PubMed

Related Articles Identification of endogenous 1-aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation. Br J Pharmacol. 2020 Mar 26;: Authors: Miao H, Cao G, Wu XQ, Chen YY, Chen DQ, Chen L, Vaziri ND, Feng YL, Su W, Gao Y, Zhuang S, Yu XY, Zhang L, Guo Y, Zhao YY Abstract BACKGROUND AND PURPOSE: Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. EXPERIMENTAL APPROACH: Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomised rat model and in CKD patients. KEY RESULTS: Six aryl-containing metabolites (ACM) were significantly increased from week 1 to week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2, and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy, and immunoglobulin A nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly upregulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR shRNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. CONCLUSION AND IMPLICATIONS: We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment. PMID: 32219844 [PubMed - as supplied by publisher]

Related Articles Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence. Gastric Cancer. 2020 Mar 26;: Authors: Kaji S, Irino T, Kusuhara M, Makuuchi R, Yamakawa Y, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Kami K, Ohashi Y, Zhang S, Orita H, Lee-Okada HC, Fukunaga T, Terashima M Abstract BACKGROUND: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). CONCLUSIONS: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor. PMID: 32219586 [PubMed - as supplied by publisher]

Related Articles The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats. Food Funct. 2020 Mar 27;: Authors: Zhang Q, Fan XY, Guo WL, Cao YJ, Lin YC, Cheng WJ, Chen LJ, Rao PF, Ni L, Lv XC Abstract Macroalgae Laminaria japonica (MLJ) has been reported to exhibit various biological activities including improving immunity, anti-aging, anti-tumor, anti-atherosclerosis and anti-diabetic, but the protective mechanisms of MLJ consumption against non-alcoholic fatty liver disease (NAFLD) associated with hyperlipidemia remain poorly understood. This study demonstrated that MLJ consumption prevented high-fat diet (HFD)-induced NAFLD associated with hyperlipidemia in a rat model, and improved hyperlipidemia-related parameters, e.g. serum and hepatic lipid profiles. Moreover, histological analysis showed that MLJ reduced lipid deposition in adipocytes and hepatocytes compared with the HFD group. Such beneficial effects may be associated with the modulation of the intestinal microbiota, especially some key microbial phylotypes involved in lipid metabolism homeostasis. The underlying protective mechanisms of MLJ consumption against HFD-induced NAFLD associated with hyperlipidemia were also studied by ultra-high performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics coupled with pathway analysis. The metabolic pathway enrichment analysis of the differentially abundant hepatic metabolites indicated that primary bile acid biosynthesis metabolism and cysteine and methionine metabolism were the two main metabolic pathways altered by MLJ consumption when compared with the model group. The analysis of the transcription levels of liver-related genes by RT-qPCR and the expressions of liver-related proteins by immunohistochemistry (IHC) showed that MLJ consumption could regulate the levels of mRNA transcription and protein expression related to hepatic lipid metabolism. In short, this study indicates that MLJ could be developed as functional food supplement for the prevention or treatment of NAFLD associated with hyperlipidemia. PMID: 32219261 [PubMed - as supplied by publisher]

Related Articles Genome Insights of the Plant-Growth Promoting Bacterium Cronobacter muytjensii JZ38 With Volatile-Mediated Antagonistic Activity Against Phytophthora infestans. Front Microbiol. 2020;11:369 Authors: Eida AA, Bougouffa S, L'Haridon F, Alam I, Weisskopf L, Bajic VB, Saad MM, Hirt H Abstract Salinity stress is a major challenge to agricultural productivity and global food security in light of a dramatic increase of human population and climate change. Plant growth promoting bacteria can be used as an additional solution to traditional crop breeding and genetic engineering. In the present work, the induction of plant salt tolerance by the desert plant endophyte Cronobacter sp. JZ38 was examined on the model plant Arabidopsis thaliana using different inoculation methods. JZ38 promoted plant growth under salinity stress via contact and emission of volatile compounds. Based on the 16S rRNA and whole genome phylogenetic analysis, fatty acid analysis and phenotypic identification, JZ38 was identified as Cronobacter muytjensii and clearly separated and differentiated from the pathogenic C. sakazakii. Full genome sequencing showed that JZ38 is composed of one chromosome and two plasmids. Bioinformatic analysis and bioassays revealed that JZ38 can grow under a range of abiotic stresses. JZ38 interaction with plants is correlated with an extensive set of genes involved in chemotaxis and motility. The presence of genes for plant nutrient acquisition and phytohormone production could explain the ability of JZ38 to colonize plants and sustain plant growth under stress conditions. Gas chromatography-mass spectrometry analysis of volatiles produced by JZ38 revealed the emission of indole and different sulfur volatile compounds that may play a role in contactless plant growth promotion and antagonistic activity against pathogenic microbes. Indeed, JZ38 was able to inhibit the growth of two strains of the phytopathogenic oomycete Phytophthora infestans via volatile emission. Genetic, transcriptomic and metabolomics analyses, combined with more in vitro assays will provide a better understanding the highlighted genes' involvement in JZ38's functional potential and its interaction with plants. Nevertheless, these results provide insight into the bioactivity of C. muytjensii JZ38 as a multi-stress tolerance promoting bacterium with a potential use in agriculture. PMID: 32218777 [PubMed - as supplied by publisher]

Related Articles Identifying Protein-metabolite Networks Associated with COPD Phenotypes. Metabolites. 2020 Mar 25;10(4): Authors: Mastej E, Gillenwater L, Zhuang Y, Pratte KA, Bowler RP, Kechris K Abstract Chronic obstructive pulmonary disease (COPD) is a disease in which airflow obstruction in the lung makes it difficult for patients to breathe. Although COPD occurs predominantly in smokers, there are still deficits in our understanding of the additional risk factors in smokers. To gain a deeper understanding of the COPD molecular signatures, we used Sparse Multiple Canonical Correlation Network (SmCCNet), a recently developed tool that uses sparse multiple canonical correlation analysis, to integrate proteomic and metabolomic data from the blood of 1008 participants of the COPDGene study to identify novel protein-metabolite networks associated with lung function and emphysema. Our aim was to integrate -omic data through SmCCNet to build interpretable networks that could assist in the discovery of novel biomarkers that may have been overlooked in alternative biomarker discovery methods. We found a protein-metabolite network consisting of 13 proteins and 7 metabolites which had a -0.34 correlation (p-value = 2.5 × 10-28) to lung function. We also found a network of 13 proteins and 10 metabolites that had a -0.27 correlation (p-value = 2.6 × 10-17) to percent emphysema. Protein-metabolite networks can provide additional information on the progression of COPD that complements single biomarker or single -omic analyses. PMID: 32218378 [PubMed - as supplied by publisher]

Related Articles An Integrative Approach to Assessing Diet-Cancer Relationships. Metabolites. 2020 Mar 25;10(4): Authors: Murphy R Abstract The relationship between diet and cancer is often viewed with skepticism by the public and health professionals, despite a considerable body of evidence and general consistency in recommendations over the past decades. A systems biology approach which integrates 'omics' data including metabolomics, genetics, metagenomics, transcriptomics and proteomics holds promise for developing a better understanding of how diet affects cancer and for improving the assessment of diet through biomarker discovery thereby renewing confidence in diet-cancer links. This review discusses the application of multi-omics approaches to studies of diet and cancer. Considerations and challenges that need to be addressed to facilitate the investigation of diet-cancer relationships with multi-omic approaches are also discussed. PMID: 32218376 [PubMed - as supplied by publisher]

Related Articles Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions. Microorganisms. 2020 Mar 25;8(4): Authors: Polimeno L, Barone M, Mosca A, Viggiani MT, Joukar F, Mansour-Ghanaei F, Mavaddati S, Daniele A, Debellis L, Bilancia M, Santacroce L, Di Leo A Abstract BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production. AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract. METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure. RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroides distasonis, Clostridium clostridioforme and Pediococcus pentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotella melaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6). CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions. PMID: 32218321 [PubMed - as supplied by publisher]

Related Articles Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro. Biomolecules. 2020 Mar 25;10(4): Authors: Tutanov O, Orlova E, Proskura K, Grigor'eva A, Yunusova N, Tsentalovich Y, Alexandrova A, Tamkovich S Abstract Exosomes are important intercellular communication vehicles, secreted into body fluids by multiple cell types, including tumor cells. They contribute to the metastatic progression of tumor cells through paracrine signalling. It has been recently discovered that blood circulating exosomes contain distinguishable fractions of free and cell-surface-associated vesicles. We evaluated the influence of protein cargoes from exosomes from plasma, and exosomes from the total blood of healthy females (HFs) and breast cancer patients (BCPs), on cell motility. We conducted a mass spectrometric analysis of exosomal contents isolated from samples using ultrafiltration and ultracentrifugation approaches and verified their nature using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry. We observed that malignant neoplasm-associated proteins in exosomes from BCP total blood were detected more often than in plasma (66% vs. 59%). FunRich analysis to assess Gene Ontology (GO) enrichment revealed that proteins with catalytic activities, transporter functions and protein metabolism activities were increased in exosomes from BCP blood. Finally, GO analysis revealed that proteomic profiles of exosomes from HF total blood were enriched with proteins inhibiting cell migration and invasion, which explains the low stimulating activity of exosomes from HF total blood on SKBR-3 cancer cell migration velocity. This allows exosomes to act as intermediaries providing intercellular communications through horizontal transfer of RNA and functionally active proteins, potentially affecting the development of both primary neoplasms and distant metastases. PMID: 32218180 [PubMed - as supplied by publisher]

Related Articles How could metabolomics change pediatric health? Ital J Pediatr. 2020 Mar 27;46(1):37 Authors: Bardanzellu F, Fanos V Abstract In the last years, 'omics' technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes.In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic "snapshot."Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors.Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products' composition.These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health.In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism.Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient's bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one. PMID: 32216818 [PubMed - as supplied by publisher]

Related Articles Rapid Prostate Cancer Non-invasive Biomarker Screening Using Segmented Flow Mass Spectrometry-based Untargeted Metabolomics. J Proteome Res. 2020 Mar 27;: Authors: Pinto FG, Mahmud I, Harmon TA, Rubio VY, Garrett TJ Abstract Spectrometric methods with rapid biomarker detection capacity through untargeted metabolomics are becoming essential in the clinical cancer research. Liquid chromatography-mass spectrometry (LC-MS) is a rapidly developing metabolomic-based biomarker technique due its high sensitivity, reproducibility, and separation efficiency. However, its transla-tion to clinical diagnostics is often limited due to long data acquisition times (~20 min/sample) and laborious sample extraction procedures when employed for large-scale metabolomics studies. Here, we developed a segmented flow approach coupled with high-resolution mass spectrometry (SF-HRMS) for untargeted metabolomics which has the capability to acquire data in less than 1.5 min/sample with robustness and reproducibility relative to LC-HRMS. The SF-HRMS results demonstrate the capability for screening metabolite-based urinary biomarkers associated with prostate cancer (PCa). The study shows that SF-HRMS-based global metabolomics has the potential to evolve into a rapid biomarker screening tool for clinical research. PMID: 32216312 [PubMed - as supplied by publisher]

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 2020/03/28PubMed 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 2020/03/28PubMed 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 2020/03/27PubMed 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 Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production. PLoS Pathog. 2020 Mar 24;16(3):e1008448 Authors: Osbelt L, Thiemann S, Smit N, Lesker TR, Schröter M, Gálvez EJC, Schmidt-Hohagen K, Pils MC, Mühlen S, Dersch P, Hiller K, Schlüter D, Neumann-Schaal M, Strowig T Abstract The composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease severity is largely unknown. Using isogenic mouse lines harboring distinct microbiota communities, we observed highly variable disease kinetics of enteric Citrobacter rodentium colonization after infection. Transfer of communities from susceptible and resistant mice into germ-free mice verified that the varying susceptibilities are determined by microbiota composition. The strongest differences in colonization were observed in the cecum and could be maintained in vitro by coculturing cecal bacteria with C. rodentium. Cohousing of animals as well as the transfer of cultivable bacteria from resistant to susceptible mice led to variable outcomes in the recipient mice. Microbiome analysis revealed that a higher abundance of butyrate-producing bacteria was associated with the resistant phenotype. Quantification of short-chain fatty acid (SCFA) levels before and after infection revealed increased concentrations of acetate, butyrate and propionate in mice with delayed colonization. Addition of physiological concentrations of butyrate, but not of acetate and/or propionate strongly impaired growth of C. rodentium in vitro. In vivo supplementation of susceptible, antibiotic-treated and germ-free mice with butyrate led to the same level of protection, notably only when cecal butyrate concentration reached a concentration higher than 50 nmol/mg indicating a critical threshold for protection. In the recent years, commensal-derived primary and secondary bacterial metabolites emerged as potent modulators of hosts susceptibility to infection. Our results provide evidence that variations in SCFA production in mice fed fibre-rich chow-based diets modulate susceptibility to colonization with Enterobacteriaceae not only in antibiotic-disturbed ecosystems but even in undisturbed microbial communities. These findings emphasise the need for microbiota normalization across laboratory mouse lines for infection experiments with the model-pathogen C. rodentium independent of investigations of diet and antibiotic usage. PMID: 32208465 [PubMed - as supplied by publisher]

Related Articles Bacterially produced metabolites protect C. elegans neurons from degeneration. PLoS Biol. 2020 Mar;18(3):e3000638 Authors: Urrutia A, García-Angulo VA, Fuentes A, Caneo M, Legüe M, Urquiza S, Delgado SE, Ugalde J, Burdisso P, Calixto A Abstract Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the mechanosensory abnormality protein 4 (MEC-4d) degenerin/epithelial Na+ (DEG/ENaC) channel, which causes the progressive degeneration of the touch receptor neurons (TRNs). Using this model, our study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. Although degeneration of TRNs was steady and completed at adulthood in the strain routinely used for C. elegans maintenance (Escherichia coli OP50), it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and was not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of DAF-16 (ortholog of the FOXO family of transcription factors), a phenomenon previously reported to underlie neuroprotection caused by down-regulation of the insulin receptor in this system. Moreover, a daf-16 loss-of-function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics, and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) and lactate as metabolites differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full HT115-mediated neuroprotection. Additionally, lactate supplementation also increased anterior ventral microtubule (AVM) neuron survival in OP50. Together, these results demonstrate that bacterially produced GABA and other metabolites exert an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis. PMID: 32208418 [PubMed - in process]

Related Articles Triclocarban-induced responses of endogenous and xenobiotic metabolism in human hepatic cells: Toxicity assessment based on nontargeted metabolomics approach. J Hazard Mater. 2020 Mar 05;392:122475 Authors: Zhang H, Lu Y, Liang Y, Jiang L, Cai Z Abstract Humans are frequently exposed to the antimicrobial triclocarban (TCC) due to its widespread use in consumer and personal care products. However, there is a paucity of research on potential hepatotoxic risks of TCC exposure. In this study, nontargeted metabolomics approach was applied to simultaneously investigate TCC-induced perturbation of endogenous metabolites and generation of xenobiotic metabolites in human hepatic cells. In normal hepatocytes, TCC exposure induced cellular redox imbalance as evidenced by the decrease of glutathione metabolism and overproduction of reactive oxygen species (ROS), resulting in DNA damage and lipid peroxidation. Defective oxidative phosphorylation and increased purine metabolism were two potential sources of elevated ROS. However, in cancerous hepatocytes, TCC exposure enhanced glutathione metabolism, glycolysis, and glutaminolysis, which contributed to the cellular homeostasis of redox and energy status, as well as the progression of liver cancer. As a xenobiotic, metabolic activation of TCC through phase I hydroxylation was observed. The hepatic cytotoxicity follows the order of 6-OH-TCC > 2'-OH-TCC > 3'-OH-TCC > DHC, with EC50 values of 2.42, 3.38, 7.38, and 24.8 μM, respectively, in 48 h-treated normal cells. This study improves current understanding of TCC-triggered hepatotoxicity, and provides novel perspectives for evaluating the interaction of environmental pollutants with biological systems. PMID: 32208312 [PubMed - as supplied by publisher]

Related Articles Integrated analysis of physiological, transcriptomic and metabolomic responses and tolerance mechanism of nitrite exposure in Litopenaeus vannamei. Sci Total Environ. 2020 Apr 01;711:134416 Authors: Xiao J, Liu QY, Du JH, Zhu WL, Li QY, Chen XL, Chen XH, Liu H, Zhou XY, Zhao YZ, Wang HL Abstract Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei. PMID: 32000302 [PubMed - indexed for MEDLINE]

Related Articles Lipidomics perturbations in the brain of adult zebrafish (Danio rerio) after exposure to chiral ibuprofen. Sci Total Environ. 2020 Apr 15;713:136565 Authors: Zhang W, Song Y, Chai T, Liao G, Zhang L, Jia Q, Qian Y, Qiu J Abstract The stereoselective effects of chiral ibuprofen (IBU) were studied using lipidomics by exposing adult zebrafish (Danio rerio) to an environmental concentration of 5 μg/L for 28 days. After treatment with rac-/R-(-)-/S-(+)-IBU, the brain tissue of the zebrafish was harvested to analyze for lipid metabolites by using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results showed that the six classes of lipids, namely, glycerophospholipids, sterol lipids, prenol lipids, fatty acyls, glycerolipids, and sphingolipids, including 46 biomarkers, were affected after exposure. The different influences on metabolites were observed in the rac-/R-(-)-/S-(+)-IBU-treated samples. The rac-IBU treatment remarkably affected nine lipids. The R-(-)-IBU and S-(+)-IBU treatments had remarkably effects on six and four lipids, respectively. According to the HMDB database and KEGG pathways, nine important lipids were successfully matched to the involved biochemical pathways, such as glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. Therefore, IBU can cause disorders in the metabolism of the brain lipids of adult zebrafish and affect the composition of biological membranes, inflammatory responses, and cardiovascular and cerebrovascular diseases. The significant difference in the effects of R-(-)-IBU and S-(+)-IBU on lipidomics indicated that chiral IBU has stereoselective toxicity to aquatic organisms. Our study provided new insights into the environmental toxicology and highlighted the hazard of pharmaceutical and personal care product pollution in aquatic environments. PMID: 31954244 [PubMed - indexed for MEDLINE]

Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria. Elife. 2020 Mar 24;9: Authors: McGregor TL, Hunt KA, Yee E, Mason D, Nioi P, Ticau S, Pelosi M, Loken PR, Finer S, Lawlor DA, Fauman EB, Huang QQ, Griffiths CJ, MacArthur DG, Trembath RC, Oglesbee D, Lieske JC, Erbe DV, Wright J, van Heel DA Abstract By sequencing autozygous human populations we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n=67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5sd outliers versus n=25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development. PMID: 32207686 [PubMed - as supplied by publisher]

NormAE: Deep Adversarial Learning Model to Remove Batch Effects in Liquid Chromatography Mass Spectrometry-Based Metabolomics Data. Anal Chem. 2020 Mar 24;: Authors: Rong Z, Tan Q, Cao L, Zhang L, Deng K, Huang Y, Zhu ZJ, Li Z, Li K Abstract Untargeted metabolomics based on liquid chromatography-mass spectrometry is affected by nonlinear batch effects, which cover up biological effects, result in nonreproducibility, and are difficult to be calibrate. In this study, we propose a novel deep learning model, called Normalization Autoencoder (NormAE), which is based on nonlinear autoencoders (AEs) and adversarial learning. An additional classifier and ranker are trained to provide adversarial regularization during the training of the AE model, latent representations are extracted by the encoder, and then the decoder reconstructs the data without batch effects. The NormAE method was tested on two real metabolomics data sets. After calibration by NormAE, the quality control samples (QCs) for both data sets gathered most closely in a PCA score plot (average distances decreased from 56.550 and 52.476 to 7.383 and 14.075, respectively) and obtained the highest average correlation coefficients (from 0.873 and 0.907 to 0.997 for both). Additionally, NormAE significantly improved biomarker discovery (median number of differential peaks increased from 322 and 466 to 1140 and 1622, respectively). NormAE was compared with four commonly used batch effect removal methods. The results demonstrated that using NormAE produces the best calibration results. PMID: 32207605 [PubMed - as supplied by publisher]