PubMed

Related Articles Discriminating gastric cancer and gastric ulcer using human plasma amino acid metabolic profile. IUBMB Life. 2018 Apr 06;: Authors: Jing F, Hu X, Cao Y, Xu M, Wang Y, Jing Y, Hu X, Gao Y, Zhu Z Abstract Patients with gastric ulcer (GU) have a significantly higher risk of developing gastric cancer (GC), especially within 2 years after diagnosis. The main way to improve the prognosis of GC is to predict the tumorigenesis and metastasis in the early stage. The objective of this study was to demonstrate the ability of human plasma amino acid metabolic profile for discriminating GC and GU. In this study, we first used liquid chromatography-tandem mass spectrometry technique to characterize the plasma amino acid metabolism in GC and GU patients. Plasma samples were collected from 84 GC patients and 82 GU patients, and 22 amino acids were detected in each patient. Partial least squares-discriminant analysis model was performed to analyze the data of these amino acids. We observed seven differential amino acids between GC and GU. A regression analysis model was established using these seven amino acids. Finally, a panel of five differential amino acids, including glutamine, ornithine, histidine, arginine and tryptophan, was identified for discriminating GC and GU with good specificity and sensitivity. The receiver operating characteristic curve was used to evaluate diagnostic ability of the regression model and area under the curve was 0.922. In conclusion, this study demonstrated the potential values of plasma amino acid metabolic profile and metabolomic analysis technique in assisting diagnosis of GC. More studies are needed to highlight the theoretical strengths of metabolomics to understand the potential metabolic mechanisms in GC. © 2018 IUBMB Life, 2018. PMID: 29626382 [PubMed - as supplied by publisher]

Related Articles Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain. J Nephrol. 2018 Apr 06;: Authors: L'Imperio V, Pieruzzi F, Sinico RA, Nebuloni M, Granata A, Smith A, Radice A, Pagni F Abstract BACKGROUND: Membranous nephropathy (MN) can be idiopathic (iMN) or manifest as a result of systemic underlying conditions as a secondary epiphenomenon. For the prognostic and predictive consequences of this discrimination, the routine use of reliable markers is crucial. This large MN series aimed to evaluate the routine and standardized immunohistochemical (IHC) employment of a panel of 3 biomarkers-phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), and immunoglobulin (Ig)G4-in the differential diagnosis of MN forms, contributing to the validation of the technique and the correct interpretation of reproducible patterns of reactivity. METHODS: We classified 95 patients with a biopsy proven diagnosis of MN as primary (n = 72) or secondary (n = 23) cases based on clinical data. After performing an IHC assay directed against PLA2R, THSD7A and IgG4 antigens, samples were interpreted by three different nephropathologists to assess the positivity/negativity of the staining according to new interpretation criteria. RESULTS: Useful interpretation criteria were introduced to exclude false positive patterns of reactivity and to identify only true granular membranous or mesangial deposits in MN. The IHC directed against PLA2R resulted positive in 51 iMN cases and negative in 21, while 4/23 secondary forms were considered positive. Based on these data the technique showed a sensitivity of 71% and specificity of 83%. On the other hand, the IHC analysis for IgG4 resulted positive in 44 cases of iMN and negative in 28 cases, while only 4/23 secondary forms were positive (same cases positive to PLA2R). Finally, THSD7A was found to be positive only in 1 case, which was negative to PLA2R and IgG4. The combination of the results allowed a classification of the series into two major groups: "double-positive" (PLA2R+/IgG4+/THSD7A-) and "triple-negative" (PLA2R-/IgG4-/THSD7A-) cases. CONCLUSIONS: Based on these data, the diagnostic performance of the three biomarkers used in a "tandem fashion" can reach 79% sensitivity and 83% specificity, significantly reducing the risk of a false-positive or false-negative result and improving the routine characterization of this frequent glomerulonephritis. PMID: 29626294 [PubMed - as supplied by publisher]

Related Articles Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose. Diabetologia. 2018 Apr 06;: Authors: Merino J, Leong A, Liu CT, Porneala B, Walford GA, von Grotthuss M, Wang TJ, Flannick J, Dupuis J, Levy D, Gerszten RE, Florez JC, Meigs JB Abstract AIMS/HYPOTHESIS: Identifying the metabolite profile of individuals with normal fasting glucose (NFG [<5.55 mmol/l]) who progressed to type 2 diabetes may give novel insights into early type 2 diabetes disease interception and detection. METHODS: We conducted a population-based prospective study among 1150 Framingham Heart Study Offspring cohort participants, age 40-65 years, with NFG. Plasma metabolites were profiled by LC-MS/MS. Penalised regression models were used to select measured metabolites for type 2 diabetes incidence classification (training dataset) and to internally validate the discriminatory capability of selected metabolites beyond conventional type 2 diabetes risk factors (testing dataset). RESULTS: Over a follow-up period of 20 years, 95 individuals with NFG developed type 2 diabetes. Nineteen metabolites were selected repeatedly in the training dataset for type 2 diabetes incidence classification and were found to improve type 2 diabetes risk prediction beyond conventional type 2 diabetes risk factors (AUC was 0.81 for risk factors vs 0.90 for risk factors + metabolites, p = 1.1 × 10-4). Using pathway enrichment analysis, the nitrogen metabolism pathway, which includes three prioritised metabolites (glycine, taurine and phenylalanine), was significantly enriched for association with type 2 diabetes risk at the false discovery rate of 5% (p = 0.047). In adjusted Cox proportional hazard models, the type 2 diabetes risk per 1 SD increase in glycine, taurine and phenylalanine was 0.65 (95% CI 0.54, 0.78), 0.73 (95% CI 0.59, 0.9) and 1.35 (95% CI 1.11, 1.65), respectively. Mendelian randomisation demonstrated a similar relationship for type 2 diabetes risk per 1 SD genetically increased glycine (OR 0.89 [95% CI 0.8, 0.99]) and phenylalanine (OR 1.6 [95% CI 1.08, 2.4]). CONCLUSIONS/INTERPRETATION: In individuals with NFG, information from a discrete set of 19 metabolites improved prediction of type 2 diabetes beyond conventional risk factors. In addition, the nitrogen metabolism pathway and its components emerged as a potential effector of earliest stages of type 2 diabetes pathophysiology. PMID: 29626220 [PubMed - as supplied by publisher]

Related Articles Translational science in albuminuria: a new view of de novo albuminuria under chronic RAS suppression. Clin Sci (Lond). 2018 Apr 16;132(7):739-758 Authors: Baldan-Martin M, Rodríguez-Sánchez E, González-Calero L, Ruilope LM, Alvarez-Llamas G, Barderas MG, Ruiz-Hurtado G Abstract The development of de novo albuminuria during chronic renin-angiotensin system (RAS) suppression is a clinical entity that remains poorly recognized in the biomedical literature. It represents a clear increment in global cardiovascular (CV) and renal risk that cannot be counteracted by RAS suppression. Although not specifically considered, it is clear that this entity is present in most published and ongoing trials dealing with the different forms of CV and renal disease. In this review, we focus on the mechanisms promoting albuminuria, and the predictors and new markers of de novo albuminuria, as well as the potential treatment options to counteract the excretion of albumin. The increase in risk that accompanies de novo albuminuria supports the search for early markers and predictors that will allow practising physicians to assess and prevent the development of de novo albuminuria in their patients. PMID: 29626149 [PubMed - in process]

Related Articles Restoring mitochondrial calcium uniporter expression in diabetic mouse heart improves mitochondrial calcium handling and cardiac function. J Biol Chem. 2018 Apr 06;: Authors: Suarez J, Cividini F, Scott BT, Lehmann K, Diaz-Juarez J, Diemer T, Dai A, Suarez JA, Jain M, Dillmann WH Abstract Diabetes mellitus is a growing health care problem, resulting in significant cardiovascular morbidity and mortality. Diabetes also increases the risk for heart failure (HF) and decreased cardiac myocyte function, which are linked to changes in cardiac mitochondrial energy metabolism. The free mitochondrial calcium level ([Ca2+]m) is fundamental in activating the mitochondrial respiratory chain complexes and ATP production and is also known to regulate pyruvate dehydrogenase complex (PDC) activity. The mitochondrial calcium uniporter (MCU) complex (MCUC) plays a major role in mediating mitochondrial Ca2+ import, and its expression and function therefore have a marked impact on cardiac myocyte metabolism and function. Here, we investigated MCU's role in mitochondrial Ca2+ handling, mitochondrial function, glucose oxidation, and cardiac function in the heart of diabetic mice. We found that diabetic mouse hearts exhibit altered expression of MCU and MCUC members and a resulting decrease in [Ca2+]m, mitochondrial Ca2+ uptake, mitochondrial energetic function, and cardiac function. Adeno-associated virus-based normalization of MCU levels in these hearts restored mitochondrial Ca2+ handling, reduced PDC phosphorylation levels, and increased PDC activity. These changes were associated with cardiac metabolic reprogramming toward normal physiological glucose oxidation. This reprogramming likely contributed to the restoration of both cardiac myocyte and heart function to non-diabetic levels without any observed detrimental effects. These findings support the hypothesis that abnormal mitochondrial Ca2+ handling and its negative consequences can be ameliorated in diabetes by restoring MCU levels via adeno-associated virus-based MCU transgene expression. PMID: 29626093 [PubMed - as supplied by publisher]

Related Articles Development of a general method for quantifying IgG-based therapeutic monoclonal antibodies in human plasma using protein G purification coupled with a two internal standard calibration strategy using LC-MS/MS. Anal Chim Acta. 2018 Aug 17;1019:93-102 Authors: Chiu HH, Liao HW, Shao YY, Lu YS, Lin CH, Tsai IL, Kuo CH Abstract Monoclonal antibody (mAb) drugs have generated much interest in recent years for treating various diseases. Immunoglobulin G (IgG) represents a high percentage of mAb drugs that have been approved by the Food and Drug Administration (FDA). To facilitate therapeutic drug monitoring and pharmacokinetic/pharmacodynamic studies, we developed a general liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify the concentration of IgG-based mAbs in human plasma. Three IgG-based drugs (bevacizumab, nivolumab and pembrolizumab) were selected to demonstrate our method. Protein G beads were used for sample pretreatment due to their universal ability to trap IgG-based drugs. Surrogate peptides that were obtained after trypsin digestion were quantified by using LC-MS/MS. To calibrate sample preparation errors and matrix effects that occur during LC-MS/MS analysis, we used two internal standards (IS) method that include the IgG-based drug-IS tocilizumab and post-column infused IS. Using two internal standards was found to effectively improve quantification accuracy, which was within 15% for all mAb drugs that were tested at three different concentrations. This general method was validated in term of its precision, accuracy, linearity and sensitivity for 3 demonstration mAb drugs. The successful application of the method to clinical samples demonstrated its' applicability in clinical analysis. It is anticipated that this general method could be applied to other mAb-based drugs for use in precision medicine and clinical studies. PMID: 29625688 [PubMed - in process]

Related Articles Evaluation of batch effect elimination using quality control replicates in LC-MS metabolite profiling. Anal Chim Acta. 2018 Aug 17;1019:38-48 Authors: Sánchez-Illana Á, Piñeiro-Ramos JD, Sanjuan-Herráez JD, Vento M, Quintás G, Kuligowski J Abstract Systematic variation of the instrument's response both within- and between-batches is frequently observed in untarget LC-MS metabolomics involving the analysis of a large number of samples. The so-called batch effect decreases the statistical power and has a negative impact on repeatability and reproducibility of the results. As there is no standard way of assessing or correcting LC-MS batch effects and there is no single method providing optimal results in all situations, the selection of the optimal approach is not trivial. This work explores the effectiveness of a set of tools for batch effect assessment. Qualitative tools include the monitoring of spiked internal standards, principal component analysis and hierarchical cluster analysis. Quantitative tools comprise the distribution of RSDQC values, the median Pearson correlation coefficient in QCs, the ratio of random features in QCs using the runs test, as well as multivariate tools such as the δ-statistic, Silhouette plots, Principal Variance Component Analysis and the expected technical variation in the prediction. Results show that qualitative and quantitative approaches are complementary and that by limiting the analysis to QCs the power to detect and evaluate both within and between batch effects is increased. Besides, the graphical integration of outputs from multiple quantitative tools facilitates the evaluation of batch effects and it is proposed as a straightforward way for comparing and tailoring batch effect elimination approaches. PMID: 29625683 [PubMed - in process]

Related Articles PepsNMR for 1H NMR metabolomic data pre-processing. Anal Chim Acta. 2018 Aug 17;1019:1-13 Authors: Martin M, Legat B, Leenders J, Vanwinsberghe J, Rousseau R, Boulanger B, Eilers PHC, De Tullio P, Govaerts B Abstract In the analysis of biological samples, control over experimental design and data acquisition procedures alone cannot ensure well-conditioned 1H NMR spectra with maximal information recovery for data analysis. A third major element affects the accuracy and robustness of results: the data pre-processing/pre-treatment for which not enough attention is usually devoted, in particular in metabolomic studies. The usual approach is to use proprietary software provided by the analytical instruments' manufacturers to conduct the entire pre-processing strategy. This widespread practice has a number of advantages such as a user-friendly interface with graphical facilities, but it involves non-negligible drawbacks: a lack of methodological information and automation, a dependency of subjective human choices, only standard processing possibilities and an absence of objective quality criteria to evaluate pre-processing quality. This paper introduces PepsNMR to meet these needs, an R package dedicated to the whole processing chain prior to multivariate data analysis, including, among other tools, solvent signal suppression, internal calibration, phase, baseline and misalignment corrections, bucketing and normalisation. Methodological aspects are discussed and the package is compared to the gold standard procedure with two metabolomic case studies. The use of PepsNMR on these data shows better information recovery and predictive power based on objective and quantitative quality criteria. Other key assets of the package are workflow processing speed, reproducibility, reporting and flexibility, graphical outputs and documented routines. PMID: 29625674 [PubMed - in process]

16 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 2018/04/07PubMed 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.

16 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 2018/04/06PubMed 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 Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa. FEMS Microbiol Lett. 2018 Mar 29;: Authors: Phan J, Gallagher T, Oliver A, England W, Whiteson K Abstract Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic products of neighboring cells-especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression profiles, and phenotypic responses of a P. aeruginosa clinical isolate to fermentation products lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional profiles of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry (GCTOF-MS), we observe that fermentation products induce pyocyanin production along with expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences. PMID: 29617986 [PubMed - as supplied by publisher]

Related Articles Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers. Cell Rep. 2018 Apr 03;23(1):255-269.e4 Authors: Peng X, Chen Z, Farshidfar F, Xu X, Lorenzi PL, Wang Y, Cheng F, Tan L, Mojumdar K, Du D, Ge Z, Li J, Thomas GV, Birsoy K, Liu L, Zhang H, Zhao Z, Marchand C, Weinstein JN, Cancer Genome Atlas Research Network, Bathe OF, Liang H Abstract Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1-master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. PMID: 29617665 [PubMed - in process]

Related Articles Involvement of organic acids and amino acids in ameliorating Ni(II) toxicity induced cell cycle dysregulation in Caulobacter crescentus: a metabolomics analysis. Appl Microbiol Biotechnol. 2018 Apr 03;: Authors: Jain A, Chen WN Abstract Nickel (Ni(II)) toxicity is addressed by many different bacteria, but bacterial responses to nickel stress are still unclear. Therefore, we studied the effect of Ni(II) toxicity on cell proliferation of α-proteobacterium Caulobacter crescentus. Next, we showed the mechanism that allows C. crescentus to survive in Ni(II) stress condition. Our results revealed that the growth of C. crescentus is severely affected when the bacterium was exposed to different Ni(II) concentrations, 0.003 mM slightly affected the growth, 0.008 mM reduced the growth by 50%, and growth was completely inhibited at 0.015 mM. It was further shown that Ni(II) toxicity induced mislocalization of major regulatory proteins such as MipZ, FtsZ, ParB, and MreB, resulting in dysregulation of the cell cycle. GC-MS metabolomics analysis of Ni(II) stressed C. crescentus showed an increased level of nine important metabolites including TCA cycle intermediates and amino acids. This indicates that changes in central carbon metabolism and nitrogen metabolism are linked with the disruption of cell division process. Addition of malic acid, citric acid, alanine, proline, and glutamine to 0.015 mM Ni(II)-treated C. crescentus restored its growth. Thus, the present work shows a protective effect of these organic acids and amino acids on Ni(II) toxicity. Metabolic stimulation through the PutA/GlnA pathway, accelerated degradation of CtrA, and Ni-chelation by organic acids or amino acids are some of the possible mechanisms suggested to be involved in enhancing C. crescentus's tolerance. Our results shed light on the mechanism of increased Ni(II) tolerance in C. crescentus which may be useful in bioremediation strategies and synthetic biology applications such as the development of whole cell biosensor. PMID: 29616314 [PubMed - as supplied by publisher]

Related Articles Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure. Front Physiol. 2018;9:236 Authors: Liu C, Liu B, Liu L, Zhang EL, Sun BD, Xu G, Chen J, Gao YQ Abstract Background: The modulation of arachidonic acid (AA) metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS) model. Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA) after integrating metabolic information with phenotypic and transcriptomic datasets, respectively. Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS), metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively elevated in subjects in maladaptation to hypoxia. Conclusion: This is the first study to construct the map of AA metabolism pathway in response to hypoxia and reveal the crosstalk between phenotypic variation under hypoxia and the AA metabolism pathway. These findings may improve our understanding of the advanced pathophysiological mechanisms in acute hypoxic diseases and provide new insights into critical roles of the AA metabolism pathway in the development and prevention of these diseases. PMID: 29615930 [PubMed]

Related Articles Distinct Metabolic features differentiating FLT3-ITD AML from FLT3-WT childhood Acute Myeloid Leukemia. Sci Rep. 2018 Apr 03;8(1):5534 Authors: Stockard B, Garrett T, Guingab-Cagmat J, Meshinchi S, Lamba J Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with dismal response warranting the need for enhancing our understanding of AML biology. One prognostic feature associated with inferior response is the presence of activating mutations in FMS-like tyrosine kinase 3 (FLT3) especially occurrence of internal tandem duplication (FLT3-ITD). Although poorly understood, differential metabolic and signaling pathways associated with FLT3-ITD might contribute towards the observed poor prognosis. We performed a non-targeted global metabolic profiling of matched cell and plasma samples obtained at diagnosis to establish metabolic differences within FLT3-ITD and FLT3-WT pediatric AML. Metabolomic profiling by Ultra-High Performance-Liquid-Chromatography-Mass Spectrometry identified differential abundance of 21 known metabolites in plasma and 33 known metabolites in leukemic cells by FLT3 status. These metabolic features mapped to pathways of significant biological importance. Of interest were metabolites with roles in cancer, cell progression and involvement in purine metabolism and biosynthesis, cysteine/methionine metabolism, tryptophan metabolism, carnitine mediated fatty acid oxidation, and lysophospholipid metabolism. Although validation in a larger cohort is required, our results for the first time investigated global metabolic profile in FLT3-ITD AML. PMID: 29615816 [PubMed - in process]

Related Articles Metabolomics coupled with pathway analysis characterizes metabolic changes in response to BDE-3 induced reproductive toxicity in mice. Sci Rep. 2018 Apr 03;8(1):5423 Authors: Wei Z, Xi J, Gao S, You X, Li N, Cao Y, Wang L, Luan Y, Dong X Abstract Polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. 4-bromodiphenyl ether (BDE-3), the photodegradation products of higher brominated PBDEs, is the most fundamental mono-BDE in environment but is less studied. The purpose of this study was to investigate the reproductive toxicity induced by BDE-3 and explore the mechanism by metabolomics approach. In this study, mice were treated intragastrically with BDE-3 for consecutive six weeks at the dosages of 0.0015, 1.5, 10 and 30 mg/kg. The reproductive toxicity was evaluated by sperm analysis and histopathology examinations. UPLC-Q-TOF/MS was applied to profile the metabolites of testis tissue, urine and serum samples in the control and BDE-3 treated mice. Results showed the sperm count was dose-dependently decreased and percentage of abnormal sperms increased by the treatment of BDE-3. Histopathology examination also revealed changes in seminiferous tubules and epididymides in BDE-3 treated mice. Metabolomics analysis revealed that different BDE-3 groups showed metabolic disturbances to varying degrees. We identified 76, 38 and 31 differential metabolites in testis tissue, urine and serum respectively. Pathway analysis revealed several pathways including Tyrosine metabolism, Purine metabolism and Riboflavin metabolism, which may give a possible explanation for the toxic mechanism of BDE-3. This study indicates that UHPLC-Q-TOFMS-based metabolomics approach provided a better understanding of PBDEs-induced toxicity dynamically. PMID: 29615664 [PubMed - in process]

Related Articles ACPA IgG galactosylation associates with disease activity in pregnant patients with rheumatoid arthritis. Ann Rheum Dis. 2018 Apr 03;: Authors: Bondt A, Hafkenscheid L, Falck D, Kuijper TM, Rombouts Y, Hazes JMW, Wuhrer M, Dolhain RJEM Abstract OBJECTIVES: Patients with autoantibody-positive rheumatoid arthritis (RA) are less likely to experience pregnancy-induced improvement of RA disease activity (DAS28-C reactive protein (CRP)) compared with patients with autoantibody-negative RA. Anti-citrullinated protein antibodies (ACPAs) are the most specific autoantibodies for RA. We previously demonstrated that disease improvement is associated with changes in total IgG glycosylation, which regulate antibody effector function. Therefore, we sought to analyse the ACPA-IgG glycosylation profile during pregnancy with the aim to understand the lower change of pregnancy-induced improvement of the disease in patients with autoantibody-positive RA. METHODS: ACPA-IgGs were purified from ACPA-positive patient sera (n=112) of the Pregnancy-induced Amelioration of Rheumatoid Arthritis cohort, a prospective study designed to investigate pregnancy-associated improvement of RA. The fragment crystallisable (Fc)glycosylation profile of ACPA-IgGs was characterised by mass spectrometry and compared with that of total IgG derived from the same patients or from ACPA-negative patients. RESULTS: All ACPA-IgG subclasses display significant changes in the level of galactosylation and sialylation during pregnancy, although less pronounced than in total IgG. The pregnancy-induced increase in ACPA-IgG galactosylation, but not sialylation, associates with lower DAS28-CRP. In ACPA-positive patients, no such association was found with changes in the galactosylation of total IgG, whereas in ACPA-negative patients changes in disease activity correlated well with changes in the galactosylation of total IgG. CONCLUSIONS: In ACPA-positive RA, the pregnancy-induced change in galactosylation of ACPA-IgG, and not that of total IgG, associates with changes in disease activity. These data may indicate that in ACPA-positive patients the galactosylation of ACPA-IgG is of more pathogenic relevance than that of total IgG. PMID: 29615411 [PubMed - as supplied by publisher]

Related Articles Metabolomics and Transcriptomics Identify Multiple Downstream Targets of Paraburkholderia phymatum σ54 During Symbiosis with Phaseolus vulgaris. Int J Mol Sci. 2018 Apr 01;19(4): Authors: Lardi M, Liu Y, Giudice G, Ahrens CH, Zamboni N, Pessi G Abstract RpoN (or σ54) is the key sigma factor for the regulation of transcription of nitrogen fixation genes in diazotrophic bacteria, which include α- and β-rhizobia. Our previous studies showed that an rpoN mutant of the β-rhizobial strain Paraburkholderia phymatum STM815T formed root nodules on Phaseolus vulgaris cv. Negro jamapa, which were unable to reduce atmospheric nitrogen into ammonia. In an effort to further characterize the RpoN regulon of P. phymatum, transcriptomics was combined with a powerful metabolomics approach. The metabolome of P. vulgaris root nodules infected by a P. phymatumrpoN Fix- mutant revealed statistically significant metabolic changes compared to wild-type Fix⁺ nodules, including reduced amounts of chorismate and elevated levels of flavonoids. A transcriptome analysis on Fix- and Fix⁺ nodules-combined with a search for RpoN binding sequences in promoter regions of regulated genes-confirmed the expected control of σ54 on nitrogen fixation genes in nodules. The transcriptomic data also allowed us to identify additional target genes, whose differential expression was able to explain the observed metabolite changes in numerous cases. Moreover, the genes encoding the two-component regulatory system NtrBC were downregulated in root nodules induced by the rpoN mutant, and contained a putative RpoN binding motif in their promoter region, suggesting direct regulation. The construction and characterization of an ntrB mutant strain revealed impaired nitrogen assimilation in free-living conditions, as well as a noticeable symbiotic phenotype, as fewer but heavier nodules were formed on P. vulgaris roots. PMID: 29614780 [PubMed - in process]

Related Articles High Glucose-Induced Cardiomyocyte Death May Be Linked to Unbalanced Branched-Chain Amino Acids and Energy Metabolism. Molecules. 2018 Apr 01;23(4): Authors: Zhang X, Lin Q, Chen J, Wei T, Li C, Zhao L, Gao H, Zheng H Abstract High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo. However, we also identified a series of common metabolic changes, including increases in branched-chain amino acids (BCAAs: leucine, isoleucine and valine) as well as decreases in aspartate and creatine under high glucose condition. Moreover, a reduced energy metabolism could also be a common metabolic characteristic, as indicated by decreases in ATP in vitro as well as AMP, fumarate and succinate in vivo. Therefore, this study reveals that a decrease in energy metabolism and an increase in BCAAs metabolism could be implicated in high glucose-induced cardiomyocyte death. PMID: 29614759 [PubMed - in process]

Related Articles A Blood Test for Alzheimer's Disease: Progress, Challenges, and Recommendations. J Alzheimers Dis. 2018 Mar 29;: Authors: Kiddle SJ, Voyle N, Dobson RJB Abstract Ever since the discovery of APOEɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer's disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting. We first review the trends and challenges in AD blood biomarker research, before giving our personal recommendations to help researchers overcome these challenges. While some degree of consistency and replication has been seen across independent studies, several high-profile studies have seemingly failed to replicate. Partly due to academic incentives, there is a reluctance in the field to report predictive ability, to publish negative findings, and to independently replicate the work of others. If this can be addressed, then we will know sooner whether a blood test for AD or related phenotypes with clinical utility can be developed. PMID: 29614671 [PubMed - as supplied by publisher]