PubMed

In silico analysis of glycinamide ribonucleotide transformylase inhibition by PY873, PY899 and DIA. Saudi J Biol Sci. 2017 Sep;24(6):1155-1161 Authors: Batool S, Nawaz MS, Mushtaq G, Parvaiz F, Kamal MA Abstract In humans, purine de novo synthesis pathway consists of multi-functional enzymes. Nucleotide metabolism enzymes are potential drug targets for treating cancer and autoimmune diseases. Glycinamide ribonucleotide transformylase (GART) is one of the most important trifunctional enzymes involved in purine synthesis. Previous studies have demonstrated the role of folate inhibitors against tumor activity. In this present study, three components of GART enzyme were targeted as receptor dataset and in silico analysis was carried out with folate ligand dataset. To accomplish the task, Autodock 4.2 was used for determining the docking compatibilities of ligand and receptor dataset. Taken together, it has been suggested that folate ligands could be potentially used as inhibitors of GART. PMID: 28855807 [PubMed]

Maximizing non-enzymatic methods for harvesting adipose-derived stem from lipoaspirate: technical considerations and clinical implications for regenerative surgery. Sci Rep. 2017 Aug 30;7(1):10015 Authors: Bellei B, Migliano E, Tedesco M, Caputo S, Picardo M Abstract In the past decade, adipose tissue has become a highly interesting source of adult stem cells for plastic surgery and regenerative medicine. The adipose source offers two options for the isolation of regenerative cells: the enzymatic digestion an expensive time-consuming procedure lacking a common standard operating protocol, or the non-enzymatic dissociation methods based on mechanical forces to break the processed adipose tissue. Here, we propose innovative inexpensive non-enzymatic protocols to collect and concentrate clinically useful regenerative cells from adipose tissue by centrifugation of the infranatant fraction of lipoaspirate as first step, usually discarded as a byproduct of the surgical procedure, and by fat shaking and wash as second enrichment step. The isolated cells were characterized according to the criteria proposed by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) to define human mesenchymal stem cells, and the results were compared with matched lipoaspirate samples processed with collagenase. The results demonstrated the usability of these new procedures as an alternative to fat grafting for treating stem cell-depleted tissues and for specific application requiring minimal or null soft tissue augmentation, such as skin diseases including severe burn and post-oncological scaring, chronic non-healing wounds, and vitiligo. PMID: 28855688 [PubMed - in process]

Retinol saturase coordinates liver metabolism by regulating ChREBP activity. Nat Commun. 2017 Aug 30;8(1):384 Authors: Heidenreich S, Witte N, Weber P, Goehring I, Tolkachov A, von Loeffelholz C, Döcke S, Bauer M, Stockmann M, Pfeiffer AFH, Birkenfeld AL, Pietzke M, Kempa S, Muenzner M, Schupp M Abstract The liver integrates multiple metabolic pathways to warrant systemic energy homeostasis. An excessive lipogenic flux due to chronic dietary stimulation contributes to the development of hepatic steatosis, dyslipidemia and hyperglycemia. Here we show that the oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. Thus, RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis.Fatty liver is one of the major features of metabolic syndrome and its development is associated with deregulation of systemic lipid and glucose homeostasis. Here Heidenreich et al. show that retinol saturase is implicated in hepatic lipid metabolism by regulating the activity of the transcription factor ChREBP. PMID: 28855500 [PubMed - in process]

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study. Am J Clin Nutr. 2017 Aug 30;: Authors: Derkach A, Sampson J, Joseph J, Playdon MC, Stolzenberg-Solomon RZ Abstract Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies.Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure.Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high- and low-sodium interventions and in 46 participants at the end of their high- and medium-sodium interventions (N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups.Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, γ-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate ≤0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold (P < 10(-5)). Adjustment for coinciding change in blood pressure did not substantively alter the association for the top-ranked metabolites.Conclusion: Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and γ-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608. PMID: 28855223 [PubMed - as supplied by publisher]

Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine. EBioMedicine. 2017 Aug 24;: Authors: Thulin E, Thulin M, Andersson DI Abstract Mecillinam (amdinocillin) is a β-lactam antibiotic used to treat uncomplicated urinary tract infections (UTIs). We have previously shown that inactivation of the Escherichia coli cysB gene is the major cause of mecillinam resistance (Mec(R)) in clinical isolates. In this study, we used different E. coli strains (laboratory and clinical isolates) that were Mec(R) due to cysB mutations to determine how mecillinam susceptibility was affected during growth in urine compared to growth in the commonly used growth medium Mueller Hinton (MHB). We also examined mecillinam susceptibility when bacteria were grown in urine obtained from 48 different healthy volunteers. Metabolome analysis was done on the urine samples and the association between the mecillinam susceptibility patterns of the bacteria and urine metabolite levels was studied. Two major findings with clinical significance are reported. First, Mec(R)E. coli cysB mutant strains (both laboratory and clinical isolates) were always more susceptible to mecillinam when grown in urine as compared to laboratory medium, with many strains showing complete phenotypic susceptibility in urine. Second, the degree of reversion to susceptibility varied between urine samples obtained from different individuals. This difference was correlated with osmolality such that in urine with low osmolality the Mec(R) mutants were more susceptible to mecillinam than in urine with high osmolality. This is the first example describing conditional resistance where a genetically stable antibiotic resistance can be phenotypically reverted to susceptibility by metabolites present in urine. These findings have several important clinical implications regarding the use of mecillinam to treat UTIs. First, they suggest that mecillinam can be used to treat also those clinical strains that are identified as Mec(R) in standard laboratory tests. Second, the results suggest that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant susceptibility testing results. Third, these findings imply that changes in patient behavior, such as increased water intake or use of diuretics to reduce urine osmolality and increased intake of cysteine, might induce antibiotic susceptibility in an infecting Mec(R)E. coli strain and thereby increase treatment efficiency. PMID: 28855073 [PubMed - as supplied by publisher]

A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity. Cell Rep. 2017 Aug 29;20(9):2144-2155 Authors: Knobloch M, Pilz GA, Ghesquière B, Kovacs WJ, Wegleiter T, Moore DL, Hruzova M, Zamboni N, Carmeliet P, Jessberger S Abstract Hippocampal neurogenesis is important for certain forms of cognition, and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity. PMID: 28854364 [PubMed - in process]

Related Articles Staging of colorectal cancer using serum metabolomics with (1)HNMR Spectroscopy. Iran J Basic Med Sci. 2017 Jul;20(7):835-840 Authors: Vahabi F, Sadeghi S, Arjmand M, Mirkhani F, Hosseini E, Mehrabanfar M, Hajhosseini R, Iravani A, Bayat P, Zamani Z Abstract OBJECTIVES: Determination of stages of colon cancer is done by biopsy usually after surgery. Metabolomics is the study of all the metabolites using LC-MS and (1)HNMR spectroscopy with chemometric techniques. The stages of colon cancer were detected from patients' sera using (1)HNMR. MATERIALS AND METHODS: Five ml blood was collected from 16 confirmed patients referred for colonoscopy. One group of eight patients were diagnosed with stage 0 to I colon cancer and the second group of 8 patients with II-IV stage colon cancer. Sera were sent for (1)HNMR. The differentiating metabolites were identified using HMDB and the metabolic cycles from Metaboanalyst. RESULTS: Six metabolites of which pyridoxine levels lowered, and glycine, cholesterol, taurocholic acid, cholesteryl ester and deoxyinosine increased. CONCLUSION: The different stages of cancer were identified by the main metabolic cycles such as primary bile acid biosynthesis, purine and vitamin B metabolic pathways and the glutathione cycle. PMID: 28852450 [PubMed]

Related Articles Insight into the metabolic mechanism of Diterpene Ginkgolides on antidepressant effects for attenuating behavioural deficits compared with venlafaxine. Sci Rep. 2017 Aug 29;7(1):9591 Authors: Bai S, Zhang X, Chen Z, Wang W, Hu Q, Liang Z, Shen P, Gui S, Zeng L, Liu Z, Chen J, Xie X, Huang H, Han Y, Wang H, Xie P Abstract Depression is a severe and chronic mental disorder, affecting about 322 million individuals worldwide. A recent study showed that diterpene ginkgolides (DG) have antidepressant-like effects on baseline behaviours in mice. Here, we examined the effects of DG and venlafaxine (VLX) in a chronic social defeat stress model of depression. Both DG and VLX attenuated stress-induced social deficits, despair behaviour and exploratory behaviour. To elucidate the metabolic changes underlying the antidepressive effects of DG and VLX, we investigated candidate functional pathways in the prefrontal cortex using a GC-MS-based metabolomics approach. Metabolic functions and pathways analysis revealed that DG and VLX affect protein biosynthesis and nucleotide metabolism to enhance cell proliferation, with DG having a weaker impact than VLX. Glutamate and aspartate metabolism played important roles in the antidepressant effects of DG and VLX. Tyrosine degradation and cell-to-cell signaling and interaction helped discriminate the two antidepressants. L-glutamic acid was negatively correlated, while hypoxanthine was positively correlated, with the social interaction ratio. Understanding the metabolic changes produced by DG and VLX should provide insight into the mechanisms of action of these drugs and aid in the development of novel therapies for depression. PMID: 28852120 [PubMed - in process]

Related Articles Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4. Sci Rep. 2017 Aug 29;7(1):9773 Authors: Verma N, Pink M, Boland S, Rettenmeier AW, Schmitz-Spanke S Abstract Benzo[a]pyrene (B[a]P), a well-known polyaromatic hydrocarbon, is known for its lung carcinogenicity, however, its role in bladder cancer development is still discussed. Comparative two-dimensional blue native SDS-PAGE analysis of protein complexes isolated from subcellular fractions of 0.5 µM B[a]P-exposed cells indicated a differential regulation of proteins involved in carbohydrate, fatty acid, and nucleotide metabolism, suggesting a possible metabolic flux redistribution. It appeared that B[a]P exposure led to a repression of enzymes (fructose-bisphosphate aldolase A, glucose-6-phosphate isomerase, lactate dehydrogenase) involved in glycolysis, and an up-regulation of proteins (glucose-6-phosphate 1-dehydrogenase, 6-phosphogluconolactonase) catalyzing the pentose phosphate pathway and one carbon metabolism (10-formyltetrahydrofolate dehydrogenase, bifunctional purine biosynthesis protein). Untargeted metabolomics further supported the proteomic data, a lower concentration of glycolytic metabolite was observed as compared to glutamine, xylulose and fatty acids. The analysis of the glutathione and NADPH/NADP(+) content of the cells revealed a significant increase of these cofactors. Concomitantly, we did not observe any detectable increase in the production of ROS. With the present work, we shed light on an early phase of the metabolic stress response in which the urothelial cells are capable of counteracting oxidative stress by redirecting the metabolic flux from glycolysis to pentose phosphate pathway. PMID: 28851999 [PubMed - in process]

Related Articles Characterization of a metabolomic profile associated with responsiveness to therapy in the acute phase of septic shock. Sci Rep. 2017 Aug 29;7(1):9748 Authors: Cambiaghi A, Pinto BB, Brunelli L, Falcetta F, Aletti F, Bendjelid K, Pastorelli R, Ferrario M Abstract The early metabolic signatures associated with the progression of septic shock and with responsiveness to therapy can be useful for developing target therapy. The Sequential Organ Failure Assessment (SOFA) score is used for stratifying risk and predicting mortality. This study aimed to verify whether different responses to therapy, assessed as changes in SOFA score at admission (T1, acute phase) and 48 h later (T2, post-resuscitation), are associated with different metabolite patterns. We examined the plasma metabolome of 21 septic shock patients (pts) enrolled in the Shockomics clinical trial (NCT02141607). Patients for which SOFAT2 was >8 and Δ = SOFAT1 - SOFAT2 < 5, were classified as not responsive to therapy (NR, 7 pts), the remaining 14 as responsive (R). We combined untargeted and targeted mass spectrometry-based metabolomics strategies to cover the plasma metabolites repertoire as far as possible. Metabolite concentration changes from T1 to T2 (Δ = T2 - T1) were used to build classification models. Our results support the emerging evidence that lipidome alterations play an important role in individual patients' responses to infection. Furthermore, alanine indicates a possible alteration in the glucose-alanine cycle in the liver, providing a different picture of liver functionality from bilirubin. Understanding these metabolic disturbances is important for developing any effective tailored therapy for these patients. PMID: 28851978 [PubMed - in process]

Related Articles Exploration of variations in proteome and metabolome for predictive diagnostics and personalized treatment algorithms: Innovative approach and examples for potential clinical application. J Proteomics. 2017 Aug 26;: Authors: Zhan X, Long Y, Lu M Abstract Genome mutually interacts with internal and external environmental factors to result in different phenome that contains two important elements of proteins and metabolites, which link genome to predictive, preventive and personalized medicine (PPPM) or precision medicine (PM). Proteomic variations are the final presentation of the genomic and transcriptomic variations, and are involved in a wide range of variations including copy number of protein, splicing, post-translational modifications, translocation/re-distribution, spatial conformation, and pathway-network systems. Metabolomic variations are the comprehensive results originated from all types of in vivo substances, and are involved in a wide range of alterations of metabolites generated from sugars, lipids, proteins, and nucleic acids, and metabolic network systems. Currently the studies on variations in proteome and in metabolome are much insufficient in the width and depth in the fields of proteomics and metabolomics. The development of high-throughput, high-sensitivity, and especially high-reproducibility approaches is necessary to maximize the coverage of variations in proteome and in metabolome. The studies of proteomic and metabolomic variations directly result in the discovery of effective biomarkers to clarify molecular mechanisms of a disease, determine reliable therapeutic targets, and benefit precise prediction, diagnosis, and prognosis assessment. It has more important scientific values in PPPM or PM. BIOLOGICAL SIGNIFICANCE. PMID: 28851587 [PubMed - as supplied by publisher]

Related Articles Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer. BMC Cancer. 2017 Aug 29;17(1):589 Authors: Yamashita Y, Nishiumi S, Kono S, Takao S, Azuma T, Yoshida M Abstract BACKGROUND: Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. METHODS: We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. RESULTS: We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. CONCLUSIONS: Marked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN. PMID: 28851309 [PubMed - in process]

22 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 2017/08/30PubMed 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.

22 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 2017/08/29PubMed 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.

Comparison of global metabolite extraction strategies for soybeans using UHPLC-HRMS. Anal Bioanal Chem. 2017 Aug 26;: Authors: Mahmud I, Sternberg S, Williams M, Garrett TJ Abstract Metabolism, downstream effectors of genomics, transcriptomics, and proteomics, can determine the potential of phenotype of an organism including plants. Profiling the global scenario of metabolism requires optimization of different solvent extraction methods. Here, we report an approach comparing three different metabolite extraction strategies, including ammonium acetate/methanol (AAM), water/methanol (WM), and sodium phosphate/methanol (PM) in soybean plant using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Interestingly, both AAM and WM methods were found to cover a wider range of metabolites and provide better detection of molecular features than the PM method. Various clustering analyses based on multivariate statistical tools revealed that both AAM and WM methods showed tight and overlapping extraction strategy compared with the PM method. Using MatLab-based Mahalanobis distance (D M) calculation, statistically significant score plot separation was observed between AAM and PM, as well as WM and PM. However, no significant separation was observed between AAM and WM, which is expected from the overlap of principal component scores for these two methods. Using differential metabolite expression analysis, we identified that a large number of metabolites were extracted at a significantly higher level using AAM vs. PM. These comparative extraction methods suggest that AAM can effectively be applied for an LC/MS-based plant metabolomics profile study. Graphical abstract Step-by-step outline of three different metabolite extraction methods and data analysis. PMID: 28844081 [PubMed - as supplied by publisher]

Physiological and metabolomic analysis of Issatchenkia orientalis MTY1 with multiple tolerance for cellulosic bioethanol production. Biotechnol J. 2017 Aug 26;: Authors: Seong YJ, Lee HJ, Lee JE, Kim S, Lee DY, Kim KH, Park YC Abstract Yeast with multiple tolerance onto harsh conditions has a number of advantages for bioethanol production. In this study, an alcohol yeast of Issatchenkia orientalis MTY1 was isolated in a Korean winery and its multiple tolerance against high temperature and acidic conditions was characterized in microaerobic batch cultures and by metabolomic analysis. In a series of batch cultures using 100 g/L glucose, I. orientalis MTY1 possessed wider growth ranges at pH 2-8 and 30-45 oC than a conventional yeast of Saccharomyces cerevisiae D452-2. Moreover, I. orientalis MTY1 showed higher cell growth and ethanol productivity in the presence of acetic acid or furfural than S. cerevisiae D452-2. I. orientalis MTY1 produced 41.4 g/L ethanol with 1.5 g/L-h productivity at 42 °C and pH 4.2 in the presence of 4 g/L acetic acid, whereas a thermo-tolerant yeast of Kluyvermyces marxianus ATCC36907 didn't grow. By metabolomics by GC-TOF MS and statistical analysis of 125 metabolite peaks, it was revealed that the thermo-tolerance of I. orientalis MTY1 might be ascribed to higher contents of unsaturated fatty acids, purines and pyrimidines than S. cerevisiae D452-2. Conclusively, I. orientalis MTY1 could be a potent workhorse with multiple tolerance against harsh conditions considered in cellulosic bioethanol production. PMID: 28843023 [PubMed - as supplied by publisher]

Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease. Mov Disord. 2017 Aug 26;: Authors: Trezzi JP, Galozzi S, Jaeger C, Barkovits K, Brockmann K, Maetzler W, Berg D, Marcus K, Betsou F, Hiller K, Mollenhauer B Abstract OBJECTIVE: The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and to determine a robust biomarker signature for early-stage PD diagnosis. METHODS: By applying a non-targeted and mass spectrometry-driven approach, we investigated the CSF metabolome of 44 early-stage sporadic PD patients yet without treatment (DeNoPa cohort). We compared all detected metabolite levels with those measured in CSF of 43 age- and gender-matched healthy controls. After this analysis, we validated the results in an independent PD study cohort (Tübingen cohort). RESULTS: We identified that dehydroascorbic acid levels were significantly lower and fructose, mannose, and threonic acid levels were significantly higher (P < .05) in PD patients when compared with healthy controls. These changes reflect pathological oxidative stress responses, as well as protein glycation/glycosylation reactions in PD. Using a machine learning approach based on logistic regression, we successfully predicted the origin (PD patients vs healthy controls) in a second (n = 18) as well as in a third and completely independent validation set (n = 36). The biomarker signature is composed of the three markers-mannose, threonic acid, and fructose-and allows for sample classification with a sensitivity of 0.790 and a specificity of 0.800. CONCLUSION: We identified PD-specific metabolic changes in CSF that were associated with antioxidative stress response, glycation, and inflammation. Our results disentangle the complexity of the CSF metabolome to unravel metabolome changes related to early-stage PD. The detected biomarkers help understanding PD pathogenesis and can be applied as biomarkers to increase clinical diagnosis accuracy and patient care in early-stage PD. © 2017 International Parkinson and Movement Disorder Society. PMID: 28843022 [PubMed - as supplied by publisher]

Related Articles Gut Microbiota and Atherosclerosis. Curr Atheroscler Rep. 2017 Aug 25;19(10):39 Authors: Li DY, Tang WHW Abstract PURPOSE OF REVIEW: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis. RECENT FINDINGS: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside. PMID: 28842845 [PubMed - in process]

Related Articles Advances in metabolome information retrieval: turning chemistry into biology. Part II: biological information recovery. J Inherit Metab Dis. 2017 Aug 25;: Authors: Tebani A, Afonso C, Bekri S Abstract This work reports the second part of a review intending to give the state of the art of major metabolic phenotyping strategies. It particularly deals with inherent advantages and limits regarding data analysis issues and biological information retrieval tools along with translational challenges. This Part starts with introducing the main data preprocessing strategies of the different metabolomics data. Then, it describes the main data analysis techniques including univariate and multivariate aspects. It also addresses the challenges related to metabolite annotation and characterization. Finally, functional analysis including pathway and network strategies are discussed. The last section of this review is devoted to practical considerations and current challenges and pathways to bring metabolomics into clinical environments. PMID: 28842777 [PubMed - as supplied by publisher]

Related Articles Glucose effectiveness, but not insulin sensitivity, is improved after short-term interval training in individuals with type 2 diabetes mellitus: a controlled, randomised, crossover trial. Diabetologia. 2017 Aug 25;: Authors: Karstoft K, Clark MA, Jakobsen I, Knudsen SH, van Hall G, Pedersen BK, Solomon TPJ Abstract AIMS/HYPOTHESIS: The role of glucose effectiveness (S G) in training-induced improvements in glucose metabolism in individuals with type 2 diabetes is unknown. The objectives and primary outcomes of this study were: (1) to assess the efficacy of interval walking training (IWT) and continuous walking training (CWT) on S G and insulin sensitivity (S I) in individuals with type 2 diabetes; and (2) to assess the association of changes in S G and S I with changes in glycaemic control. METHODS: Fourteen participants with type 2 diabetes underwent three trials (IWT, CWT and no training) in a crossover study. Exclusion criteria were exogenous insulin treatment, smoking, pregnancy, contraindications to structured physical activity and participation in recurrent training (>90 min/week). The trials were performed in a randomised order (computerised-generated randomisation). IWT and CWT consisted of ten supervised treadmill walking sessions, each lasting 60 min, over 2 weeks. IWT was performed as repeated cycles of 3 min slow walking and 3 min fast walking (aiming for 54% and 89% of [Formula: see text], respectively, which was measured during the last minute of each interval), and CWT was performed aiming for a moderate walking speed (73% of [Formula: see text]). A two-step (pancreatic and hyperinsulinaemic) hyperglycaemic clamp was implemented before and after each trial. All data were collected in a hospitalised setting. Neither participants nor assessors were blinded to the trial interventions. RESULTS: Thirteen individuals completed all procedures and were included in the analyses. IWT improved S G (mean ± SEM: 0.6 ± 0.1 mg kg(-1) min(-1), p < 0.05) but not S I (p > 0.05), whereas CWT matched for energy expenditure and time duration improved neither S G nor S I (both p > 0.05). Changes in S G, but not in S I, were associated with changes in mean (β = -0.62 ± 0.23, r (2) = 0.17, p < 0.01) and maximum (β = -1.18 ± 0.52, r (2) = 0.12, p < 0.05) glucose levels during 24 h continuous glucose monitoring. CONCLUSIONS/INTERPRETATION: Two weeks of IWT, but not CWT, improves S G but not S I in individuals with type 2 diabetes. Moreover, changes in S G are associated with changes in glycaemic control. Therefore, increased S G is likely an important mechanism by which training improves glycaemic control in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02320526 FUNDING: CFAS is supported by a grant from TrygFonden. During the study period, the Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55). The study was further supported by grants from Diabetesforeningen, Augustinusfonden and Krista og Viggo Petersens Fond. CIM/CFAS is a member of DD2-the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, grant no. 09-067009 and 09-075724). PMID: 28842722 [PubMed - as supplied by publisher]