PubMed

The Carnitine Shuttle Pathway is Altered in Patients With Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2018 Oct 01;59(12):4978-4985 Authors: Mitchell SL, Uppal K, Williamson SM, Liu K, Burgess LG, Tran V, Umfress AC, Jarrell KL, Cooke Bailey JN, Agarwal A, Pericak-Vance M, Haines JL, Scott WK, Jones DP, Brantley MA Abstract Purpose: To identify metabolites and metabolic pathways altered in neovascular age-related macular degeneration (NVAMD). Methods: We performed metabolomics analysis using high-resolution C18 liquid chromatography-mass spectrometry on plasma samples from 100 NVAMD patients and 192 controls. Data for mass/charge ratio ranging from 85 to 850 were captured, and metabolic features were extracted using xMSanalyzer. Nested feature selection was used to identify metabolites that discriminated between NVAMD patients and controls. Pathway analysis was performed with Mummichog 2.0. Hierarchical clustering was used to examine the relationship between the discriminating metabolites and NVAMD patients and controls. Results: Of the 10,917 metabolic features analyzed, a set of 159 was identified that distinguished NVAMD patients from controls (area under the curve of 0.83). Of these features, 39 were annotated with confidence and included multiple carnitine metabolites. Pathway analysis revealed that the carnitine shuttle pathway was significantly altered in NVAMD patients (P = 0.0001). Tandem mass spectrometry confirmed the molecular identity of five carnitine shuttle pathway acylcarnitine intermediates that were increased in NVAMD patients. Hierarchical cluster analysis revealed that 51% of the NVAMD patients had similar metabolic profiles, whereas the remaining 49% displayed greater variability in their metabolic profiles. Conclusions: Multiple long-chain acylcarnitines that are part of the carnitine shuttle pathway were significantly increased in NVAMD patients compared to controls, suggesting that fatty acid metabolism may be involved in NVAMD pathophysiology. Cluster analysis suggested that clinically indistinguishable NVAMD patients can be separated into distinct subgroups based on metabolic profiles. PMID: 30326066 [PubMed - in process]

METABOLOMIC PROFILING OF ZEBRAFISH (DANIO RERIO) EMBRYOS EXPOSED TO THE ANTIBACTERIAL AGENT TRICLOSAN. Environ Toxicol Chem. 2018 Oct 16;: Authors: Fu J, Gong Z, Kelly BC Abstract Triclosan (TCS), a widely used antibacterial and antifungal agent, is ubiquitously detected in the natural environment. There is increasing evidence TCS can produce cytotoxic, genotoxic, and endocrine disruptor effects in aquatic biota, including algae, crustaceans, and fish. Metabolomics can provide important information regarding molecular-level effects and toxicity of xenobiotic chemicals in aquatic organisms. The aim of the present study was to assess the toxicity of TCS in developing zebrafish (Danio rerio) embryos using gas chromatography-mass spectrometry (GC-MS) based metabolomics. The studied embryos were exposed to a wide range of TCS concentrations (from 10 ng/L to 500 µg/L). Endogenous metabolites were extracted using acetonitrile: isopropanol: water (3:3:2, v/v/v). Derivatization of metabolites was performed prior to identification and quantification via GC-MS analysis. A total of twenty-nine metabolites were positively identified in embryos. Univariate (One-way ANOVA) and multivariate (PCA, PLS-DA) analyses were employed to determine metabolic profile changes in TCS exposed embryos. Eight metabolites showed significant differences (p < 0.05) in embryos exposed to TCS. Significantly altered metabolites included urea, citric acid, D(+)galactose, D-glucose, stearic acid, L-proline, phenylalanine and L-glutamic acid. The results suggest TCS exposure can result in impairment of several pathways in developing zebrafish embryos, with implications on energy metabolism, amino acid metabolism, as well as nitrogen metabolism and gill function. These findings will benefit future risk assessments of TCS and other contaminants of emerging concern.This article is protected by copyright. All rights reserved. PMID: 30325051 [PubMed - as supplied by publisher]

Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial. Int J Cancer. 2018 Oct 16;: Authors: Beynon R, Richmond RC, Santos Ferreira DL, Ness AR, May M, Davey Smith G, Vincent EE, Adams C, Ala-Korpela M, Würtz P, Soidinsalo S, Metcalfe C, Donovan JL, ProtecT Study Group, The PRACTICAL consortium, Lane AJ, Martin RM Abstract Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomization, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate (β (standard deviation difference versus placebo): 0.69; 95% CI= 0.24, 1.15; p=0.003), valine (β: -0.62; -1.03, -0.02; p=0.004), pyruvate (β: -0.56; -0.95, -0.16; p=0.006), and docosahexaenoic acid (β: -0.50; -085, -0.14; p=0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (β: -0.65; -1.04, -0.26; p=0.001 and β: -0.59; -1.01, -0.18; p=0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p=0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomization analysis suggests may be causally related to reduced prostate cancer risk. This article is protected by copyright. All rights reserved. PMID: 30325021 [PubMed - as supplied by publisher]

Related Articles Investigating the aetiology of adverse events following HPV vaccination with systems vaccinology. Cell Mol Life Sci. 2018 Oct 16;: Authors: Campbell-Tofte J, Vrahatis A, Josefsen K, Mehlsen J, Winther K Abstract In contrast to the insidious and poorly immunogenic human papillomavirus (HPV) infections, vaccination with the HPV virus-like particles (vlps) is non-infectious and stimulates a strong neutralizing-antibody response that protects HPV-naïve vaccinees from viral infection and associated cancers. However, controversy about alleged adverse events following immunization (AEFI) with the vlps have led to extensive reductions in vaccine acceptance, with countries like Japan dropping it altogether. The AEFIs are grouped into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). In this review, we present a hypothesis that the AEFIs might arise from malfunctions within the immune system when confronted with the unusual antigen. In addition, we outline how the pathophysiology of the AEFIs can be cost-effectively investigated with the holistic principles of systems vaccinology in a two-step process. First, comprehensive immunological profiles of HPV vaccinees exhibiting the AEFIs are generated by integrating the data derived from serological profiling for prominent HPV antibodies and serum cytokines, with data from serum metabolomics, peripheral white blood cells transcriptomics and gut microbiome profiling. Next, the immunological profiles are compared with corresponding profiles generated for matched (a) HPV vaccinees without AEFIs; (b) non-HPV-vaccinated individuals with CFS/ME-like symptoms; and (c) non-HPV-vaccinated individuals without CFS/ME. In these comparisons, any causal links between HPV vaccine and the AEFIs, as well as the underlying molecular basis for the links will be revealed. Such a study should provide an objective basis for evaluating HPV vaccine safety and for identifying biomarkers for individuals at risk of developing AEFI with HPV vaccination. PMID: 30324425 [PubMed - as supplied by publisher]

Related Articles Milk Fat Globule Membrane Supplementation in Formula-fed Rat Pups Improves Reflex Development and May Alter Brain Lipid Composition. Sci Rep. 2018 Oct 15;8(1):15277 Authors: Moukarzel S, Dyer RA, Garcia C, Wiedeman AM, Boyce G, Weinberg J, Keller BO, Elango R, Innis SM Abstract Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the "pup in a cup" model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies. PMID: 30323309 [PubMed - in process]

Related Articles Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations. Sci Rep. 2018 Oct 15;8(1):15249 Authors: Barrios C, Zierer J, Würtz P, Haller T, Metspalu A, Gieger C, Thorand B, Meisinger C, Waldenberger M, Raitakari O, Lehtimäki T, Otero S, Rodríguez E, Pedro-Botet J, Kähönen M, Ala-Korpela M, Kastenmüller G, Spector TD, Pascual J, Menni C Abstract Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease. PMID: 30323304 [PubMed - in process]

Related Articles Rapid discovery of quality-markers from Kaixin San using chinmedomics analysis approach. Phytomedicine. 2017 Dec 18;: Authors: Wang XJ, Zhang AH, Kong L, Yu JB, Gao HL, Liu ZD, Sun H Abstract BACKGROUND: Alzheimer's disease (AD), a progressive neurodegenerative disease, is more common disease of dementia among the elderly by multiple factors and presents enormous challenges in terms of diagnosis and treatment. Kaixin San (KXS), is a classic prescription for the treatment of memory decline and applied for AD nowadays. However, the quality-markers of KXS for the treatment of AD remain unclear. PURPOSE: To investigate the effects and potential quality-markers of KXS against an APP/PS1 transgenic mouse model of AD. METHODS: Two month old APP/PS1 transgenic model mice of AD were orally given KXS for 10 month to intervene. Through the novel object recognition (NOR), the classic Morris water maze (MWM), immunohistochemistry detection of Aβ1-42, Hematoxylin-eosin staining (HE), blood metabolic profiling evaluated the therapeutic effect of KXS on AD. PCMS software was applied to analysis correlations between biomarkers and serum constituents and became a powerful tool for excavating effective material basis. Behavior, histopathology and Chinmedomics were applied for assessing the efficacy and discovering potential quality-markers. RESULTS: The result of MWM showed oral KXS could shorten the escape latency and increased the times of crossing the platform. The result of NOR showed oral KXS increased discrimination index (DI). Though the histopathology, KXS reduced the necrosis of neuron in brain tissue and the deposition of Aβ1-42. Chinmedomics strategy was used to analyze the biomarkers and blood components. KXS called back 20 biomarkers of AD. The effective material basis of KXS was ginsenoside Rf, ginsenoside F1, 20-O-glucopyranosyl ginsenoside Rf, dehydropachymic acid and E-3, 4, 5-trimethoxycinnamic acid. CONCLUSION: This study demonstrate that KXS significantly improved cognitive function of transgenic mice of AD, repaired the damage caused by Aβ, regulated amino acid metabolism and lipid metabolism abnormalities and determined the effective material basis of KXS treating AD. Clarifying the quality-markers of KXS can establish scientific quality standard to reflect the safety and effectiveness of Traditional Chinese Medicine (TCM). PMID: 30322673 [PubMed - as supplied by publisher]

Related Articles Baseline metabolic profiles of early rheumatoid arthritis patients achieving sustained drug-free remission after initiating treat-to-target tocilizumab, methotrexate, or the combination: insights from systems biology. Arthritis Res Ther. 2018 Oct 15;20(1):230 Authors: Teitsma XM, Yang W, Jacobs JWG, Pethö-Schramm A, Borm MEA, Harms AC, Hankemeier T, van Laar JM, Bijlsma JWJ, Lafeber FPJG Abstract BACKGROUND: We previously identified, in newly diagnosed rheumatoid arthritis (RA) patients, networks of co-expressed genes and proteomic biomarkers associated with achieving sustained drug-free remission (sDFR) after treatment with tocilizumab- or methotrexate-based strategies. The aim of this study was to identify, within the same patients, metabolic pathways important for achieving sDFR and to subsequently study the complex interactions between different components of the biological system and how these interactions might affect the therapeutic response in early RA. METHODS: Serum samples were analyzed of 60 patients who participated in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) and initiated treatment with methotrexate, tocilizumab, or the combination and who were thereafter able to achieve sDFR (n = 37); as controls, patients were selected who never achieved a drug-free status (n = 23). Metabolomic measurements were performed using mass spectrometry on oxidative stress, amine, and oxylipin platforms covering various compounds. Partial least square discriminant analyses (PLSDA) were performed to identify, per strategy arm, relevant metabolites of which the biological pathways were studied. In addition, integrative analyses were performed correlating the previously identified transcripts and proteins with the relevant metabolites. RESULTS: In the tocilizumab plus methotrexate, tocilizumab, and methotrexate strategy, respectively, 19, 13, and 12 relevant metabolites were found, which were subsequently used for pathway analyses. The most significant pathway in the tocilizumab plus methotrexate strategy was "histidine metabolism" (p < 0.001); in the tocilizumab strategy it was "arachidonic acid metabolism" (p = 0.018); and in the methotrexate strategy it was "arginine and proline metabolism" (p = 0.022). These pathways have treatment-specific drug interactions with metabolites affecting either the signaling of interleukin-6, which is inhibited by tocilizumab, or affecting protein synthesis from amino acids, which is inhibited by methotrexate. CONCLUSION: In early RA patients treated-to-target with a tocilizumab- or methotrexate-based strategy, several metabolites were found to be associated with achieving sDFR. In line with our previous observations, by analyzing relevant transcripts and proteins within the same patients, the metabolic profiles were found to be different between the strategy arms. Our metabolic analysis further supports the hypothesis that achieving sDFR is not only dependent on predisposing biomarkers, but also on the specific treatment that has been initiated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01034137 . Registered on January 2010. PMID: 30322408 [PubMed - in process]

Related Articles Metabolomics identifies increases in the acylcarnitine profiles in the plasma of overweight subjects in response to mild weight loss: a randomized, controlled design study. Lipids Health Dis. 2018 Oct 15;17(1):237 Authors: Kang M, Yoo HJ, Kim M, Kim M, Lee JH Abstract BACKGROUND: Using metabolomics technique to analyze the response to a dietary intervention generates valuable information concerning the effects of the prescribed diet on metabolic regulation. To determine whether low calorie diet (LCD)-induced weight reduction causes changes in plasma metabolites and metabolic characteristics. METHODS: Overweight subjects consumed a LCD (n = 47) or a weight maintenance diet (control, n = 50) in a randomized, controlled design study with a 12-week clinical intervention period. Plasma samples were analyzed using an UPLC-LTQ-Orbitrap MS. RESULTS: The 12-week LCD intervention resulted in significant mild weight loss, with an 8.3% and 10.6% reduction observed in the visceral fat area (VFA) at the level of the lumbar vertebrae L1 and L4, respectively. The LCD group showed a significant increase in the mean change of serum free fatty acids compared to the control group. In the LCD group, we observed a significant increase in the acylcarnitine (AC) levels, including hexanoylcarnitine, L-octanoylcarnitine, 9-decenoylcarnitine, trans-2-dodecenoylcanitine, dodecanoylcarnitine, 3,5-tetradecadiencarnitine, cis-5-tetradecenoylcarnitine, 9,12-hexadecadienoylcarnitine, and 9-hexadecenoylcarnitne at the 12-week follow-up assessment. When the plasma metabolite changes from baseline were compared between the control and LCD groups, the LCD group showed significant increases in hexanoylcarnitine, L-octanoylcarnitine, trans-2-dodecenoylcanitine, and 3,5-tetradecadiencarnitine than the control group. Additionally, the changes in these ACs in the LCD group strongly negatively correlated with the changes in the VFA at L1 and/or L4. CONCLUSION: Mild weight loss from 12-week calorie restriction increased the plasma levels of medium- and long-chain ACs. These changes were coupled with a decrease in VFA and an increase in free fatty acids. TRIAL REGISTRATION: NCT03135132 ; April 26, 2017. PMID: 30322392 [PubMed - in process]

Related Articles Biotinylated naringenin intensified anticancer effect of gefitinib in urethane-induced lung cancer in rats: favourable modulation of apoptotic regulators and serum metabolomics. Artif Cells Nanomed Biotechnol. 2018 Oct 16;:1-13 Authors: Parashar P, Tripathi CB, Arya M, Kanoujia J, Singh M, Yadav A, Kumar A, Guleria A, Saraf SA Abstract Co-therapy through biotin modified nanoparticles (NPs) of gefitinib (Gnb) and naringenin (Nar) was investigated for its therapeutic and synergistic potential against lung cancer. The biotin-conjugated polymeric NPs (bty-Nar/Gnb) were developed using oil in water emulsion technique and optimized using central composite design. The formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. Co-administration of Gnb and Nar NPs displayed a significant reduction in tumour volume while restoring the biochemical parameters and serum metabolites to normal levels. Significant down-regulation of anti-apoptotic proteins (P-16, MMP-9 and Bcl-2) and up-regulation of pro-apoptotic proteins (caspase-9 and BAX) was displayed with co-therapy. This investigation demonstrated the superiority of co-therapy over individual therapy for improved therapeutic efficacy and is favourable for developing a safe, effective and targeted delivery for lung carcinoma therapy. PMID: 30322263 [PubMed - as supplied by publisher]

Related Articles Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells. Vaccines (Basel). 2018 Oct 13;6(4): Authors: Alqarni AM, Ferro VA, Parkinson JA, Dufton MJ, Watson DG Abstract Melittin, the major active peptide of honeybee venom (BV), has potential for use in adjuvant immunotherapy. The immune system response to different stimuli depends on the secretion of different metabolites from macrophages. One potent stimulus is lipopolysaccharide (LPS), a component isolated from gram-negative bacteria, which induces the secretion of pro-inflammatory cytokines in macrophage cell cultures. This secretion is amplified when LPS is combined with melittin. In the present study, pure melittin was isolated from whole BV by flash chromatography to obtain pure melittin. The ability of melittin to enhance the release of tumour necrosis factor-α (TNF-α), Interleukin (IL-1β, IL-6, and IL-10) cytokines from a macrophage cell line (THP-1) was then assessed. The response to melittin and LPS, applied alone or in combination, was characterised by metabolic profiling, and the metabolomics results were used to evaluate the potential of melittin as an immune adjuvant therapy. The addition of melittin enhanced the release of inflammatory cytokines induced by LPS. Effective chromatographic separation of metabolites was obtained by liquid chromatography-mass spectrometry (LC-MS) using a ZIC-pHILIC column and an ACE C4 column. The levels of 108 polar and non-polar metabolites were significantly changed (p ˂ 0.05) following cell activation by the combination of LPS and melittin when compared to untreated control cells. Overall, the findings of this study suggested that melittin might have a potential application as a vaccine adjuvant. PMID: 30322119 [PubMed]

Related Articles Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry. Chin J Nat Med. 2018 Aug;16(8):628-640 Authors: Gu YY, Shi L, Zhang DD, Huang X, Chen DZ Abstract Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways. PMID: 30197129 [PubMed - indexed for MEDLINE]

Related Articles Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome. Mamm Genome. 2018 02;29(1-2):63-79 Authors: Chi L, Gao B, Tu P, Liu CW, Xue J, Lai Y, Ru H, Lu K Abstract Arsenic (As) contamination in water or food is a global issue affecting hundreds of millions of people. Although As is classified as a group 1 carcinogen and is associated with multiple diseases, the individual susceptibility to As-related diseases is highly variable, such that a proportion of people exposed to As have higher risks of developing related disorders. Many factors have been found to be associated with As susceptibility. One of the main sources of the variability found in As susceptibility is the variation in the host genome, namely, polymorphisms of many genes involved in As transportation, biotransformation, oxidative stress response, and DNA repair affect the susceptibility of an individual to As toxicity and then influence the disease outcomes. In addition, lifestyles and many nutritional factors, such as folate, vitamin C, and fruit, have been found to be associated with individual susceptibility to As-related diseases. Recently, the interactions between As exposure and the gut microbiome have been of particular concern. As exposure has been shown to perturb gut microbiome composition, and the gut microbiota has been shown to also influence As metabolism, which raises the question of whether the highly diverse gut microbiota contributes to As susceptibility. Here, we review the literature and summarize the factors, such as host genetics and nutritional status, that influence As susceptibility, and we also present potential mechanisms of how the gut microbiome may influence As metabolism and its toxic effects on the host to induce variations in As susceptibility. Challenges and future directions are also discussed to emphasize the importance of characterizing the specific role of these factors in interindividual susceptibility to As-related diseases. PMID: 29429126 [PubMed - indexed for MEDLINE]

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 2018/10/16PubMed 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 2018/10/16PubMed 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.

Integrated analysis of proteomics-delineated and metabolomics-delineated hepatic metabolic responses to (-)-hydroxycitric acid in chick embryos. J Cell Biochem. 2018 Oct 14;: Authors: Peng M, He Q, Li S, Li L, Ma H Abstract (-)-Hydroxycitric acid [(-)-HCA] is widely used as a nutritional supplement to control body weight and fat accumulation in animals and humans, whereas the underlying biochemical mechanism is unclear. Broiler chicken was used as a model for studies of obesity due to its natural hyperglycemia and being insulin resistant. The current study aimed to obtain a systematic view of serum metabolites and hepatic proteins and well understand the mechanism of hepatic metabolic response to (-)-HCA treatment in chick embryos. The results showed that 22, 90, and 82 of differentially expressed proteins were identified at E14d, E19d, and H1d in chick embryos treated with (-)-HCA, respectively. Meanwhile, 5, 83, and 88 of serum metabolites significantly changed at E14d, E19d, and H1d in chick embryos after (-)-HCA treatment. Bioinformatics analysis showed that the key proteins and metabolites, which were significantly altered in chick embryos treated with (-)-HCA, were mainly involved in the citrate cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and pyruvate metabolism. Our data indicated that (-)-HCA treatment might promote fat metabolism via regulating the key protein expression levels and metabolite contents in the citrate cycle, glycolysis/gluconeogenesis, and oxidative phosphorylation during chicken embryonic development. These results will deepen our understanding of the mechanism of fat reduction by (-)-HCA and provide substantial information for (-)-HCA as a nutritional supplement to control body weight gain and curb obesity-related diseases. PMID: 30317645 [PubMed - as supplied by publisher]

Study on urine metabolic profile of Aβ25-35-induced Alzheimer's disease by using UHPLC-Q-TOF-MS. Neuroscience. 2018 Oct 11;: Authors: Liu Y, Wei M, Yue K, Hu M, Li S, Men L, Pi Z, Liu Z, Liu Z Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25-35 (Aβ 25-35) solution into bilateral hippocampus was developed on Sprague-Dawley rats. After 8 weeks of modeling, the impairment of spatial learning and memory ability in AD rats were assessed by Morris water maze task. Hematoxylin and eosin staining and immunohistochemistry were used to investigate the pathological changes of hippocampus. The neurotransmitter concentrations in the hippocampus were measured by using UHPLC-TQ-MS. Urinary metabolomics based on UHPLC-Q-TOF-MS was established to delineate the alterations of endogenous metabolites in AD rats. The results showed that compared with healthy control rats, AD rats were suffered from cognitive dysfunction, hippocampus damage, Aβ formation and tau phosphorylation at 8 weeks after surgery, suggesting that the Aβ25-35-induced AD model was successfully established. In addition, the levels of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, serotonin, taurine and dopamine decreased and glutamate and aspartic acid increased in hippocampal tissue of AD rats. 45 altered metabolites mainly involved in 8 metabolic pathways were identified as the endogenous biomarkers of AD. According to the analysis of the biological significance of metabolic profiles, the pathogenesis of AD was mainly due to gut microbiome dysbiosis, inhibition of energy metabolism, oxidative stress injury and loss of neuronal protective substances. PMID: 30316910 [PubMed - as supplied by publisher]

Comparison of sequential derivatization with concurrent methods for GC/MS-based metabolomics. J Biosci Bioeng. 2018 Oct 10;: Authors: Miyagawa H, Bamba T Abstract The gas chromatography/mass spectrometry (GC/MS)-based metabolomics requires a two-step derivatization procedure consisting of oximation and silylation. However, due to the incomplete derivatization and degeneration of the metabolites, good repeatability is difficult to obtain during the batch derivatization, as the time between completing the derivatization process and GC analysis differs from sample to sample. In this research, we successfully obtained good repeatability for the peak areas of 52 selected metabolites by sequential derivatization and interval injection, in which the oximation and silylation times were maintained at constant values. In addition, the derivatization times and amount of reagents employed were varied to confirm that the optimal derivatization conditions differed for the various metabolites. In conventional batch derivatization, six metabolites, viz. glutamine, glutamic acid, histidine, alanine, asparagine, and tryptophan, exhibited fluctuations in their peak areas. Indeed, we found that for all six metabolites these differences originated from the silylation process, while the variations for glutamine and glutamic acid were related to the oximation process. PMID: 30316697 [PubMed - as supplied by publisher]

Related Articles High-throughput metabolomics for discovering metabolic biomarkers from intestinal tumorigenesis in APC min/+ mice based on liquid chromatography/mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 02;1100-1101:131-139 Authors: Guo XD, Liu L, Xiao HY Abstract As a major public health concern, colon cancer is one of the most common cancer types, which is also the second cause of cancer death in developed countries and the third most common cancer in other parts of the world. It was reported that patients diagnosed at early stage have a chance to obtain 5-year survival rates at least compared to patients with late stage. Facing the multistep process in intestinal tumorigenesis, there is an urgent need to develop more effective early detection strategies for ameliorating the patient clinical outcome. Metabolomics open up a novel avenue of seeking valuable potential biomarkers for assessing disease severity and prognosticating course by dynamic snapshot of small molecule metabolites. The study aims to provide deeper insights into the discovery, identification and functional pathways analysis of differentially expressed metabolites in intestinal tumorigenesis in APC min/+ mice used by the serum metabolomics, and bring about useful information for further effective prevention and treatment of the disease. 17 marker metabolites and related metabolism pathway were identified using non-targeted metabolomics based on liquid chromatography/mass spectrometry (LC/MS) associated with multivariate statistical analysis. The ingenuity pathway analysis platform involved multiple-pathways was applied to metabolic network analysis for further understanding the relationship between functional metabolic pathways and disease. PMID: 30316137 [PubMed - as supplied by publisher]

Related Articles Urinary metabonomic study of patients with acute coronary syndrome using UPLC-QTOF/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 07;1100-1101:122-130 Authors: Wang Y, Sun W, Zheng J, Xu C, Wang X, Li T, Tang Y, Li Z Abstract This urinary metabonomic study aimed to identify the potential metabolic biomarkers in acute coronary syndrome (ACS) patients. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to analyze the urine samples from ACS patients and healthy controls. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to characterizing the endogenous metabolites and potential biomarker, respectively. Among twenty biomarkers that functioned in nine metabolic pathways, nine biomarkers were found up-regulated significantly, including of isobutyryl‑l‑carnitine, 3‑methylglutarylcarnitine, cinnavalininate, l‑tryptophan, 3‑methyldioxyindole, palmitic acid, N4‑acetylaminobutanal, 3‑sulfino‑l‑alanine and S‑adenosyl‑l‑homocysteine. The other eleven biomarkers were showed down-regulated, including of l‑lactic acid, trigonelline, nicotinuric acid, l‑alanine, d‑alanyl‑d‑alanine, creatine, N4‑acetylaminobutanoate, glutathionyl spermidine, 5‑methoxytryptamine, kynurenic acid and xanthurenic acid. This study also implied that fatty acid metabolism, fatty acid β‑oxidation metabolism, amino acid metabolism and TCA cycle played important roles in ACS. Therefore, urinary metabolomics may improve the diagnosis efficacy of ACS and make it more accurate and comprehensive for ACS diagnosis. PMID: 30316136 [PubMed - as supplied by publisher]