PubMed

Related Articles Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice. Sci Rep. 2017 Jul 21;7(1):6120 Authors: Tu LN, Showalter MR, Cajka T, Fan S, Pillai VV, Fiehn O, Selvaraj V Abstract Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients. PMID: 28733574 [PubMed - in process]

Related Articles Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol. J Am Heart Assoc. 2017 Jul 21;6(7): Authors: Lawler PR, Akinkuolie AO, Chu AY, Shah SH, Kraus WE, Craig D, Padmanabhan L, Glynn RJ, Ridker PM, Chasman DI, Mora S Abstract BACKGROUND: Levels of LDL (low-density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid-related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. METHODS AND RESULTS: We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low-density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo-allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides, but not LDL-c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On-statin levels of the smallest VLDL particle subclass were associated with a 68% per-SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk-this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C-index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein-related risk were observed. CONCLUSIONS: Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. PMID: 28733430 [PubMed - in process]

Related Articles SG2-type R2R3-MYB transcription factor MYB15 controls defense-induced lignification and basal immunity in Arabidopsis. Plant Cell. 2017 Jul 21;: Authors: Chezem WR, Memon A, Li FS, Weng JK, Clay NK Abstract Lignification of cell wall appositions is a conserved basal defense mechanism in the plant innate immune response. However, the genetic pathway controlling defense-induced lignification remains unknown. Here, we demonstrate the Arabidopsis thaliana SG2-type R2R3-MYB transcription factor MYB15 as a regulator of defense-induced lignification and basal immunity. Loss of MYB15 reduces the content but not the composition of defense-induced lignin, whereas constitutive expression of MYB15 increases lignin content independently of immune activation. Comparative transcriptional and metabolomics analyses implicate MYB15 as necessary for the defense-induced synthesis of guaiacyl lignin and the basal synthesis of the coumarin metabolite scopoletin. MYB15 directly binds to the secondary wall MYB-responsive element consensus sequence, which encompasses the AC elements, to drive lignification. The myb15 and lignin biosynthetic mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with defense-induced lignin having a major role in basal immunity. A scopoletin biosynthetic mutant also shows increased susceptibility independently of immune activation, consistent with a role in preformed defense. Our results support a role for phenylalanine-derived small molecules in preformed and inducible Arabidopsis defense, a role previously dominated by tryptophan-derived small molecules. Understanding the regulatory network linking lignin biosynthesis to plant growth and defense will help lignin engineering efforts to improve the production of biofuels and aromatic industrial products as well as increase disease resistance in energy and agricultural crops. PMID: 28733420 [PubMed - as supplied by publisher]

Related Articles Metabolomics reveal physiological changes in mayfly larvae (Neocloeon triangulifer) at ecological upper thermal limits. J Insect Physiol. 2017 Jul 18;: Authors: Chou H, Pathmasiri W, Deese-Spruill J, Sumner S, Buchwalter DB Abstract Aquatic insects play critical roles in freshwater ecosystems and temperature is a fundamental driver of species performance and distributions. However, the physiological mechanisms that determine the thermal performance of species remain unclear. Here we used a metabolomics approach to gain insights into physiological changes associated with a short-term, sublethal thermal challenge in the mayfly Neocloeon triangulifer (Ephemeroptera: Baetidae). Larvae were subjected to a thermal ramp (from 22 to 30 °C at a rate of 1°C/h) and metabolomics analysis (both Nuclear Magnetic Resonance (NMR) Spectroscopy and Gas Chromatography coupled Time-of-Flight Mass Spectrometry (GC-TOF-MS)) indicated that processes related to energetics (sugar metabolism) and membrane stabilization primarily differentiated heat treated larvae from controls. Limited evidence of anaerobic metabolism was observed in the heat treated larvae at 30°C, a temperature that is chronically lethal to larvae. PMID: 28733240 [PubMed - as supplied by publisher]

Related Articles Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study. J Clin Lipidol. 2017 Jun 21;: Authors: Harada PHN, Demler OV, Dugani SB, Akinkuolie AO, Moorthy MV, Ridker PM, Cook NR, Pradhan AD, Mora S Abstract BACKGROUND: Type II diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, high-density lipoprotein (HDL) cholesterol and triglycerides. OBJECTIVE: Whether lipoprotein insulin resistance (LPIR) score, a metabolomic marker, is associated with incident diabetes and improves risk reclassification over traditional markers on extended follow-up. METHODS: Among 25,925 nondiabetic women aged 45 years or older, LPIR was measured by nuclear magnetic resonance spectroscopy as a weighted score of very low density lipoprotein, low-density lipoprotein, and HDL particle sizes, and their subsets concentrations. We run adjusted cox regression models for LPIR with incident T2D (20.4 years median follow-up). RESULTS: Adjusting for demographics, body mass index, life style factors, blood pressure, and T2D family history, the LPIR hazard ratio for T2D (hazard ratio [HR] per standard deviation, 95% confidence interval) was 1.95 (1.85, 2.06). Further adjusting for HbA1c, C-reactive protein, triglycerides, HDL and low-density lipoprotein cholesterol, LPIR HR was attenuated to 1.41 (1.31, 1.53) and had the strongest association with T2D after HbA1C in mutually adjusted models. The association persisted even in those with optimal clinical profiles, adjusted HR per standard deviation 1.91 (1.17, 3.13). In participants deemed at intermediate T2D risk by the Framingham Offspring T2D score, LPIR led to a net reclassification of 0.145 (0.117, 0.175). CONCLUSION: In middle-aged or older healthy women followed prospectively for over 20 years, LPIR was robustly associated with incident T2D, including among those with an optimal clinical metabolic profile. LPIR improved T2D risk classification and may guide early and targeted prevention strategies. PMID: 28733174 [PubMed - as supplied by publisher]

Multi-approach metabolomics analysis and artificial simplified phytocomplexes reveal cultivar-dependent synergy between polyphenols and ascorbic acid in fruits of the sweet cherry (Prunus avium L.). PLoS One. 2017;12(7):e0180889 Authors: Commisso M, Bianconi M, Di Carlo F, Poletti S, Bulgarini A, Munari F, Negri S, Stocchero M, Ceoldo S, Avesani L, Assfalg M, Zoccatelli G, Guzzo F Abstract Fruits of the sweet cherry (Prunus avium L.) accumulate a range of antioxidants that can help to prevent cardiovascular disease, inflammation and cancer. We tested the in vitro antioxidant activity of 18 sweet cherry cultivars collected from 12 farms in the protected geographical indication region of Marostica (Vicenza, Italy) during two growing seasons. Multiple targeted and untargeted metabolomics approaches (NMR, LC-MS, HPLC-DAD, HPLC-UV) as well as artificial simplified phytocomplexes representing the cultivars Sandra Tardiva, Sandra and Grace Star were then used to determine whether the total antioxidant activity reflected the additive effects of each compound or resulted from synergistic interactions. We found that the composition of each cultivar depended more on genetic variability than environmental factors. Furthermore, phenolic compounds were the principal source of antioxidant activity and experiments with artificial simplified phytocomplexes indicated strong synergy between the anthocyanins and quercetins/ascorbic acid specifically in the cultivar Sandra Tardiva. Our data therefore indicate that the total antioxidant activity of sweet cherry fruits may originate from cultivar-dependent interactions among different classes of metabolite. PMID: 28732012 [PubMed - in process]

Related Articles Deconstructing the Metabolic Networks of Oncogenic Signaling Using Targeted Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Methods Mol Biol. 2017;1636:405-414 Authors: Poulogiannis G Abstract Metabolic reprogramming is recognized as an emerging hallmark of oncogenic signaling and cancer development. Hence the need to identify novel quantitative analytical platforms for studying metabolism in vitro and in vivo has dramatically increased. Here, we describe the experimental workflow for a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach involving positive/negative ion switching to analyze >250 metabolites of central carbon metabolism, nucleotides, and amino acids. PMID: 28730494 [PubMed - in process]

Related Articles Advances in Applications of Metabolomics in Pluripotent Stem Cell Research. Curr Opin Chem Eng. 2017 Feb;15:36-43 Authors: Bhute VJ, Bao X, Palecek SP Abstract Stem cells undergo extensive metabolic rewiring during reprogramming, proliferation and differentiation, and numerous studies have demonstrated a significant role of metabolism in controlling stem cell fates. Recent applications of metabolomics, the study of concentrations and fluxes of small molecules in cells, have advanced efforts to characterize and maturate stem cell fates, assess drug toxicity in stem cell tissue models, identify biomarkers, and study the effects of environment on metabolic pathways in stem cells and their progeny. Looking to the future, combining metabolomics with other -omics approaches will provide a deeper understanding of the complex regulatory mechanisms of stem cells. PMID: 28729963 [PubMed]

Related Articles Serum and Plasma Metabolomic Biomarkers for Lung Cancer. Bioinformation. 2017;13(6):202-208 Authors: Kumar N, Shahjaman M, Mollah MNH, Islam SMS, Hoque MA Abstract In drug invention and early disease prediction of lung cancer, metabolomic biomarker detection is very important. Mortality rate can be decreased, if cancer is predicted at the earlier stage. Recent diagnostic techniques for lung cancer are not prognosis diagnostic techniques. However, if we know the name of the metabolites, whose intensity levels are considerably changing between cancer subject and control subject, then it will be easy to early diagnosis the disease as well as to discover the drug. Therefore, in this paper we have identified the influential plasma and serum blood sample metabolites for lung cancer and also identified the biomarkers that will be helpful for early disease prediction as well as for drug invention. To identify the influential metabolites, we considered a parametric and a nonparametric test namely student׳s t-test as parametric and Kruskal-Wallis test as non-parametric test. We also categorized the up-regulated and down-regulated metabolites by the heatmap plot and identified the biomarkers by support vector machine (SVM) classifier and pathway analysis. From our analysis, we got 27 influential (p-value<0.05) metabolites from plasma sample and 13 influential (p-value<0.05) metabolites from serum sample. According to the importance plot through SVM classifier, pathway analysis and correlation network analysis, we declared 4 metabolites (taurine, aspertic acid, glutamine and pyruvic acid) as plasma biomarker and 3 metabolites (aspartic acid, taurine and inosine) as serum biomarker. PMID: 28729763 [PubMed]

Related Articles Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes. Sci Rep. 2017 Jul 20;7(1):6037 Authors: Jäger S, Wahl S, Kröger J, Sharma S, Hoffmann P, Floegel A, Pischon T, Prehn C, Adamski J, Müller-Nurasyid M, Waldenberger M, Strauch K, Peters A, Gieger C, Suhre K, Grallert H, Boeing H, Schulze MB, Meidtner K Abstract Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5). Gene-based tests on all exome chip variants revealed associations between GFRAL and PC aa C42:1/PC aa C42:0, BIN1 and SM (OH) C22:2/SM C18:0 and TFRC and SM (OH) C22:2/SM C16:1). Selecting variants for gene-based tests based on functional annotation identified one additional association between OR51Q1 and hexoses. Among single genetic variants consistently associated with diabetes-related metabolites, two (rs174550 (FADS1), rs3204953 (REV3L)) were significantly associated with type 2 diabetes in large-scale meta-analysis for type 2 diabetes. In conclusion, we identified a novel metabolite locus in single variant analyses and four genes within gene-based tests and confirmed two previously known mGWAS loci which might be relevant for the risk of type 2 diabetes. PMID: 28729637 [PubMed - in process]

Related Articles pyQms enables universal and accurate quantification of mass spectrometry data. Mol Cell Proteomics. 2017 Jul 20;: Authors: Leufken J, Niehues A, Sarin P, Wessel F, Hippler M, Leidel SA, Fufezan C Abstract Quantitative mass spectrometry (MS) is a key technique in many research areas (1), including proteomics, metabolomics, glycomics, and lipidomics. Because all of the corresponding molecules can be described by chemical formulas, universal quantification tools are highly desirable. Here we present pyQms, an open-source software for accurate quantification of all types of molecules measurable by MS. pyQms uses isotope pattern matching which offers an accurate quality assessment of all quantifications and the ability to directly incorporate mass spectrometer accuracy. pyQms is, due to its universal design, applicable to every research field, labeling strategy, and acquisition technique. This opens ultimate flexibility for researchers to design experiments employing innovative and hitherto unexplored labeling strategies. Importantly, pyQms performs very well to accurately quantify partially labeled proteomes in large-scale and high-throughput, the most challenging task for a quantification algorithm. PMID: 28729385 [PubMed - as supplied by publisher]

Related Articles Sialylation of IgG antibodies inhibits IgG-mediated allergic reactions. J Allergy Clin Immunol. 2017 Jul 17;: Authors: Epp A, Hobusch J, Bartsch YC, Petry J, Lilienthal GM, Koeleman CAM, Eschweiler S, Möbs C, Hall A, Morris SC, Braumann D, Engellenner C, Bitterling J, Rahmöller J, Leliavski A, Thurmann R, Collin M, Moremen KW, Strait RT, Blanchard V, Petersen A, Gemoll T, Habermann JK, Petersen F, Nandy A, Kahlert H, Hertl M, Wuhrer M, Pfützner W, Jappe U, Finkelman FD, Ehlers M Abstract In presence of high allergen dosis besides IgE also IgG antibodies can induce allergic reactions, whose severity is dependent on the induced type of IgG Fc glycosylation, what should be considered for new AIT protocols containing new adjuvants. PMID: 28728998 [PubMed - as supplied by publisher]

Related Articles Prioritizing Natural Product Diversity in a Collection of 146 Bacterial Strains Based on Growth and Extraction Protocols. J Nat Prod. 2017 Mar 24;80(3):588-597 Authors: Crüsemann M, O'Neill EC, Larson CB, Melnik AV, Floros DJ, da Silva RR, Jensen PR, Dorrestein PC, Moore BS Abstract In order to expedite the rapid and efficient discovery and isolation of novel specialized metabolites, while minimizing the waste of resources on rediscovery of known compounds, it is crucial to develop efficient approaches for strain prioritization, rapid dereplication, and the assessment of favored cultivation and extraction conditions. Herein we interrogated bacterial strains by systematically evaluating cultivation and extraction parameters with LC-MS/MS analysis and subsequent dereplication through the Global Natural Product Social Molecular Networking (GNPS) platform. The developed method is fast, requiring minimal time and sample material, and is compatible with high-throughput extract analysis, thereby streamlining strain prioritization and evaluation of culturing parameters. With this approach, we analyzed 146 marine Salinispora and Streptomyces strains that were grown and extracted using multiple different protocols. In total, 603 samples were analyzed, generating approximately 1.8 million mass spectra. We constructed a comprehensive molecular network and identified 15 molecular families of diverse natural products and their analogues. The size and breadth of this network shows statistically supported trends in molecular diversity when comparing growth and extraction conditions. The network provides an extensive survey of the biosynthetic capacity of the strain collection and a method to compare strains based on the variety and novelty of their metabolites. This approach allows us to quickly identify patterns in metabolite production that can be linked to taxonomy, culture conditions, and extraction methods, as well as informing the most valuable growth and extraction conditions. PMID: 28335604 [PubMed - indexed for MEDLINE]

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/07/21PubMed 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.

Nutrition, inflammation and cancer. Nat Immunol. 2017 Jul 19;18(8):843-850 Authors: Zitvogel L, Pietrocola F, Kroemer G Abstract Quantitative and qualitative aspects of nutrition have a profound effect on leukocytes and thereby affect proinflammatory carcinogenic effects or anticancer immune responses. As a result, nutrition affects the incidence, natural progression and therapeutic response of malignant diseases, both in humans and in preclinical animal models. Here we discuss the molecular mechanisms through which alimentary cues modulate metabolic, microbial and neuroendocrine circuitries and thus affect the probability of developing premalignant lesions that progress to clinically manifested disease and the response to therapeutic intervention. We examine each of the connections that compose the triangle of nutrition, immunological and inflammatory reactions and cancer while focusing on the mechanistic aspects of these relationships. PMID: 28722707 [PubMed - in process]

Follicular metabolic changes and effects on oocyte quality in polycystic ovary syndrome patients. Oncotarget. 2017 Jul 06;: Authors: Zhang Y, Liu L, Yin TL, Yang J, Xiong CL Abstract Polycystic ovary syndrome (PCOS) is a common complex and heterogeneous disorder, affecting up to 10% women at reproductive age. It causes three fourth of the ovulatory infertility and PCOS patients often give poor IVF quality. Although some metabolic profiles have been investigated in PCOS patient sera and urine, the follicular fluid, providing fruitful biochemical information about oocyte environment during development has been ignored. In this work, based on NMR metabolomics approach, metabolic profile of follicular fluid of PCOS patients has been explored and compared with healthy controls. Significant increases of glycoprotein, acetate, cholesterol, significant decreases of lactic acid, glutamine, pyruvate, and alanine, have been discovered in PCOS follicular fluids. Furthermore, the Pearson correlations analysis indicated significant relationship existed between ART results and NMR detected follicular metabolites. All these results indicated that PCOS may induce dyslipidemia, low-grade inflammation, and disorder of glycolysis, pyruvate and amino acid metabolism in follicular fluids. PMID: 28722670 [PubMed - as supplied by publisher]

First time view on human metabolome changes after a single intake of 3,4 methylenedioxymethamphetamine (MDMA) in healthy placebo-controlled subjects. J Proteome Res. 2017 Jul 19;: Authors: Boxler MI, Liechti ME, Schmid Y, Kraemer T, Steuer AE Abstract 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') is widely consumed recreationally. Currently little is known about its effects on the human metabolome. Mapping biochemical changes after drug exposure can complement traditional approaches by revealing potential biomarkers of organ toxicity or discovering new metabolomic features in a time- and dose-dependent manner. We aimed to analyze for the first time plasma samples from a randomized, double-blind, placebo-controlled crossover study in healthy adults to explore changes in endogenous plasma metabolites following a single intake of MDMA. Plasma samples from 15 subjects taken at four different time points were analyzed with the commercially available AbsoluteIDQ® kit (Biocrates). Time series analysis revealed a total of nine metabolites which showed a significant concentration change after MDMA administration compared with placebo. Paired t-tests of the single time points showed statistically significant concentration changes mainly of glycerophospholipids and the metabolic ratio of methionine-sulfoxide over methionine. Changes of this metabolic ratio may be indicative for changes in systemic oxidative stress levels, the increased amount of glycerophospholipids could be interpreted as an upregulation of energy production. Baseline samples within the experimental study design were crucial for evaluation of metabolomics data as inter-day individuality within subjects was high otherwise resulting in overestimations of the findings. PMID: 28722422 [PubMed - as supplied by publisher]

Urine metabonomics reveals early biomarkers in diabetic cognitive dysfunction. J Proteome Res. 2017 Jul 19;: Authors: Song L, Zhuang P, Lin M, Kang M, Liu H, Zhang Y, Yang Z, Chen Y, Zhang Y Abstract Recently, increasing attention has been paid to diabetic encephalopathy which is one of frequent diabetic complications and affects nearly 30% diabetics. Since cognitive dysfunction from diabetic encephalopathy might develop irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in the urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. Ultra high performance liquid-flight time-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from the diabetic mice which were associated with mild cognitive impairment (MCI) and non-associated with MCI at the stage of diabetes (prior to the onset of DCD), and then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found 7 metabolites could be accepted as early biomarkers of DCD. And the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism and sphingolipid metabolism. The present study firstly revealed reliable biomarkers for early diagnosis of DCD. It would provide a new insight and strategy for the early diagnosis and treatment of DCD. PMID: 28722418 [PubMed - as supplied by publisher]

Related Articles Myopes have significantly higher serum melatonin concentrations than non-myopes. Ophthalmic Physiol Opt. 2017 Jul 18;: Authors: Kearney S, O'Donoghue L, Pourshahidi KL, Cobice D, Saunders KJ Abstract PURPOSE: Experimental animal models of myopia demonstrate that higher melatonin (Mel) and lower dopamine (DA) concentrations actively promote axial elongation. This study explored the association between myopia and serum concentrations of DA and Mel in humans. METHODS: Morning serum concentrations of DA and Mel were measured by solid phase extraction-liquid chromatography-tandem mass spectrometry from 54 participants (age 19.1 ± 0.81 years) in September/October 2014 (phase 1) and March/April 2016 (phase 2). Axial length (AL), corneal radii (CR) and spherical equivalent refraction (SER) were also recorded. Participants were defined as myopic if non-cycloplegic spherical equivalent refractive error ≤-0.50 DS at phase 1. RESULTS: Nine participants were lost to follow up. Mel concentrations were measurable for all myopes (phase 1 n = 25, phase 2 n = 22) and non-myopes (phase 1 n = 29, phase 2 n = 23). SER did not change significantly between phases (p = 0.51). DA concentrations were measurable for fewer myopes (phase 1 n = 13, phase 2 n = 12) and non-myopes (phase 1 n = 23, phase 2 n = 16). Myopes exhibited significantly higher Mel concentrations than non-myopes at phase 1 (Median difference: 10 pg mL(-1) , p < 0.001) and at phase 2 (Median difference: 7.3 pg mL(-1) , p < 0.001) and lower DA concentrations at phase 2 (Median difference: 4.7 pg mL(-1) , p = 0.006). Mel concentrations were positively associated with more negative SER (all r ≥ -0.53, all p < 0.001), longer AL (all r ≥ 0.37, all p ≤ 0.008) and higher AL/CR ratio (all r ≥ 0.51, all p < 0.001). CONCLUSION: This study reports for the first time in humans that myopes exhibit higher serum Mel concentrations than non-myopes. This may indicate a role for light exposure and circadian rhythm in the human myopic growth mechanism. Further research should focus on younger cohorts exhibiting more dynamic myopic progression and explore the profile of these neurochemicals alongside evaluation of sleep patterns in myopic and non-myopic groups. PMID: 28721695 [PubMed - as supplied by publisher]

Related Articles Increased oxidative phosphorylation in response to acute and chronic DNA damage. NPJ Aging Mech Dis. 2016;2:16022 Authors: Brace LE, Vose SC, Stanya K, Gathungu RM, Marur VR, Longchamp A, Treviño-Villarreal H, Mejia P, Vargas D, Inouye K, Bronson RT, Lee CH, Neilan E, Kristal BS, Mitchell JR Abstract Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa(-/-)|Xpa(-/-) mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes. PMID: 28721274 [PubMed]