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80 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/12/12PubMed 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.

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/12/07PubMed 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.

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 2018/12/06PubMed 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.

Effects of Gut Bacteria Depletion and High-Na+ and Low-K+ Intake on Circulating Levels of Biogenic Amines. Mol Nutr Food Res. 2018 Dec 04;:e1801184 Authors: Blaženović I, Oh YT, Li F, Ji J, Nguyen AK, Wancewicz B, Bender JM, Fiehn O, Youn JH Abstract SCOPE: High-sodium and low-potassium (HNaLK) content in Western diets increases the risk of hypertension and cardiovascular disease (CVD). We investigated if the dietary minerals interact with gut bacteria to modulate circulating levels of biogenic amines, which are implicated in various pathologies, including hypertension and CVD. METHODS AND RESULTS: Using a metabolomic approach to target biogenic amines, we examined the effects of gut-bacteria depletion and HNaLK intake on circulating levels of biogenic amines in rats. We found 45 metabolites whose plasma levels were significantly altered by gut-bacteria depletion (P < 0.05), indicating their regulation by gut bacteria. Many of them were not previously linked to gut bacteria; therefore, these data provide novel insights into physiological or pathological roles of gut bacteria. We also found a number of plasma metabolites that were altered both by gut bacteria and HNaLK intake, suggesting possible interactions of the diet and gut bacteria in the modulation of these metabolites. The diet effects were observed with significant changes in the gut bacterial taxa Porphyromonadaceae and Prevotellaceae (P < 0.05). CONCLUSION: The dietary minerals may regulate abundances of certain gut bacteria to alter circulating levels of biogenic amines, which may be linked to host physiology or pathology. This article is protected by copyright. All rights reserved. PMID: 30513547 [PubMed - as supplied by publisher]

Changes in the serum metabolite profile correlate with decreased brain gray matter volume in moderate-to-heavy drinking young adults. Alcohol. 2018 May 31;75:89-97 Authors: Heikkinen N, Kärkkäinen O, Laukkanen E, Kekkonen V, Kaarre O, Kivimäki P, Könönen M, Velagapudi V, Nandania J, Lehto SM, Niskanen E, Vanninen R, Tolmunen T Abstract Our aim was to analyze metabolite profile changes in serum associated with moderate-to-heavy consumption of alcohol in young adults and to evaluate whether these changes are connected to reduced brain gray matter volumes. These study population consisted of young adults with a 10-year history of moderate-to-heavy alcohol consumption (n = 35) and light-drinking controls (n = 27). We used the targeted liquid chromatography mass spectrometry method to measure concentrations of metabolites in serum, and 3.0 T magnetic resonance imaging to assess brain gray matter volumes. Alterations in amino acid and energy metabolism were observed in the moderate-to-heavy drinking young adults when compared to the controls. After correction for multiple testing, the group of moderate-to-heavy drinking young adults had increased serum concentrations of 1-methylhistamine (p = 0.001, d = 0.82) when compared to the controls. Furthermore, concentrations of 1-methylhistamine (r = -0.48, p = 0.004) and creatine (r = -0.52, p = 0.001) were negatively correlated with the brain gray matter volumes in the females. Overall, our results show association between moderate-to-heavy use of alcohol and altered metabolite profile in young adults as well as suggesting that some of these changes could be associated with the reduced brain gray matter volume. PMID: 30513444 [PubMed - as supplied by publisher]

Metabolic regulation protects mice against Klebsiella pneumoniae lung infection. Exp Lung Res. 2018 Dec 04;:1-10 Authors: Liu S, Zhang P, Liu Y, Gao X, Hua J, Li W Abstract PURPOSE: Klebsiella pneumoniae-caused pneumonia is a risk factor for development of lung injury. However, the current clinical isolates of K. pneumoniae are mostly multidrug-resistance and thus must be addressed with new treatments. One ideal approach is to enhance the innate immunity of the infected host through metabolic modulators. MATERIALS AND METHODS: We used GC/MS-based metabolomics to profile the metabolomes among Control, Dead and Survival groups. The key metabolites were administrated in mice, and the bacterial loads in lung and survival were measured. The effect of the key metabolites on macrophage phagocytosis was determined by flow cytometry. RESULTS: Compared with the mice that compromised from K. pneumoniae lung infection, mice that survived the infection displayed the varied metabolomic profile. The differential analysis of metabolome showed D-Glucose, Glutamine, L-Serine, Myo-inositol, Ethanedioic acid and Lactic acid related to the host surviving a K. pneumoniae lung infection. Further pathway enrichment analysis proposed that valine, leucine and isoleucine biosynthesis involved in outcome of lung infection. The follow-up data showed that exogenous L-Serine, L-Valine and L-Leucine could decline the load of K. pneumoniae in infected lung and increases the mouse survival. More interestingly, L-Serine, L-Valine and L-Leucine also were able to promote macrophage phagocytosis that is the natural way to promote hosts to clear lung pathogens. CONCLUSIONS: Our study establishes a novel strategy of identifying metabolic modulator from surviving host and emphasizes the feasibility of employing the metabolic modulator as a therapy for K. pneumoniae lung infection. PMID: 30513234 [PubMed - as supplied by publisher]

Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods. J Nutr Sci. 2018;7:e32 Authors: Hefni ME, Witthöft CM, Moazzami AA Abstract Public health authorities recommend all fertile women to increase their folate intake to 400 µg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 µg/d synthetic folic acid from a supplement (n 18), 250 µg/d folate from intervention foods (n 19), or no additional folate (0 µg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently. PMID: 30510697 [PubMed]

Urinary metabolomics reveals novel interactions between metal exposure and amino acid metabolic stress during pregnancy. Toxicol Res (Camb). 2018 Nov 01;7(6):1164-1172 Authors: Wang M, Xia W, Liu H, Liu F, Li H, Chang H, Sun J, Liu W, Sun X, Jiang Y, Liu H, Wu C, Pan X, Li Y, Rang W, Lu S, Xu S Abstract Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, N2-succinyl-l-glutamic acid 5-semialdehyde, N-methyltryptamine and N-succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy. PMID: 30510686 [PubMed]

Plasma metabolic profiling analysis of Strychnos nux-vomica Linn. and Tripterygium wilfordii Hook F-induced renal toxicity using metabolomics coupled with UPLC/Q-TOF-MS. Toxicol Res (Camb). 2018 Nov 01;7(6):1153-1163 Authors: Luo H, Gu C, Liu C, Wang Y, Wang H, Li Y Abstract Both Strychnos nux-vomica Linn. (SNV) and Tripterygium wilfordii Hook F (TwHF) have received extensive attention due to their excellent clinical efficacies. However, clinical applications of SNV and TwHF have been limited by their narrow therapeutic windows and severe kidney toxicities. In this paper, based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), endogenous metabolites after administration of SNV and TwHF extracts were detected, and biomarkers were screened successfully. Additionally, the levels of Cr and BUN in serum and pathological findings of kidneys were detected and observed. Finally, both biochemical and pathological tests of the SNV group and TwHF group indicated that kidney damage had occurred. After comparison with the normal saline group, 15 nephrotoxic biomarkers were selected from the SNV group, and 17 nephrotoxic biomarkers were selected from the TwHF group. The experimental results showed that there are some differences in the mechanisms of nephrotoxicity induced by SNV and TwHF, which are significant for revealing the mechanisms of renal injury of different medicines. PMID: 30510685 [PubMed]

Capillary electrophoresis with dual diode array detection and tandem mass spectrometry to access cardiovascular biomarkers candidates in human urine: Trimethylamine-N-Oxide and l-carnitine. J Chromatogr A. 2018 Nov 02;: Authors: Cieslarova Z, Magaldi M, Barros LA, do Lago CL, Oliveira DR, Fonseca FAH, Izar MC, Lopes AS, Tavares MFM, Klassen A Abstract A capillary electrophoresis with diode array and tandem mass spectrometry detection (CE-UV-MS/MS) method has been developed for the targeted assessment of cardiovascular biomarkers candidates, trimethylamine-N-Oxide (TMAO) and l-carnitine, and creatinine in human urine samples. The dual detection was applied due to the high concentration of creatinine (monitored by UV detection at 200 nm) in relation to TMAO and l-carnitine (quantified by selected reaction monitoring (SRM) mass spectrometry), in human urine. All instrumental parameters, sheath liquid (SHL) and background electrolyte (BGE) compositions were optimized with a pool of urine provided by adult healthy volunteers and evaluated by signal-to-noise ratio (SNR) and peak shape of TMAO. The compositions for the optimized BGE was formic acid at concentration of 0.10 mol L-1, and for SHL was 70:30 MeOH:H2O containing 0.05% (v/v) formic acid, delivered at a flow rate of 5 μL min-1. Limits of detection for TMAO, l-carnitine and creatinine were 0.76, 0.54 and 303 μmol L-1, respectively. Limits of quantification were 2.5, 1.8 and 1000 μmol L-1, respectively. Linearity was evaluated by ANOVA and presented R2 from 0.993 to 0.997. Precision and accuracy were evaluated at three concentration levels. Coefficients of variation (CV) from 1 to 21% were obtained for the intra-day precision evaluation and from 2 to 16% for the inter-day precision evaluation. The recovery ranged from 75 to 116%. Quantitation of TMAO and l-carnitine in infarcted patients urine in comparison to healthy individuals indicated a 2.2 fold increase of TMAO and a 7.0 fold increase of l-carnitine. These results showed the potential applicability of the proposed method for the evaluation of TMAO and l-carnitine in urine within a panel of candidate metabolites in targeted metabolomics studies of cardiovascular diseases among other conditions. PMID: 30509618 [PubMed - as supplied by publisher]

Automatic data analysis workflow for ultra-high performance liquid chromatography-high resolution mass spectrometry-based metabolomics. J Chromatogr A. 2018 Nov 26;: Authors: Yu YJ, Zheng QX, Zhang YM, Zhang Q, Zhang YY, Liu PP, Lu P, Fan MJ, Chen QS, Bai CC, Fu HY, She Y Abstract Data analysis for ultra-performance liquid chromatography high-resolution mass spectrometry-based metabolomics is a challenging task. The present work provides an automatic data analysis workflow (AntDAS2) by developing three novel algorithms, as follows: (i) a density-based ion clustering algorithm is designed for extracted-ion chromatogram extraction from high-resolution mass spectrometry; (ii) a new maximal value-based peak detection method is proposed with the aid of automatic baseline correction and instrumental noise estimation; and (iii) the strategy that clusters high-resolution m/z peaks to simultaneously align multiple components by a modified dynamic programing is designed to efficiently correct time-shift problem across samples. Standard compounds and complex datasets are used to study the performance of AntDAS2. AntDAS2 is better than several state-of-the-art methods, namely, XCMS Online, Mzmine2, and MS-DIAL, to identify underlying components and improve pattern recognition capability. Meanwhile, AntDAS2 is more efficient than XCMS Online and Mzmine2. A MATLAB GUI of AntDAS2 is designed for convenient analysis and is available at the following webpage: http://software.tobaccodb.org/software/antdas2. PMID: 30509617 [PubMed - as supplied by publisher]

Different effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on sex hormone levels, metabolic profile and oxidative stress in adult mice testes. Environ Res. 2018 Nov 20;169:315-325 Authors: Yan J, Zhu W, Wang D, Teng M, Yan S, Zhou Z Abstract In the environment, endosulfan persists in forms of two isomers (α and β) and a toxic metabolite, endosulfan sulfate. The toxicity of endosulfan on various mammalian tissues has been investigated, but whether the different isomers and metabolites of endosulfans affect mammalian reproductive function remains unclear. This study is aimed to elucidate the different toxicological effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on adult mice testes. We found that the three endosulfans (α endosulfan, β endosulfan and endosulfan sulfate) altered serum sex steroid hormone levels, and changed expression of steroidogenesis genes. By comparing results of 1H-NMR and LC-MS/MS metabolomics between samples treated with different endosulfans, we found that endosulfans changed levels of metabolites involved in energy metabolism and oxidative stress, and these were associated with the imbalance of sex sterol hormone synthesis. Moreover, endosulfan isomers and sulfate metabolite treatment disrupted the mice testicular antioxidant systems and caused an increase in lipid peroxidation. Interestingly, the three endosulfans tested in this study each yielded different effects on serum sex hormone levels and testicular metabolic profiles in the adult mice. Beta-endosulfan exposure caused the strongest disturbance in the testes compared to the other endosulfans, with significantly higher testosterone levels and more pronounced changes to endogenous metabolites. Taken together, we identified the different effects of endosulfans on the testis by exposing mice to α endosulfan, β endosulfan and endosulfan sulfate, and we found that changes in sex sterol hormone levels induced by treatment with endosulfans were correlated to changes in endogenous metabolites. These findings provide new insight into mechanism of endosulfan-induced testicular toxicity. PMID: 30502743 [PubMed - as supplied by publisher]

Both low- and regular-fat cheeses mediate improved insulin sensitivity and modulate serum phospholipid profiles in insulin-resistant rats. J Nutr Biochem. 2018 Nov 06;64:144-151 Authors: Hanning AR, Wang X, Hashemi Z, Wan S, England A, Jacobs RL, Chan CB Abstract Dietary recommendations for cheese usually promote low (LOW)- over regular (REG)-fat versions due to the saturated fat. Conversely, epidemiological evidence shows that cheese consumption associates with reduced risk of type 2 diabetes. To investigate how cheese influences diabetes-related outcomes, a feeding trial comparing LOW and REG cheese was conducted in high-fat, lard-based diet (HFD)-fed insulin-resistant rats followed by evaluation of potential mechanisms. After 4 weeks of HFD, LOW or REG was added at 7 and 10 g/100 g diet, respectively, for another 8 weeks. Following either an oral glucose or insulin tolerance test to assess glucoregulation, rats were euthanized and serum was collected for metabolomic and lipid analyses. Hepatic tissue was used to measure glucoregulatory enzymes and lipid content. Both LOW and REG improved insulin sensitivity without effect on oral glucose tolerance, insulin secretion or body weight. Serum metabolomics identified 33 metabolites of interest, with 21 being phosphatidylcholines (PCs) or lysophosphatidylcholines (LPCs). HFD rats had significantly reduced LPC C16:1, C17:0, C18:1, C20:3 and C24:0, and these effects were normalized by LOW or REG cheese. Fourteen PC species were lowest in the HFD group and normalized by cheese feeding. Serum choline was elevated sevenfold in HFD- but not cheese-fed rats compared with rats fed low-fat diet. Liver triglyceride was elevated by LOW feeding. In conclusion, inclusion of both LOW and REG cheeses in the diet of insulin-resistant rats improves in vivo glucoregulation. This is associated with altered phospholipid metabolism, including cheese-mediated normalization of species that are decreased by high-fat feeding. PMID: 30502658 [PubMed - as supplied by publisher]

Liquid chromatography-mass spectrometry-based urinary metabolomics study on a rat model of simulated microgravity-induced depression. J Pharm Biomed Anal. 2018 Nov 26;165:31-40 Authors: Xu T, Lu C, Feng L, Fan LX, Sun J, Fan B, Wang Q, Wang Y, Liu XM, Wang FZ Abstract The pathophysiological mechanism of depression is complex and its etiology remains unclear. Metabolomics can be used to monitor multiple metabolic pathways simultaneously, thereby investigating the mechanisms of depression onset and its regulation. Therefore, we studied the metabolic profile of urine samples from a rat model of depression for identifying potential metabolic biomarkers associated with depression. The depression model of rats was induced by 14-d simulated microgravity (SMG) treatment. Principal component analysis and orthogonal partial least squares discriminate analysis were performed to classify and identify the differences of endogenous metabolites in urine between the normal and depressed rats. Multivariate statistical analysis revealed distinct separation between the urinary metabolic profiles of SMG-treated and control rats. Citric acid, oxalosuccinic acid, creatine, proline, cyclic AMP, L-dihydroxyphenylalanine (DOPA), phenylacetylglycine, 5-hydroxyindole acetaldehyde, succinylcholine, deoxyuridine, 3-hydroxyhippuric acid, glutamine, and 5-hydroxytryptophan levels were significantly reduced, whereas indole-3-acetaldehyde, xanthurenic acid, taurine, kynurenic acid, hippuric acid, 5-hydroxyindoleacetic acid, 2-phenylethanol glucuronide, 2-isopropyl-3-oxosuccinate, and adrenaline levels were elevated significantly in model group. These biochemical changes were related to tryptophan, arginine, proline, and phenylalanine metabolism, and perturbations in energy metabolism. These details of depression will be helpful to the clinical diagnosis of depression caused by space and gravity. PMID: 30502550 [PubMed - as supplied by publisher]

Related Articles Differential metabolomics analysis allows characterization of diversity of metabolite networks between males and females. PLoS One. 2018;13(11):e0207775 Authors: Li Z, Zhang Y, Hu T, Likhodii S, Sun G, Zhai G, Fan Z, Xuan C, Zhang W Abstract Females and males are known to have different abilities to cope with stress and disease. This study was designed to investigate the effect of sex on properties of a complex interlinked network constructed of central biochemical metabolites. The study involved the blood collection and analysis of a large set of blood metabolic markers from a total of 236 healthy participants, which included 140 females and 96 males. Metabolic profiling yielded concentrations of 168 metabolites for each subject. A differential correlation network analysis approach was developed for this study that allowed detection and characterization of interconnection differences in metabolites in males and females. Through topological analysis of the differential network that depicted metabolite differences in the sexes, we identified metabolites with high centralities in this network. These key metabolites were identified as 10 phosphatidylcholines (PCaaC34:4, PCaaC36:6, PCaaC34:3, PCaaC42:2, PCaeC38:1, PCaeC38:2, PCaaC40:1, PCaeC34:1, PC aa C32:1 and PC aa C40:6) and 4 acylcarnitines (C3-OH, C7-DC, C3 and C0). Identification of these metabolites may help further studies of sex-specific differences in the metabolome that may underlie different responses to stress and disease in males and females. PMID: 30500833 [PubMed - in process]

Related Articles Metabolomics analysis explores the rescue to neurobehavioral disorder induced by maternal PM2.5 exposure in mice. Ecotoxicol Environ Saf. 2018 Nov 27;169:687-695 Authors: Cui J, Fu Y, Lu R, Bi Y, Zhang L, Zhang C, Aschner M, Li X, Chen R Abstract Reproductive epidemiological studies have suggested associations between perinatal exposure to fine particulate matter (PM2.5) and adverse birth outcomes. To explore the effects of early prenatal exposure to PM2.5 on subsequent generations, pregnant mice were exposed to PM2.5 or filtered clean air in whole body dynamic exposure chambers for 14 consecutive days from gestation day (GD) 1.5 to GD15.5. Neurobehavioral tests showed that spontaneous locomotion and exploratory behaviors in the offspring were significantly enhanced in the open field test. Meanwhile, metabolomics analysis suggested activation of dopamine pathway while inhibition of glycine pathway in murine brains. Administration of the DRD4 antagonist, clozapine; or supplementation of glycine receptor agonist, taurine, to mice offspring attenuated the locomotor hyperactivities to levels indistinguishable from controls. These data provide strong evidence that maternal exposure to air pollution might increase the risk for neural disorders in the offspring during critical periods of brain development. PMID: 30500738 [PubMed - as supplied by publisher]

Related Articles Immune responses induced by different genotypes of the disease-specific protein of Rice stripe virus in the vector insect. Virology. 2018 Nov 27;527:122-131 Authors: Zhao W, Wang Q, Xu Z, Liu R, Cui F Abstract Persistent plant viruses circulate between host plants and vector insects, possibly leading to the genetic divergence in viral populations. We analyzed the single nucleotide polymorphisms (SNPs) of Rice stripe virus (RSV) when it incubated in the small brown planthopper and rice. Two SNPs, which lead to nonsynonymous substitutions in the disease-specific protein (SP) of RSV, produced three genotypes, i.e., GG, AA and GA. The GG type mainly existed in the early infection period of RSV in the planthoppers and was gradually substituted by the other two genotypes during viral transmission. The two SNPs did not affect the interactions of SP with rice PsbP or with RSV coat protein. The GG genotype of SP induced stronger immune responses than those of the other two genotypes in the pattern recognition molecule and immune-responsive effector pathways. These findings demonstrated the population variations of RSV during the circulation between the vector insect and host plant. PMID: 30500711 [PubMed - as supplied by publisher]

Related Articles Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells. Cell. 2018 Nov 29;175(6):1546-1560.e17 Authors: Zheng Y, Lin TY, Lee G, Paddock MN, Momb J, Cheng Z, Li Q, Fei DL, Stein BD, Ramsamooj S, Zhang G, Blenis J, Cantley LC Abstract Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF). This repair capacity is overwhelmed when cytosolic THF hyperaccumulates in the absence of mitochondrially produced formate, leading to THF degradation. Unexpectedly, we also find that the classic antifolate methotrexate, by inhibiting its well-known target DHFR, causes even more extensive folate degradation in nearly all tested cancer cell lines. These findings shed light on design features of folate metabolism, provide a biochemical basis for clinically observed folate deficiency in QDPR-deficient patients, and reveal a hitherto unknown and unexplored cellular effect of methotrexate. PMID: 30500537 [PubMed - in process]

Related Articles Disruption of Kidney Metabolism in Rats after Subchronic Combined Exposure to Low-Dose Cadmium and Chlorpyrifos. Chem Res Toxicol. 2018 Nov 30;: Authors: Xu MY, Wang P, Sun YJ, Wu YJ Abstract Cadmium (Cd) and chlorpyrifos (CPF) often coexist in the environment and induce combined toxicity to organisms. Here we studied the combined nephrotoxicity of environmentally relevant low doses of Cd and CPF. We treated the mice for 90 days with different doses of Cd and CPF and their mixtures via oral gavage. Then histopathological evaluation and biochemical analysis for kidney tissues were carried out. The change of metabolites in kidney was detected by using a metabolomics approach using GC-MS. We found that Cd, CPF, and their mixtures caused oxidative damage, as well as disturbance of renal amino acid metabolism. We identified potential metabolite biomarkers in kidney, which included acetic acid for CPF treatment, glycerol and carboxylic acid for Cd treatment, and L-ornithine for the mixture of CPF and Cd treatment, respectively. In addition, we found that Cd promoted the metabolism of CPF in kidney. This may contribute to the result that the toxicity of the mixtures was lower than the sum of the toxicities of Cd and CPF alone. In conclusion, our results indicated that CPF and Cd could disrupt the kidney metabolism in rats even when they were exposed to very low dose of CPF and Cd. PMID: 30500169 [PubMed - as supplied by publisher]

Related Articles MetNet: Metabolite network prediction from high-resolution mass spectrometry data in R aids metabolite annotation. Anal Chem. 2018 Nov 30;: Authors: Naake T, Fernie AR Abstract A major bottleneck of mass spectrometric metabolomic analysis is still the rapid detection and annotation of unknown m/z features across biological matrices. This kind of analysis is especially cumbersome for complex samples with hundreds to thousands of unknown features. Traditionally, the annotation was done manually imposing constraints in reproducibility and automatization. Furthermore, different analysis tools are typically used at different steps which requires parsing of data and changing of environments. We present here MetNet, implemented in the R programming language and available as an open-source package via the Bioconductor project. MetNet that is compatible with the output of the xcms/CAMERA suite uses the data-rich output of mass spectrometry metabolomics to putatively link features on their relation to other features in the data set. MetNet uses both structural and quantitative information of metabolomics data for network inference and enables the annotation of unknown analytes. PMID: 30500168 [PubMed - as supplied by publisher]