-labeled phenylalanine was determined using this new method that consists of three steps: optimization of the HPLC conditions, evaluation of the isotope fractionation effects, and evaluation of the effect of pre-processing on the phenylalanine nitrogen stable isotope. In addition, the use of a 15N-labeled inorganic nitrogen source, rather than 15N-labeled amino acids, was explored using this method.Conclusions
The method described here can also be applied to the analysis of metabolic flux.20.
Ruiyang Zhang Weiyun Zhu Linshu Jiang Shengyong Mao 《Metabolomics : Official journal of the Metabolomic Society》2017,13(6):74