PubMed

Related Articles [Shift work as a factor increasing the risk of civilization diseases - what's new in the old issue?] Pol Merkur Lekarski. 2019 Oct 29;47(280):157-161 Authors: Wolska A, Sznabel D, Stachowska E Abstract People are more and more often taking up shift work, which in the long run may have harmful health effects. Whether a person working in a shift system gets sick is influenced by many external factors (rotation and type of changes and work performed, socio-psychological factors) and endogenous (sex, age, health and physiological status, individual, internal biological clock - chronotype, physiological tolerance work at night). Many authors in their work prove that work in a rotational rotation system affects the occurrence of various types of cancer, hormone production, occurrence of metabolic disorders and civilization diseases (type II diabetes, insulin resistance, overweight and obesity, hypertension and coronary heart disease), microflora differentiation intestinal and contributes to increased stress of the body. In addition, the time in which a person works has a direct impact on the consumption and quality of meals. Shift workers often do not have time to eat regular, properly balanced meals that would satisfy their energy and nutritional needs. For this reason, most often reach for ready-to-eat foods that are characterized by low nutritional value at a relatively high energy value. Shift work also carries a risk of circadian rhythm disturbances and sleep disorders. Many studies indicate that there is an increased risk of some types of cancer and civilization diseases, but there is no clear evidence as to whether this is only the fault of rotary night work. PMID: 31760400 [PubMed - in process]

Related Articles α-Linolenic acid-enriched butter attenuated high fat diet-induced insulin resistance and inflammation by promoting bioconversion of n-3 PUFA and subsequent oxylipin formation. J Nutr Biochem. 2019 Nov 12;76:108285 Authors: Fan R, Kim J, You M, Giraud D, Toney AM, Shin SH, Kim SY, Borkowski K, Newman JW, Chung S Abstract α-Linolenic acid (ALA) is an essential fatty acid and the precursor for long-chain n-3 PUFA. However, biosynthesis of n-3 PUFA is limited in a Western diet likely due to an overabundance of n-6 PUFA. We hypothesized that dietary reduction of n-6/n-3 PUFA ratio is sufficient to promote the biosynthesis of long-chain n-3 PUFA, leading to an attenuation of high fat (HF) diet-induced obesity and inflammation. C57BL/6 J mice were fed a HF diet from ALA-enriched butter (n3Bu, n-6/n-3=1) in comparison with isocaloric HF diets from either conventional butter lacking both ALA and LA (Bu, n-6/n-3=6), or margarine containing a similar amount of ALA and abundant LA (Ma, n-6/n-3=6). Targeted lipidomic analyses revealed that n3Bu feeding promoted the bioconversion of long-chain n-3 PUFA and their oxygenated metabolites (oxylipins) derived from ALA and EPA. The n3Bu supplementation attenuated hepatic TG accumulation and adipose tissue inflammation, resulting in improved insulin sensitivity. Decreased inflammation by n3Bu feeding was attributed to the suppression of NF-κB activation and M1 macrophage polarization. Collectively, our work suggests that dietary reduction of the n-6/n-3 PUFA ratio, as well as total n-3 PUFA consumed, is a crucial determinant that facilitates n-3 PUFA biosynthesis and subsequent lipidomic modifications, thereby conferring metabolic benefits against obesity-induced inflammation and insulin resistance. PMID: 31760228 [PubMed - as supplied by publisher]

Related Articles Elucidating the time-dependent changes in the urinary metabolome under doxorubicin-induced nephrotoxicity. Toxicol Lett. 2019 Nov 21;: Authors: Li A, Zhang W, Zhang L, Liu Y, Li K, Du G, Qin X Abstract Doxorubicin has been indicated to be cardiotoxic and nephrotoxic, and thus it is often used as a model drug. Possible molecular mechanisms of this toxicity have been proposed, however, the systematic investigation of time-related metabolic trajectories specific to renal toxicity has rarely been reported. The present study was designed to assess time-dependent changes in doxorubicin-induced nephropathy through urinary metabolomics and to reveal the molecular mechanism based on key pathways. Urinary metabolomics revealed that the 14th day was the critical time point for model construction. Pathway analysis results showed that 5 pathways with impact (>0.01), FDR (<0.1) and p value (<0.05) were important. Furthermore, three pathways, including butanoate metabolism, alanine, aspartate and glutamate metabolism and arginine and proline metabolism, were focused on and validated by partial least squares regression analysis (PLS-RA) and molecular docking techniques. Our findings also showed that robust metabolomics combined with PLS-RA and molecular docking techniques is promising for elucidating time-dependent changes due to doxorubicin toxicity and for clarifying mechanisms, and the results provide a research foundation for the construction of a nephropathy model. PMID: 31760061 [PubMed - as supplied by publisher]

Related Articles Omics approach reveals perturbation of metabolism and phenotype in Caenorhabditis elegans triggered by perfluorinated compounds. Sci Total Environ. 2019 Nov 13;:135500 Authors: Kim HM, Long NP, Yoon SJ, Anh NH, Kim SJ, Park JH, Kwon SW Abstract Perfluorinated compounds (PFCs) are widely used in consumer products because of their remarkable endurance. However, their distinct stability prolongs degradation, resulting in bioaccumulation in the environment which is a severe environmental issue. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are principal constituents in the PFCs. In this study, the potential toxic effects of PFOS and PFOA were evaluated by adopting an in vivo animal model, Caenorhabditis elegans (C. elegans). The uptake of PFCs was confirmed by the quantification of internal concentration in C. elegans. Metabolomics and lipidomics were applied along with reproduction assay and reactive oxygen species (ROS) assay. In the C. elegans exposed to PFOS and PFOA, amino acids including phenylalanine, tyrosine, and tryptophan, were significantly affected. Also, various species that belong to glycerophospholipids and triacylglycerol were perturbed in the exposed groups. The alteration patterns of the lipidome in PFOS and PFOA treated C. elegans were significantly different. Additionally, dichlorodihydrofluorescein diacetate (H2DCFDA)-based ROS assay revealed increased internal ROS in PFOS (1.5 fold, p-value = 0.0067) and PFOA (1.46 fold, p-value = 0.0253) groups. Decrease in reproduction was confirmed in PFOS (0.53 fold, p-value < 0.0001) and PFOA (0.69 fold, p-value = 0.0003) by counting progeny. Collectively, our findings suggest that exposure to PFCs in C. elegans leads to perturbation of various phenotypes as well as crucial amino acid and lipid metabolism. PMID: 31759720 [PubMed - as supplied by publisher]

Related Articles The authors reply. Kidney Int. 2019 Dec;96(6):1422-1423 Authors: Saez-Rodriguez J, Rinschen MM, Floege J, Kramann R PMID: 31759488 [PubMed - in process]

Related Articles NMR-based metabolomics analysis identifies discriminatory metabolic disturbances in tissue and biofluid samples for progressive prostate cancer. Clin Chim Acta. 2019 Nov 20;: Authors: Zheng H, Dong B, Ning J, Shao X, Zhao L, Jiang Q, Ji H, Cai A, Xue W, Gao H Abstract BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men, but its metabolic characteristics during tumor progression are still far from being fully understood. METHODS: The metabolic profiles of matched tissue, serum and urine samples from the same patients were analyzed using a 1H NMR-based metabolomics approach. We identified several important metabolites that significantly altered at different stages of PCa, including benign prostatic hyperplasia (BPH), early PCa (EPC), advanced PCa (APC), metastatic PCa (MPC) and castration-resistant PCa (CRPC). Metabolic correlation networks among tissue, serum and urine samples were examined using Pearson's correlation. RESULTS: The changes in metabolic phenotypes during the progression of PCa were more noticeable in tissue samples when compared with serum and urine samples. Herein we identified a series of important metabolic disturbances, including decreased trends of citrate, creatinine, acetate, leucine, valine, glycine, lysine, histidine, glutamine and choline as well as increased trends of uridine and formate. These metabolites are mainly implicated in energy metabolism, amino acid metabolism, choline and fatty acid metabolism as well as uridine metabolism. We also found that energy metabolism in tumor tissues was positively associated with amino acid metabolism in serum and urine. Additionally, CRPC patients had a peculiar metabolic phenotype, especially decreased amino acid metabolism in serum. CONCLUSIONS: The present study characterizes metabolic disturbances in both tissue and biofluid samples during PCa progression and provides potential diagnostic biomarkers and therapeutic targets for PCa. PMID: 31758937 [PubMed - as supplied by publisher]

Related Articles Metabolic alterations associated with polycystic ovary syndrome: a UPLC Q-Exactive based metabolomic study. Clin Chim Acta. 2019 Nov 20;: Authors: Chen X, Lu T, Wang X, Sun X, Zhang J, Zhou K, Ji X, Sun R, Wang X, Chen M, Ling X Abstract BACKGROUND: The polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder syndrome of women in reproductive age. Metabolomic studies of the follicular fluid can reveal the potential metabolic pathways related to PCOS. The objection of this study was to explore the changes of metabolites in the follicular fluid of PCOS. METHODS: We collected follicular fluid samples of 35 patients with PCOS and 33 controls without PCOS for metabolomic analysis with UPLC Q-Exactive. The identified metabolites were annotated with KEGG and HMDB to determine the disturbances of metabolic pathways in PCOS. Based on the regression model, we conducted the ROC analysis to find the biomarker of PCOS in the follicular fluid. RESULTS: Metabolomic analysis identified 21 differential metabolites in PCOS, which revealed that the Vitamin B6 metabolism, phenylalanine metabolism and carnitine synthesis were the key changed pathways. We found that 7β-Hydroxycholesterol was potential biomarker of PCOS based on the ROC analysis. CONCLUSION: We identified metabolic alterations and biomarker in the follicular fluid of PCOS, providing novel ways for the diagnosis and treatment of PCOS. PMID: 31758934 [PubMed - as supplied by publisher]

Related Articles Disruption of Arabidopsis neutral ceramidases 1 and 2 results in specific sphingolipid imbalances triggering different phytohormone-dependent plant cell death programs. New Phytol. 2019 Nov 23;: Authors: Zienkiewicz A, Gömann J, König S, Herrfurth C, Liu YT, Meldau D, Feussner I Abstract Sphingolipids act as regulators of programmed cell death (PCD) and the plant defense response. The homeostasis between long-chain base (LCB) and ceramide (Cer) seems to play an important role in executions of PCD. Therefore, deciphering the role of neutral ceramidases (NCER) is crucial to identify the sphingolipid compounds that trigger and execute PCD. We performed comprehensive sphingolipid and phytohormone analyses of Arabidopsis ncer mutants, combined with gene expression profiling and microscopic analyses. While ncer1 exhibited early leaf senescence (developmentally-controlled PCD - dPCD) and an increase in hydroxyceramides, ncer2 showed spontaneous cell death (pathogen-triggered PCD-like - pPCD) accompanied by an increase in LCB t18:0 at 35 days, respectively. Loss of NCER1 function resulted in accumulation of jasmonoyl-isoleucine (JA-Ile) in the leaves, whereas disruption of NCER2 was accompanied by higher levels of salicylic acid (SA) and increased sensitivity to Fumonisin B1 (FB1 ). All mutants were also found to activate plant defense pathways. These data strongly suggest that NCER1 hydrolyses ceramides whereas NCER2 functions as a ceramide synthase. Our results reveal an important role of neutral ceramidases in the regulation of both dPCD and pPCD via a tight connection between the phytohormone and sphingolipid levels in these two processes. PMID: 31758808 [PubMed - as supplied by publisher]

Related Articles Metabolic impairments, metal traffic, and dyshomeostasis caused by the antagonistic interaction of cadmium and selenium using organic and inorganic mass spectrometry. Environ Sci Pollut Res Int. 2019 Nov 22;: Authors: Rodríguez-Moro G, Roldán FN, Baya-Arenas R, Arias-Borrego A, Callejón-Leblic B, Gómez-Ariza JL, García-Barrera T Abstract Cadmium (Cd) has become one of the most important environmental pollutants in the world, derived from natural and industrial sources, which is known to be accumulated in the human body, producing serious health effects. On the other hand, Selenium (Se) is an essential element for mammals, which is well known for its antagonistic interaction against Cd toxicity, such as the prevention of oxidative stress induced by this element. For this reason, the use of complementary analytical methods to study the homeostasis of metals, "traffic" between different organs and massive information about metabolites altered by the exposure, is of great interest. To this end, a metabolomic workflow based on the use of direct infusion mass spectrometry (DIMS) and gas chromatography mass spectrometry (GC-MS) was applied in mice serum. On the other hand, metal homeostasis and traffic between different organs and serum of mice exposed to Cd and Se have been evaluated by determining the concentration of metals by inductively coupled plasma mass spectrometry. This work demonstrates for the first time that Cd exposure causes a decrease of all the elements studied in the lung except itself. On the other hand, Se provokes As trafficking from metabolically less active organs (brain, lung, and testes) to others with greater metabolic activity (kidney), which also facilitates its excretion. Moreover, when mice are only exposed to Se, it provokes the accumulation of almost all the elements in the kidney, except Cd that increases also in the liver and brain. However, when both elements are simultaneously administered, Se increases Cd concentration in all the organs except in the serum and especially in the testis. On the other hand, important metabolic alterations have been detected in the energy and amino acid metabolism, as well as degradation of phospholipidic membranes, and in free fatty acids. In summary, the results show the high potential of the combined use of organic and inorganic mass spectrometry to establish Cd and Se interaction and the biological impairments caused and to provide information about metal traffic and metabolomic changes in exposure experiments. PMID: 31758476 [PubMed - as supplied by publisher]

Related Articles Metabolomic Analysis of Toxoplasma gondii Tachyzoites. Methods Mol Biol. 2020;2071:435-452 Authors: King EFB, Cobbold SA, Uboldi AD, Tonkin CJ, McConville MJ Abstract This protocol describes the use of 13C-stable isotope labeling, combined with metabolite profiling, to investigate the metabolism of the tachyzoite stage of the protozoan parasite Toxoplasma gondii. T. gondii tachyzoites can infect any nucleated cell in their vertebrate (including human) hosts, and utilize a range of carbon sources that freely permeate across the limiting membrane of the specialized vacuole within which they proliferate. Methods for cultivating tachyzoites in human foreskin fibroblasts and metabolically labeling intracellular and naturally egressed tachyzoites with a range of 13C-labeled carbon sources are described. Parasites are harvested and purified from host metabolites, with rapid metabolic quenching and 13C-enrichment in intracellular polar metabolites quantified by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The mass isotopomer distribution of key metabolites is determined using DExSI software. This method can be used to measure perturbations in parasite metabolism induced by drug inhibition or genetic manipulation of enzyme levels and is broadly applicable to other cultured or intracellular parasite stages. PMID: 31758465 [PubMed - in process]

Related Articles Analytical considerations for postmortem metabolomics using GC-high-resolution MS. Anal Bioanal Chem. 2019 Nov 22;: Authors: Brockbals L, Kraemer T, Steuer AE Abstract Metabolomics studies that aim to qualitatively and quantitatively characterize the entirety of small endogenous biomolecules in an organism are widely conducted in the clinical setting. They also become more and more popular in the field of forensics (toxicology), e.g., to assist in postmortem investigations by objective postmortem interval estimation. However, other issues in postmortem toxicology, such as the phenomenon of (time-dependent) postmortem redistribution, have not yet been tackled by metabolomics studies. Hence, the aim of the current study was to develop an (un)targeted gas chromatography-high-resolution mass spectrometry-based method for endogenous metabolites as a tool for large-scale (un)targeted human postmortem metabolomics investigations (e.g., to objectively assess PMR) with thorough analytical evaluation of this method to ensure fitness-to-purpose in terms of reliability and robustness. This was achieved by using a targeted metabolite subset (n = 56) and a targeted processing workflow. Evaluation experiments have shown that using an artificial matrix (revised simulated body fluid (rSBF) + 5% bovine serum albumin (BSA)) for calibration purposes, all parameters lay within the scope of the method (sensitivity, selectivity, calibration model, accuracy, precision, processed sample stability, and extraction efficiency). When applying this method to large-scale studies, samples should be run in randomized order if analysis time is expected to exceed 18-24 h and potential biomarkers that are found with this method should be verified by a specialized, targeted method (e.g., by using standard addition in authentic matrix for quantification purposes). Overall, the current method can be successfully used for conduction of time-dependent postmortem metabolomics investigations. Graphical abstract. PMID: 31758199 [PubMed - as supplied by publisher]

Related Articles Long-read sequencing based clinical metagenomics for the detection and confirmation of Pneumocystis jirovecii directly from clinical specimens: A paradigm shift in mycological diagnostics. Med Mycol. 2019 Nov 23;: Authors: Irinyi L, Hu Y, Hoang MTV, Pasic L, Halliday C, Jayawardena M, Basu I, McKinney W, Morris AJ, Rathjen J, Stone E, Chen S, Sorrell TC, Schwessinger B, Meyer W Abstract The advent of next generation sequencing technologies has enabled the characterization of the genetic content of entire communities of organisms, including those in clinical specimens, without prior culturing. The MinION from Oxford Nanopore Technologies offers real-time, direct sequencing of long DNA fragments directly from clinical samples. The aim of this study was to assess the ability of unbiased, genome-wide, long-read, shotgun sequencing using MinION to identify Pneumocystis jirovecii directly from respiratory tract specimens and to characterize the associated mycobiome. Pneumocystis pneumonia (PCP) is a life-threatening fungal disease caused by P. jirovecii. Currently, the diagnosis of PCP relies on direct microscopic or real-time quantitative polymerase chain reaction (PCR) examination of respiratory tract specimens, as P. jirovecii cannot be cultured readily in vitro. P. jirovecii DNA was detected in bronchoalveolar lavage (BAL) and induced sputum (IS) samples from three patients with confirmed PCP. Other fungi present in the associated mycobiome included known human pathogens (Aspergillus, Cryptococcus, Pichia) as well as commensal species (Candida, Malassezia, Bipolaris). We have established optimized sample preparation conditions for the generation of high-quality data, curated databases, and data analysis tools, which are key to the application of long-read MinION sequencing leading to a fundamental new approach in fungal diagnostics. PMID: 31758176 [PubMed - as supplied by publisher]

Related Articles Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice. Sci Rep. 2019 Nov 22;9(1):17423 Authors: Reyes-Caballero H, Rao X, Sun Q, Warmoes MO, Penghui L, Sussan TE, Park B, Fan TW, Maiseyeu A, Rajagopalan S, Girnun GD, Biswal S Abstract Exposure to ambient air particulate matter (PM2.5) is well established as a risk factor for cardiovascular and pulmonary disease. Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as diabetes. Given the central role of the liver in peripheral glucose homeostasis, we exposed mice to filtered air or PM2.5 for 16 weeks and examined its effect on hepatic metabolic pathways using stable isotope resolved metabolomics (SIRM) following a bolus of 13C6-glucose. Livers were analyzed for the incorporation of 13C into different metabolic pools by IC-FTMS or GC-MS. The relative abundance of 13C-glycolytic intermediates was reduced, suggesting attenuated glycolysis, a feature found in diabetes. Decreased 13C-Krebs cycle intermediates suggested that PM2.5 exposure led to a reduction in the Krebs cycle capacity. In contrast to decreased glycolysis, we observed an increase in the oxidative branch of the pentose phosphate pathway and 13C incorporations suggestive of enhanced capacity for the de novo synthesis of fatty acids. To our knowledge, this is one of the first studies to examine 13C6-glucose utilization in the liver following PM2.5 exposure, prior to the onset of insulin resistance (IR). PMID: 31757983 [PubMed - in process]

Related Articles Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase-HIF-1α axis. Biochem Biophys Res Commun. 2019 Nov 19;: Authors: Su W, Shi J, Zhao Y, Yan F, Lei L, Li H Abstract Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis. PMID: 31757417 [PubMed - as supplied by publisher]

Related Articles Contribution of Berry Polyphenols to the Human Metabolome. Molecules. 2019 Nov 20;24(23): Authors: Chandra P, Rathore AS, Kay KL, Everhart JL, Curtis P, Burton-Freeman B, Cassidy A, Kay CD Abstract Diets rich in berries provide health benefits, however, the contribution of berry phytochemicals to the human metabolome is largely unknown. The present study aimed to establish the impact of berry phytochemicals on the human metabolome. A "systematic review strategy" was utilized to characterize the phytochemical composition of the berries most commonly consumed in the USA; (poly)phenols, primarily anthocyanins, comprised the majority of reported plant secondary metabolites. A reference standard library and tandem mass spectrometry (MS/MS) quantitative metabolomics methodology were developed and applied to serum/plasma samples from a blueberry and a strawberry intervention, revealing a diversity of benzoic, cinnamic, phenylacetic, 3-(phenyl)propanoic and hippuric acids, and benzyldehydes. 3-Phenylpropanoic, 2-hydroxybenzoic, and hippuric acid were highly abundant (mean > 1 µM). Few metabolites at concentrations above 100 nM changed significantly in either intervention. Significant intervention effects (P < 0.05) were observed for plasma/serum 2-hydroxybenzoic acid and hippuric acid in the blueberry intervention, and for 3-methoxyphenylacetic acid and 4-hydroxyphenylacetic acid in the strawberry intervention. However, significant within-group effects for change from baseline were prevalent, suggesting that high inter-individual variability precluded significant treatment effects. Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline, rather than the appearance of unique berry-derived metabolites, which likely reflects the ubiquitous nature of (poly)phenols in the background diet. PMID: 31757061 [PubMed - in process]

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 2019/11/23PubMed 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.

23 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 2019/11/22PubMed 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.

23 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 2019/11/22PubMed 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 2019/11/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2019/11/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.