Aberrant expression of some tumour suppressor genes and oncogenes by thymocytes had been involved in the development of primary thymic lymphomas induced by gamma-irradiation, but genetic alterations affecting critical genes expressed by stromal cells have not been yet explored. This paper analyzes a series of such tumours induced in C57BL/6J and in F1 hybrids of BALB/c and C57BL/6J mouse strains. As expected, hystopathological analyses revealed profound disorganizations within the thymus with a poor demarcation of the cortical and medullar areas. Immunological and quantitative on-line RT-PCR analyses confirm that E-cadherin (Cdh1) is essentially expressed by stromal cells of the thymus, while evidencing that the expression of this gene is significantly reduced in all tumours. In addition, and contrary to what one would expect, N-cadherin (Cdh2) that is exclusively expressed by stromal cells is likewise down-regulated in most of the thymic lymphomas. Although hypermethylation of the promoter region appears to be involved in the inactivation of Cdh2 in all tumours, additional epigenetic mechanisms mediated by repressors such as Snai1 may also play a role in Cdh1 silencing. These results represent the first reported case for tumour-associated gene alterations occurring not in the tumour cells per se, but in the stromal cells of primary thymic lymphomas. Additionally, since the expression of both genes is significantly up-regulated after a single high dose of gamma-radiation, but remained unchanged in treated thymic-lymphoma-free-mice, epigenetic down-regulation of E- and N-cadherin appears to occur concomitantly with the progression towards the most advanced stages of gamma-radiation-induced thymic lymphomas.
Atopic dermatitis is classified as a chronic inflammatory skin disease, which is characterized by alterations in barrier function and immune system of the skin. In a previous study, the efficacy of REPAVAR ATOPIC SKIN BODY CREAM EXTREME (a product containing "SKIN CALM COMPLEX") on the epidermal barrier structure was demonstrated. However, the product has also been formulated to improve inflammation and itching. The aim of this study is to analyze product effectiveness on skin inflammation and itching which is associated with atopic dermatitis, by quantification of IL-1α and IL-8 interleukins secreted by human keratinocytes from reconstructed epidermis by ELISA assay. Mature (aged 17 days) sample tissues were treated with pro-inflammatory agents (PBS 1X and LPS) and with the product containing synergistic mix from plants extracts and Dihydroavenanthramide D, among other ingredients ("SKIN CALM COMPLEX") for 24 hours. Measuring the amounts of interleukins by ELISA assay showed 1) decreased levels of IL-1α and 2) no differences about IL-8 secretion. Product REPAVAR ATOPIC SKIN BODY CREAM EXTREME has an antiinflammatory effect on the release of pro-inflammatory cytokines, becoming an effective preventive agent on inflammation and itching due to maintenance and improvement of the keratinocyte epidermal structure.
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