PubMed

Related Articles Impact of matrix effects and ionization efficiency in non-quantitative untargeted metabolomics. Metabolomics. 2019 Oct 04;15(10):135 Authors: Chamberlain CA, Rubio VY, Garrett TJ Abstract INTRODUCTION: LC-MS-based untargeted metabolomics has become increasingly popular due to the vast amount of information gained in a single analysis. Many studies utilize metabolomics to profile metabolic changes in various representative biofluids, tissues, or other sample types. Most analyses are performed measuring changes in the metabolic pool of a single biological matrix due to an altered phenotype, such as disease versus normal. Measurements in such experiments are typically highly reproducible with little variation due to analytical and technological advancements in mass spectrometry. With the expanded application of metabolomics into various non-analytical scientific disciplines, the emergence of studies comparing the signal intensities of specific analytes across different biological matrices (e.g. plasma vs. urine) is becoming more common, but the matrix effect between sample types is often neglected. Additionally, the practice of comparing the signal intensities of different analytes and correlating to relative abundance is also increasingly prevalent, but the response ratio between analytes due to differences in ionization efficiency is not always accounted for in data analysis. This report serves to communicate and raise awareness of these two well-recognized issues to prevent improper data interpretation in the field of metabolomics. OBJECTIVES: We demonstrate the impact of matrix effects and ionization efficiency with labeled analytical standards in human plasma, serum, and urine and describe how the direct comparison of non-quantitative signal intensities between biofluids, as well as between different analytes in the same biofluid, in untargeted metabolomics is inaccurate without proper response corrections. METHODS: Human plasma, serum, and urine (n = 4 technical replicates per biofluid) were spiked with a panel of labeled internal standards all at identical concentrations, simultaneously extracted, and analyzed by UHPLC-HRMS. Signal intensities were compared for demonstration of the impact of matrix effects in untargeted metabolomics. A neat mixture of two co-eluting, structurally-similar labeled standards at the same concentration was also analyzed to demonstrate the effect of ionization efficiency on signal intensity. RESULTS: Despite being spiked at identical concentrations, labeled standards we examined in this study showed significant differences in their signal intensities between biofluids, as well as from each other in the same biofluid, due to matrix effects. Co-eluting standards were also found to yield significantly different signal intensities at identical concentrations due to differences in ionization efficiency. CONCLUSIONS: Due to the presence of matrix effects in untargeted, non-quantitative metabolomics, the signal intensity of any single analyte cannot be directly compared to the signal intensity of that same analyte (or any other analyte) between any two different matrices. Due to differences in ionization efficiency, the signal intensity of any single analyte cannot be directly compared to the signal intensity of any other analyte, even in the same matrix. PMID: 31584114 [PubMed - in process]

Related Articles Multi-block PLS discriminant analysis for the joint analysis of metabolomic and epidemiological data. Metabolomics. 2019 Oct 03;15(10):134 Authors: Brandolini-Bunlon M, Pétéra M, Gaudreau P, Comte B, Bougeard S, Pujos-Guillot E Abstract INTRODUCTION: Metabolomics is a powerful phenotyping tool in nutrition and health research, generating complex data that need dedicated treatments to enrich knowledge of biological systems. In particular, to investigate relations between environmental factors, phenotypes and metabolism, discriminant statistical analyses are generally performed separately on metabolomic datasets, complemented by associations with metadata. Another relevant strategy is to simultaneously analyse thematic data blocks by a multi-block partial least squares discriminant analysis (MBPLSDA) allowing determining the importance of variables and blocks in discriminating groups of subjects, taking into account data structure. OBJECTIVE: The present objective was to develop a full open-source standalone tool, allowing all steps of MBPLSDA for the joint analysis of metabolomic and epidemiological data. METHODS: This tool was based on the mbpls function of the ade4 R package, enriched with functionalities, including some dedicated to discriminant analysis. Provided indicators help to determine the optimal number of components, to check the MBPLSDA model validity, and to evaluate the variability of its parameters and predictions. RESULTS: To illustrate the potential of this tool, MBPLSDA was applied to a real case study involving metabolomics, nutritional and clinical data from a human cohort. The availability of different functionalities in a single R package allowed optimizing parameters for an efficient joint analysis of metabolomics and epidemiological data to obtain new insights into multidimensional phenotypes. CONCLUSION: In particular, we highlighted the impact of filtering the metabolomic variables beforehand, and the relevance of a MBPLSDA approach in comparison to a standard PLS discriminant analysis method. PMID: 31583480 [PubMed - in process]

Related Articles In vitro profiling of endothelial volatile organic compounds under resting and pro-inflammatory conditions. Metabolomics. 2019 Oct 03;15(10):132 Authors: Longo V, Forleo A, Capone S, Scoditti E, Carluccio MA, Siciliano P, Massaro M Abstract INTRODUCTION: The evaluation of volatile organic compounds(VOCs) emitted by human body offers a unique tool to set up new non-invasive devices for early diagnosis and long-lasting monitoring of most human diseases. However, their cellular origin and metabolic fate have not been completely elucidated yet, thus limiting their clinical application. Endothelium acts as an interface between blood and surrounding tissues. As such, it adapts its physiology in response to different environmental modifications thus playing a role in the pathogenesis of many metabolic and inflammatory diseases. OBJECTIVES: Since endothelium specifically reshapes its physiologic functions upon environmental changes the objective of this study was to evaluate if and how pro-inflammatory stimuli affect VOC metabolism in endothelial cell in culture. METHODS: Gas chromatography with mass spectrometric detection was applied to profile VOCs in the headspace of cultured endothelial cells (EC) in the absence or presence of the pro-inflammatory stimulus lipopolysaccharide (LPS). RESULTS: We observed that, under resting conditions, EC affected the amount of 58 VOCs belonging to aldehyde, alkane and ketone families. Among these, LPS significantly altered the amount of 15 VOCs. ROC curves show a perfect performance (AUC = 1) for 10 metabolites including 1-butanol, 3-methyl-1-butanol and 2-ethyl-1-hexanol. DISCUSSION: The emission and uptake of the aforementioned VOCs disclose potential unexplored metabolic pathways for EC that deserve to be investigated. Overall, we identified new candidate VOC potentially exploitable, upon experimental confirm in in vivo model of disease, as potential biomarkers of sepsis and pro-inflammatory clinical settings. PMID: 31583479 [PubMed - in process]

Related Articles Predicting response to lisinopril in treating hypertension: a pilot study. Metabolomics. 2019 Oct 03;15(10):133 Authors: Sonn BJ, Saben JL, McWilliams G, Shelton SK, Flaten HK, D'Alessandro A, Monte AA Abstract INTRODUCTION: Only ~ 50% of hypertensive patients will respond to treatment. OBJECTIVE: This pilot study aims to identify clinical and metabolite markers that predict response to lisinopril. METHODS: Hypertensive patients (n = 45) received lisinopril (10 mg) at their baseline visit. Blood pressures were reevaluated one week later. Responders to lisinopril (n = 19) were defined by a 10% decline in systolic blood pressure. Plasma metabolites were evaluated with mass spectrometry. RESULTS: BMI (p = 0.009), GFR (p = 0.015) and 2-oxoglutarate were included in a logistic regression model to predict response to lisinopril. CONCLUSIONS: Further validation cohorts are needed to confirm the predictive values of these clinical and metabolic markers. PMID: 31583478 [PubMed - in process]

Related Articles Metabolomics analysis of children with autism, idiopathic-developmental delays, and Down syndrome. Transl Psychiatry. 2019 Oct 03;9(1):243 Authors: Orozco JS, Hertz-Picciotto I, Abbeduto L, Slupsky CM Abstract Although developmental delays affect learning, language, and behavior, some evidence suggests the presence of disturbances in metabolism are associated with psychiatric disorders. Here, the plasma metabolic phenotype of children with autism spectrum disorder (ASD, n = 167), idiopathic-developmental delay (i-DD, n = 51), and Down syndrome (DS, n = 31), as compared to typically developed (TD, n = 193) controls was investigated in a subset of children from the case-control Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Metabolome profiles were obtained using nuclear magnetic resonance spectroscopy and analyzed in an untargeted manner. Forty-nine metabolites were identified and quantified in each sample that included amino acids, organic acids, sugars, and other compounds. Multiple linear regression analysis revealed significant associations between 11 plasma metabolites and neurodevelopmental outcome. Despite the varied origins of these developmental disabilities, we observed similar perturbation in one-carbon metabolism pathways among DS and ASD cases. Similarities were also observed in the DS and i-DD cases in the energy-related tricarboxylic acid cycle. Other metabolites and pathways were uniquely associated with DS or ASD. By comparing metabolic signatures between these conditions, the current study expands on extant literature demonstrating metabolic alterations associated with developmental disabilities and provides a better understanding of overlapping vs specific biological perturbations associated with these disorders. PMID: 31582732 [PubMed - in process]

Related Articles MFF REGULATION OF MITOCHONDRIAL CELL DEATH IS A THERAPEUTIC TARGET IN CANCER. Cancer Res. 2019 Oct 03;: Authors: Seo JH, Chae YC, Kossenkov AV, Lee YG, Tang HY, Agarwal E, Gabrilovich DI, Languino LR, Speicher DW, Shastrula PK, Storaci AM, Ferrero S, Gaudioso G, Caroli M, Tosi D, Giroda M, Vaira V, Rebecca VW, Herlyn M, Xiao M, Fingerman D, Martorella A, Skordalakes E, Altieri DC Abstract The regulators of mitochondrial cell death in cancer have remained elusive, hampering the development of new therapies. Here, we showed that protein isoforms of Mitochondrial Fission Factor (MFF1 and MFF2), a molecule that controls mitochondrial size and shape, i.e. mitochondrial dynamics, were overexpressed in patients with non-small cell lung cancer and formed homo- and heterodimeric complexes with the voltage-dependent anion channel-1 (VDAC1), a key regulator of mitochondrial outer membrane permeability. MFF inserted into the interior hole of the VDAC1 ring using Arg225, Arg236 and Gln241 as key contact sites. A cell-permeable MFF Ser223-Leu243 D-enantiomeric peptidomimetic disrupted the MFF-VDAC1 complex, acutely depolarized mitochondria and triggered cell death in heterogeneous tumor types, including drug-resistant melanoma, but had no effect on normal cells. In preclinical models, treatment with the MFF peptidomimetic was well-tolerated and demonstrated anticancer activity in patient-derived xenografts, primary breast and lung adenocarcinoma 3D organoids and glioblastoma neurospheres. These data identify the MFF-VDAC1 complex as a novel regulator of mitochondrial cell death and an actionable therapeutic target in cancer. PMID: 31582380 [PubMed - as supplied by publisher]

Related Articles The Association between Alcohol Consumption and Serum Metabolites and the Modifying Effect of Smoking. Nutrients. 2019 Oct 01;11(10): Authors: Langenau J, Boeing H, Bergmann MM, Nöthlings U, Oluwagbemigun K Abstract Alcohol consumption is an important lifestyle factor that is associated with several health conditions and a behavioral link with smoking is well established. Metabolic alterations after alcohol consumption have yet to be comprehensively investigated. We studied the association of alcohol consumption with metabolite patterns (MPs) among 2433 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, and a potential modification by smoking. Alcohol consumption was self-reported through dietary questionnaires and serum metabolites were measured by a targeted approach. The metabolites were summarized as MPs using the treelet transform analysis (TT). We fitted linear models with alcohol consumption continuously and in five categories. We stratified the continuously modelled alcohol consumption by smoking status. All models were adjusted for potential confounders. Among men, alcohol consumption was positively associated with six MPs and negatively associated with one MP. In women, alcohol consumption was inversely associated with one MP. Heavy consumers differed from other consumers with respect to the "Long and short chain acylcarnitines" MP. Our findings suggest that long and short chain acylcarnitines might play an important role in the adverse effects of heavy alcohol consumption on chronic diseases. The relations seem to depend on gender and smoking status. PMID: 31581552 [PubMed - in process]

Related Articles Bis-allylic Deuterated DHA Alleviates Oxidative Stress in Retinal Epithelial Cells. Antioxidants (Basel). 2019 Oct 01;8(10): Authors: Rosell M, Giera M, Brabet P, Shchepinov MS, Guichardant M, Durand T, Vercauteren J, Galano JM, Crauste C Abstract Oxidative stress plays a crucial role in developing and accelerating retinal diseases including age-related macular degeneration (AMD). Docosahexaenoic acid (DHA, C22:6, n-3), the main lipid constituent of retinal epithelial cell membranes, is highly prone to radical and enzymatic oxidation leading to deleterious or beneficial metabolites for retinal tissue. To inhibit radical oxidation while preserving enzymatic metabolism, deuterium was incorporated at specific positions of DHA, resulting in D2-DHA when incorporated at position 6 and D4-DHA when incorporated at the 6,9 bis-allylic positions. Both derivatives were able to decrease DHAs' toxicity and free radical processes involved in lipid peroxidation, in ARPE-19 cells (Adult Retinal Pigment Epithelial cell line), under pro-oxidant conditions. Our positive results encouraged us to prepare lipophenolic-deuterated-DHA conjugates as possible drug candidates for AMD treatment. These novel derivatives proved efficient in limiting lipid peroxidation in ARPE-19 cells. Finally, we evaluated the underlying mechanisms and the enzymatic conversion of both deuterated DHA. While radical abstraction was affected at the deuterium incorporation sites, enzymatic conversion by the lipoxygenase 15s-LOX was not impacted. Our results suggest that site-specifically deuterated DHA could be used in the development of DHA conjugates for treatment of oxidative stress driven diseases, or as biological tools to study the roles, activities and mechanisms of DHA metabolites. PMID: 31581525 [PubMed]

Related Articles Development of an SNP-based parentage verification panel for lovebirds. Anim Genet. 2019 Oct 03;: Authors: van der Zwan H, Visser C, Schoonen M, van der Sluis R Abstract The genus Agapornis, or lovebirds, are popular pet parrots worldwide. Currently, breeders are dependent on pedigree records as a selection tool as no molecular parentage verification test is available for any of the nine species. The A. roseicollis reference genome was recently assembled. This was followed by the sequencing of the whole genomes of the parents of the reference genome individual at 30× coverage. The parents' reads were mapped against the reference genome to identify SNPs. Over 1.6 million SNPs, shared between the parents, were discovered using the Genome Analysis Toolkit pipeline. SNPs were filtered to a panel of 480 SNPs based on Genome Analysis Toolkit parameters. The panel of 480 SNPs was genotyped in a population of 960 lovebirds across seven species. A panel of 262 SNPs was compiled that included SNPs successfully amplified across all species. The 262-SNP panel was reduced based on the observed heterozygosity (HO ) and minor allele frequency (MAF) values per SNP to include the lowest number of SNPs with the highest exclusion power for parentage verification. Two smaller panels consisting of 195 SNPs with MAF and HO values >0.1 and 40 SNPs with MAF and HO values >0.3, were constructed. The panels were verified using 43 families from different species with known relationships to evaluate the exclusion power of each panel. The 195 SNP panel with an average exclusion probability of 99.9% and MAF and HO values >0.1 was proposed as the routine Agapornis parentage verification panel. PMID: 31579954 [PubMed - as supplied by publisher]

Related Articles A comparison of inducible, ontogenetic, and interspecific sources of variation in the foliar metabolome in tropical trees. PeerJ. 2019;7:e7536 Authors: Sedio BE, Durant Archibold A, Rojas Echeverri JC, Debyser C, Boya P CA, Wright SJ Abstract Plant interactions with other organisms are mediated by chemistry, yet chemistry varies among conspecific and within individual plants. The foliar metabolome-the suite of small-molecule metabolites found in the leaf-changes during leaf ontogeny and is influenced by the signaling molecule jasmonic acid. Species differences in secondary metabolites are thought to play an important ecological role by limiting the host ranges of herbivores and pathogens, and hence facilitating competitive coexistence among plant species in species-rich plant communities such as tropical forests. Yet it remains unclear how inducible and ontogenetic variation compare with interspecific variation, particularly in tropical trees. Here, we take advantage of novel methods to assemble mass spectra of all compounds in leaf extracts into molecular networks that quantify their chemical structural similarity in order to compare inducible and ontogenetic chemical variation to among-species variation in species-rich tropical tree genera. We ask (i) whether young and mature leaves differ chemically, (ii) whether jasmonic acid-inducible chemical variation differs between young and mature leaves, and (iii) whether interspecific exceeds intraspecific chemical variation for four species from four hyperdiverse tropical tree genera. We observed significant effects of the jasmonic acid treatment for three of eight combinations of species and ontogenetic stage evaluated. Three of the four species also exhibited large metabolomic differences with leaf ontogenetic stage. The profound effect of leaf ontogenetic stage on the foliar metabolome suggests a qualitative turnover in secondary chemistry with leaf ontogeny. We also quantified foliar metabolomes for 45 congeners of the four focal species. Chemical similarity was much greater within than between species for all four genera, even when within-species comparisons included leaves that differed in age and jasmonic acid treatment. Despite ontogenetic and inducible variation within species, chemical differences among congeneric species may be sufficient to partition niche space with respect to chemical defense. PMID: 31579568 [PubMed]

Related Articles Systematic identification of metabolites controlling gene expression in E. coli. Nat Commun. 2019 Oct 02;10(1):4463 Authors: Lempp M, Farke N, Kuntz M, Freibert SA, Lill R, Link H Abstract Metabolism controls gene expression through allosteric interactions between metabolites and transcription factors. These interactions are usually measured with in vitro assays, but there are no methods to identify them at a genome-scale in vivo. Here we show that dynamic transcriptome and metabolome data identify metabolites that control transcription factors in E. coli. By switching an E. coli culture between starvation and growth, we induce strong metabolite concentration changes and gene expression changes. Using Network Component Analysis we calculate the activities of 209 transcriptional regulators and correlate them with metabolites. This approach captures, for instance, the in vivo kinetics of CRP regulation by cyclic-AMP. By testing correlations between all pairs of transcription factors and metabolites, we predict putative effectors of 71 transcription factors, and validate five interactions in vitro. These results show that combining transcriptomics and metabolomics generates hypotheses about metabolism-transcription interactions that drive transitions between physiological states. PMID: 31578326 [PubMed - in process]

Related Articles Metabolic profiling of adolescent non-alcoholic fatty liver disease. Wellcome Open Res. 2018;3:166 Authors: Hartley A, Santos Ferreira DL, Anderson EL, Lawlor DA Abstract Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health. PMID: 30687796 [PubMed]

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 2019/10/03PubMed 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.

18 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 2019/10/02PubMed 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.

35 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 2019/10/01PubMed 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.

Leaf metabolic signatures induced by real and simulated herbivory in black mustard (Brassica nigra). Metabolomics. 2019 Sep 28;15(10):130 Authors: Papazian S, Girdwood T, Wessels BA, Poelman EH, Dicke M, Moritz T, Albrectsen BR Abstract INTRODUCTION: The oxylipin methyl jasmonate (MeJA) is a plant hormone active in response signalling and defence against herbivores. Although MeJA is applied experimentally to mimic herbivory and induce plant defences, its downstream effects on the plant metabolome are largely uncharacterized, especially in the context of primary growth and tissue-specificity of the response. OBJECTIVES: We investigated the effects of MeJA-simulated and real caterpillar herbivory on the foliar metabolome of the wild plant Brassica nigra and monitored the herbivore-induced responses in relation to leaf ontogeny. METHODS: As single or multiple herbivory treatments, MeJA- and mock-sprayed plants were consecutively exposed to caterpillars or left untreated. Gas chromatography (GC) and liquid chromatography (LC) time-of-flight mass-spectrometry (TOF-MS) were combined to analyse foliar compounds, including central primary and specialized defensive plant metabolites. RESULTS: Plant responses were stronger in young leaves, which simultaneously induced higher chlorophyll levels. Both MeJA and caterpillar herbivory induced similar, but not identical, accumulation of tricarboxylic acids (TCAs), glucosinolates (GSLs) and phenylpropanoids (PPs), but only caterpillar feeding led to depletion of amino acids. MeJA followed by caterpillars caused higher induction of defence compounds, including a three-fold increase in the major defence compound allyl-GSL (sinigrin). When feeding on MeJA-treated plants, caterpillars gained less weight indicative of the reduced host-plant quality and enhanced resistance. CONCLUSIONS: The metabolomics approach showed that plant responses induced by herbivory extend beyond the regulation of defence metabolism and are tightly modulated throughout leaf development. This leads to a new understanding of the plant metabolic potential that can be exploited for future plant protection strategies. PMID: 31563978 [PubMed - in process]

Proteobacteria Acts as a Pathogenic Risk-Factor for Chronic Abdominal Pain and Diarrhea in Post-Cholecystectomy Syndrome Patients: A Gut Microbiome Metabolomics Study. Med Sci Monit. 2019 Sep 29;25:7312-7320 Authors: Kang Z, Lu M, Jiang M, Zhou D, Huang H Abstract BACKGROUND Laparoscopic cholecystectomy (LC) is regarded as the criterion standard for gallstone therapy, but post-cholecystectomy syndrome (PCS) is a common complication. This study aimed to analyze and identify differences in gut microbiome in PCS patients. MATERIAL AND METHODS This study involved 8 PCS patients (RS1), 8 asymptomatic PCS patients (RS2), and 8 healthy individuals (RS3). Genomic DNA of gut microbiome was extracted and amplified with CTAB method. PCR products were sequenced with Illumina High-Through Sequencing. Sequencing data were analyzed with QIIME software. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs using UPARSE software. Species annotations were evaluated using Mothur software. QIIME software was used to conduct complexity analysis and calculate UniFrac distances. R software was used to generate PCoA plots. RESULTS Bacterial 16S-rDNA gene sequences showed that the effective species annotative data were more than 97%. According to Ternary plot, Firmicutes and Bacteroidetes had similar abundance and contents among the 3 groups. Contents of Proteobacteria in RS1 were higher compared to RS2 and RS3. Bacterial genomic DNAs samples were clustered together in the same group; however, distances were relative far between different groups. RS1 illustrated significantly higher abundance of Proteobacteria colonies compared to healthy people (p<0.05), and illustrated higher abundance of Verrucomicrobia and lower abundance of Bacteroidetes and Firmicutes, but without significant differences (p>0.05). CONCLUSIONS Gut microbiome of PCS patients was dominated by Proteobacteria in feces and contained little Firmicutes and Bacteroidetes. The enhanced abundance of Proteobacteria might be the highly pathogenic risk factor for chronic abdominal pain and diarrhea in PCS patients. PMID: 31563920 [PubMed - in process]

Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters. J Pharm Biomed Anal. 2019 Sep 21;177:112888 Authors: Xu Y, Lu H, Wang Y, Zhang Z, Wu Q Abstract Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility. PMID: 31563758 [PubMed - as supplied by publisher]

The influence of polyphenols on metabolic disorders caused by compounds released from plastics - Review. Chemosphere. 2019 Sep 20;240:124901 Authors: Żwierełło W, Maruszewska A, Skórka-Majewicz M, Goschorska M, Baranowska-Bosiacka I, Dec K, Styburski D, Nowakowska A, Gutowska I Abstract Persistent organic pollutants (POPs) released from plastics into water, soil and air are significant environmental and health problem. Continuous exposure of humans to these substances results not only from the slow biodegradation of plastics but also from their ubiquitous use as industrial materials and everyday products. Exposure to POPs may lead to neurodegenerative disorders, induce inflammation, hepatotoxicity, nephrotoxicity, insulin resistance, allergies, metabolic diseases, and carcinogenesis. This has spurred an increasing intense search for natural compounds with protective effects against the harmful components of plastics. In this paper, we discuss the current state of knowledge concerning the protective functions of polyphenols against the toxic effects of POPs: acrylonitrile, polychlorinated biphenyls, dioxins, phthalates and bisphenol A. We review in detail papers from the last two decades, analyzing POPs in terms of their sources of exposure and demonstrate how polyphenols may be used to counteract the harmful environmental effects of POPs. The protective effect of polyphenols results from their impact on the level and activity of the components of the antioxidant system, enzymes involved in the elimination of xenobiotics, and as a consequence - on the level of reactive oxygen species (ROS). Polyphenols present in daily diet may play a protective role against the harmful effects of POPs derived from plastics, and this interaction is related, among others, to the antioxidant properties of these compounds. To our knowledge, this is the first extensive review of in vitro and in vivo studies concerning the molecular mechanisms of interactions between selected environmental toxins and polyphenols. PMID: 31563713 [PubMed - as supplied by publisher]

The study of neuroprotective effect of ferulic acid based on cell metabolomics. Eur J Pharmacol. 2019 Sep 26;:172694 Authors: Yin CL, Lu RG, Zhu JF, Zhu HJ, Liu X, Li QF, Mo YY, Huang HM, Chin B, Wu JX, Liu XW, Cheng B, Ruan JX, Liang YH, Song H, Zheng H, Guo HW, Su ZH Abstract Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA. PMID: 31563648 [PubMed - as supplied by publisher]