PubMed

Related Articles The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat. Hepatology. 2018 Jan;67(1):282-295 Authors: Yip LY, Aw CC, Lee SH, Hong YS, Ku HC, Xu WH, Chan JMX, Cheong EJY, Chng KR, Ng AHQ, Nagarajan N, Mahendran R, Lee YK, Browne ER, Chan ECY Abstract The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher β-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral β-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. CONCLUSION: This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (Hepatology 2018;67:282-295). PMID: 28646502 [PubMed - indexed for MEDLINE]

Related Articles Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice. Blood Adv. 2017 Aug 22;1(19):1551-1564 Authors: Gillissen MA, de Jong G, Kedde M, Yasuda E, Levie SE, Moiset G, Hensbergen PJ, Bakker AQ, Wagner K, Villaudy J, van Helden PM, Spits H, Hazenberg MD Abstract Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s). Strikingly, CD43s is expressed on all World Health Organization 2008 types of AML and MDS. AT1413 induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of AML cells in vitro. Of note, AT1413 was highly efficacious against AML cells in a humanized mouse model without affecting nonmalignant human myeloid cells, suggesting AT1413 has potential as a therapeutic antibody. PMID: 29296797 [PubMed]

Related Articles Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats. Blood Adv. 2017 Jul 25;1(17):1296-1305 Authors: Reisz JA, Slaughter AL, Culp-Hill R, Moore EE, Silliman CC, Fragoso M, Peltz ED, Hansen KC, Banerjee A, D'Alessandro A Abstract Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg). Steady-state measurements were accompanied by metabolic flux analysis upon tracing of in vivo-injected 13C15N-glutamine or inhibition of glutaminolysis using the anticancer drug CB-839. RBC metabolic phenotypes recapitulated the systemic metabolic reprogramming observed in plasma from the same rodent model. Results indicate that shock RBCs rely on glutamine to fuel glutathione (GSH) synthesis and pyruvate transamination, whereas abrogation of glutaminolysis conferred early mortality and exacerbated lactic acidosis and systemic accumulation of succinate, a predictor of mortality in the military and civilian critically ill populations. Glutamine is here identified as an essential amine group donor in HS RBCs, plasma, liver, and lungs, providing additional rationale for the central role glutaminolysis plays in metabolic reprogramming and survival following severe hemorrhage. PMID: 29296771 [PubMed]

Related Articles Multiplexed targeted proteomic assay to assess coagulation factor concentrations and thrombosis-associated cancer. Blood Adv. 2017 Jun 27;1(15):1080-1087 Authors: Mohammed Y, van Vlijmen BJ, Yang J, Percy AJ, Palmblad M, Borchers CH, Rosendaal FR Abstract The plasma levels of pro- and anticoagulant proteins are important markers for venous thrombosis (VT) risk and can be affected by both genetic and acquired factors, including cancer. Generally, these markers are measured using activity- or antibody-based assays. Targeted proteomics with stable-isotope-labeled internal standards has proven adept at the rapid, multiplex, and precise quantification of proteins in complex biological samples such as plasma. We used liquid chromatography coupled to multiple reaction monitoring (MRM) mass spectrometry to evaluate the concentrations of 31 coagulation- and fibrinolysis-related proteins in plasma from 25 healthy controls, 25 patients with VT, and 25 patients with VT who were also diagnosed with cancer. The concentration level of 1 to 3 proteotypic peptides per protein was determined, and all samples were previously characterized using traditional antibody- or activity-based methods. When comparing the conventional and the MRM strategies, the mean Pearson correlation for the 13 proteins (covered by 36 target peptides) shared between the 2 approaches was 0.77, indicating a good correlation. Additionally, MRM offers higher sensitivity (mean regression slope, 0.81), higher multiplicity in a single run, and good ability to leverage all measurements to discriminate groups using unsupervised clustering, which identified vitamin K antagonist users as well as patients with VT and cancer. The data collected using MRM show that the combination of coagulation factor levels yields signature information on VT and cancer, which was not obvious from a single measurement. These results encourage the further validation and investigation of MRM in profiling protein signature of disease. PMID: 29296750 [PubMed]

Related Articles Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models. Chin Med. 2017;12:35 Authors: Dai M, Wang F, Zou Z, Xiao G, Chen H, Yang H Abstract Background: Dysfunctional metabolisms are contributed to LPS/GALN-induced hepatitis. However, whether Hedyotis diffusa (HD) employs metabolic strategies against hepatitis is unknown. Methods: We use the cytokines expression, levels of serum alanine transaminase and aspartate transaminase, survival and histological analysis to measure the effect of decoction of HD on acute severe hepatitis of mouse induced by LPS/GALN. Meanwhile, we utilize GC/MS-based metabolomics to characterize the variation of metabolomes. Results: The present study shows the relieving liver damage in HD decoction-treated mice. Metabolic category using differential metabolites indicates the lower percentage of carbohydrates in LPS/GALN + HD group than LPS/GALN group, revealing the value of carbohydrate metabolism in HD decoction-administrated mouse liver. Further pathway enrichment analysis proposes that citrate cycle, galactose metabolism, and starch and sucrose metabolism are three important carbohydrate metabolisms that involve in the protective effect of decoction of HD during acute hepatitis. Furthermore, other important enrichment pathways are biosynthesis of unsaturated fatty acids, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Fatty acids or amino acids involved in above-mentioned pathways are also detected in high loading distribution on IC01 and IC02, thereby manifesting the significance of these metabolites. Other key metabolites detect in ICA analysis were cholesterol, lactic acid and tryptophan. Conclusions: The variation tendency of above-mentioned metabolites is totally consistent with the protective nature of decoction of HD. These findings give a viewpoint that HD decoction-effected metabolic strategies are linked to underlying mechanisms of decoction of HD and highlight the importance of metabolic mechanisms against hepatitis. PMID: 29296119 [PubMed]

Related Articles Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics. Nat Commun. 2018 Jan 02;9(1):39 Authors: Earl DC, Ferrell PB, Leelatian N, Froese JT, Reisman BJ, Irish JM, Bachmann BO Abstract Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling. Arrayed metabolites are tested against acute myeloid leukemia patient bone marrow and molecules that specifically targeted blast cells or nonleukemic immune cell subsets within the same tissue biopsy are revealed. Cell-targeting polyketides are identified in extracts from biosynthetically prolific bacteria, including a previously unreported leukemia blast-targeting anthracycline and a polyene macrolactam that alternates between targeting blasts or nonmalignant cells by way of light-triggered photochemical isomerization. High-resolution cell profiling with mass cytometry confirms response mechanisms and is used to validate initial observations. PMID: 29295987 [PubMed - in process]

21 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 2018/01/03PubMed 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.

21 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 2018/01/03PubMed 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 Impaired pentose phosphate pathway in the development of 3D MCF-7 cells mediated intracellular redox disturbance and multi-cellular resistance without drug induction. Redox Biol. 2017 Dec 21;15:253-265 Authors: Wang W, Cai Q, Zhou F, Liu J, Jin X, Ni P, Lu M, Wang G, Zhang J Abstract Although metabolic reprogramming and redox imbalance are widely reported to be involved in chemo-resistance in cancer treatment, much more attention was paid to anti-cancer drug induced effect. Our previous studies showed that cancer cells can develop P-gp overexpression-mediated intrinsic drug resistance in the formation of 3D MCF-7 multi-cellular layers (MCLs) without any drug induction. However, whether metabolic reprogramming and redox imbalance functioned during this progress remained unrevealed. In our present study, LC-Q/TOF-MS and GC-MS were used in combination for analysing intracellular metabolites. The contribution of pentose phosphate pathway (PPP) and its related redox status were checked by chemical interfering and silencing/over-expression of glucose-6-phosphate dehydrogenase (G6PD). The downstream products of G6PD were assayed by quantitative real-time PCR, western blot and flow cytometry. Results showed that not only G6PD expression but also G6PD activity was significantly lowered along with 3D MCF-7 cells culture time. Impaired PPP disturbed redox-cycling, generated reactive oxygen species (ROS), which triggered cell cycle arrest and caused the switch to Chk2/p53/NF-κB pathway-mediated P-gp induction. Our results provided a new attempt to associate intrinsic small molecule metabolites (impaired PPP) communicating with cell signalling pathways through disturbed intracellular redox status to elucidate multi-cellular resistance (MCR) in 3D MCF-7 cells, which improved the understanding of the mechanisms of P-gp up-regulation in MCR with metabolomic and related redox status support. PMID: 29291545 [PubMed - as supplied by publisher]

Related Articles Enhanced glycometabolism as a mechanism of NQO1 potentiated growth of NSCLC revealed by metabolomic profiling. Biochem Biophys Res Commun. 2017 Dec 29;: Authors: Cheng X, Liu F, Liu H, Wang G, Hao H Abstract NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoplasmic 2-electron reductase, has been considered as a potential poor prognostic biomarker and a promising therapeutic target for patients with non-small cell lung cancer (NSCLC) due to its frequent overexpression and significantly increased activity in NSCLC. Previous studies have shown that depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. However, the underlying mechanisms whereby NQO1 potentiates proliferation have not been fully understood. In this study, based on a metabolomics analysis, we found that cell proliferation inhibition upon NQO1 depletion was accompanied by suppressed glycometabolism in NQO1 high expression human NSCLC A549 cells. Also we found that NQO1 depletion significantly decreased the gene expression levels of hexokinase II (HKII), a key mediator of aerobic glycolysis responsible for the transformation of glucose into glucose-6-phosphate. Taken together, we proposed that NQO1 could potentiate NSCLC cell proliferation by enhancing cellular glycometabolism, and HKII is a key mediator of this mechanism. PMID: 29291405 [PubMed - as supplied by publisher]

Related Articles A pilot study of the metabolomic profiles of saliva from female orthodontic patients with external apical root resorption. Clin Chim Acta. 2017 Dec 29;: Authors: Zhou J, Hu H, Huang R Abstract BACKGROUND: Orthodontically induced external apical root resorption (OIEARR) is one of the most severe complications of orthodontic treatment, which is hard to diagnose at early stage by merely radiographic examination. This study aimed to identify salivary metabolic products using unbiased metabolic profiling in order to discover biomarkers that may indicate OIEARR. MATERIALS AND METHODS: Unstimulated saliva samples were analyzed from 19 healthy orthodontic patients with EARR (n=8) and non-EARR (n=11). Metabolite profiling was performed using 1H Nuclear Magnetic Resonance (NMR) spectroscopy. RESULTS: A total of 187 metabolites were found in saliva samples. With supervised partial least squares discriminant analysis and regression analysis, samples from 2 groups were well separated, attributed by a series of metabolites of interest, including butyrate, propane-1,2-diol, α-linolenic acid (Ala), α-glucose, urea, fumarate, formate, guanosine, purine, etc. Indicating the increased inflammatory responses in the periodontal tissues possibly associated with energy metabolism and oxidative stress. CONCLUSIONS: The effective separation capacity of 1H NMR based metabolomics suggested potential feasibility of clinical application in monitoring periodontal and apical condition in orthodontic patients during treatment and make early diagnosis of OIEARR. Metabolites detected in this study need further validation to identify exact biomarkers of OIEARR. Saliva biomarkers may assist in diagnosis and monitoring of this disease. PMID: 29291387 [PubMed - as supplied by publisher]

Related Articles Hypothesis: Induction of biomarkers for detection of colonic neoplasms. J Cancer. 2018;9(1):166-173 Authors: Bordonaro M, Lazarova D Abstract The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC. Considering the need for a sensitive and non-invasive detection of early stage neoplastic lesions in the colon, we propose the development of a test based on a novel concept - the concept of induced biomarkers. The proposal is based upon our findings that the food additives propolis and gamma-cyclodextrin (gCD) (a) decrease the neoplastic burden in normal weight and obese ApcMin mice, a model of early stage intestinal neoplasia, and (b) elicit significant changes in the serum proteome in ApcMin mice. We posit that gCD and propolis induce the release of neoplasm-associated biomarkers in systemic circulation (e.g., metabolites, neoplastic, apoptotic, and immune response proteins), and these markers could be used to detect early stage intestinal neoplasms. Additional dietary bioactives may also elicit a complement of induced markers. The hypothesis could be ascertained by utilizing a mouse model, the Apc+/1638Nmice, as well as through human subject studies that integrate proteomics and metabolomics analyses. The concept of detecting inducible markers of colonic neoplasms is novel, and is substantiated by the significant physiological effects of gCD and propolis on neoplastic colonic cells in culture and on early neoplastic development in ApcMinmice. The long-term objective is to develop a minimally invasive method that detects early stage neoplastic development in the human colon. PMID: 29290782 [PubMed]

Related Articles CMPF, a Metabolite Formed Upon Prescription Omega-3-Acid Ethyl Ester Supplementation, Prevents and Reverses Steatosis. EBioMedicine. 2017 Dec 19;: Authors: Prentice KJ, Wendell SG, Liu Y, Eversley JA, Salvatore SR, Mohan H, Brandt SL, Adams AC, Serena Wang X, Wei D, FitzGerald GA, Durham TB, Hammond CD, Sloop KW, Skarke C, Schopfer FJ, Wheeler MB Abstract Prescription ω-3 fatty acid ethyl ester supplements are commonly used for the treatment of hypertriglyceridemia. However, the metabolic profile and effect of the metabolites formed by these treatments remain unknown. Here we utilized unbiased metabolomics to identify 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) as a significant metabolite of the ω-3-acid ethyl ester prescription Lovaza™ in humans. Administration of CMPF to mice before or after high-fat diet feeding at exposures equivalent to those observed in humans increased whole-body lipid metabolism, improved insulin sensitivity, increased beta-oxidation, reduced lipogenic gene expression, and ameliorated steatosis. Mechanistically, we find that CMPF acutely inhibits ACC activity, and induces long-term loss of SREBP1c and ACC1/2 expression. This corresponds to an induction of FGF21, which is required for long-term steatosis protection, as FGF21KO mice are refractory to the improved metabolic effects. Thus, CMPF treatment in mice parallels the effects of human Lovaza™ supplementation, revealing that CMPF may contribute to the improved metabolic effects observed with ω-3 fatty acid prescriptions. PMID: 29290411 [PubMed - as supplied by publisher]

Related Articles Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic dyslipidemia. J Clin Lipidol. 2017 Mar - Apr;11(2):551-561.e7 Authors: Amor AJ, Pinyol M, Solà E, Catalan M, Cofán M, Herreras Z, Amigó N, Gilabert R, Sala-Vila A, Ros E, Ortega E Abstract BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly prevalent, cardiovascular risk factor, and lipoprotein proatherogenic disturbances likely explain a large part of this risk. However, information regarding associations between detailed nuclear magnetic resonance (NMR) lipoprotein changes and noninvasive NAFLD scores is lacking. OBJECTIVE: The objective of the study was to investigate the NMR-assessed atherogenic lipoprotein profile according to noninvasive NAFLD status. METHODS: Lipoprotein profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and Gholam's models. RESULTS: We assessed 173 participants (55% males), mean age 60.8 ± 7.8 years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and >60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI >60 had lower high-density lipoprotein (HDL)-cholesterol (P < .001), higher triglyceride (P < .001), and similar non-HDL-cholesterol (P = .912) concentrations. In NMR analysis, FLI was related with very-low-density lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle number (P < .001) and VLDL size (39.1 ± 0.99, 39.7 ± 0.96, 40.8 ± 1.19 nm, P < .001) increased with increased FLI (<30, 30-60, and >60, respectively). Conversely, although total HDL particle number did not differ by FLI (P = .377), larger HDL particles (P < .001), amount of cholesterol within HDL particles (P < .001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04 [7.93-8.16] nm, P < .001) decreased as FLI increased. FLI >60 (vs <60) was associated with a higher proportion of small LDL particles (P = .010) and lower LDL size (19.85 ± 0.34 vs 19.98 ± 0.25 nm; P = .005). Similar findings were found for Gholam's model. CONCLUSION: Simple and noninvasive NAFLD scores are useful to detect many of the proatherogenic changes (especially in VLDL and HDL), beyond conventional lipids parameters that are common in individuals with this high-risk condition. PMID: 28502513 [PubMed - indexed for MEDLINE]

Related Articles Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls. Clin Chim Acta. 2017 Jun;469:42-52 Authors: Chatterji T, Singh S, Sen M, Singh AK, Agarwal GR, Singh DK, Srivastava JK, Singh A, Srivastava RN, Roy R Abstract BACKGROUND: Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). METHODS: The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). RESULTS: The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R2 of 0.97 and Q2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R2 of 0.80 and Q2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. CONCLUSION: On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. PMID: 28315295 [PubMed - indexed for MEDLINE]

Priorities for future research into asthma diagnostic tools: A PAN-EU Consensus exercise from the European asthma research innovation partnership (EARIP). Clin Exp Allergy. 2017 Dec 31;: Authors: Garcia-Marcos L, Edwards J, Kennington E, Aurora P, Baraldi E, Carraro S, Gappa M, Louis R, Moreno-Galdo A, Peroni DG, Pijnenburg M, Priftis KN, Sanchez-Solis M, Schuster A, Walker S, EARIP collaboration Abstract The diagnosis of asthma is currently based on clinical history, physical examination and lung function; and to date there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state-of-the-art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarising workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face to face workshop. The three most important diagnostic/predictive tools ranked were: "New biological markers of asthma (e.g. genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring", "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath". This article is protected by copyright. All rights reserved. PMID: 29290104 [PubMed - as supplied by publisher]

A multi-omics analysis reveals metabolic reprogramming in THP-1 cells upon treatment with the contact allergen DNCB. Toxicol Appl Pharmacol. 2017 Dec 28;: Authors: Mussotter F, Potratz S, Budczies J, Luch A, Haase A Abstract Dendritic cell (DC) activation by contact allergens is one of the key steps in the development of allergic contact dermatitis (ACD). Recent evidence suggests that metabolic reprogramming is a prerequisite for the activation of DCs, macrophages and monocytes. Therefore, we used an integrated approach by combining proteomics and metabolomics to investigate the metabolism of human THP-1 cells in response to the strong contact allergen, 2,4-dinitrochlorobenzene (DNCB). Cells were treated with 5, 10 and 20μM DNCB for 4, 8, and 24h, respectively. Using a targeted metabolomics approach, we quantified levels of 188 endogenous metabolites, among them phospholipids, acylcarnitines, amino acids and hexoses. In addition, proteomic changes were analyzed using an untargeted quantitative approach based on stable isotope labeling with amino acids in cell culture (SILAC). We detected several alterations in the metabolome and consistently in the proteome indicating metabolic reprogramming of THP-1 cells by DNCB. In particular, we found an increase in phospholipids that was accompanied by an up-regulation of fatty acid synthase (FAS), a key enzyme in lipid synthesis. PMID: 29289672 [PubMed - as supplied by publisher]

Construction, immune protection and innate immune response of shuffled polyvalent ompAs vaccines. Fish Shellfish Immunol. 2017 Dec 28;: Authors: Wang SN, Cheng ZX, Ling XP, Chu X, Peng XX, Li H Abstract Our previous studies demonstrated that molecular breeding via DNA shuffling directs the evolution of polyvalent vaccines with desired traits, which leads to generation of polyvalent ompA vaccines using Vibrio alginolyticus VA0764 primers. Here, we replaced VA0764 primers with Edwardsiella tarda ompA primers to generate new polyvalent ompA vaccines by DNA shuffling of the same five ompA genes from four species of bacteria E. tarda, V. parahaemolyticus, V. alginolyticus and Escherichia coli. We identified four polyvalent vaccine candidates from a eukaryotic expressing library EompAs-FE containing 82 ompAs using active immune protection against V. alginolyticus and E. tarda. Furthermore, we explored mechanisms of polyvalent vaccine candidates by investigation of the innate immune response to these ompAs, and found that expression of IL-1β, IL-8, IL-15, COX-2, IFN-γ, TLR-1, TLR-3 and C3b genes was elevated as a characteristic feature of these polyvalent vaccine candidates. These results indicate that use of different primers to construct a DNA library selects new evolution of polyvalent vaccines with desired traits, and polyvalent ompA vaccines elicit high innate immune response. PMID: 29289655 [PubMed - as supplied by publisher]

Mass spectrometry based analytical approaches and pitfalls for toxicometabolomics of arsenic in mammals: A tutorial review. Anal Chim Acta. 2018 Feb 13;1000:41-66 Authors: García-Barrera T, Rodríguez-Moro G, Callejón-Leblic B, Arias-Borrego A, Gómez-Ariza JL Abstract The present review focus on the analytical platforms and the workflow for toxicometabolomics with a special emphasis on their strengths and pitfalls presenting as a case study the toxicometabolomics of arsenic in mammals. Although powerful analytical methods and techniques are currently available for metabolomics, the main "bottleneck" is still the absence of unified protocols for sample preparation (e.g. quenching, solvents used) as well as several important factors in toxicometabolomics, which drastically affect the metabolism (e.g. selection of model organisms, xenobiotic doses, chemical form of the xenobiotic, exposure route, biological sample). In this context, the applicability to complex samples, higher sensitivity, specificity and the possibility to perform quantitative analysis offered by MS is crucial to probe xenobiotic induced metabolic changes to evaluate the stress responses. Nowadays, the use of different metabolomic platforms allowed determining important changes in the metabolism induced by arsenic in mammals such as alterations in the energy (e.g. Glycolysis, Kreb's cycle), amino acid, lipid, nucleotide and androgen metabolisms. PMID: 29289324 [PubMed - in process]

Related Articles Effect of pomegranate based marinades on the microbiological, chemical and sensory quality of chicken meat: A metabolomics approach. Int J Food Microbiol. 2017 Dec 21;267:42-53 Authors: Lytou AE, Nychas GE, Panagou EZ Abstract Pomegranate juice is a product with enhanced functional properties that could be used as an alternative to traditional marination ingredients and effectively retard microbial growth along with providing an improved sensory result. In this study, two pomegranate based marinades were prepared for the marination of chicken breast fillets and the marinated samples were aerobically stored at 4 and 10°C for 9days. Raw, non-marinated chicken samples were used as control. Levels of total viable counts (TVC), Pseudomonas spp., Brochothrix thermosphacta, Enterobacteriaceae and lactic acid bacteria (LAB) were determined together with sensory assessment to evaluate the evolution of spoilage. The profile of organic acids and volatile compounds was also analyzed during storage. The shelf life of marinated samples was significantly extended compared to control samples at both storage temperatures (e.g., up to 5 and 6days for the pomegranate/lemon marinated samples stored at 4 and 10°C, respectively) as evaluated by both microbiological and sensory analyses. The profile of the organic acids and the volatilome of marinated and control samples were remarkably differentiated according to storage time, microbial load and sensory score. The findings of this study suggest that pomegranate juice could be used as a novel ingredient in marinades to improve the sensory attributes, while prolonging the shelf life of chicken meat. PMID: 29288907 [PubMed - as supplied by publisher]