PubMed

The analytical process to search for metabolomics biomarkers. J Pharm Biomed Anal. 2017 Jul 06;: Authors: Luque de Castro MD, Priego-Capote F Abstract The scant number of available metabolomics biomarkers does not reflect the extent of the research in this field. Looking for the reasons of failure, the authors, as analytical chemists, critically discuss each of the steps in the analytical process that requires improvements. They find insufficient information about how the experimental part is developed. After revising the steps from sampling to obtainment of the analytical sample (from typical samples such as blood and urine to others less common such as sweat or saliva), the need for data and metadata for either reproduction of a given study or for taking the study as starting point after biomarker discovery is criticized. The separation and analysis steps are also revised as does data treatment. After the sources of errors from the analytical process are overcome, subsequent steps in the implementation of biomarkers to reach the final aim of clinical adoption should be supported as required. PMID: 28709716 [PubMed - as supplied by publisher]

Peripheral biomarkers of major depression and antidepressant treatment response: Current knowledge and future outlooks. J Affect Disord. 2017 Jul 05;: Authors: Gadad BS, Jha MK, Czysz A, Furman JL, Mayes TL, Emslie MP, Trivedi MH Abstract BACKGROUND: In recent years, we have accomplished a deeper understanding about the pathophysiology of major depressive disorder (MDD). Nevertheless, this improved comprehension has not translated to improved treatment outcome, as identification of specific biologic markers of disease may still be crucial to facilitate a more rapid, successful treatment. Ongoing research explores the importance of screening biomarkers using neuroimaging, neurophysiology, genomics, proteomics, and metabolomics measures. RESULTS: In the present review, we highlight the biomarkers that are differentially expressed in MDD and treatment response and place a particular emphasis on the most recent progress in advancing technology which will continue the search for blood-based biomarkers. LIMITATIONS: Due to space constraints, we are unable to detail all biomarker platforms, such as neurophysiological and neuroimaging markers, although their contributions are certainly applicable to a biomarker review and valuable to the field. CONCLUSIONS: Although the search for reliable biomarkers of depression and/or treatment outcome is ongoing, the rapidly-expanding field of research along with promising new technologies may provide the foundation for identifying key factors which will ultimately help direct patients toward a quicker and more effective treatment for MDD. PMID: 28709695 [PubMed - as supplied by publisher]

A novel Alzheimer's disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimers Res Ther. 2017 Jul 14;9(1):50 Authors: Daugherty D, Goldberg J, Fischer W, Dargusch R, Maher P, Schubert D Abstract BACKGROUND: CAD-31 is an Alzheimer's disease (AD) drug candidate that was selected on the basis of its ability to stimulate the replication of human embryonic stem cell-derived neural precursor cells as well as in APPswe/PS1ΔE9 AD mice. To move CAD-31 toward the clinic, experiments were undertaken to determine its neuroprotective and pharmacological properties, as well as to assay its therapeutic efficacy in a rigorous mouse model of AD. RESULTS: CAD-31 has potent neuroprotective properties in six distinct nerve cell assays that mimic toxicities observed in the old brain. Pharmacological and preliminary toxicological studies show that CAD-31 is brain-penetrant and likely safe. When fed to old, symptomatic APPswe/PS1ΔE9 AD mice starting at 10 months of age for 3 additional months in a therapeutic model of the disease, there was a reduction in the memory deficit and brain inflammation, as well as an increase in the expression of synaptic proteins. Small-molecule metabolic data from the brain and plasma showed that the major effect of CAD-31 is centered on fatty acid metabolism and inflammation. Pathway analysis of gene expression data showed that CAD-31 had major effects on synapse formation and AD energy metabolic pathways. CONCLUSIONS: All of the multiple physiological effects of CAD-31 were favorable in the context of preventing some of the toxic events in old age-associated neurodegenerative diseases. PMID: 28709449 [PubMed - in process]

Integrating multi-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4'-OH)MeLeu](4)-CsA overproduction. Microb Cell Fact. 2017 Jul 14;16(1):120 Authors: Liu H, Huang D, Jin L, Wang C, Liang S, Wen J Abstract BACKGROUND: Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu](4)-CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu](4)-CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu](4)-CsA so far. RESULTS: To investigate the effect of soybean oil on CsA conversion, some other plant oils (corn oil and peanut oil) and the major hydrolysates of soybean oil were fed into the production medium, respectively. The results demonstrated that the plant oils, rather than the hydrolysates, could significantly improve the [(4'-OH)MeLeu](4)-CsA production, suggesting that soybean oil might not play its role in the lipid metabolic pathway. To further unveil the mechanism of [(4'-OH)MeLeu](4)-CsA overproduction under the soybean oil condition, a proteomic analysis based on the two-dimensional gel electrophoresis coupled with MALDI TOF/TOF mass spectrometry was implemented. The results showed that central carbon metabolism, genetic information processing and energy metabolism were significantly up-regulated under the soybean oil condition. Moreover, the gas chromatography-mass spectrometry-based metabolomic analysis indicated that soybean oil had a great effect on amino acid metabolism and tricarboxylic acid cycle. In addition, the transcription levels of cytochrome P450 hydroxylase (CYP) genes for CsA conversion were determined by RT-qPCR and the results showed that most of the CYP genes were up-regulated under the soybean oil condition. CONCLUSIONS: These findings indicate that soybean oil could strengthen the primary metabolism and the CYP system to enhance the mycelium growth and the monooxygenation reaction, respectively, and it will be a guidance for the further metabolic engineering of this strain. PMID: 28709434 [PubMed - in process]

Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth. BMC Cancer. 2017 Jul 14;17(1):485 Authors: Amaya CN, Mitchell DC, Bryan BA Abstract BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells. METHODS: In this study, we compared ROCK1 and 2 protein expression in a large panel of benign and malignant vascular tumors to that of normal vasculature. We then utilized shRNA technology to knockdown the expression of ROCK1 and 2 in SVR tumor-forming vascular cells, and evaluated tumor size and proliferation rate in a xenograft model. Finally, we employed proteomics and metabolomics to assess how knockdown of the ROCK paralogs induced alterations in protein expression/phosphorylation and metabolite concentrations in the xenograft tumors. RESULTS: Our findings revealed that ROCK1 was overexpressed in malignant vascular tumors such as hemangioendotheliomas and angiosarcomas, and ROCK2 was overexpressed in both benign and malignant vascular tumors including hemangiomas, hemangioendotheliomas, hemangiopericytomas, and angiosarcomas. shRNA-mediated knockdown of ROCK2, but not ROCK1, in xenograft vascular tumors significantly reduced tumor size and proliferative index compared to control tumors. Proteomics and metabolomics analysis of the xenograft tumors revealed both overlapping as well as unique roles for the ROCK paralogs in regulating signal transduction and metabolite concentrations. CONCLUSIONS: Collectively, these data indicate that ROCK proteins are overexpressed in diverse vascular tumors and suggest that specific targeting of ROCK2 proteins may show efficacy against malignant vascular tumors. PMID: 28709411 [PubMed - in process]

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data. Metabolomics. 2017;13(8):92 Authors: Zhang Q, Ford LA, Evans AM, Toal DR Abstract INTRODUCTION: A major bottleneck in metabolomic studies is metabolite identification from accurate mass spectrometric data. Metabolite x17299 was identified in plasma as an unknown in a metabolomic study using a compound-centric approach where the associated ion features of the compound were used to determine the true molecular mass. OBJECTIVES: The aim of this work is to elucidate the chemical structure of x17299, a new compound by de novo interpretation of mass spectrometric data. METHODS: An Orbitrap Elite mass spectrometer was used for acquisition of mass spectra up to MS(4) at high resolution. Synthetic standards of N,N,N-trimethyl-l-alanyl-l-proline betaine (l,l-TMAP), a diastereomer, and an enantiomer were chemically prepared. RESULTS: The planar structure of x17299 was successfully proposed by de novo mechanistic interpretation of mass spectrometric data without any laborious purification and nuclear magnetic resonance spectroscopic analysis. The proposed structure was verified by deuterium exchanged mass spectrometric analysis and confirmed by comparison to a synthetic standard. Relative configuration of x17299 was determined by direct chromatographic comparison to a pair of synthetic diastereomers. Absolute configuration was assigned after derivatization of x17299 with a chiral auxiliary group followed by its chromatographic comparison to a pair of synthetic standards. CONCLUSION: The chemical structure of metabolite x17299 was determined to be l,l-TMAP. PMID: 28706470 [PubMed]

Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae: a leap into disease pathophysiology. Metabolomics. 2017;13(7):83 Authors: Welle T, Hoekstra AT, Daemen IAJJM, Berkers CR, Costa MO Abstract INTRODUCTION: Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available. OBJECTIVE: The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae. METHODS: Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes. RESULTS: Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae. CONCLUSIONS: The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO. PMID: 28706469 [PubMed]

Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics. Metabolomics. 2017;13(3):22 Authors: de la Barca JMC, Huang NT, Jiao H, Tessier L, Gadras C, Simard G, Natoli R, Tcherkez G, Reynier P, Valter K Abstract INTRODUCTION: Light is the primary stimulus for vision, but may also cause damage to the retina. Pre-exposing the retina to sub-lethal amount of light (or preconditioning) improves chances for retinal cells to survive acute damaging light stress. OBJECTIVES: This study aims at exploring the changes in retinal metabolome after mild light stress and identifying mechanisms that may be involved in preconditioning. METHODS: Retinas from 12 rats exposed to mild light stress (1000 lux × for 12 h) and 12 controls were collected one and seven days after light stress (LS). One retina was used for targeted metabolomics analysis using the Biocrates p180 kit while the fellow retina was used for histological and immunohistochemistry analysis. RESULTS: Immunohistochemistry confirmed that in this experiment, a mild LS with retinal immune response and minimal photoreceptor loss occurred. Compared to controls, LS induced an increased concentration in phosphatidylcholines. The concentration in some amino acids and biogenic amines, particularly those related to the nitric oxide pathway (like asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day after LS. 7 days after LS, the concentration in two sphingomyelins and phenylethylamine was found to be higher. We further found that in controls, retina metabolome was different between males and females: male retinas had an increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and (acyl)-carnitines. CONCLUSIONS: Besides retinal sexual metabolic dimorphism, this study shows that preconditioning is mostly associated with re-organisation of lipid metabolism and changes in amino acid composition, likely reflecting the involvement of arginine-dependent NO signalling. PMID: 28706468 [PubMed]

Affinity purification of erythropoietin from cell culture supernatant combined with MALDI-TOF-MS analysis of erythropoietin N-glycosylation. Sci Rep. 2017 Jul 13;7(1):5324 Authors: Falck D, Haberger M, Plomp R, Hook M, Bulau P, Wuhrer M, Reusch D Abstract Erythropoietin (EPO) is a heavily glycosylated hormone whose recombinant forms are used for treatment of anaemia. EPO glycosylation is important for its pharmacological properties. An analytical workflow, which can determine EPO glycosylation in an accurate and high-throughput fashion from cell culture supernatant (CCS) in approximately 24 h, offers the possibility to follow changes during production. To address this challenge, we present a complete workflow consisting of protein purification, glycan release, sialic acid derivatization, solid phase extraction, matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) analysis and MassyTools data processing. EPO purification from CCS by anti-EPO antibody coupled Sepharose beads yielded excellent purity with acceptable recovery and was free of glycoform bias. Glycosylation profiles obtained by MALDI-MS were highly comparable to those obtained with an established capillary gel electrophoresis-laser induced fluorescence method. Our method delivers accurate results for the analysis of changes of important glycosylation parameters, such as sialylation and number of N-acetyllactosamine units, for the time course of a fermentation. We could resolve differences in glycosylation between several CCS samples. PMID: 28706253 [PubMed - in process]

Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget. 2017 Jul 06;: Authors: Sica V, Bravo-San Pedro JM, Chen G, Mariño G, Lachkar S, Izzo V, Maiuri MC, Niso-Santano M, Kroemer G Abstract Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions. Depletion of ING4 stimulated the enzymatic activity of PIK3C3, as visualized by means of a red fluorescent protein-tagged short peptide (FYVE) that specifically binds to phosphatidylinositol-3-phosphate (PI3P)-containing subcellular vesicles and enhanced autophagy, as indicated by an enhanced lipidation of microtubule-associated proteins 1A/1B light chain 3 beta (LC3B) and the redistribution of a green-fluorescent protein (GFP)-LC3B fusion protein to cytoplasmic puncta. The generation of GFP-LC3B puncta stimulated by ING4 depletion was reduced by simultaneous depletion, or pharmacological inhibition, of PIK3C3/VPS34. In conclusion, ING4 acts as a negative regulator of the lipid kinase activity of the BECN1 complex, and starvation-induced autophagy is accompanied by the dissociation of the ING4/BECN1 interaction. PMID: 28706153 [PubMed - as supplied by publisher]

Integration of flux measurements to resolve changes in anabolic and catabolic metabolism in cardiac myocytes. Biochem J. 2017 Jul 13;: Authors: Gibb AA, Lorkiewicz PK, Zheng YT, Zhang X, Bhatnagar A, Jones SP, Hill BG Abstract Although ancillary pathways of glucose metabolism are critical for synthesizing cellular building blocks and modulating stress responses, how they are regulated remains unclear.  In this study, we used radiometric glycolysis assays, [(13)C6]-glucose isotope tracing, and extracellular flux analysis to understand how phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon partitioning into catabolic and anabolic pathways. Expression of kinase-deficient or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat neonatal cardiomyocytes coordinately regulated glycolytic rate and lactate production. Nevertheless, in all groups, >40% of glucose consumed by the cells was unaccounted for via catabolism to pyruvate, which suggests entry of glucose carbons into ancillary pathways branching from metabolites formed in the preparatory phase of glycolysis. Analysis of (13)C fractional enrichment patterns suggests that PFK activity regulates glucose carbon incorporation directly into the ribose and the glycerol moieties of purines and phospholipids, respectively. Pyrimidines, UDP-N-acetyl-hexosamine, and the fatty acyl chains of phosphatidylinositol and triglycerides showed lower (13)C incorporation under conditions of high PFK activity; the isotopologue (13)C enrichment pattern of each metabolite indicated limitations in mitochondria-engendered oxaloacetate, acetyl CoA, and fatty acids. Consistent with this notion, high glycolytic rate diminished mitochondrial activity and the coupling of glycolysis to glucose oxidation. These findings suggest that a major portion of intracellular glucose in cardiac myocytes is apportioned for ancillary biosynthetic reactions and that PFK coordinates the activities of the pentose phosphate, hexosamine biosynthetic, and glycerolipid synthesis pathways by directly modulating glycolytic intermediate entry into auxiliary glucose metabolism pathways and indirectly regulating mitochondrial cataplerosis. PMID: 28706006 [PubMed - as supplied by publisher]

Related Articles Molecular definitions of autophagy and related processes. EMBO J. 2017 Jul 03;36(13):1811-1836 Authors: Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, Cuervo AM, Debnath J, Deretic V, Dikic I, Eskelinen EL, Fimia GM, Fulda S, Gewirtz DA, Green DR, Hansen M, Harper JW, Jäättelä M, Johansen T, Juhasz G, Kimmelman AC, Kraft C, Ktistakis NT, Kumar S, Levine B, Lopez-Otin C, Madeo F, Martens S, Martinez J, Melendez A, Mizushima N, Münz C, Murphy LO, Penninger JM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Santambrogio L, Scorrano L, Simon AK, Simon HU, Simonsen A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Kroemer G Abstract Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research. PMID: 28596378 [PubMed - indexed for MEDLINE]

Related Articles Association of Radiomics and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme. Int J Radiat Oncol Biol Phys. 2017 Mar 01;97(3):586-595 Authors: Lopez CJ, Nagornaya N, Parra NA, Kwon D, Ishkanian F, Markoe AM, Maudsley A, Stoyanova R Abstract PURPOSE: To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient. In radiation therapy of GBM the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl aspartate (NAA) and choline (Cho). The corresponding clinical target volumes (CTVs) for radiation therapy are based on contrast-enhanced T1-weighted (CE-T1w) and T2-weighted (T2w)/fluid-attenuated inversion recovery MRI. METHODS AND MATERIALS: Necrotic portions, enhancing lesion, and edema were manually contoured on CE-T1w/T2w images for 17 GBM patients. Clinical target volumes and MTVs for NAA (MTVNAA) and Cho (MTVCho) were constructed. Imaging and metabolic features related to size, shape, and signal intensities of the volumes were extracted. Tumors were also scored categorically for 10 semantic imaging traits by a neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and CTVs/MTVs features were visualized as heatmaps. Associations between MTVNAA and MTVCho and imaging features were studied using Spearman correlation. RESULTS: Forty-eight imaging features were extracted per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. Twenty features were extracted from CTVs and MTVs. A series of semantic imaging traits were replaced with automatically extracted continuous variables. There were multiple (22) significant correlations of imaging measures with CTVs/MTVNAA, whereas there were only 6 with CTVs/MTVCho. CONCLUSIONS: A framework for investigation of codependencies between MRI and magnetic resonance spectroscopic imaging radiomic features and CTVs/MTVs has been established. The MTV for NAA was found to be closely associated with MRI volumes, whereas very few imaging features were related to MTVCho, indicating that Cho provides additional information to imaging. PMID: 28011044 [PubMed - indexed for MEDLINE]

Related Articles The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease. J Clin Microbiol. 2016 May;54(5):1191-6 Authors: Theel ES Abstract Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies to Borrelia burgdorferi remains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined. PMID: 26865690 [PubMed - indexed for MEDLINE]

31 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 2017/07/14PubMed 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 Profiling to Determine the Effect of Postmortem Aging on Color and Lipid Oxidative Stabilities of Different Bovine Muscles. J Agric Food Chem. 2017 Jul 12;: Authors: Ma D, Kim YHB, Cooper BR, Oh JH, Chun H, Choe J, Schoonmaker JP, Ajuwon KM, Min B Abstract The objective of this study was to identify the metabolites that could be associated with oxidative stability of aged bovine muscles. Three muscles (longissimus lumbrum (LL), semimembranosus (SM), and psoas major (PM)) from 7 beef carcasses at 1 day postmortem were divided into three sections and assigned to three aging periods (9, 16 and 23 days). While an increase in discoloration was found in all muscles with aging, LL was the most color/lipid oxidative stable, followed by SM and PM (P < 0.05). Lower myoglobin and non-heme iron contents were observed in LL compared to SM and PM (P < 0.05). The HPLC-ESI-MS based metabolomics analysis identified metabolites that were significantly responsive to aging and/or muscle type, such as acyl carnitines, free amino acids, nucleotides, nucleosides, and glucuronides. The results from the current study suggested that color and oxidative stability is inversely associated with aging, but is also muscle-specific. Further studies determining the exact role of the identified metabolites in color and oxidative stability of beef muscles should be warranted. PMID: 28700223 [PubMed - as supplied by publisher]

Related Articles Proteomics and metabolomics in ageing research: from biomarkers to systems biology. Essays Biochem. 2017 Jul 15;61(3):379-388 Authors: Hoffman JM, Lyu Y, Pletcher SD, Promislow DEL Abstract Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying 'endophenotypes' in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. PMID: 28698311 [PubMed - in process]

18 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 2017/07/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a (1)H-NMR-based untargeted metabolomics approach. J Nutr Biochem. 2017 Jun 07;48:36-43 Authors: Almanza-Aguilera E, Urpi-Sarda M, Llorach R, Vázquez-Fresno R, Garcia-Aloy M, Carmona F, Sanchez A, Madrid-Gambin F, Estruch R, Corella D, Andres-Lacueva C Abstract The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A (1)H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases. PMID: 28692847 [PubMed - as supplied by publisher]

Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus. PLoS One. 2017;12(7):e0180331 Authors: Figueiredo AS, Kouril T, Esser D, Haferkamp P, Wieloch P, Schomburg D, Ruoff P, Siebers B, Schaber J Abstract Sulfolobus solfataricus is a thermoacidophilic Archaeon that thrives in terrestrial hot springs (solfatares) with optimal growth at 80°C and pH 2-4. It catabolizes specific carbon sources, such as D-glucose, to pyruvate via the modified Entner-Doudoroff (ED) pathway. This pathway has two parallel branches, the semi-phosphorylative and the non-phosphorylative. However, the strategy of S.solfataricus to endure in such an extreme environment in terms of robustness and adaptation is not yet completely understood. Here, we present the first dynamic mathematical model of the ED pathway parameterized with quantitative experimental data. These data consist of enzyme activities of the branched pathway at 70°C and 80°C and of metabolomics data at the same temperatures for the wild type and for a metabolic engineered knockout of the semi-phosphorylative branch. We use the validated model to address two questions: 1. Is this system more robust to perturbations at its optimal growth temperature? 2. Is the ED robust to deletion and perturbations? We employed a systems biology approach to answer these questions and to gain further knowledge on the emergent properties of this biological system. Specifically, we applied deterministic and stochastic approaches to study the sensitivity and robustness of the system, respectively. The mathematical model we present here, shows that: 1. Steady state metabolite concentrations of the ED pathway are consistently more robust to stochastic internal perturbations at 80°C than at 70°C; 2. These metabolite concentrations are highly robust when faced with the knockout of either branch. Connected with this observation, these two branches show different properties at the level of metabolite production and flux control. These new results reveal how enzyme kinetics and metabolomics synergizes with mathematical modelling to unveil new systemic properties of the ED pathway in S.solfataricus in terms of its adaptation and robustness. PMID: 28692669 [PubMed - in process]