The rhythms of histones in regeneration: The epigenetic modifications determined by clock genes.

The evolutionary establishment of an internal biological clock is a primordial event tightly associated with a 24-h period. Changes in the circadian rhythm can affect cellular functions, including proliferation, DNA repair and redox state. Even isolated organs, tissues and cells can maintain an autonomous circadian rhythm. These cell-autonomous molecular mechanisms are driven by intracellular clock genes, such as BMAL1. Little is known about the role of core clock genes and epigenetic modifications in the skin. Our focus was to identify BMAL1-driven epigenetic modifications associated with gene transcription by mapping the acetylation landscape of histones in epithelial cells responding to injury. We explored the role of BMAL1 in epidermal wound and tissue regeneration using a loss-of-function approach in vivo. We worked with BMAL1 knockout mice and a contraction-resistance wound healing protocol, determining the histone modifications using specific antibodies to detect the acetylation levels of histones H3 and H4. We found significant differences in the acetylation levels of histones in both homeostatic and injured skin with deregulated BMAL1. The intact skin displayed varied acetylation levels of histones H3 and H4, including hyperacetylation of H3 Lys 9 (H3K9). The most pronounced changes were observed at the repair site, with notable alterations in the acetylation pattern of histone H4. These findings reveal the importance of histone modifications in response to injury and indicate that modulation of BMAL1 and its associated epigenetic events could be therapeutically harnessed to improve skin regeneration.

Immunoexpression of Th17-related cytokines in oral lichen planus.

A recently described lineage of lymphocytes, Th17 cells, has been associated with inflammatory and autoimmune diseases. The aim of this article was to assess the immunoexpression of cytokines related to this lineage, interleukin-17 (IL-17) and IL-23 and in reticular and erosive oral lichen planus (OLP). The sample included 41 cases of OLP (23 reticular and 18 erosive) and 10 cases of inflammatory fibrous hyperplasia (IFH). Lymphocytes exhibiting cytoplasmic immunostaining were counted. Epithelial immunostaining was also evaluated. There was no statistical differences in the number of IL-17 and IL-23 lymphocytes between the OLP (55.40 and 48.40, respectively) and IFH (39.30 and 44.40, respectively). A significantly higher number of IL-23 lymphocytes was found in erosive OLP group (63.80) when compared with reticular (41.40) and IFH lesions (44.40) (P=0.019). Furthermore, epithelial immunopositivity for IL-17 and IL-23 was higher in OLP lesions than in IFH (P=0.012 and P=0.011, respectively). A significantly higher number of IL-23 lymphocytes in erosive OLP and the strong epithelial immunopositivity for IL-23 and IL-17 in OLP group could suggest an important participation of TCD4 Th17 response in this disorder.

Significance of galectins-1, -3, -4 and -7 in the progression of squamous cell carcinoma of the tongue.

The aim of this study was to analyze the immunohistochemical expression of galectins-1, -3, -4, and -7 in 65 cases of squamous cell carcinoma of the tongue and to correlate this expression with clinical (disease outcome, metastasis, and clinical stage) and morphological parameters (histological grade of malignancy). Clinical data were obtained from the patient records. The histological grading system of malignancy proposed by Bryne (1998) [9] was used for the analysis of morphological parameters. The results were analyzed statistically by χ(2) test (p < 0.05). Galectin-1 expression was observed in 87.7% of cases and was significantly correlated with metastasis (p = 0.033) and clinical stage (p = 0.016). Immunoexpression of galectin-3 was observed in 87.7% of cases and was correlated with the presence of metastasis (p = 0.033) and histological grade of malignancy (p = 0.031). Galectin-4 showed no significant correlation with any of the parameters studied. Expression of galectin-7 was observed in 73.8% of cases and was significantly correlated with the histological grade of malignancy (p = 0.005). In conclusion, the intense immunoexpression of galectins-1, -3, and -7 suggests the participation of these proteins in oral carcinogenesis and their use as markers of biological behavior and tumor progression in squamous cell carcinoma of the tongue.