Project description:1,2‑Dichlorobenzene (1,2‑DCB) is a chlorinated aromatic hydrocarbon that is widely used in industrial applications, including as a solvent for waxes, resins, and paints, and it serves as an ingredient in the production of disinfectants and deodorants. 1,4‑Dichlorobenzene (1,4‑DCB) is a chlorinated aromatic hydrocarbon that is used in various industrial and household applications, including as a fumigant for moth control, a deodorizer in urinal cakes, and an air freshener in domestic and public settings. Short-term in vivo transcriptomic studies were used to assess the biological potency of 1,2‑DCB and 1,4-DCB. The data from these studies are intended to support risk assessment and establishment of acceptable exposure levels of 1,2‑DCB and 1,4‑DCB in environmental and occupational settings.
Project description:1,2‑Dichlorobenzene (1,2‑DCB) is a chlorinated aromatic hydrocarbon that is widely used in industrial applications, including as a solvent for waxes, resins, and paints, and it serves as an ingredient in the production of disinfectants and deodorants. 1,4‑Dichlorobenzene (1,4‑DCB) is a chlorinated aromatic hydrocarbon that is used in various industrial and household applications, including as a fumigant for moth control, a deodorizer in urinal cakes, and an air freshener in domestic and public settings. Short-term in vivo transcriptomic studies were used to assess the biological potency of 1,2‑DCB and 1,4-DCB. The data from these studies are intended to support risk assessment and establishment of acceptable exposure levels of 1,2‑DCB and 1,4-DCB in environmental and occupational settings.
Project description:In this study we performed MeRIP-Seq to study N6-methyl adenosine (m6A) and and N6,2′ -O-dimethyladenosine (m6Am) modification of mRNA. We investigated the effect of the microbiota on the transcriptome and epitranscriptomic modifications in murine liver and cecum. We compared m6A/m modification profiles in cecum of conventionally raised (CONV) and germ-free (GF) mice. We additionally included GF mice colonised with the flora of CONV mice for four weeks (ex-GF), for which show that they exhibit similar patterns of the most abundant genera of gut bacteria as CONV mice. We added mice treated with several antibiotics to deplete the gut flora (abx)and vancomycin treated mice in which the genera Akkermansia, Escherichia/Shigella and Lactobacillus were enriched. Furthermore, we included GF mice colonised with the commensal bacterium Akkermansia muciniphila (Am), Lactobacillus plantarum (Lp) and Escherichia coli Nissle (Ec) and analysed their m6A/m modification profiles. In addition, we analysed changes in m6A/m- modified liver RNA for CONV, GF, and Am, Lp and Ec mice.
Project description:There are 10 mice in the experiment, named REC. The mice were fed with high salt diets (5% NaCl) for 4 weeks and then fed with normal salt diets for 4 weeks. Then extracted DNA from mice gastric flora to detect changes in the gastric flora of mice.
Project description:Constant availability of food can contribute to the pathogenesis of metabolic syndrome and type 2 diabetes. Short term intermittent fasting (IF) can reset the central, light-entrained (suprachiastmatic nucleus) clock and also the peripheral, food-entrained (liver) clock to restore metabolic homeostasis in T2D. We asked if long term IF could prevent development of diabetic retinopathy (DR) in a type 2 diabetes model, the db/db mouse. After 7 months, IF corrected diabetes-induced increases in triglycerides, cholesteryl esters and diglycerides. IF protocol in db/db mice also prevented development of DR. In addition, host frequency and time of food intake affected the gut microbiome composition. IF led to decreased levels of Clostridiales and Akkermansia muciniphila in db/db mice and these changes in flora were accompanied by increased gut mucin, goblet cell number and villus length. Increased levels of Firmicutes in db/db mice on IF supported improved bile acid metabolism. To confirm that the restoration of bile acid function could contribute to the beneficial effects induced by IF on DR, the dual FXR/TGR-5 agonist INT-767 was administered to a second diabetes model, DBA2J mice injected with streptozotocin (STZ) and placed on Western diet (WD). In this model, INT-767 prevented development of DR. These findings support the concept that long-term IF mediates multiple beneficial effect by restoring the gut-liver axis homeostasis.
Project description:1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, we performed chronic and short-term dosing studies in female BDF-1 mice to explore the toxic effects of 1,4-DX. Histopathology studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Mice were exposed to various concentrations of 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks. Immunohistochemical analysis of the liver revealed an increase in the number of H2AXγ-positive hepatocytes (a marker of DNA double strand breaks) in mice exposed to 5,000 mg/L 1,4-DX for one and four weeks. In addition, an expansion of precholangiocytes was observed after four weeks of 5,000 mg/L 1,4-DX exposure, as reflected by CK-7 immunostaining. An increase in these markers reflect both DNA damage and repair mechanisms. Liver transcriptomics profiling showed that exposure to 5,000 mg/L 1,4-DX for four weeks resulted in the differential expression of 65 genes compared to controls. Pathway analysis of the transcriptomic data revealed 1,4-DX-induced perturbations in multiple signaling pathways in the liver, including those involved in xenobiotic metabolism, nicotine degradation and glutathione-mediated detoxification. Changes to these pathways as a result of 1,4-DX exposure reflect would be predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, stool and urine metabolomics profiling revealed no effect of 5,000 mg/L 1,4-DX exposure for one or four weeks on metabolites. We speculate that this may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death, but have activated the repair systems in response to 1,4-DX exposure