PubMed

Related Articles Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway. PLoS One. 2014;9(3):e92597 Authors: Tomioka H, Nakagami H, Tenma A, Saito Y, Kaga T, Kanamori T, Tamura N, Tomono K, Kaneda Y, Morishita R Abstract We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions. PMID: 24675668 [PubMed - indexed for MEDLINE]

Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants. J Exp Bot. 2015 Dec 17; Authors: Vigani G, Bashir K, Ishimaru Y, Lehmann M, Casiraghi FM, Nakanishi H, Seki M, Geigenberger P, Zocchi G, Nishizawa NK Abstract Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. PMID: 26685186 [PubMed - as supplied by publisher]

Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of high-grade serous ovarian carcinomas. Cancer Res. 2015 Dec 18; Authors: Hilvo M, de Santiago I, Gopalacharyulu P, Schmitt WD, Budczies J, Kuhberg M, Dietel M, Aittokallio T, Markowetz F, Denkert C, Sehouli J, Frezza C, Darb-Esfahani S, Braicu EI Abstract Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID: 26685161 [PubMed - as supplied by publisher]

Metabolic profiling for the identification of huntington biomarkers by on-line solid-phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools. Electrophoresis. 2015 Dec 18; Authors: Pont L, Benavente F, Jaumot J, Tauler R, Alberch J, Ginés S, Barbosa J, Sanz-Nebot V Abstract In this work, an untargeted metabolomic approach based on sensitive analysis by on-line solid-phase extraction capillary electrophoresis mass spectrometry (SPE-CE-MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild type (wt) and HD (R6/1) mice of different ages (8, 12 and 30 weeks), were analysed by C18 -SPE-CE-MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the multiple full scan MS data sets. This strategy permitted the resolution of a large number of metabolites being characterised by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow-up the HD progression. The intracellular signalling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors and changed expression of neurotransmitters. This article is protected by copyright. All rights reserved. PMID: 26685060 [PubMed - as supplied by publisher]

Comparative study of comprehensive gas chromatography-nitrogen chemiluminescence detection and gas chromatography-ion trap-tandem mass spectrometry for determining nicotine and carcinogen organic nitrogen compounds in thirdhand tobacco smoke. J Chromatogr A. 2015 Nov 17; Authors: Ramírez N, Vallecillos L, Lewis AC, Borrull F, Marcé RM, Hamilton JF Abstract Thirdhand tobacco smoke (THS) constitutes a poorly understood pathway of exposure of non-smokers, especially toddlers, to tobacco-related carcinogens. However, to date most of the carcinogens present in tobacco smoke have not been detected in THS and, therefore, the significance of THS health risk is still unknown. In this study, we have compared the performance of two analytical methods - one based on gas chromatography coupled to ion trap mass spectrometry detection (GC-IT-MS) and the other on comprehensive two-dimensional gas chromatography coupled to a nitrogen chemiluminescence detector (GC×GC-NCD) - for simultaneously determining, in settled house dust, the presence of 16 organic nitrogen carcinogens already detected in tobacco smoke. The target compounds included four aromatic amines, two nitrocompounds, eight N-nitrosamines and two tobacco-specific nitrosamines, as well as nicotine as a tobacco marker. Dust samples were extracted using in-cell clean up pressurized liquid extraction with silica as clean up sorbent and ethyl acetate as the organic solvent, with average recovery of 89%. Although GC-IT-MS, using chemical ionization with methanol and tandem MS, performed well, the optimized GC×GC-NCD gave lower limits of detection (from 4 to 22ngg(-1)) and better repeatability and reproducibility a low concentration levels (%RSD<8%) and, therefore, was applicable for determining these different groups of carcinogens without the need for derivatization prior to the GC analysis. The performance of the optimized PLE/GC×GC-NCD method was tested by quantifying the target compounds in house dust samples from smokers' and non-smokers' homes. The median carcinogen compounds detected was 3.8μgg(-1) and 1.1μgg(-1) in smokers' and non-smokers' house dust, respectively. In this study, we have detected highly carcinogenic aromatic amines and nitro compounds for the first time in settled house dust complementing the state of knowledge of THS composition and providing fresh evidence about THS health risks. PMID: 26684592 [PubMed - as supplied by publisher]

Prediction of Declining Renal Function and Albuminuria in Patients with Type 2 Diabetes by Metabolomics. J Clin Endocrinol Metab. 2015 Dec 18;:jc20153345 Authors: Solini A, Manca ML, Penno G, Pugliese G, Cobb JE, Ferrannini E Abstract CONTEXT: Renal disease in type 2 diabetes (T2DM) is associated with excess morbidity/mortality. While glomerular filtration rate (eGFR) and albuminuria are routine for assessing renal impairment, novel biomarkers could improve risk stratification and prediction. OBJECTIVE: To identify specific biomarkers of progression of renal dysfunction Design Prospective observational: Setting Academic diabetes clinics Patients: 286 T2DM patients (age 62±8 years, HbA1c 7.2±0.9%, eGFR 85±20 mL(.)min(-1.)1.73m(2)). INTERVENTIONS: None Main Outcome Measures: Progression of eGFR and albuminuria Results: We performed screening metabolomics in serum and urine samples by GC/MS and UPLC/MS/MS. Biomarker identification was performed by random forest using an eGFR cutoff of <60 or an albumin/creatinine (ACR) cutoff of ≥30 mg/g as response variables. At follow-up, eGFR had declined by 16 [9] (median [IQR]) mL(.)min(-1.)1.73m(2) and ACR had increased by 41 [135] mg/g in patients in the respective top quartile of changes from baseline. Clinical parameters (gender, age, fasting glucose, and baseline eGFR) predicted outcome with ROC=0.671. The 5 serum metabolites best correlated with either eGFR<60 or ACR≥30 at baseline were tested for their ability to improve clinical prediction. Sum of C-glycosyltryptophan, pseudouridine, and N-acetylthreonine (MetIndex) raised ROC to 0.739 (p<0.0001). eGFR decline was predicted by the top MetaIndex quartile (OR=5.48 [95%CI=2.23-14.47]. MetIndex also predicted ACR increase with an OR of 2.82[1.20-7.03] and a ROC of 0.750. Top urine metabolites did not add significant predictivity. CONCLUSIONS: A limited number of circulating intermediates of amino acid and nucleotide pathways carry clinically significant predictivity for deterioration of renal function in well-controlled T2DM. PMID: 26684276 [PubMed - as supplied by publisher]

Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. J Neuroinflammation. 2015;12(1):235 Authors: Wuhrer M, Selman MH, McDonnell LA, Kümpfel T, Derfuss T, Khademi M, Olsson T, Hohlfeld R, Meinl E, Krumbholz M Abstract BACKGROUND: Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospinal fluid (CSF) in general. METHODS: We applied mass spectrometry of tryptic Fc glycopeptides to analyze IgG Fc glycosylation (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc)) in 48 paired CSF and serum samples from adult patients with MS or a first demyelinating event highly suggestive of MS (designated as MS cases), and from healthy volunteers and patients with other non-inflammatory diseases (control group). p values were adjusted for multiple testing. RESULTS: Our experiments revealed four main results. First, IgG1 glycosylation patterns were different in CSF vs. serum, in the MS group and even in control donors without intrathecal IgG synthesis. Second, in MS patients vs. controls, IgG1 glycosylation patterns were altered in CSF, but not in serum. Specifically, in CSF from the MS group, bisecting GlcNAc were elevated, and afucosylation and galactosylation were reduced. Elevated bisecting GlcNAc and reduced galactosylation are known to enhance IgG effector functions. Third, hypothesis-free regression analysis revealed that alterations of afucosylation and bisecting GlcNAc in CSF from MS cases peaked 2-3 months after the last relapse. Fourth, CSF IgG1 glycosylation correlated with the degree of intrathecal IgG synthesis and CSF cell count. CONCLUSIONS: The CNS compartment as well as the inflammatory milieu in MS affect IgG1 Fc glycosylation. In MS, the CSF IgG1 glycosylation has features that enhance Fc effector functions. PMID: 26683050 [PubMed - as supplied by publisher]

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 2015/12/19PubMed comprises more than 24 million 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.

Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine. Methods Mol Biol. 2016;1386:253-281 Authors: Aurich MK, Thiele I Abstract Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine. PMID: 26677187 [PubMed - as supplied by publisher]

Comprehensive analysis of serum metabolites in gestational diabetes mellitus by UPLC/Q-TOF-MS. Anal Bioanal Chem. 2015 Dec 16; Authors: Liu T, Li J, Xu F, Wang M, Ding S, Xu H, Dong F Abstract Gestational diabetes mellitus (GDM) refers to the first sign or onset of diabetes mellitus during pregnancy rather than progestation. In recent decades, more and more research has focused on the etiology and pathogenesis of GDM in order to further understand GDM progress and recovery. Using an advanced metabolomics platform based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), we explored the changes in serum metabolites between women with GDM and healthy controls during and after pregnancy. Some significant differences were discovered using multivariate analysis including partial least-squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA). The dysregulated metabolites were further compared and verified in several databases to understand how these compounds might function as potential biomarkers. Analyses of the metabolic pathways associated with these potential biomarkers were subsequently explored. A total of 35 metabolites were identified, contributing to GDM progress to some extent. The identified biomarkers were involved in some important metabolic pathways including glycine, serine, and threonine metabolism; steroid hormone biosynthesis; tyrosine metabolism; glycerophospholipid metabolism; and fatty acid metabolism. The above mentioned metabolic pathways mainly participate in three major metabolic cycles in humans, including lipid metabolism, carbohydrate metabolism, and amino acid metabolism. In this pilot study, the valuable comprehensive analysis gave us further insight into the etiology and pathophysiology of GDM, which might benefit the feasibility of a rapid, accurate diagnosis and reasonable treatment as soon as possible but also prevent GDM and its related short- and long-term complications. PMID: 26677023 [PubMed - as supplied by publisher]

Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.). J Sci Food Agric. 2015 Dec 17; Authors: Zhen S, Dong K, Deng X, Zhou J, Xu X, Han C, Zhang W, Xu Y, Wang Z, Yan Y Abstract BACKGROUND: Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to human. These metabolites are important to the health of human. However, the metabolome of the grain during the development of bread wheat has not been studied. RESULTS: In the present work, we analyzed the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175. We used a non-targeted gas chromatography-mass spectrometry (GC-MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids, was interrelated. An integrated metabolic map revealed a distinct regulatory profile. Our results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. CONCLUSIONS: Our metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. Our work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. PMID: 26676564 [PubMed - as supplied by publisher]

Understanding Metabolomics in Biomedical Research. Endocrinol Metab (Seoul). 2015 Dec 9; Authors: Kim SJ, Kim SH, Kim JH, Hwang S, Yoo HJ Abstract The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced. PMID: 26676338 [PubMed - as supplied by publisher]

Serum metabolomics analysis of rat after intragastric infusion of Pu-erh theabrownin. J Sci Food Agric. 2015 Dec 17; Authors: Liu J, Peng CX, Gao B, Gong JS Abstract BACKGROUND: To study the effects of Pu-erh theabrownin (TB) (Mw > 50kDa) on the metabolism of rats serum by nuclear magnetic resonance (NMR)-based metabolomics and identify candidate marker metabolites associated with Pu-erh TB and, thus, provide fundamental information for better understanding the metabolism of Pu-erh tea in animals. RESULTS: The TB infusion induced different changes in endogenous serum metabolites depending on the type of diet. Compared with the control group, the TB infusion group showed significantly reduced serum glycine and choline levels, as well as significantly increased taurine, carnitine, and HDL (all p<0.05). Compared with the high lipid group, the high lipid-TB infusion group exhibited significantly reduced LDL and acetate levels, as well as significantly increased inositol, carnitine, and glycine levels (all p<0.05). CONCLUSION: Examination of the variations of these differential expressed metabolites and their individual functions revealed that, the TB extract accelerated the lipid catabolism in rats and might affect the glucose metabolism. Of these, the carnitine level significantly increased after intragastric infusion of TB regardless of the type of diet, and carnitine palmitoyltransferases Ι and ΙΙ activities have significantly changed, suggesting carnitine may be a candidate serum marker for tracking the metabolism of TB in rats. PMID: 26676261 [PubMed - as supplied by publisher]

Studying the effect of storage conditions on the metabolite content of red wine using HILIC LC-MS based metabolomics. Food Chem. 2016 Apr 15;197(Pt B):1331-1340 Authors: Arapitsas P, Corte AD, Gika H, Narduzzi L, Mattivi F, Theodoridis G Abstract The main aim of this work was to develop an untargeted normal phase LC-MS method, starting from a targeted method already validated for the analysis of 135 polar metabolites. Since the LC instrument and column were the same, most of the chromatographic conditions remained identical, while the adaptations focused on maintaining the ionic strength of the eluents constant. The sample preparation was simplified and the effectiveness of LC-MS for long batches was evaluated, in order to record the maximum number of metabolites with good chromatographic resolution and the best MS stability and accuracy. The method was applied to study the influence of storage conditions on wine composition. Slightly sub-optimum storage conditions had a major impact on the polar metabolite fingerprint of the red wines analysed and the markers revealed included phenolics, vitamins and metabolites indentified in wine for the first time (4-amino-heptanedioic acid and its ethyl ester). PMID: 26675875 [PubMed - as supplied by publisher]

Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception. J Neurosci. 2015 Dec 16;35(50):16418-16430 Authors: Ferrier J, Bayet-Robert M, Dalmann R, El Guerrab A, Aissouni Y, Graveron-Demilly D, Chalus M, Pinguet J, Eschalier A, Richard D, Daulhac L, Marchand F, Balayssac D Abstract Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS (1)H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT: Our study describes a decrease in cholinergic neurotransmission in the posterior insular cortex in neuropathic pain condition and the involvement of M2 receptors. Targeting these cortical muscarinic M2 receptors using central cholinomimetics could be an effective therapy for neuropathic pain treatment. PMID: 26674867 [PubMed - as supplied by publisher]

Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats. J Nutr. 2015 Dec 16; Authors: Liu Z, Roy NC, Guo Y, Jia H, Ryan L, Samuelsson L, Thomas A, Plowman J, Clerens S, Day L, Young W Abstract BACKGROUND: In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value. OBJECTIVE: The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model. METHODS: In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats. RESULTS: Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF. CONCLUSIONS: Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012-024. PMID: 26674765 [PubMed - as supplied by publisher]

Hepatotoxicity and nephrotoxicity induced by the chlorpyrifos and chlorpyrifos-methyl metabolite, 3,5,6-trichloro-2-pyridinol, in orally exposed mice. Sci Total Environ. 2015 Dec 8;544:507-514 Authors: Deng Y, Zhang Y, Lu Y, Zhao Y, Ren H Abstract 3,5,6-Trichloro-2-pyridinol (TCP) is a primary degradation product of chlorpyrifos and chlorpyrifos-methyl. TCP has longer half-life in soil and greater solubility in water than its parent compound, and cause wide contamination in environments. However, studies about the toxic effects of TCP are limited and outdate. In this study, 5mg/kg/day, 50mg/kg/day, and 150mg/kg/day TCP were given to male mice through gavage for four weeks. As a result, the final body weights of TCP treated groups were significantly lower than control, and the relative organ weights of the liver and kidney were significantly higher than that of control. In addition, NMR-based metabolomics was used to investigate the toxic effects of TCP. It was found that a total of 39 serum metabolites were significantly changed in the TCP-treated groups, and these metabolites are related to hepatotoxicity and nephrotoxicity. These results were also confirmed by histopathology, serum biochemical, and oxidative stress analysis. In addition, metabolic disturbances due to TCP exposure were also observed based on altered metabolites. As far as we know, these results are the first to show the metabolomic toxicity of TCP, which warrants further research. PMID: 26674679 [PubMed - as supplied by publisher]

Metabolomics of dates (Phoenix dactylifera) reveals a highly dynamic ripening process accounting for major variation in fruit composition. BMC Plant Biol. 2015;15(1):291 Authors: Diboun I, Mathew S, Al-Rayyashi M, Elrayess M, Torres M, Halama A, Méret M, Mohney RP, Karoly ED, Malek J, Suhre K Abstract BACKGROUND: Dates are tropical fruits with appreciable nutritional value. Previous attempts at global metabolic characterization of the date metabolome were constrained by small sample size and limited geographical sampling. In this study, two independent large cohorts of mature dates exhibiting substantial diversity in origin, varieties and fruit processing conditions were measured by metabolomics techniques in order to identify major determinants of the fruit metabolome. RESULTS: Multivariate analysis revealed a first principal component (PC1) significantly associated with the dates' countries of production. The availability of a smaller dataset featuring immature dates from different development stages served to build a model of the ripening process in dates, which helped reveal a strong ripening signature in PC1. Analysis revealed enrichment in the dry type of dates amongst fruits with early ripening profiles at one end of PC1 as oppose to an overrepresentation of the soft type of dates with late ripening profiles at the other end of PC1. Dry dates are typical to the North African region whilst soft dates are more popular in the Gulf region, which partly explains the observed association between PC1 and geography. Analysis of the loading values, expressing metabolite correlation levels with PC1, revealed enrichment patterns of a comprehensive range of metabolite classes along PC1. Three distinct metabolic phases corresponding to known stages of date ripening were observed: An early phase enriched in regulatory hormones, amines and polyamines, energy production, tannins, sucrose and anti-oxidant activity, a second phase with on-going phenylpropanoid secondary metabolism, gene expression and phospholipid metabolism and a late phase with marked sugar dehydration activity and degradation reactions leading to increased volatile synthesis. CONCLUSIONS: These data indicate the importance of date ripening as a main driver of variation in the date metabolome responsible for their diverse nutritional and economical values. The biochemistry of the ripening process in dates is consistent with other fruits but natural dryness may prevent degenerative senescence in dates following ripening. Based on the finding that mature dates present varying extents of ripening, our survey of the date metabolome essentially revealed snapshots of interchanging metabolic states during ripening empowering an in-depth characterization of underlying biology. PMID: 26674306 [PubMed - as supplied by publisher]

UV-visible scanning spectrophotometry and chemometric analysis as tools for carotenoids analysis in cassava genotypes (Manihot esculenta Crantz). J Integr Bioinform. 2015;12(4):280 Authors: Moresco R, Uarrota VG, Pereira A, Tomazzoli MM, Nunes ED, Peruch LA, Gazzola J, Costa C, Rocha M, Maraschin M Abstract In this study, the metabolomics characterization focusing on the carotenoid composition of ten cassava (Manihot esculenta) genotypes cultivated in southern Brazil by UV-visible scanning spectrophotometry and reverse phase-high performance liquid chromatography was performed. Cassava roots rich in β-carotene are an important staple food for populations with risk of vitamin A deficiency. Cassava genotypes with high pro-vitamin A activity have been identified as a strategy to reduce the prevalence of deficiency of this vitamin. The data set was used for the construction of a descriptive model by chemometric analysis. The genotypes of yellow-fleshed roots were clustered by the higher concentrations of cis-β-carotene and lutein. Inversely, cream-fleshed roots genotypes were grouped precisely due to their lower concentrations of these pigments, as samples rich in lycopene (redfleshed) differed among the studied genotypes. The analytical approach (UV-Vis, HPLC, and chemometrics) used showed to be efficient for understanding the chemodiversity of cassava genotypes, allowing to classify them according to important features for human health and nutrition. PMID: 26673931 [PubMed - as supplied by publisher]

A roadmap for the XCMS family of software solutions in metabolomics. Curr Opin Chem Biol. 2015 Dec 10;30:87-93 Authors: Mahieu NG, Genenbacher JL, Patti GJ Abstract Global profiling of metabolites in biological samples by liquid chromatography/mass spectrometry results in datasets too large to evaluate manually. Fortunately, a variety of software programs are now available to automate the data analysis. Selection of the appropriate processing solution is dependent upon experimental design. Most metabolomic studies a decade ago had a relatively simple experimental design in which the intensities of compounds were compared between only two sample groups. More recently, however, increasingly sophisticated applications have been pursued. Examples include comparing compound intensities between multiple sample groups and unbiasedly tracking the fate of specific isotopic labels. The latter types of applications have necessitated the development of new software programs, which have introduced additional functionalities that facilitate data analysis. The objective of this review is to provide an overview of the freely available bioinformatic solutions that are either based upon or are compatible with the algorithms in XCMS, which we broadly refer to here as the 'XCMS family' of software. These include CAMERA, credentialing, Warpgroup, metaXCMS, X(13)CMS, and XCMS Online. Together, these informatic technologies can accommodate most cutting-edge metabolomic applications and offer unique advantages when compared to the original XCMS program. PMID: 26673825 [PubMed - as supplied by publisher]