PubMed

Related Articles Metabolomic identification of novel diagnostic biomarkers in ectopic pregnancy. Metabolomics. 2019 Oct 19;15(11):143 Authors: Turkoglu O, Citil A, Katar C, Mert I, Kumar P, Yilmaz A, Uygur DS, Erkaya S, Graham SF, Bahado-Singh RO Abstract INTRODUCTION: Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture. OBJECTIVES: To identify putative plasma biomarkers for the detection of tubal EP and elucidate altered biochemical pathways in EP compared to intrauterine pregnancies. METHODS: This case-control study included prospective recruitment of 39 tubal EP cases and 89 early intrauterine pregnancy controls. Plasma samples were biochemically profiled using proton nuclear magnetic resonance spectroscopy (1H NMR). To avoid over-fitting, datasets were randomly divided into a discovery group (26 cases vs 60 controls) and a test group (13 cases and 29 controls). Logistic regression models were developed in the discovery group and validated in the independent test group. Area under the receiver operating characteristics curve (AUC), 95% confidence interval (CI), sensitivity, and specificity values were calculated. RESULTS: In total 13 of 43 (30.3%) metabolite concentrations were significantly altered in EP plasma (p < 0.05). Metabolomic profiling yielded significant separation between EP and controls (p < 0.05). Independent validation of a two-metabolite model consisting of lactate and acetate, achieved an AUC (95% CI) = 0.935 (0.843-1.000) with a sensitivity of 92.3% and specificity of 96.6%. The second metabolite model (D-glucose, pyruvate, acetoacetate) performed well with an AUC (95% CI) = 0.822 (0.657-0.988) and a sensitivity of 84.6% and specificity of 86.2%. CONCLUSION: We report novel metabolomic biomarkers with a high accuracy for the detection of EP. Accurate biomarkers could potentially result in improved early diagnosis of tubal EP cases. PMID: 31630278 [PubMed - in process]

Related Articles Risk profiling using metabolomic characteristics for susceptible individuals of drug-induced liver injury caused by Polygonum multiflorum. Arch Toxicol. 2019 Oct 19;: Authors: Zhang L, Niu M, Wei AW, Tang JF, Tu C, Bai ZF, Zou ZS, Xiao XH, Liu YP, Wang JB Abstract Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case-control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography-mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion. PMID: 31630224 [PubMed - as supplied by publisher]

Related Articles NMR-based metabolomics study of asafoetida. Fitoterapia. 2019 Oct 17;:104361 Authors: Farhadi F, Asili J, Iranshahy M, Iranshahi M Abstract Asafoetida, an oleo-gum-resin obtained from the exudates of Ferula assa-foetida L. roots, is traditionally used to treat various diseases including asthma, gastrointestinal disorders, and intestinal parasites. On the basis of Iranian traditional medicine, the main source of asafetida is F. assa-foetida roots. In folk medicine, however, different Ferula species have been used as sources of asafoetida. To identify the original asafoetida that possesses medicinal properties, we should compare metabolic profiles of different asafoetida sources which are commonly used for the oleo-gum-resin preparation.1H-NMR based metabolomics was used to obtain metabolic profiles of eight asafoetida oleo-gum-resin samples and forty-six samples of Ferula species roots from two main regions of Iran. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projection to latent structures discriminant analysis (OPLS-DA) to identify the metabolic differences and similarities between the samples. Asafoetida is usually produced from Ferula species of southern and eastern regions of Iran. A clear metabolic differentiation was evident between asafoetida oleo-gum- resin samples from the southern and those of the eastern Iran. The distinguished metabolites, umbelliprenin, farnesiferol B, farnesiferol C, samarcandin and galbanic acid are significantly found in southern samples. Only southern asafoetida is obtained from F. assa-foetida. Asafoetida from eastern region of Iran is obtained from other species of Ferula such as F. alliacea and its metabolic profile is far different from that of southern asafoetida. PMID: 31629871 [PubMed - as supplied by publisher]

Related Articles Integrated metabolomics and network toxicology to reveal molecular mechanism of celastrol induced cardiotoxicity. Toxicol Appl Pharmacol. 2019 Oct 17;:114785 Authors: Liu C, Zhang C, Wang W, Yuan F, He T, Chen Y, Wang Q, Huang J Abstract Celastrol (CS), an active triterpene derived from traditional Chinese medicine Tripterygium wilfordii Hook. f, has been used to treat chronic inflammation, arthritis and other diseases. However, it has been reported that CS can trigger cardiotoxicity and the molecular mechanism of heart injury induced by CS is not clear. Considering the wide application of Tripterygium wilfordii Hook. f in clinics, it is necessary to develop an accurate and reliable method to assess the safety of CS, and to elucidate as much as possible the mechanism of cardiotoxicity induced by CS. In this study, Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics revealed clues to the mechanism of CS-induced heart injury. Palmitic acid significantly increased in plasma from CS-treated rats, and this increase resulted in oxidative stress response in vivo. Excessive ROS further activate TNF signaling pathway and caspase family, which were obtained from the KEGG enrichment analysis of network toxicology strategy. Protein expression level of caspase-3, caspase-8, bax were significantly increased by western blot. Q-PCR also showed the similar results as western blot. It means that apoptosis plays a key role in the process of celastrol induced cardiotoxicity. Blocking this signal axis may be a potential way to protect myocardial tissue. PMID: 31629732 [PubMed - as supplied by publisher]

Related Articles Association between the perturbation of bile acid homeostasis and valproic acid-induced hepatotoxicity. Biochem Pharmacol. 2019 Oct 16;:113669 Authors: Chen Y, Zhou J, Xu S, Liu M, Wang M, Ma Y, Zhao M, Wang Z, Guo J, Zhao L Abstract Valproic acid (VPA), a widely prescribed antiepileptic drug, is known to induce hepatotoxicity. However, the mechanisms underlying this toxicity are not well understood. In this study, we performed a nontargeted metabolomic analysis of children with epilepsy treated with VPA (n=23). Metabolic pathway analysis showed that the fatty acid pathway, citrate cycle, urea cycle, amino acid metabolism, and bile acid pathway were altered in children with epilepsy exhibiting VPA hepatotoxicity. In particular, the VPA-induced perturbation of bile acid homeostasis has not been observed previously. Based on these findings, we performed a targeted metabolomic analysis to characterize bile acid profiles and further determined the effects of VPA on the synthesis, transport, and regulation of bile acids in mice. The bile acid metabolomic profiles of the livers of mice treated with VPA indicated an increase in most bile acids, especially chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), as well as unconjugated bile acids. The upregulation of genes related to bile acid synthesis (CYP7A1and CYP8B1) and the downregulation of genes related to conjugation (BAAT and BACS) and regulation (FXR and SHP) were detected in the liver, suggesting that hydrophobic bile acid production was increased and FXR signaling was impaired. Our results suggest that the perturbation of bile acid homeostasis and impaired FXR signaling are involved in VPA-induced hepatotoxicity, providing a novel insight into VPA hepatotoxicity. PMID: 31628911 [PubMed - as supplied by publisher]

Related Articles Non-enzymatic reaction of carnosine and glyceraldehyde-3-phosphate accompanies metabolic changes of the pentose phosphate pathway. Cell Prolif. 2019 Oct 19;:e12702 Authors: Oppermann H, Birkemeyer C, Meixensberger J, Gaunitz F Abstract OBJECTIVES: Carnosine (β-alanyl-l-histidine) is a naturally occurring dipeptide that selectively inhibits cancer cell growth, possibly by influencing glucose metabolism. As its precise mode of action and its primary targets are unknown, we analysed carnosine's effect on metabolites and pathways in glioblastoma cells. MATERIALS AND METHODS: Glioblastoma cells, U87, T98G and LN229, were treated with carnosine, and metabolites were analysed by gas chromatography coupled with mass spectrometry. Furthermore, mitochondrial ATP production was determined by extracellular flux analysis and reaction products of carnosine were investigated using mass spectrometry. RESULTS: Carnosine decreased the intracellular abundance of several metabolites indicating a reduced activity of the pentose phosphate pathway, the malate-aspartate shuttle and the glycerol phosphate shuttle. Mitochondrial respiration was reduced in U87 and T98G but not in LN229 cells, independent of whether glucose or pyruvate was used as substrate. Finally, we demonstrate non-enzymatic reaction of carnosine with dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. However, glycolytic flux from glucose to l-lactate appeared not to be affected by the reaction of carnosine with the metabolites. CONCLUSIONS: Carnosine reacts non-enzymatically with glycolytic intermediates reducing the activity of the pentose phosphate pathway which is required for cell proliferation. Although the activity of the malate-aspartate and the glycerol phosphate shuttle appear to be affected, reduced mitochondrial ATP production under the influence of the dipeptide is cell-specific and appears to be independent of the effect on the shuttles. PMID: 31628715 [PubMed - as supplied by publisher]

Related Articles The application of artificial neural networks in metabolomics: a historical perspective. Metabolomics. 2019 Oct 18;15(11):142 Authors: Mendez KM, Broadhurst DI, Reinke SN Abstract BACKGROUND: Metabolomics data, with its complex covariance structure, is typically modelled by projection-based machine learning (ML) methods such as partial least squares (PLS) regression, which project data into a latent structure. Biological data are often non-linear, so it is reasonable to hypothesize that metabolomics data may also have a non-linear latent structure, which in turn would be best modelled using non-linear equations. A non-linear ML method with a similar projection equation structure to PLS is artificial neural networks (ANNs). While ANNs were first applied to metabolic profiling data in the 1990s, the lack of community acceptance combined with limitations in computational capacity and the lack of volume of data for robust non-linear model optimisation inhibited their widespread use. Due to recent advances in computational power, modelling improvements, community acceptance, and the more demanding needs for data science, ANNs have made a recent resurgence in interest across research communities, including a small yet growing usage in metabolomics. As metabolomics experiments become more complex and start to be integrated with other omics data, there is potential for ANNs to become a viable alternative to linear projection methods. AIM OF REVIEW: We aim to first describe ANNs and their structural equivalence to linear projection-based methods, including PLS regression. We then review the historical, current, and future uses of ANNs in the field of metabolomics. KEY SCIENTIFIC CONCEPT OF REVIEW: Is metabolomics ready for the return of artificial neural networks? PMID: 31628551 [PubMed - in process]

Related Articles NMR-based metabolic profiling and comparison of Japanese persimmon cultivars. Sci Rep. 2019 Oct 18;9(1):15011 Authors: Ryu S, Muramatsu T, Furihata K, Wei F, Koda M, Miyakawa T, Tanokura M Abstract Persimmons are a traditional, autumnal, and healthy fruit commonly consumed in Japan and East Asia based on the saying, "a persimmon a day keeps the doctor away." The differences in metabolites among five major Japanese persimmon cultivars were investigated using a nuclear magnetic resonance (NMR)-based metabolomics approach. By using a broadband water suppression enhanced through T1 effects (WET) method for the sensitive detection of minor metabolites, better discrimination among cultivars and more informative details regarding their metabolic differences have been achieved compared to those achieved in conventional 1H NMR sequences. Among the nonastringent cultivars analyzed, the Taishu cultivar has the highest abundance of amino acids. The Matsumotowase-Fuyu cultivar contains ethyl-β-glycosides as characteristic components, which may relate to fruit softening. Citric acid concentration is higher in Maekawa Jiro than in other nonastringent cultivars. Among the two astringent cultivars analyzed, ethanol was significantly higher in Hiratanenashi than in Yotsumizo, which indicates different reactivity during deastringency treatments. The present study proposes an efficient and relatively quantitative metabolomics approach based on broadband WET NMR spectra. PMID: 31628382 [PubMed - in process]

Related Articles Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors. Nat Commun. 2019 Oct 18;10(1):4766 Authors: Powers RK, Culp-Hill R, Ludwig MP, Smith KP, Waugh KA, Minter R, Tuttle KD, Lewis HC, Rachubinski AL, Granrath RE, Carmona-Iragui M, Wilkerson RB, Kahn DE, Joshi M, Lleó A, Blesa R, Fortea J, D'Alessandro A, Costello JC, Sullivan KD, Espinosa JM Abstract Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS. PMID: 31628327 [PubMed - in process]

Related Articles Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis. Reprod Biomed Online. 2019 Aug 12;: Authors: Bouet PE, Chao de la Barca JM, El Hachem H, Descamps P, Legendre G, Reynier P, May-Panloup P Abstract RESEARCH QUESTION: Is there any metabolomic evidence of impairment of the cumulus-oocyte complex (COC) microenvironment in the follicular fluid of women with endometriosis? DESIGN: A prospective observational study from January to July 2018 at the Angers University Hospital, France. Seventy-nine women undergoing IVF with or without intracytoplasmic sperm injection (ICSI) were included: 39 for endometriosis-related infertility and 40 controls with other causes of infertility. A targeted quantitative metabolomic and lipidomic analysis was performed. RESULTS: Patient characteristics (age, body mass index, smoking status, hormonal profile and ovarian reserve markers) were comparable between the endometriosis and the control groups. There was no significant difference in the cumulative FSH dose used for stimulation between the endometriosis and the control groups (2732 versus 2257 IU, respectively). There were no differences in the oocyte maturity rates (72.2% versus 77.7%), or in the fertilization rates in IVF and ICSI (49.4% versus 50.2% and 76.4% versus 68.8%, respectively) between the endometriosis and control groups. Among the 188 metabolites analysed, 150 were accurately measured. Univariate analysis did not reveal any significant modification of metabolite concentrations, and none of the multivariate models discriminated between the two groups of patients, even when the study was restricted to the most severe form of endometriosis. CONCLUSIONS: No specific metabolomic signature of endometriosis was found in the follicular fluid of women undergoing IVF. These results suggest that there is no microenvironmental impairment of the COC in cases of isolated endometriosis among women with infertility. PMID: 31628036 [PubMed - as supplied by publisher]

Related Articles Development and validation of a high performance liquid chromatography-tandem mass spectrometry method for the absolute analysis of 17 α D-amino acids in cooked meals. J Chromatogr A. 2019 Oct 04;:460598 Authors: Barbas-Bernardos C, Garcia-Perez I, Lorenzo MP, Alonso-Herranz V, Nicholson J, Garcia A Abstract In the nutrition field, there is a lack of understanding about the impact that dietary chiral composition may have on health, especially regarding cooked meals. Chiral amino acids (AAs) are naturally present in food and their proportion may vary quite a lot. Besides, the D-amino acids (D-AAs) are present in very low concentration compared to L-AAs, so very sensitive methods are required for their accurate quantitation. Moreover, some of them have been described as indicators of quality and different food processes. In this research, we propose a robust method for the absolute quantitation and enantiomeric ratio of 17 D-AAs in cooked meals. The AAs were extracted from 1 g of the homogenised meal with methanol, derivatised with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester ((S)-NIFE) and analysed by RP-LC-MS/MS. The separation was carried out with an Acquity BEH C18 (100 mm x 2.1 mm, 1.7 µm) column at 70 ºC, with 10 mmol/L ammonium bicarbonate in water as eluent A and acetonitrile as eluent B at a 0.3 mL/min flow rate in gradient elution. The MS operated in positive electrospray ionisation method in multiple reaction monitoring (MRM) mode. Isotopically labelled AAs were used as internal standards for the quantitation. The method was validated for 17 D-AAs in the cooked food samples in terms of specificity, linearity, precision, accuracy, matrix effect and stability. LLOQ are 2.0 ng/mL for most of them. Additionally, linearity was also studied for L-AAs. After optimization and validation, the method was applied to real breakfast, lunch and dinner samples of cooked meals (n = 18) that were part of a diet with a very high concordance with WHO dietary guidelines. Level of concentration of major and minor D-AAs have been described per total daily intake and within each of the three main meals. This method can be used for quality control purposes as well as to investigate the role of chiral composition in food and clinical outcomes. PMID: 31627969 [PubMed - as supplied by publisher]

28 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 2019/10/19PubMed 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.

20 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 2019/10/18PubMed 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.

25 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 2019/10/17PubMed 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.

25 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 2019/10/16PubMed 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.

22 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 2019/10/15PubMed 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.

Related Articles Systematic mapping of protein-metabolite interactions with mass spectrometry-based techniques. Curr Opin Biotechnol. 2019 Oct 10;64:24-31 Authors: Li S, Shui W Abstract The recent rapid advance of systematic mapping of protein-metabolite interactions (PMIs) in both prokaryotic and eukaryotic cells has been catalyzed by development of innovative and effective proteomics or metabolomics strategies all based on large-scale mass spectrometry (MS) analysis of biomolecules. Both metabolite-centric and protein-centric approaches have been established to profile PMIs in the native cellular matrix treated by specific metabolites or proteins. Here we will review the development and application of versatile MS-based proteomics and metabolomics techniques for global PMI mapping in different species, which lead to the discovery of numerous uncharacterized PMIs that may reveal new interaction-derived functionality. We further discuss the strengths and limitations of different PMI mapping approaches as well as the key elements in MS quantification and data mining for reliable PMI identification. PMID: 31606719 [PubMed - as supplied by publisher]

Related Articles Allergic Disease and low ASQ Communication Score in Children. Brain Behav Immun. 2019 Oct 10;: Authors: Yadama AP, Kelly RS, Lee-Sarwar K, Mirzakhani H, Chu SH, Kachroo P, Litonjua AA, Lasky-Su J, Weiss ST Abstract Autism Spectrum Disorders (ASD) are complex and multifactorial. Previous investigations have revealed associations between allergic disease and ASD, which are characterized by impaired communication skills. In this study we observed an association between allergic disease and communication skills development as assessed by the Ages and Stages Questionnaire (ASQ) communication score, as a proxy for ASD, among children who participated in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). In particular, we observed significant associations between both a diagnosis of eczema at age 3 years (OR=1.87; confidence interval [CI]: 0.97-3.47; p=0.054) and a diagnosis of food allergy at age 6 years (OR=3.61; 95% CI: 1.18-9.85; p=0.015) with ASQ communication score. Plasma metabolomics analyses suggest that dysregulated tryptophan metabolism may contribute to the pathogenesis of these co-morbidities. PMID: 31606476 [PubMed - as supplied by publisher]

Related Articles Metabolomics analysis of lipid metabolizing enzyme activity. Methods Enzymol. 2019;626:407-428 Authors: Ware TB, Shin M, Hsu KL Abstract Lipids exert key structural, metabolic, and signaling functions in cells. Lipid diversity found in cells and tissues is regulated principally by metabolic enzymes whose activity is modulated posttranslationally to shape head group and fatty acyl composition of membrane lipids. Methodologies capable of monitoring in vivo changes in the lipidome are needed to assign substrate specificity of metabolic enzymes, which represents a key step toward understanding structure-function of lipids in living systems. The resulting lipid annotations also serve as important biomarkers for understanding mode of action for pharmacological agents targeting metabolic enzymes in cells and animal models. In this chapter, we describe a general metabolomics workflow to complement (chemo)proteomic efforts to modulate lipid pathways for basic science and translational applications. PMID: 31606084 [PubMed - in process]

Related Articles Metabolic profiling of seminal plasma from teratozoospermia patients. J Pharm Biomed Anal. 2019 Oct 03;178:112903 Authors: Mehrparvar B, Chashmniam S, Nobakht F, Amini M, Javidi A, Minai-Tehrani A, Arjmand B, Gilany K Abstract Teratozoospermia is one of conditions that can cause male infertility. The mechanism of teratozoospermia remains unclear. The knowledge of the metabolites in human seminal plasma (HSP) is meaningful for the pathological study of teratozoospermia. Analysis of changed metabolites in HSP can help understand the cellular mechanism, find the novel biomarkers and subsequently design a diagnosis test. In this study, the analysis of samples performed by proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) to identify the various metabolites, with the aim of finding metabolic profiles and biomarkers related to male infertility. Eighteen de-regulated metabolites were identified in fertile men compared to teratozoospermia patients. These changes illustrate the deficiencies in absorption or metabolism of these metabolites in teratozoospermia. Furthermore, metabolic profiling showed that it is not possible to classify teratozoospermia based on teratozoospermia index (TZI). To the best of our knowledge, this is the first metabolic profiling analysis of HSP described the metabolic features of teratozoospermia in a holistic view. PMID: 31605879 [PubMed - as supplied by publisher]