PubMed

Comparing alpha-cypermethrin induced dose/gender-dependent responses of lizards in hepatotoxicity and nephrotoxicity in a food chain. Chemosphere. 2020 May 13;256:127069 Authors: Chen L, Wang D, Zhou Z, Diao J Abstract Pesticides are proposed as one reason for the worldwide decline in the reptile. Effects of pesticides on food intake and organ toxicity could affect wildlife populations dynamics. To explore the hepatotoxicity of alpha-cypermethrin (ACP) in reptiles, we designed a tri-trophic food chain with three concentrations (0, 2, and 20 mg/kgwet weight). Although the enzymes changes were similar between male and female lizards, the significant variations in anti-oxidative enzymes' activities, lactic dehydrogenase activities and acetylcholine esterase activities in liver and kidney suggesting that oxidative stress, decreased metabolic ability and neurotoxicity on lizards. The results of hepatic metabolomics showed that ACP could affect amino acid, energy and lipid metabolism on lizards. Comparing with female lizards, there were more significant changes of metabolites in male lizards. The histopathology analysis in the liver (such as hepatic lobule congestion and hepatocyte vacuolation) and kidney (such as renal tubule necrosis and glomerulus necrosis), dose- and gender dependent changes of lesions suggested the functions of organ were damaged. In summary, the reduction of detoxification and elimination capacities of the liver and kidney showed dose/gender-dependent in lizards. PMID: 32447111 [PubMed - as supplied by publisher]

Toll-like receptor signaling induces a temporal switch towards a resolving lipid profile in monocyte-derived macrophages. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 May 21;:158740 Authors: von Hegedus JH, Kahnt AS, Ebert R, Heijink M, Toes REM, Giera M, Ioan-Facsinay A Abstract Inflammation is a tightly regulated process. During the past decade it has become clear that the resolution of inflammation is an active process and its dysregulation can contribute to chronic inflammation. Several cells and soluble mediators, including lipid mediators, regulate the course of inflammation and its resolution. It is, however, unclear which signals and cells are involved in initiating the resolution process. Macrophages are tissue resident cells and key players in regulating tissue inflammation through secretion of soluble mediators, including lipids. We hypothesize that persistent inflammatory stimuli can initiate resolution pathways in macrophages. In this study, we detected 21 lipids in LPS-stimulated human monocyte-derived macrophages by liquid chromatography coupled to tandem mass spectrometry. Cyclooxygenase-derived Prostaglandins were observed in the first six hours of stimulation. Interestingly, a switch towards 15-lipoxygenase products, such as the pro-resolving lipid precursors 15-HEPE and 17-HDHA was observed after 24 h. The RNA and protein expression of cyclooxygenase and 15-lipoxygenase were in line with this trend. Treatment with 17-HDHA increased IL-10 production of monocyte-derived macrophages and decreased LTB4 production by neutrophils, indicating the anti-inflammatory property of this lipid. These data reveal that monocyte-derived macrophages contribute to the resolution of inflammation in time by the production of pro-resolving lipids after an initial inflammatory stimulus. PMID: 32447052 [PubMed - as supplied by publisher]

Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ. Brain Behav Immun. 2020 May 21;: Authors: Chausse B, Lewen A, Poschet G, Kann O Abstract Microglia are tissue resident macrophages (innate immunity) and universal sensors of alterations in CNS physiology. In response to pathogen or damage signals, microglia feature rapid activation and can acquire different phenotypes exerting neuroprotection or neurotoxicity. Although transcriptional aspects of microglial phenotypic transitions have been described, the underlying metabolic reprogramming is widely unknown. Employing postnatal organotypic hippocampal slice cultures, we describe that microglia transformed into a mild reactive phenotype by single TLR4 stimulation with lipopolysaccharide (LPS), which was boosted into a severe neurotoxic phenotype by IFN-γ (LPS+INF-γ). The two reactive phenotypes associated with reduction of microglial homeostatic markers, increase of cytokine release (IL-6, TNF-α) as well as enhancement of tissue energy demand and lactate production. These reactive phenotypes differed in the pattern of inhibition of the respiratory chain in mitochondria, however. TLR4 stimulation induced succinate dehydrogenase (complex II) inhibition by the metabolite itaconate. By contrast, TLR4+IFN-γ receptor stimulation mainly resulted in complex IV inhibition by nitric oxide (NO) that also associated with severe oxidative stress, neuronal dysfunction and death. Notably, pharmacological depletion of microglia or treatment with itaconate resulted in effective neuroprotection reflected by well-preserved cytoarchitecture and electrical network activity, i.e., neuronal gamma oscillations (30-70 Hz) that underlie higher cognitive functions in vivo. Our findings provide in situ evidence that (i) proinflammatory microglia can substantially alter brain energy metabolism and (ii) fine-tuning of itaconate and NO metabolism determines microglial reactivity, impairment of neural network function and neurodegeneration. These data add mechanistic insights into microglial activation, with relevance to disorders featuring neuroinflammation and to drug discovery. PMID: 32446944 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/05/24PubMed 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.

24 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 2020/05/23PubMed 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.

17 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 2020/05/22PubMed 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.

17 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 2020/05/22PubMed 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.

35 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 2020/05/21PubMed 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.

35 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 2020/05/21PubMed 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.

30 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 2020/05/20PubMed 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 2020/05/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2020/05/19PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites. Appl Microbiol Biotechnol. 2020 May 17;: Authors: Zou J, Shen Y, Chen M, Zhang Z, Xiao S, Liu C, Wan Y, Yang L, Jiang S, Shang E, Qian D, Duan J Abstract Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract. PMID: 32418127 [PubMed - as supplied by publisher]

Mechanism of Huang-lian-Jie-du decoction and its effective fraction in alleviating acute ulcerative colitis in mice: Regulating arachidonic acid metabolism and glycerophospholipid metabolism. J Ethnopharmacol. 2020 May 14;:112872 Authors: Yuan Z, Yang L, Zhang X, Ji P, Hua Y, Wei Y Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Huang-lian-Jie-du decoction (HLJDD) is a traditional Chinese medicine prescription for clearing away heat, purging fire and detoxifying, which can be used to treat sepsis, stroke, Alzheimer's disease and gastrointestinal diseases. Our previous studies have shown that HLJDD can effectively alleviate acute ulcerative colitis (UC) in mice, and its n-butanol fraction (HLJDD-NBA) is the effective fraction. The aim of this study is to further investigate the mechanism of HLJDD and HLJDD-NBA in relieving UC in mice from a holistic perspective. METHODS: The acute UC model of BABL/c mice was induced by 3.5% (w/v) dextran sodium sulfate drinking water. At the same time of modeling, HLJDD and HLJDD-NBA were given orally for treatment respectively. During the experiment, the clinical symptoms of mice were recorded and the physiological and biochemical indexes of mice were detected after the experiment. In addition, the plasma metabolites of mice in each group were detected and analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry and multivariate statistical analysis method. Then, the potential target metabolic pathway of drug intervention was screened through the enrichment analysis of differential metabolites. Finally, we use molecular simulation docking technology to further explore the molecular regulatory mechanism of HLJDD and HLJDD-NBA on potential target metabolic pathways. RESULTS: HLJDD and HLJDD-NBA intervention can significantly reduce the disease activity index of UC mice, inhibit colon length shortening and pathological damage, and relieve the abnormal changes of physiological and biochemical parameters of UC mice. Moreover, HLJDD and HLJDD-NBA can significantly inhibit the metabolic dysfunction of UC mice by reversing the abnormal changes of 24 metabolites in UC mice, and the arachidonic acid metabolic pathway and glycerophospholipid metabolic pathway are the target metabolic pathways regulated by them. Further literature review and molecular simulation docking analysis showed that HLJDD and HLJDD-NBA may inhibit the disorder of arachidonic acid metabolism pathway and glycerophospholipid metabolism pathway by inhibiting COX-2 protein expression and PLA2, 5-LOX activity. CONCLUSIONS: Our experiments revealed that HLJDD and HLJDD-NBA can alleviate UC of mice by regulating arachidonic acid metabolism and glycerophospholipid metabolism, which points out the direction for further research and development of HLJDD as a new anti-ulcer drug. PMID: 32417423 [PubMed - as supplied by publisher]

Use of Single Cell -omic Technologies to Study the Gastrointestinal Tract and Diseases, From Single Cell Identities to Patient Features. Gastroenterology. 2020 May 14;: Authors: Islam M, Chen B, Spraggins JM, Kelly RT, Lau KS Abstract Single cells are the building blocks of tissue systems that determine organ phenotypes, behaviors, and function. Understanding the differences between cell types and their activities might provide us with insights into normal tissue functions, development of disease, and new therapeutic strategies. Although -omic level single cell technologies are a relatively recent development that been used only in laboratory studies, these approaches might eventually be used in the clinic. We review the prospects of applying single cell genome, transcriptome, epigenome, proteome, and metabolome analyses to gastroenterology and hepatology research. Combining data from multi-omic platforms and rapid technological developments could lead to new diagnostic, prognostic, and therapeutic approaches. PMID: 32417404 [PubMed - as supplied by publisher]

Psychopharmacological effects of riparin III from Aniba riparia (Nees) Mez. (Lauraceae) supported by metabolic approach and multivariate data analysis. BMC Complement Med Ther. 2020 May 16;20(1):149 Authors: Golzio Dos Santos S, Fernandes Gomes I, Fernandes de Oliveira Golzio AM, Lopes Souto A, Scotti MT, Fechine Tavares J, Chavez Gutierrez SJ, Nóbrega de Almeida R, Barbosa-Filho JM, Sobral da Silva M Abstract BACKGROUND: Currently there is a high prevalence of humor disorders such as anxiety and depression throughout the world, especially concerning advanced age patients. Aniba riparia (Nees) Mez. (Lauraceae), popular known as "louro", can be found from the Amazon through Guianas until the Andes. Previous studies have already reported the isolation of alkamide-type alkaloids such as riparin III (O-methyl-N-2,6-dyhydroxy-benzoyl tyramine) which has demonstrated anxiolytic and antidepressant-like effects in high doses by intraperitoneal administration. METHODS: Experimental protocol was conducted in order to analyze the anxiolytic-like effect of riparin III at lower doses by intravenous administration to Wistar rats (Rattus norvegicus) (n = 5). The experimental approach was designed to last 15 days, divided in 3 distinct periods of five days: control, anxiogenic and treatment periods. The anxiolytic-like effect was evaluated by experimental behavior tests such as open field and elevated plus-maze test, combined with urine metabolic footprint analysis. The urine was collected daily and analyzed by 1H NMR. Generated data were statistically treated by Principal Component Analysis in order to detect patterns among the distinct periods evaluated as well as biomarkers responsible for its distinction. RESULTS: It was observed on treatment group that cortisol, biomarker related to physiological stress was reduced, indicating anxiolytic-like effect of riparin III, probably through activation of 5-HT2A receptors, which was corroborated by behavioral tests. CONCLUSION: 1H NMR urine metabolic footprint combined with multivariate data analysis have demonstrated to be an important diagnostic tool to prove the anxiolytic-like effect of riparin III in a more efficient and pragmatic way. PMID: 32416725 [PubMed - as supplied by publisher]

Related Articles A simple and rapid LC-MS/MS method for the simultaneous determination of eight antipsychotics in human serum, and its application to therapeutic drug monitoring. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Apr 29;1147:122129 Authors: Cao Y, Zhao F, Chen J, Huang T, Zeng J, Wang L, Sun X, Miao Y, Wang S, Chen C Abstract A simple and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and used to determine eight antipsychotics (aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) in human serum for practical clinical usage. Stable isotope-labeled internal standards were used for all drugs to compensate for method variability, including matrix effects, ion extraction and ionization variations. Samples were prepared by simple protein precipitation with methanol. Chromatographic separation was accomplished in less than 3.3 min on a KINTEX C18 column (50 mm × 3.0 mm, 5 μm) using a gradient elution of 2 mM aqueous ammonium formate and methanol at a flow rate of 0.5 mL/min. Quantification was performed by multiple reaction monitoring (MRM) in the positive mode. The method was fully validated according to the latest recommendations of international guidelines. The correlation coefficients of calibration curves were all greater than 0.9945. Internal standard-normalized matrix effects ranged from 96.3% to 115%, and extraction recoveries were between 88.1% and 107%. Coefficients of variation ranged from 1.82 - 13.5% for intra-day precision, 5.69-14.7% for inter-day precision, and the relative error for accuracy did not exceed ± 13.5% for any analyte. The method was successfully applied to routine clinical therapeutic drug monitoring for 2,173 samples. PMID: 32416590 [PubMed - as supplied by publisher]

Related Articles Metabolomics analyses to characterize metabolic alterations in Korean native calves by oral vitamin A supplementation. Sci Rep. 2020 May 15;10(1):8092 Authors: Peng DQ, Kim SJ, Lee HG Abstract Previous studies have reported that vitamin A administration in the birth stage of calves could promote preadipocyte and muscle development. However, the metabolic change after vitamin A administration remains unknown. Thus, the objective of this study was to perform metabonomics analyses to investigate the effect of vitamin A in Korean native calves. Ten newborn calves (initial average body weight: 30.4 kg [SD 2.20]) were randomly divided into two groups treated with or without vitamin A supplementation (0 IU vs. 25,000 IU vitamin A/day) for two months until weaning. Metabolic changes in the serum and longissimus dorsi muscle of calves were investigated using GC-TOF-MS and multivariate statistical analysis. As a result, ten metabolic parameters in the serum and seven metabolic parameters in the longissimus dorsi muscle were down-regulated in the vitamin A treatment group compared to those in the control group (VIP value > 1.0, p < 0.05). Both serum and longissimus dorsi muscle showed lower levels of cholesterol and myo-inositol in the vitamin A treatment group than in the control group (p < 0.05). These results indicate that vitamin A supplementation in the early growth period of calf could maintain the preadipocyte status, which can contribute to future adipogenesis in the intramuscular fat production of Korean native cattle. PMID: 32415141 [PubMed - as supplied by publisher]

Related Articles Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal. Nat Commun. 2020 May 15;11(1):2420 Authors: Lau KX, Mason EA, Kie J, De Souza DP, Kloehn J, Tull D, McConville MJ, Keniry A, Beck T, Blewitt ME, Ritchie ME, Naik SH, Zalcenstein D, Korn O, Su S, Romero IG, Spruce C, Baker CL, McGarr TC, Wells CA, Pera MF Abstract Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells. PMID: 32415101 [PubMed - as supplied by publisher]

Related Articles Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR -21-Peli1-c-Rel Pathway Prevents Autoimmunity. J Immunol. 2020 May 15;: Authors: Qiu R, Yu X, Wang L, Han Z, Yao C, Cui Y, Hou G, Dai D, Jin W, Shen N Abstract It is well known that some pathogenic cells have enhanced glycolysis; the regulatory network leading to increased glycolysis are not well characterized. In this study, we show that CNS-infiltrated pathogenic TH17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal TH17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic TH17 cells are highly glycolytic compared with nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo that show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-κB binding sites. Mechanistic studies reveal that miR-21 targets the E3 ubiquitin ligase Peli1-c-Rel pathway to promote glucose metabolism of pathogenic TH17 cells. Therapeutic targeting c-Rel-mediated glycolysis in pathogenic TH17 cells represses autoimmune diseases. These findings extend our understanding of the regulation TH17 cell glycolysis in vivo and provide insights for future therapeutic intervention to TH17 cell-mediated autoimmune diseases. PMID: 32414810 [PubMed - as supplied by publisher]