PubMed
UPLC/Q‑TOF‑MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome.
UPLC/Q‑TOF‑MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome.
Mol Med Rep. 2018 Nov 12;:
Authors: Fan X, Jiang J, Huang Z, Gong J, Wang Y, Xue W, Deng Y, Wang Y, Zheng T, Sun A, Luo G
Abstract
The present study aimed to develop novel diagnostic methods for polycystic ovarian syndrome (PCOS) by screening and identifying specific PCOS‑associated metabolic markers using plasma metabolomics. Ultra‑performance liquid chromatography/quadrapole‑time of flight‑mass spectrometry was adopted to establish the plasma metabolic fingerprint of 49 patients and 50 normal controls, in order to screen the potential metabolic markers. In addition, these markers were integrated with the clinical indexes, followed by focused analysis to obtain diagnostic markers. The present results demonstrated that not only was the concentration of palmitoyl sphingomyelin in plasma of patients with PCOS significantly increased; however, a statistically significant difference between the two PCOS subgroups was additionally demonstrated. At the same time, the concentrations of cyclic guanosine monophosphate (cGMP) and dehydroepiandrosterone sulphate in the plasma of patients of the subgroup 1 were significantly elevated. These markers were additionally integrated with the clinical index number of follicles in the left ovary and high‑density lipoprotein (HDL‑C), followed by receiver operating characteristic curve analysis, which demonstrated a diagnostic accuracy of ~90% in the control and the two subgroups. The integrated marker system consisting of palmitoyl sphingomyelin, cGMP and androsterone sulfate, as well as the number of left follicles and HDL‑C may be used for the accurate diagnosis and classification of PCOS. These results confirmed that the abnormalities in hormone metabolism and lipid metabolism disorder were primarily involved in the onset of PCOS.
PMID: 30431132 [PubMed - as supplied by publisher]
Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults.
Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults.
Int J Mol Med. 2018 Nov 14;:
Authors: Tsoukalas D, Alegakis AK, Fragkiadaki P, Papakonstantinou E, Tsilimidos G, Geraci F, Sarandi E, Nikitovic D, Spandidos DA, Tsatsakis A
Abstract
Fatty acids (FAs) play critical roles in health and disease. The detection of FA imbalances through metabolomics can provide an overview of an individual's health status, particularly as regards chronic inflammatory disorders. In this study, we aimed to establish sensitive reference value ranges for targeted plasma FAs in a well‑defined population of healthy adults. Plasma samples were collected from 159 participants admitted as outpatients. A total of 24 FAs were analyzed using gas chromatography‑mass spectrometry, and physiological values and 95% reference intervals were calculated using an approximate method of analysis. The differences among the age groups for the relative levels of stearic acid (P=0.005), the omega‑6/omega‑3 ratio (P=0.027), the arachidonic acid/eicosapentaenoic acid ratio (P<0.001) and the linoleic acid‑produced dihomo‑gamma‑linolenic acid (P=0.046) were statistically significant. The majority of relative FA levels were higher in males than in females. The levels of myristic acid (P=0.0170) and docosahexaenoic acid (P=0.033) were significantly different between the sexes. The reference values for the FAs examined in this study represent a baseline for further studies examining the reproducibility of this methodology and sensitivities for nutrient deficiency detection and investigating the biochemical background of pathological conditions. The application of these values to clinical practice will allow for the discrimination between health and disease and contribute to early prevention and treatment.
PMID: 30431095 [PubMed - as supplied by publisher]
The challenge and potential of photosynthesis: unique considerations for metabolic flux measurements in photosynthetic microorganisms.
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The challenge and potential of photosynthesis: unique considerations for metabolic flux measurements in photosynthetic microorganisms.
Biotechnol Lett. 2018 Nov 14;:
Authors: Sake CL, Metcalf AJ, Boyle NR
Abstract
Photosynthetic microorganisms have the potential for sustainable production of chemical feedstocks and products but have had limited success due to a lack of tools and deeper understanding of metabolic pathway regulation. The application of instationary metabolic flux analysis (INST-MFA) to photosynthetic microorganisms has allowed researchers to quantify fluxes and identify bottlenecks and metabolic inefficiencies to improve strain performance or gain insight into cellular physiology. Additionally, flux measurements can also highlight deviations between measured and predicted fluxes, revealing weaknesses in metabolic models and highlighting areas where a lack of understanding still exists. In this review, we outline the experimental steps necessary to successfully perform photosynthetic flux experiments and analysis. We also discuss the challenges unique to photosynthetic microorganisms and how to account for them, including: light supply, quenching, concentration, extraction, analysis, and flux calculation. We hope that this will enable a larger number of researchers to successfully apply isotope assisted metabolic flux analysis (13C-MFA) to their favorite photosynthetic organism.
PMID: 30430405 [PubMed - as supplied by publisher]
Combined transcriptomics-metabolomics profiling of the heat shock response in the hyperthermophilic archaeon Pyrococcus furiosus.
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Combined transcriptomics-metabolomics profiling of the heat shock response in the hyperthermophilic archaeon Pyrococcus furiosus.
Extremophiles. 2018 Nov 14;:
Authors: Esteves AM, Graça G, Peyriga L, Torcato IM, Borges N, Portais JC, Santos H
Abstract
Pyrococcus furiosus is a remarkable archaeon able to grow at temperatures around 100 °C. To gain insight into how this model hyperthermophile copes with heat stress, we compared transcriptomic and metabolomic data of cells subjected to a temperature shift from 90 °C to 97 °C. In this study, we used RNA-sequencing to characterize the global variation in gene expression levels, while nuclear magnetic resonance (NMR) and targeted ion exchange liquid chromatography-mass spectrometry (LC-MS) were used to determine changes in metabolite levels. Of the 552 differentially expressed genes in response to heat shock conditions, 257 were upregulated and 295 were downregulated. In particular, there was a significant downregulation of genes for synthesis and transport of amino acids. At the metabolite level, 37 compounds were quantified. The level of di-myo-inositol phosphate, a canonical heat stress solute among marine hyperthermophiles, increased considerably (5.4-fold) at elevated temperature. Also, the levels of mannosylglycerate, UDP-N-acetylglucosamine (UDPGlcNac) and UDP-N-acetylgalactosamine were enhanced. The increase in the pool of UDPGlcNac was concurrent with an increase in the transcript levels of the respective biosynthetic genes. This work provides the first metabolomic analysis of the heat shock response of a hyperthermophile.
PMID: 30430272 [PubMed - as supplied by publisher]
PGE2 Augments Inflammasome Activation and M1 Polarization in Macrophages Infected With Salmonella Typhimurium and Yersinia enterocolitica.
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PGE2 Augments Inflammasome Activation and M1 Polarization in Macrophages Infected With Salmonella Typhimurium and Yersinia enterocolitica.
Front Microbiol. 2018;9:2447
Authors: Sheppe AEF, Kummari E, Walker A, Richards A, Hui WW, Lee JH, Mangum L, Borazjani A, Ross MK, Edelmann MJ
Abstract
Eicosanoids are cellular metabolites, which shape the immune response, including inflammatory processes in macrophages. The effects of these lipid mediators on inflammation and bacterial pathogenesis are not clearly understood. Certain eicosanoids are suspected to act as molecular sensors for the recruitment of neutrophils, while others regulate bacterial uptake. In this study, gene expression analyses indicated that genes involved in eicosanoid biosynthesis including COX-1, COX-2, DAGL, and PLA-2 are differentially regulated in THP-1 human macrophages infected with Salmonella enterica Typhimurium or Yersinia enterocolitica. By using targeted metabolomics approach, we found that the eicosanoid precursor, arachidonic acid (AA) as well as its derivatives, including prostaglandins (PGs) PGF2α or PGE2/PGD2, and thromboxane TxB2, are rapidly secreted from macrophages infected with these Gram-negative pathogenic bacteria. The magnitude of eicosanoid biosynthesis in infected host cells depends on the presence of virulence factors of Y. enterocolitica and S. Typhimurium strains, albeit in an opposite way in Y. enterocolitica compared to S. Typhimurium infection. Trials with combinations of EP2/EP4 PGE2 receptor agonists and antagonists suggest that PGE2 signaling in these infection models works primarily through the EP4 receptor. Downstream of EP4 activation, PGE2 enhances inflammasome activation and represses M2 macrophage polarization while inducing key M1-type markers. PGE2 also led to a decreased numbers of Y. enterocolitica within macrophages. To summarize, PGE2 is a potent autocrine/paracrine activator of inflammation during infection in Gram-negative bacteria, and it affects macrophage polarization, likely controlling bacterial clearance by macrophages.
PMID: 30429830 [PubMed]
Identification of Chaoborus kairomone chemicals that induce defences in Daphnia.
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Identification of Chaoborus kairomone chemicals that induce defences in Daphnia.
Nat Chem Biol. 2018 Nov 14;:
Authors: Weiss LC, Albada B, Becker SM, Meckelmann SW, Klein J, Meyer M, Schmitz OJ, Sommer U, Leo M, Zagermann J, Metzler-Nolte N, Tollrian R
Abstract
Infochemicals play important roles in aquatic ecosystems. They even modify food web interactions, such as by inducing defenses in prey. In one classic but still not fully understood example, the planktonic freshwater crustacean Daphnia pulex forms specific morphological defenses (neckteeth) induced by chemical cues (kairomones) released from its predator, the phantom midge larva Chaoborus. On the basis of liquid chromatography, mass spectrometry, and chemical synthesis, we report here the chemical identity of the Chaoborus kairomone. The biologically active cues consist of fatty acids conjugated to the amino group of glutamine via the N terminus. These cues are involved in Chaoborus digestive processes, which explains why they are consistently released despite the disadvantage for its emitter. The identification of the kairomone may allow in-depth studies on multiple aspects of this inducible defense system.
PMID: 30429602 [PubMed - as supplied by publisher]
Metabolic programming a lean phenotype by deregulation of RNA polymerase III.
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Metabolic programming a lean phenotype by deregulation of RNA polymerase III.
Proc Natl Acad Sci U S A. 2018 Nov 14;:
Authors: Willis IM, Moir RD, Hernandez N
Abstract
As a master negative regulator of RNA polymerase (Pol) III, Maf1 modulates transcription in response to nutrients and stress to balance the production of highly abundant tRNAs, 5S rRNA, and other small noncoding RNAs with cell growth and maintenance. This regulation of Pol III transcription is important for energetic economy as mice lacking Maf1 are lean and resist weight gain on normal and high fat diets. The lean phenotype of Maf1 knockout (KO) mice is attributed in part to metabolic inefficiencies which increase the demand for cellular energy and elevate catabolic processes, including autophagy/lipophagy and lipolysis. A futile RNA cycle involving increased synthesis and turnover of Pol III transcripts has been proposed as an important driver of these changes. Here, using targeted metabolomics, we find changes in the liver of fed and fasted Maf1 KO mice consistent with the function of mammalian Maf1 as a chronic Pol III repressor. Differences in long-chain acylcarnitine levels suggest that energy demand is higher in the fed state of Maf1 KO mice versus the fasted state. Quantitative metabolite profiling supports increased activity in the TCA cycle, the pentose phosphate pathway, and the urea cycle and reveals changes in nucleotide levels and the creatine system. Metabolite profiling also confirms key predictions of the futile RNA cycle hypothesis by identifying changes in many metabolites involved in nucleotide synthesis and turnover. Thus, constitutively high levels of Pol III transcription in Maf1 KO mice reprogram central metabolic pathways and waste metabolic energy through a futile RNA cycle.
PMID: 30429315 [PubMed - as supplied by publisher]
Prediagnostic plasma branched chain amino acids and the risk of amyotrophic lateral sclerosis.
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Prediagnostic plasma branched chain amino acids and the risk of amyotrophic lateral sclerosis.
Neurology. 2018 Nov 14;:
Authors: Bjornevik K, O'Reilly ÉJ, Berry JD, Clish CB, Jeanfavre S, Kato I, Kolonel LN, Le Marchand L, McCullough ML, Paganoni S, Schwarzschild MA, Talbott EO, Wallace RB, Zhang Z, Manson JE, Ascherio A
Abstract
OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk.
METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk.
RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset.
CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.
PMID: 30429276 [PubMed - as supplied by publisher]
A novel approach to assess the quality and authenticity of Scotch Whisky based on gas chromatography coupled to high resolution mass spectrometry.
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A novel approach to assess the quality and authenticity of Scotch Whisky based on gas chromatography coupled to high resolution mass spectrometry.
Anal Chim Acta. 2018 Dec 26;1042:60-70
Authors: Stupak M, Goodall I, Tomaniova M, Pulkrabova J, Hajslova J
Abstract
Whisky is one of the most popular spirit drinks in the world. Unfortunately, this highly valued commodity is vulnerable to fraud. To detect fraudulent practices and document quality parameters, a number of laboratory tests based on various principles including chromatography and spectroscopy have been developed. In most cases, the analytical methods are based on targeted screening strategies. Non-targeted screening (metabolomics fingerprinting) of (semi)volatile substances was used in our study. Following the pre-concentration of these compounds, either by solid phase microextraction (SPME) or by ethyl acetate extraction, gas chromatography (GC) coupled to tandem mass spectrometry (Q-TOF mass analyser) was employed. Unsupervised principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) were used for evaluation of data obtained by analysis of a unique set of 171 authentic whisky samples provided by the Scotch Whisky Research Institute. Very good separation of malt whiskies according to the type of cask in which they were matured (bourbon versus bourbon and wine) was achieved, and significant ´markers' for bourbon and wine cask maturation, such as N-(3-methylbutyl) acetamide and 5-oxooxolane-2-carboxylic acid, were identified. Subsequently, the unique sample set was used to construct a statistical model for distinguishing malt and blended whiskies. In the final phase, 20 fake samples were analysed and the data processed in the same way. Some differences could be observed in the (semi)volatile profiles of authentic and fake samples. Employing the statistical model developed by PLS-DA for this purpose, marker compounds that positively distinguish fake samples were identified.
PMID: 30428989 [PubMed - in process]
Chemical markers for quality control of bran-fried sulfur-fumigated Paeoniae Radix Alba.
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Chemical markers for quality control of bran-fried sulfur-fumigated Paeoniae Radix Alba.
J Pharm Biomed Anal. 2018 Sep 10;159:305-310
Authors: Xu YY, Long F, Zhang YQ, Xu JD, Kong M, Li SL
Abstract
In traditional Chinese medicine practice, crude herbs are often subjected to traditional processing (Paozhi in Chinese) for a special medicinal purpose. Bran-frying is one of processing methods for Paeoniae Radix Alba (PRA). Previous studies found that paeoniflorin and paeoniflorin sulfonate, a principle bioactive compound and its sulfur-fumigation induced characteristic sulfur-containing derivative, could be used together with sulfur dioxide residue as chemical markers for the quality control of sulfur-fumigated PRA crude material. In this paper, the feasibility of these three markers used for the quality control of bran-fried sulfur-fumigated PRA was further investigated. First, homemade samples of sulfur-fumigated PRA with different sulfur-fumigation duration (0.5-6 h) were bran-fried, and stored for 12 months. Second, the contents of sulfur dioxide residue, paeoniflorin and paeoniflorin sulfonate were dynamically quantified respectively. Third, the variation of the marker contents and their correlation during bran-frying and storage was evaluated. A validation was conducted using commercial bran-fried PRA samples. The results showed that bran-frying caused an averaged reduction of 20% in the content of sulfur dioxide residue, and during the first two months of storage the content of sulfur dioxide residue was decreased by up to 27%, then the content was tending towards stability for the subsequent ten months of storage (RSD = 3.92%). Meanwhile, paeoniflorin and paeoniflorin sulfonate were relatively stable, the contents of which were not affected by bran-frying processing and 12 months of storage. The correlations between the contents of sulfur dioxide residue and paeoniflorin/paeoniflorin sulfonate were obviously influenced by storage duration. Since sulfur dioxide residue is a safety marker, while paeoniflorin and paeoniflorin sulfonate can reflect the inner quality and the impact extent of sulfur-fumigation on the quality of bran-fried PRA respectively, these three chemicals might be used together as markers for the quality control, and consequently to ensure the safety and efficacy of bran-fried PRA.
PMID: 30015100 [PubMed - indexed for MEDLINE]
Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by 1H-NMR-based metabonomics and network pharmacology approaches.
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Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by 1H-NMR-based metabonomics and network pharmacology approaches.
J Pharm Biomed Anal. 2018 Sep 10;159:252-261
Authors: Liu XW, Tang CL, Zheng H, Wu JX, Wu F, Mo YY, Liu X, Zhu HJ, Yin CL, Cheng B, Ruan JX, Song FM, Chen ZN, Song H, Guo HW, Liang YH, Su ZH
Abstract
Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance (1H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl4)-induced liver fibrosis in rats after CS treatment were performed using 1H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines.
PMID: 29990893 [PubMed - indexed for MEDLINE]
metabolomics; +19 new citations
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metabolomics
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metabolomics; +19 new citations
19 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2018/11/15PubMed 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.
metabolomics; +32 new citations
32 new pubmed citations were retrieved for your search.
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metabolomics
These pubmed results were generated on 2018/11/14PubMed 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.
metabolomics; +32 new citations
32 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 2018/11/14PubMed 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.
metabolomics; +18 new citations
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 2018/11/13PubMed 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.
metabolomics; +18 new citations
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 2018/11/13PubMed 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.
Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction.
Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction.
Chemosphere. 2018 Oct 30;217:140-149
Authors: Deng P, Barney J, Petriello MC, Morris AJ, Wahlang B, Hennig B
Abstract
The deleterious effects of PCB 126 are complex, and the role of the liver in modifying toxic insult is not well understood. We utilized metabolomics approaches to compare liver metabolites significantly affected by PCB 126 in control mice and a diet induced liver injury mouse model. In this 14-week study, mice were fed either an amino acid supplemented control diet (CD) or a methionine-choline deficient diet (MCD) which promoted nonalcoholic steatohepatitis (NASH) and were subsequently exposed to PCB 126. The liver metabolome was profiled by a global metabolomic analysis using LC-MS. There were clear differences between PCB 126 exposed and control mice in the hepatic metabolomic profiles (216 and 266 metabolites were altered in CD-fed and MCD-fed mice respectively after PCB 126 exposure). PCB 126 modulated glycerophospholipid metabolism, glutathione metabolism, and CoA biosynthesis pathways irrespective of diet; indicating that the disturbance in lipid metabolism and thiol metabolites are general markers of PCB 126 exposure irrespective of liver health. Additionally, metabolites associated with oxidative stress and mitochondrial dysfunction were greatly elevated in PCB 126 exposed mice with compromised livers (e.g., 4-hydroxy-nonenal glutathione, oxylipids, uric acid, and acylcarnitines). Moreover, PCB 126 exposure downregulated redox genes, and the effect was more pronounced in liver injury mice. In conclusion, this study demonstrates that PCB 126 could induce oxidative stress and metabolic dysfunction, and pre-existing liver injury can markedly modify PCB 126-induced metabolic changes. Using metabolic profiling, this study suggests mechanism of enhanced PCB 126 toxicity under liver injury settings.
PMID: 30415113 [PubMed - as supplied by publisher]
Added value of plasma metabolomics to describe maternal effects in rat maternal and prenatal toxicity studies.
Added value of plasma metabolomics to describe maternal effects in rat maternal and prenatal toxicity studies.
Toxicol Lett. 2018 Nov 08;:
Authors: Keller J, Mellert W, Sperber S, Kamp H, Jiang X, Fabian E, Herold M, Walk T, Strauss V, van Ravenzwaay B
Abstract
For regulatory purposes prenatal developmental toxicity (OECD 414) studies are routinely performed in our laboratories. The suitability of metabolomics as technology to identify maternal toxicity in such studies was investigated. Plasma was sampled from pregnant, non-fasted rats on gestation day 20 before cesarean section. Metabolite profiling was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. The sensitivity of routinely examined maternal toxicity parameters (OECD No. 414) was compared to those of metabolome analysis. Evaluating 44 studies, the metabolome-derived NOEL was more sensitive in 45% of the cases in detecting maternal toxicity than the maternal NOAEL. Metabolome patterns indicative for liver effects and 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme-inhibition were established in pregnant rats based on regulated metabolites using reference compounds. The HPPD inhibition and liver toxicity patterns in pregnant rats were reasonably comparable to the ones established in non-pregnant, fasted rats. Metabolomics is a useful tool for an improved and mechanism-based identification of maternal toxicity in maternal and prenatal toxicity studies. The data suggest that the current classical maternal toxicity parameters may underestimate the extent of effects of compounds on the dams.
PMID: 30414988 [PubMed - as supplied by publisher]
Variations in Microbial Diversity and Metabolite Profiles of the Tropical Marine Sponge Xestospongia muta with Season and Depth.
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Variations in Microbial Diversity and Metabolite Profiles of the Tropical Marine Sponge Xestospongia muta with Season and Depth.
Microb Ecol. 2018 Nov 10;:
Authors: Villegas-Plazas M, Wos-Oxley ML, Sanchez JA, Pieper DH, Thomas OP, Junca H
Abstract
Xestospongia muta is among the most emblematic sponge species inhabiting coral reefs of the Caribbean Sea. Besides being the largest sponge species growing in the Caribbean, it is also known to produce secondary metabolites. This study aimed to assess the effect of depth and season on the symbiotic bacterial dynamics and major metabolite profiles of specimens of X. muta thriving in a tropical marine biome (Portobelo Bay, Panamá), which allow us to determine whether variability patterns are similar to those reported for subtropical latitudes. The bacterial assemblages were characterized using Illumina deep-sequencing and metabolomic profiles using UHPLC-DAD-ELSD from five depths (ranging 9-28 m) across two seasons (spring and autumn). Diverse symbiotic communities, representing 24 phyla with a predominance of Proteobacteria and Chloroflexi, were found. Although several thousands of OTUs were determined, most of them belong to the rare biosphere and only 23 to a core community. There was a significant difference between the structure of the microbial communities in respect to season (autumn to spring), with a further significant difference between depths only in autumn. This was partially mirrored in the metabolome profile, where the overall metabolite composition did not differ between seasons, but a significant depth gradient was observed in autumn. At the phyla level, Cyanobacteria, Firmicutes, Actinobacteria, and Spirochaete showed a mild-moderate correlation with the metabolome profile. The metabolomic profiles were mainly characterized by known brominated polyunsaturated fatty acids. This work presents findings about the composition and dynamics of the microbial assemblages of X. muta expanding and confirming current knowledge about its remarkable diversity and geographic variability as observed in this tropical marine biome.
PMID: 30413836 [PubMed - as supplied by publisher]