Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
Project description:Age and parity are well-known factors that influence breast cancer development (1-3). Epidemiological studies have shown that women who have had multiple pregnancies are at a lower risk of developing breast cancer than women who have no history of pregnancy (4, 5). However, mechanisms that link parity and cancer protection are unclear. We discovered that CD8+ T cells with a tissue-resident memory (TRM) phenotype enriched in the mammary glands of parous women and mice compared to their virgin counterparts. Developmental kinetics revealed that these cells seeded the mammary gland during early gestation but persisted post lactation and was specific to the mammary glands. While these CD8 T cells expressed the TRM specific transcription factor Hobit, single cell transcriptomics revealed expansion of transcriptionally distinct canonical and non-canonical TRM populations, including a novel Hobit+ innate T cells (ITCs) in the parous mammary gland compared to their virgin counterparts. Furthermore, imaging analysis uncovered that the TRM like cells were associated with mammary epithelial cells and impairment in mammary gland branching during pregnancy significantly affected their differentiation or population expansion. In keeping with their association with mammary epithelial cells, all TRM subsets, including the Hobit+ITCs commonly required the cytokines TGF-β and IL-15 for their differentiation. Notably, depletion of CD103+ T cells exacerbated tumour growth in parous mice and lineage tracing experiments revealed that the canonical TRM like cells switched to an effector phenotype in tumours and contributed to tumour control. Together, we show for the first time that parity induces novel and heterogenous TRM like populations in the mammary gland that are central in providing protection against breast cancer.
Project description:Early full-term pregnancy affords lifetime protection against development of breast cancer. Parity-induced protection can be reproduced in a carcinogen-induced rat mammary carcinoma model. The molecular mechanisms of parity-induced protection against carcinogenic stimuli in rat mammary glands have not been fully characterized. In order to gain a better understanding of these molecular mechanisms, we performed gene expression analyses in parous and age-matched virgin (AMV) mammary glands of Lewis rats before and after carcinogen (N-methyl-N-nitrosourea; MNU) treatment. Keywords: other
Project description:Early full-term pregnancy affords lifetime protection against development of breast cancer. Parity-induced protection can be reproduced in a carcinogen-induced rat mammary carcinoma model. The molecular mechanisms of parity-induced protection against carcinogenic stimuli in rat mammary glands have not been fully characterized. In order to gain a better understanding of these molecular mechanisms, we performed gene expression analyses in parous and age-matched virgin (AMV) mammary glands of Lewis rats before and after carcinogen (N-methyl-N-nitrosourea; MNU) treatment.
Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
2023-07-26 | PXD044099 |
Project description:Parity-induced changes to mammary epithelial cells control NKT-like cell expansion and mammary oncogenesis