Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabolomics Research in Chronic Kidney Disease.

Mon, 07/05/2018 - 22:26
Related Articles Metabolomics Research in Chronic Kidney Disease. J Am Soc Nephrol. 2018 May 03;: Authors: Grams ME, Shafi T, Rhee EP PMID: 29724883 [PubMed - as supplied by publisher]

Empowering thyroid hormone research in human subjects using OMICs-technologies.

Mon, 07/05/2018 - 22:26
Related Articles Empowering thyroid hormone research in human subjects using OMICs-technologies. J Endocrinol. 2018 May 03;: Authors: Pietzner M, Kacprowski T, Friedrich N Abstract OMICs subsume different physiological layers including the genome, transcriptome, proteome, and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of bio-molecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma bio-molecules have been suggested as surrogates of tissue-specific action of thyroid hormones. This review provides a brief introduction to OMICs in thyroid research with a particular focus on metabolomics studies in humans elucidating the important role of thyroid hormones for whole body metabolism in adults. PMID: 29724864 [PubMed - as supplied by publisher]

Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients.

Mon, 07/05/2018 - 22:26
Related Articles Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients. J Med Microbiol. 2018 May 04;: Authors: Monleón D, Talaya A, Giménez E, Vinuesa V, Morales JM, Hernández-Boluda JC, Pérez A, Piñana JL, Solano C, Navarro D Abstract A plasma metabolomic model obtained by means of untargeted 1H nuclear magnetic resonance, to which taurine, choline, methylamine, total glutathione, trimethylamine N-oxide, lactate, lysine, isoleucine, total fatty acids and unsaturated fatty acids contributed, was validated for the prediction of first episodes of cytomegalovirus (CMV) DNAaemia in a cohort of 79 allogeneic stem haematopoietic stem cell transplant (allo-HSCT) recipients. The predictive success rate was nearly 65 % for patients at both low and high risk of CMV-related complications according to their baseline characteristics. Plasma metabolomics profiling shortly after engraftment (day 21 after transplantation) allowed the anticipation of the occurrence of CMV DNAaemia in 71 % of patients. Plasma metabolomics analyses may be ancillary for identifying allo-HSCT patients at the highest risk of CMV DNAaemia who may benefit from early targeted antiviral prophylaxis. PMID: 29724268 [PubMed - as supplied by publisher]

Cigarette Smoking and the Pathogenesis of Systemic Lupus Erythematosus.

Mon, 07/05/2018 - 22:26
Related Articles Cigarette Smoking and the Pathogenesis of Systemic Lupus Erythematosus. Expert Rev Clin Immunol. 2018 May 03;: Authors: Speyer CB, Costenbader KH Abstract INTRODUCTION: Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures "trigger" or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE- specific autoantibodies. Research has begun to search for possible explanations for the temporal nature of the relationship between current smoking and autoantibody positive-SLE. Here we review potential biologic mechanisms linking smoking and SLE risk, including effects upon T and B cells, inflammatory cytokines, oxidative stress, and the formation of short-lived DNA adducts. Expert Commentary: The directions for future research in this field include studies of gene-environment interactions, epigenetics, metabolomics and putative biologic mechanisms. PMID: 29724134 [PubMed - as supplied by publisher]

Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches.

Mon, 07/05/2018 - 22:26
Related Articles Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches. Antibiotics (Basel). 2018 May 01;7(2): Authors: Ordóñez-Robles M, Santos-Beneit F, Martín JF Abstract Streptomyces tsukubaensis stands out among actinomycetes by its ability to produce the immunosuppressant tacrolimus. Discovered about 30 years ago, this macrolide is widely used as immunosuppressant in current clinics. Other potential applications for the treatment of cancer and as neuroprotective agent have been proposed in the last years. In this review we introduce the discovery of S. tsukubaensis and tacrolimus, its biosynthetic pathway and gene cluster (fkb) regulation. We have focused this work on the omic studies performed in this species in order to understand tacrolimus production. Transcriptomics, proteomics and metabolomics have improved our knowledge about the fkb transcriptional regulation and have given important clues about nutritional regulation of tacrolimus production that can be applied to improve production yields. Finally, we address some points of S. tsukubaensis biology that deserve more attention. PMID: 29724001 [PubMed]

Improved phosphometabolome profiling applying isotope dilution strategy and capillary ion chromatography-tandem mass spectrometry.

Mon, 07/05/2018 - 22:26
Related Articles Improved phosphometabolome profiling applying isotope dilution strategy and capillary ion chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 15;1083:278-283 Authors: Stafsnes MH, Røst LM, Bruheim P Abstract The phosphometabolome is comprised of all phosphorylated metabolites including the major metabolite classes sugar phosphates and nucleoside phosphates. Phosphometabolites are invaluable in any cell as a part of primary- and energy- metabolism, and as building blocks in the biosynthesis of macromolecules. Here, we report quantitative profiling of the phosphometabolome by applying capillary ion chromatography-tandem mass spectrometry (capIC-MS/MS), ensuring improved chromatographic separation, robustness and quantitative precision. Baseline separation was achieved for six out of eight tested hexose phosphates. Quantitative precision and reproducibility was improved by introducing a fully uniformly (U) 13C-labeled biological extract and applying an isotope dilution (ID) correction strategy. A 13C-labeled biological extract does in principle contain internal standards (IS) for all metabolites, but low abundant metabolites pose a challenge, and solutions to this are discussed. The extreme reproducibility and reliability of this capIC-MS/MS method was demonstrated by running the instrumentation continuously for ten days. PMID: 29571119 [PubMed - indexed for MEDLINE]

Development and validation of an ultra high performance liquid chromatography-electrospray tandem mass spectrometry method using selective derivatisation, for the quantification of two reactive aldehydes produced by lipid peroxidation, HNE (4-hydroxy-2...

Mon, 07/05/2018 - 22:26
Related Articles Development and validation of an ultra high performance liquid chromatography-electrospray tandem mass spectrometry method using selective derivatisation, for the quantification of two reactive aldehydes produced by lipid peroxidation, HNE (4-hydroxy-2(E)-nonenal) and HHE (4-hydroxy-2(E)-hexenal) in faecal water. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 15;1083:171-179 Authors: Chevolleau S, Noguer-Meireles MH, Jouanin I, Naud N, Pierre F, Gueraud F, Debrauwer L Abstract Red or processed meat rich diets have been shown to be associated with an elevated risk of colorectal cancer (CRC). One major hypothesis involves dietary heme iron which induces lipid peroxidation. The quantification of the resulting reactive aldehydes (e.g. HNE and HHE) in the colon lumen is therefore of great concern since these compounds are known for their cytotoxic and genotoxic properties. UHPLC-ESI-MS/MS method has been developed and validated for HNE and HHE quantification in rat faeces. Samples were derivatised using a brominated reagent (BBHA) in presence of pre-synthesized deuterated internal standards (HNE-d11/HHE-d5), extracted by solid phase extraction, and then analysed by LC-positive ESI-MS/MS (MRM) on a TSQ Vantage mass spectrometer. The use of BBHA allowed the efficient stabilisation of the unstable and reactive hydroxy-alkenals HNE and HHE. The MRM method allowed selective detection of HNE and HHE on the basis of characteristic transitions monitored from both the 79 and 81 bromine isotopic peaks. This method was validated according to the European Medicines Agency (EMEA) guidelines, by determining selectivity, sensitivity, linearity, carry-over effect, recovery, matrix effect, repeatability, trueness and intermediate precision. The performance of the method enabled the quantification of HNE and HHE in concentrations 0.10-0.15 μM in faecal water. Results are presented on the application to the quantification of HNE and HHE in different faecal waters obtained from faeces of rats fed diets with various fatty acid compositions thus corresponding to different pro-oxidative features. PMID: 29549740 [PubMed - indexed for MEDLINE]

metabolomics; +26 new citations

Fri, 04/05/2018 - 14:57
26 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 2018/05/04PubMed 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.

metabolomics; +19 new citations

Thu, 03/05/2018 - 14:20
19 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 2018/05/03PubMed 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.

metabolomics; +23 new citations

Wed, 02/05/2018 - 13:52
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 2018/05/02PubMed 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.

metabolomics; +29 new citations

Tue, 01/05/2018 - 19:29
29 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 2018/05/01PubMed 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.

13C-labelled yeast as internal standard for LC-MS/MS and LC high resolution MS based amino acid quantification in human plasma.

Mon, 30/04/2018 - 18:44
Related Articles 13C-labelled yeast as internal standard for LC-MS/MS and LC high resolution MS based amino acid quantification in human plasma. J Pharm Biomed Anal. 2018 Mar 27;155:329-334 Authors: Hermann G, Schwaiger M, Volejnik P, Koellensperger G Abstract Extracts from isotopically labelled organisms can be a versatile source for isotopically labelled chemical compounds providing ideal internal standards in mass spectrometry based assays. In this work, the application of 13C enriched yeast (Pichia pastoris) for accurate absolute metabolite quantification in human samples was investigated. >99% 13C enriched Pichia pastoris was produced via fermentation and extracted employing established protocols. Quantitative assays based on LC-triple quadrupole mass spectrometry (QQQ-MS) and LC-high resolution mass spectrometry (HRMS) were validated using the Standard Reference Material, SRM 1950 - metabolites in frozen human plasma. 14 amino acids (as given in the certificate) were quantified using separations by reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). The latter chromatographic separation provided retention and selectivity for the amino acid panel, while the studied approaches employing RPLC relied on the selectivity of the MS detection. Cross-validation using the different MS platforms showed that in all cases the application of in-vivo labelled standards resulted in a significant improvement of trueness and precision. LODs and LOQs ranged, regardless of the detection system and addition of internal standards, in the same order of magnitude. The linear dynamic range of the employed detection systems was enhanced at least for one order of magnitude for several analytes when the internal standards were applied. PMID: 29704823 [PubMed - as supplied by publisher]

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Mon, 30/04/2018 - 18:44
Related Articles Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer. Methods. 2018 Apr 25;: Authors: Hale VL, Jeraldo P, Mundy M, Yao J, Keeney G, Scott N, Heidi Cheek E, Davidson J, Green M, Martinez C, Lehman J, Pettry C, Reed E, Lyke K, White BA, Diener C, Resendis-Antonio O, Gransee J, Dutta T, Petterson XM, Boardman L, Larson D, Nelson H, Chia N Abstract Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue. PMID: 29704665 [PubMed - as supplied by publisher]

Enhancement of mitochondrial biogenesis and paradoxical inhibition of lactate dehydrogenase mediated by 14-3-3η in oncocytomas.

Mon, 30/04/2018 - 18:44
Related Articles Enhancement of mitochondrial biogenesis and paradoxical inhibition of lactate dehydrogenase mediated by 14-3-3η in oncocytomas. J Pathol. 2018 Apr 27;: Authors: Feng J, Zhang Q, Li C, Zhou Y, Zhao S, Hong L, Song Q, Yu S, Hu C, Wang H, Mao C, Shepard MJ, Hao S, Dominah G, Sun M, Wan H, Park DM, Gilbert MR, Xu G, Zhuang Z, Zhang Y Abstract Oncocytomas represent a subset of benign pituitary adenomas that are characterized by significant mitochondrial hyperplasia. Mitochondria are key organelles for energy generation and metabolic intermediate production for biosynthesis in tumor cells, so understanding the mechanism underlying mitochondrial biogenesis and its impact on cellular metabolism in oncocytoma is imperative. Here we studied surgically resected pituitary oncocytomas using multi-omic analyses. Whole-exome sequencing did not detect any nuclear mutations but identified several somatic mutations of mitochondrial DNA (mtDNA), and dysfunctional respiratory complex I. Metabolomic analysis suggested that oxidative phosphorylation was reduced within individual mitochondrion and that there was no reciprocal increase in glycolytic activity. Interestingly, we found a reduction in cellular lactate and reduced expression of lactate dehydrogenase A (LDHA), which contributed to mitochondrial biogenesis in an in vitro cell model. Of note, the hypoxia-response signaling pathway was not up-regulated in pituitary oncocytomas thereby failing to enhance glycolysis. Proteomic analysis identified that 14-3-3η was exclusively overexpressed in oncocytomas and that 14-3-3η was capable of inhibiting glycolysis, leading to mitochondrial biogenesis in the presence of rotenone. Particularly, 14-3-3η inhibited LDHA by direct interaction in the setting of complex I dysfunction, highlighting the role of 14-3-3η overexpression and inefficient oxidative phosphorylation in oncocytoma mitochondrial biogenesis. These findings deepen our understanding of the metabolic changes that occur within oncocytomas and shine a light on the mechanism of mitochondrial biogenesis, providing a novel perspective of metabolic adaption in tumor cells. PMID: 29704241 [PubMed - as supplied by publisher]

Relationships between digestive efficiency and metabolomic profiles of serum and intestinal contents in chickens.

Mon, 30/04/2018 - 18:44
Related Articles Relationships between digestive efficiency and metabolomic profiles of serum and intestinal contents in chickens. Sci Rep. 2018 Apr 27;8(1):6678 Authors: Beauclercq S, Nadal-Desbarats L, Hennequet-Antier C, Gabriel I, Tesseraud S, Calenge F, Le Bihan-Duval E, Mignon-Grasteau S Abstract The increasing cost of conventional feedstuffs has bolstered interest in genetic selection for digestive efficiency (DE), a component of feed efficiency, assessed by apparent metabolisable energy corrected to zero nitrogen retention (AMEn). However, its measurement is time-consuming and constraining, and its relationship with metabolic efficiency poorly understood. To simplify selection for this trait, we searched for indirect metabolic biomarkers through an analysis of the serum metabolome using nuclear magnetic resonance (1H NMR). A partial least squares (PLS) model including six amino acids and two derivatives from butyrate predicted 59% of AMEn variability. Moreover, to increase our knowledge of the molecular mechanisms controlling DE, we investigated 1H NMR metabolomes of ileal, caecal, and serum contents by fitting canonical sparse PLS. This analysis revealed strong associations between metabolites and DE. Models based on the ileal, caecal, and serum metabolome respectively explained 77%, 78%, and 74% of the variability of AMEn and its constitutive components (utilisation of starch, lipids, and nitrogen). In our conditions, the metabolites presenting the strongest associations with AMEn were proline in the serum, fumarate in the ileum and glucose in caeca. This study shows that serum metabolomics offers new opportunities to predict chicken DE. PMID: 29703927 [PubMed - in process]

An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Septic Shock Patients Stratified for Mortality.

Mon, 30/04/2018 - 18:44
Related Articles An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Septic Shock Patients Stratified for Mortality. Sci Rep. 2018 Apr 27;8(1):6681 Authors: Cambiaghi A, Díaz R, Martinez JB, Odena A, Brunelli L, Caironi P, Masson S, Baselli G, Ristagno G, Gattinoni L, de Oliveira E, Pastorelli R, Ferrario M Abstract In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information. PMID: 29703925 [PubMed - in process]

Plant hormonomics: multiple phytohormone profiling by targeted metabolomics.

Mon, 30/04/2018 - 18:44
Related Articles Plant hormonomics: multiple phytohormone profiling by targeted metabolomics. Plant Physiol. 2018 Apr 27;: Authors: Šimura J, Antoniadi I, Široká J, Tarkowska D, Strnad M, Ljung K, Novak O Abstract Phytohormones are physiologically important small molecules, which play essential roles in intricate signaling networks that regulate diverse processes in plants. We present a method for the simultaneous targeted profiling of 101 phytohormone-related analytes from minute amounts of fresh plant material (< 20 mg). Rapid and non-selective extraction, fast one-step sample purification, and extremely sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) enable concurrent quantification of the main phytohormone classes: cytokinins, auxins, brassinosteroids, gibberellins, jasmonates, salicylates, and abscisates. We validated this 'hormonomic' approach in salt-stressed and control Arabidopsis thaliana seedlings, quantifying a total of 43 endogenous compounds in both root and shoot samples. Subsequent multivariate statistical data processing and cross-validation with transcriptomic data highlighted the main hormone metabolites involved in plant adaptation to salt stress. PMID: 29703867 [PubMed - as supplied by publisher]

Proteomics and immunohistochemistry identify the expression of α-cardiac myosin heavy chain in the jaw-closing muscles of sooty mangabeys (order Primates).

Mon, 30/04/2018 - 18:44
Related Articles Proteomics and immunohistochemistry identify the expression of α-cardiac myosin heavy chain in the jaw-closing muscles of sooty mangabeys (order Primates). Arch Oral Biol. 2018 Feb 03;: Authors: Wall CE, Holmes M, Soderblom EJ, Taylor AB Abstract OBJECTIVE: The jaw-closing muscles of humans and nonprimate mammals express alpha-cardiac fibers but MyHC α-cardiac has not been identified in the jaw adductors of nonhuman primates. We determined whether MyHC α-cardiac is expressed in the superficial masseter and temporalis muscles of the sooty mangabey (Cercocebus atys), an African Old World monkey that specializes on hard seeds. DESIGN: LC-MS/MS based proteomics was used to identify the presence of MyHC Iα. Immunohistochemistry was used to analyze the composition and distribution of fiber types in the superficial masseter and temporalis muscles of eight C. atys. Serial sections were stained against MyHC α-cardiac (MYH6), as well as MyHC-1 (NOQ7.5.4D), MyHC-2 (MY-32), and MyHC-M (2F4). RESULTS: Proteomics analysis identified the presence of Myosin-6 (MyHC α-cardiac) in both heart atrium and superficial masseter. MyHC α-cardiac was expressed in abundance in the superficial masseter and temporalis muscles of all eight individuals and hybrid fibers were common. CONCLUSIONS: The identification of MyHC α-cardiac in the jaw adductors of sooty mangabeys is a novel finding for nonhuman primates. The abundance of MyHC α-cardiac indicates a fatigue-resistant fiber population characterized by intermediate speed of contraction between pure MyHC-1 and MyHC-2 isoforms. We suggest that α-cardiac fibers may be advantageous to sooty mangabeys, whose feeding behavior includes frequent crushing of relatively large, hard seeds during the power stroke of ingestion. Additional studies comparing jaw-adductor fiber phenotype of hard-object feeding primates and other mammals are needed to explore this relationship further. PMID: 29703519 [PubMed - as supplied by publisher]

Next generation microbiological risk assessment-Potential of omics data for hazard characterisation.

Mon, 30/04/2018 - 18:44
Related Articles Next generation microbiological risk assessment-Potential of omics data for hazard characterisation. Int J Food Microbiol. 2018 Apr 12;: Authors: Haddad N, Johnson N, Kathariou S, Métris A, Phister T, Pielaat A, Tassou C, Wells-Bennik MHJ, Zwietering MH Abstract According to the World Health Organization estimates in 2015, 600 million people fall ill every year from contaminated food and 420,000 die. Microbial risk assessment (MRA) was developed as a tool to reduce and prevent risks presented by pathogens and/or their toxins. MRA is organized in four steps to analyse information and assist in both designing appropriate control options and implementation of regulatory decisions and programs. Among the four steps, hazard characterisation is performed to establish the probability and severity of a disease outcome, which is determined as function of the dose of toxin and/or pathogen ingested. This dose-response relationship is subject to both variability and uncertainty. The purpose of this review/opinion article is to discuss how Next Generation Omics can impact hazard characterisation and, more precisely, how it can improve our understanding of variability and limit the uncertainty in the dose-response relation. The expansion of omics tools (e.g. genomics, transcriptomics, proteomics and metabolomics) allows for a better understanding of pathogenicity mechanisms and virulence levels of bacterial strains. Detection and identification of virulence genes, comparative genomics, analyses of mRNA and protein levels and the development of biomarkers can help in building a mechanistic dose-response model to predict disease severity. In this respect, systems biology can help to identify critical system characteristics that confer virulence and explain variability between strains. Despite challenges in the integration of omics into risk assessment, some omics methods have already been used by regulatory agencies for hazard identification. Standardized methods, reproducibility and datasets obtained from realistic conditions remain a challenge, and are needed to improve accuracy of hazard characterisation. When these improvements are realized, they will allow the health authorities and government policy makers to prioritize hazards more accurately and thus refine surveillance programs with the collaboration of all stakeholders of the food chain. PMID: 29703417 [PubMed - as supplied by publisher]

1H NMR-based metabolomics approach to investigating the renal protective effects of Genipin in diabetic rats.

Mon, 30/04/2018 - 18:44
Related Articles 1H NMR-based metabolomics approach to investigating the renal protective effects of Genipin in diabetic rats. Chin J Nat Med. 2018 Apr;16(4):261-270 Authors: Tian JS, Zhao L, Shen XL, Liu H, Qin XM Abstract Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance (NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin. PMID: 29703326 [PubMed - in process]

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