PubMed

Related Articles Mechanisms of the active components from Korean pine nut preventing and treating d-galactose-induced aging rats. Biomed Pharmacother. 2018 Apr 18;103:680-690 Authors: Zhang J, Lin W, Wu R, Liu Y, Zhu K, Ren J, Zhang S, Ling X Abstract Age-related neuronal injury and oxidative damage are the predominant factors for neurodegenerative diseases like Alzheimer's disease (AD). The aim of this study was to explore whether chronic administration of d-galactose (d-gal) can cause neuronal injury and oxidative damage, and to investigate the neuroprotective and antioxidative effects of the active components (UPNO-1) from Korean pine nut (Pinus koraiensis). Two dosing regimens were designed, one for the evaluation of preventive effects in which the rats were simultaneously administrated d-gal and UPNO-1/fishoil for 12 weeks, the other for the evaluation of therapeutic effects in which the rats were given d-gal for 8 weeks before treated with UPNO-1/selegiline for 8 weeks. The experimental results demonstrated that chronic administration of d-gal produced histopathological changes and increased neuronal apoptosis, and decreased significantly the activities of T-AOC, T-SOD and CAT. Additionally, a comprehensive metabolic profiling of d-gal-treated rats was performed for the first time to investigate the metabolic disorders in the hippocampus, cortex and plasma, and a total of 32 annotated metabolites were significantly increased or decreased in the modeled rats. Major disturbed metabolic pathways were fatty acid, glycerolphospholipid and arachidonic acid metabolic pathways. UPNO-1 significantly diminished neuronal apoptosis, ameliorated histopathological findings, and increased the activities of T-SOD and CAT but not T-AOC. Furthermore, UPNO-1 attenuated the decreased plasma levels of 3-oxooctanoic acid, l-tryptophan, 12-hydroxyheptadecanoic acid, lysophosphatidylcholine (16:0) (LPC(16:0)), LPC(18:3) and LPC(18:1) in the modeled rats. These results illustrated the mechanisms of d-gal induced neurotoxicity and oxidative stress and proved the positive effects of UPNO-1 on preventing and treating d-gal-induced-aging rats. PMID: 29679909 [PubMed - as supplied by publisher]

Related Articles Integrated genomic and metabolomic profiling of ISC1, an emerging Leishmania donovani population in the Indian subcontinent. Infect Genet Evol. 2018 Apr 18;: Authors: Cuypers B, Berg M, Imamura H, Dumetz F, De Muylder G, Domagalska MA, Rijal S, Bhattarai NR, Maes I, Sanders M, Cotton JA, Meysman P, Laukens K, Dujardin JC Abstract Leishmania donovani is the responsible agent for visceral leishmaniasis (VL) in the Indian subcontinent (ISC). The disease is lethal without treatment and causes 0.2 to 0.4 million cases each year. Recently, reports of VL in Nepalese hilly districts have increased as well as VL cases caused by L. donovani from the ISC1 genetic group, a new and emerging genotype. In this study, we perform for the first time an integrated, untargeted genomics and metabolomics approach to characterize ISC1, in comparison with the Core Group (CG), main population that drove the last outbreak of VL in the ISC. We show that the ISC1 population is very different from the CG, both at genome and metabolome levels. These differences included SNPs, CNV and small indels in genes coding for known virulence factors, immunogens and surface proteins. Both genomic and metabolic approaches highlighted dissimilarities related to membrane lipids, the nucleotide salvage pathway and the urea cycle in ISC1 versus CG. Many of these pathways and molecules are important for the interaction with the host/extracellular environment. Altogether, our data predict major functional differences in ISC1 parasites, including virulence. Therefore, particular attention is required to monitor the fate of this emerging population in the ISC, especially in a post-VL elimination context. PMID: 29679745 [PubMed - as supplied by publisher]

Related Articles A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol. 2018 Apr 20;: Authors: Tankou SK, Regev K, Healy BC, Tjon E, Laghi L, Cox LM, Kivisäkk P, Pierre IV, Lokhande H, Gandhi R, Cook S, Glanz B, Stankiewicz J, Weiner HL Abstract OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. RESULTS: Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients such as methane metabolism following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased HLA-DR MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic induced increased in the abundance of Lactobacillus and Bifidobacterium were associated with decreased expression of MS risk allele HLA.DPB1 in controls. INTERPRETATION: Our results suggest that probiotic could have a synergistic effect with current MS therapies. This article is protected by copyright. All rights reserved. PMID: 29679417 [PubMed - as supplied by publisher]

Related Articles Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood. Pediatr Allergy Immunol. 2018 Apr 21;: Authors: Chiu CY, Lin G, Cheng ML, Chiang MH, Tsai MH, Su KW, Hua MC, Liao SL, Lai SH, Yao TC, Yeh KW, Huang JL Abstract BACKGROUND: Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified. METHODS: We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time-series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years were assessed using 1 H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures. RESULTS: A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = 0.032 and P = 0.021 respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -0.297 P = 0.035). CONCLUSIONS: Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma. This article is protected by copyright. All rights reserved. PMID: 29679407 [PubMed - as supplied by publisher]

Related Articles LC-MS/MS-Based Metabolome Analysis of Biochemical Pathways Altered by Food Limitation in Larvae of Ivory Shell, Babylonia areolata. Mar Biotechnol (NY). 2018 Apr 20;: Authors: Fu J, Shen M, Shen Y, Lü W, Huang M, Luo X, Yu J, Ke C, You W Abstract Ivory shell, Babylonia areolata, is one of the commercially important mariculture species in China and South East Asia. Survival varies in the artificial hatching and larval rearing of B. areolata. Food deprivation may be involved in rearing mortality, and so, a better understanding of how larvae respond and adjust to starvation is needed. In this study, the metabolite profiles of newly hatched larvae with yolk (I), larvae with yolk exhaustion (II), larvae suffering 24 h starvation after yolk exhaustion (III), and larvae fed with exogenous nutrients after yolk exhaustion (IV) were analyzed by LC-MS/MS. Principal component and cluster analyses revealed differential abundance of metabolite profiles across groups. When compared to metabolite levels of the I group, significantly up-regulated metabolites included polyunsaturated fatty acids, phospholipids, nucleotide, amino acids, and their derivatives were found in the II group, indicating that organisms relied predominantly on glycerophospolipid metabolism and protein-based catabolism for energy production during this stage. During starvation after yolk exhaustion, the levels of all energy related metabolites were significantly reduced, but an increase in products of purine and pyrimidine metabolism indicated an insufficient energy supply and an increase in cellular disintegration. Larvae fed exogenous nutrients can have significantly improved metabolism compared to starved larvae. These findings suggest that metabolomics, using LC-MS/MS, can be used to assess the physiological status and food-affected metabolic changes affecting B. areolata larvae. PMID: 29679249 [PubMed - as supplied by publisher]

Related Articles A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence. Geroscience. 2018 Apr 20;: Authors: Lewis KN, Rubinstein ND, Buffenstein R Abstract Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives. PMID: 29679203 [PubMed - as supplied by publisher]

Related Articles Thromboxane A2 facilitates IL-17A production from Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. J Allergy Clin Immunol. 2018 Apr 17;: Authors: Ueharaguchi Y, Honda T, Kusuba N, Hanakawa S, Adachi A, Sawada Y, Otsuka A, Kitoh A, Dainichi T, Egawa G, Nakashima C, Nakajima S, Murata T, Ono S, Arita M, Narumiya S, Miyachi Y, Kabashima K Abstract Thromboxane A2-TP signaling facilitates IL-17A production from dermal Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. Regulation of TP activation may become a novel therapeutic target for psoriasis. PMID: 29678752 [PubMed - as supplied by publisher]

Related Articles Severity of Allergic Rhinitis Assessed by Urine Metabolomic Profiling: Proof of Concept. J Allergy Clin Immunol. 2018 Apr 17;: Authors: Adamko DJ, Khamis MM, Steacy LM, Regush S, Bryce R, Ellis AK Abstract Patients with chronic airway diseases tend to become "accustomed" to their impairments and fail to recognize the significance of their symptoms. We suggest that a metabolomic approach could become a diagnostic/monitoring solution in clinical trials or in a typical doctor's office. PMID: 29678748 [PubMed - as supplied by publisher]

Related Articles Mass spectrometry-based metabolomics for tuberculosis meningitis. Clin Chim Acta. 2018 Apr 17;: Authors: Zhang P, Zhang W, Lang Y, Qu Y, Chu F, Chen J, Cui L Abstract Tuberculosis meningitis (TBM) is a prevalent form of extra-pulmonary tuberculosis that causes substantial morbidity and mortality. Diagnosis of TBM is difficult because of the limited sensitivity of existing laboratory techniques. A metabolomics approach can be used to investigate the sets of metabolites of both bacteria and host, and has been used to clarify the mechanisms underlying disease development, and identify metabolic changes, leadings to improved methods for diagnosis, treatment, and prognostication. Mass spectrometry (MS) is a major analysis platform used in metabolomics, and MS-based metabolomics provides wide metabolite coverage, because of its high sensitivity, and is useful for the investigation of Mycobacterium tuberculosis (Mtb) and related diseases. It has been used to investigate TBM diagnosis; however, the processes involved in the MS-based metabolomics approach are complex and flexible, and often consist of several steps, and small changes in the methods used can have a huge impact on the final results. Here, the process of MS-based metabolomics is summarized and its applications in Mtb and Mtb-related diseases discussed. Moreover, the current status of TBM metabolomics is described. PMID: 29678632 [PubMed - as supplied by publisher]

Related Articles Clinical and Inflammatory Phenotyping: Can Electronic Nose and NMR-based Metabolomics Work at the Bedside? Arch Med Res. 2018 Apr 17;: Authors: Maniscalco M, Motta A Abstract Electronic nose (eNose) and nuclear magnetic resonance (NMR)-based metabolomics seem to be able to identify metabolic and inflammatory profiles in patients with chronic obstructive diseases. The hypothesis arises from three recent studies using two different methods in patients with asthma and chronic obstructive pulmonary diseases (COPD), opening promising diagnostic perspectives. The possibility that the use of eNose and NMR-based metabolomics might provide clinical/inflammatory characteristics is intriguing. This might classify specific phenotypes of chronic airway disease regardless of the diagnosis asthma or COPD, therefore suggesting therapeutical targets for a personalized respiratory medicine through more efficient "tailored" strategies. PMID: 29678351 [PubMed - as supplied by publisher]

Related Articles Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome. 2018 Apr 20;6(1):73 Authors: Hoyles L, Jiménez-Pranteda ML, Chilloux J, Brial F, Myridakis A, Aranias T, Magnan C, Gibson GR, Sanderson JD, Nicholson JK, Gauguier D, McCartney AL, Dumas ME Abstract BACKGROUND: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes. RESULTS: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. CONCLUSIONS: Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota. PMID: 29678198 [PubMed - in process]

Related Articles A randomized controlled cross-over trial investigating the effect of anti-inflammatory diet on disease activity and quality of life in rheumatoid arthritis: the Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study protocol. Nutr J. 2018 Apr 20;17(1):44 Authors: Winkvist A, Bärebring L, Gjertsson I, Ellegård L, Lindqvist HM Abstract BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. METHODS: In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2 × 10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. DISCUSSION: The nutritional status of patients with RA often is poor and many ask their physician for diet advice. No evidence-based dietary guidelines for patients with RA exist because of the paucity of well-conducted sufficiently large diet intervention trials. ADIRA is an efficacy study and will provide evidence as to whether dietary treatment of RA can reduce disease activity and improve quality of life as well as reduce individual and societal costs. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT02941055 . PMID: 29678183 [PubMed - in process]

Related Articles SECIMTools: a suite of metabolomics data analysis tools. BMC Bioinformatics. 2018 Apr 20;19(1):151 Authors: Kirpich AS, Ibarra M, Moskalenko O, Fear JM, Gerken J, Mi X, Ashrafi A, Morse AM, McIntyre LM Abstract BACKGROUND: Metabolomics has the promise to transform the area of personalized medicine with the rapid development of high throughput technology for untargeted analysis of metabolites. Open access, easy to use, analytic tools that are broadly accessible to the biological community need to be developed. While technology used in metabolomics varies, most metabolomics studies have a set of features identified. Galaxy is an open access platform that enables scientists at all levels to interact with big data. Galaxy promotes reproducibility by saving histories and enabling the sharing workflows among scientists. RESULTS: SECIMTools (SouthEast Center for Integrated Metabolomics) is a set of Python applications that are available both as standalone tools and wrapped for use in Galaxy. The suite includes a comprehensive set of quality control metrics (retention time window evaluation and various peak evaluation tools), visualization techniques (hierarchical cluster heatmap, principal component analysis, modular modularity clustering), basic statistical analysis methods (partial least squares - discriminant analysis, analysis of variance, t-test, Kruskal-Wallis non-parametric test), advanced classification methods (random forest, support vector machines), and advanced variable selection tools (least absolute shrinkage and selection operator LASSO and Elastic Net). CONCLUSIONS: SECIMTools leverages the Galaxy platform and enables integrated workflows for metabolomics data analysis made from building blocks designed for easy use and interpretability. Standard data formats and a set of utilities allow arbitrary linkages between tools to encourage novel workflow designs. The Galaxy framework enables future data integration for metabolomics studies with other omics data. PMID: 29678131 [PubMed - in process]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/04/21PubMed 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.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/04/20PubMed 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 on preadolescent children with high urinary Bisphenol A: response to Dr. Williams. Toxicol Sci. 2018 Apr 14;: Authors: Khan A, Park YH PMID: 29669048 [PubMed - as supplied by publisher]

Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses. PLoS Biol. 2018 Apr 18;16(4):e2005504 Authors: Kaisar MMM, Ritter M, Del Fresno C, Jónasdóttir HS, van der Ham AJ, Pelgrom LR, Schramm G, Layland LE, Sancho D, Prazeres da Costa C, Giera M, Yazdanbakhsh M, Everts B Abstract The molecular mechanisms through which dendritic cells (DCs) prime T helper 2 (Th2) responses, including those elicited by parasitic helminths, remain incompletely understood. Here, we report that soluble egg antigen (SEA) from Schistosoma mansoni, which is well known to drive potent Th2 responses, triggers DCs to produce prostaglandin E2 (PGE2), which subsequently-in an autocrine manner-induces OX40 ligand (OX40L) expression to license these DCs to drive Th2 responses. Mechanistically, SEA was found to promote PGE2 synthesis through Dectin-1 and Dectin-2, and via a downstream signaling cascade involving spleen tyrosine kinase (Syk), extracellular signal-regulated kinase (ERK), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase 1 and 2 (COX-1 and COX-2). In addition, this pathway was activated independently of the actions of omega-1 (ω-1), a previously described Th2-priming glycoprotein present in SEA. These findings were supported by in vivo murine data showing that ω-1-independent Th2 priming by SEA was mediated by Dectin-2 and Syk signaling in DCs. Finally, we found that Dectin-2-/-, and to a lesser extent Dectin-1-/- mice, displayed impaired Th2 responses and reduced egg-driven granuloma formation following S. mansoni infection, highlighting the physiological importance of this pathway in Th2 polarization during a helminth infection. In summary, we identified a novel pathway in DCs involving Dectin-1/2-Syk-PGE2-OX40L through which Th2 immune responses are induced. PMID: 29668708 [PubMed - as supplied by publisher]

A longitudinal 1H-NMR metabolomics analysis of urine from newborns with hypoxic-ischemic encephalopathy undergoing hypothermia therapy. Clinical and medical legal insights. PLoS One. 2018;13(4):e0194267 Authors: Locci E, Noto A, Puddu M, Pomero G, Demontis R, Dalmazzo C, Delogu A, Fanos V, d'Aloja E, Gancia P Abstract Perinatal asphyxia is an event affecting around four million newborns worldwide. The 0.5 to 2 per 1000 of full term asphyxiated newborns suffer from hypoxic-ischemic encephalopathy (HIE), which is a frequent cause of death or severe disability and, as consequence, the most common birth injury claim for obstetrics, gynaecologists, and paediatricians. Perinatal asphyxia results from a compromised gas exchange that leads to hypoxemia, hypercapnia, and metabolic acidosis. In this work, we applied a metabolomics approach to investigate the metabolic profiles of urine samples collected from full term asphyxiated newborns with HIE undergoing therapeutic hypothermia (TH), with the aim of identifying a pattern of metabolites associated with HIE and to follow their modifications over time. Urine samples were collected from 10 HIE newborns at birth, during hypothermia (48 hours), at the end of the therapeutic treatment (72 hours), at 1 month of life, and compared with a matched control population of 16 healthy full term newborns. The metabolic profiles were investigated by 1H NMR spectroscopy coupled with multivariate statistical methods such as principal component analysis and orthogonal partial least square discriminant analysis. Multivariate analysis indicated significant differences between the urine samples of HIE and healthy newborns at birth. The altered metabolic patterns, mainly originated from the depletion of cellular energy and homeostasis, seem to constitute a characteristic of perinatal asphyxia. The HIE urine metabolome changes over time reflected either the effects of TH and the physiological growth of the newborns. Of interest, the urine metabolic profiles of the HIE non-surviving babies, characterized by the increased excretion of lactate, resulted significantly different from the rest of HIE population. PMID: 29668681 [PubMed - in process]

Correlated metabolomic, genomic, and histologic phenotypes in histologically normal breast tissue. PLoS One. 2018;13(4):e0193792 Authors: Sun X, Stewart DA, Sandhu R, Kirk EL, Pathmasiri WW, McRitchie SL, Clark RF, Troester MA, Sumner SJ Abstract Breast carcinogenesis is a multistep process accompanied by widespread molecular and genomic alterations, both in tumor and in surrounding microenvironment. It is known that tumors have altered metabolism, but the metabolic changes in normal or cancer-adjacent, nonmalignant normal tissues and how these changes relate to alterations in gene expression and histological composition are not well understood. Normal or cancer-adjacent normal breast tissues from 99 women of the Normal Breast Study (NBS) were evaluated. Data of metabolomics, gene expression and histological composition was collected by mass spectrometry, whole genome microarray, and digital image, respectively. Unsupervised clustering analysis determined metabolomics-derived subtypes. Their association with genomic and histological features, as well as other breast cancer risk factors, genomic and histological features were evaluated using logistic regression. Unsupervised clustering of metabolites resulted in two main clusters. The metabolite differences between the two clusters suggested enrichment of pathways involved in lipid metabolism, cell growth and proliferation, and migration. Compared with Cluster 1, subjects in Cluster 2 were more likely to be obese (body mass index ≥30 kg/m2, p<0.05), have increased adipose proportion (p<0.01) and associated with a previously defined Active genomic subtype (p<0.01). By the integrated analyses of histological, metabolomics and transcriptional data, we characterized two distinct subtypes of non-malignant breast tissue. Further research is needed to validate our findings, and understand the potential role of these alternations in breast cancer initiation, progression and recurrence. PMID: 29668675 [PubMed - in process]

New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Age. Protein Pept Lett. 2018 Apr 18;: Authors: Dipresa S, De Toni L, Foresta C, Garolla A Abstract A number of test have been proposed to assess male fertility potential, ranging from routine testing by light microscopic method for evaluating semen samples, to screening test for DNA integrity aimed to look at sperm chromatin abnormalities. Spermatozoa are an extremely differentiated cell, they have critical functions for embryo development and heredity, in addiction to delivering a haploid paternal genome to the oocyte. Towards this goal certain requirements must always be met. The ability of spermatozoa to perform its reproductive function taking place in the spermatogenesis, a highly specialized process depending on multiple factors with effect on male fertility. In the past 30 years, large-scale analyses of transcriptomic and genome expression in mammals have generated a large amount of informations on numberless biomolecules involved in spermatogenesis and male germ cell reproductive function. Sperm proteome represents the protein content that spermatozoa needs to survive and work correctly and modifications of sperm proteome play a role in determining functional changes leading to a decrease of reproductive competence into affected spermatozoa. The post-genomic approach consists of different methodologies for concurrently testicular transcriptome studies, protein compositional analysis and metabolomics findings of the spermatozoa in humans. PMID: 29667547 [PubMed - as supplied by publisher]