Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.

This study aimed to analyze the effects of the quercetin (100 mg/kg), 1% glutamine and 1% α-tocopherol antioxidants in the myocardium of rats with streptozotocin-induced diabetes mellitus. Twenty male rats were subdivided into four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants); and DT (diabetic treated with antioxidants) treated for 60 days. Clinical parameters, oxidative stress markers, inflammatory cytokines, myocardial collagen fibers and immunoexpression of superoxide dismutase 1 (SOD-1), glutathione peroxidase-1 (GPx-1), interleukin-1ß (IL-1-ß), transforming growth factor-beta (TGF-ß), and fibroblast growth factor-2 (FGF-2) were evaluated. Results showed reduced body weight, hyperphagia, polydipsia and hyperglycemic state in groups D and DT. The levels of glutathione (GSH) were higher in NT and DT compared to N (p < 0.01) and D (p < 0.001) groups, respectively. Greater GSH levels were found in DT when compared to N animals (p < 0.001). In DT, there was an increase in IL-10 in relation to N, D and NT (p < 0.05), while GPx-1 expression was similar to N and lower compared to D (p < 0.001). TGF-ß expression in DT was greater than N (p < 0.001) group, whereas FGF-2 in DT was higher than in the other groups (p < 0.001). A significant reduction in collagen fibers (type I) was found in DT compared to D (p < 0.05). The associated administration of quercetin, glutamine and α-tocopherol increased the levels of circulating interleukin-10 (IL-10) and GSH, and reduced the number of type I collagen fibers. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.

Crude extract from Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz leaves decreased intra articular inflammation induced by zymosan in rats.

BACKGROUND: Libidibia ferrea (L. ferrea) has been used in folk medicine to treat several conditions and to prevent cancer. This study performed a chromatographic analysis of the crude aqueous extract of Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz (LfAE) leaves and evaluated its in vivo antioxidant and anti-inflammatory potential. METHODS: Polyphenols present in LfAE were characterized by high performance liquid chromatography (HPLC). Anti-inflammatory activity was studied in an experimental model of zymosan-induced intra-articular inflammation, conducted in Wistar rats treated with LfAE at the doses of 100, 200 and 300 mg/kg by gavage. Synovial fluid was collected for global leukocyte count, for spectrocopical UV/VIS analysis of myeloperoxidase (MPO) activity, total glutathione and malondialdehyde (MDA), and for quantification of inflammatory cytokines IL1-ß and TNF-α by enzyme-linked immunosorbent assay. Synovial membrane was collected for histological analysis. The level of statistical significance was p < 0.05. RESULTS: HPLC detected concentrations of 1.56 (0.77) %m/m for ellagic acid and 1.20 (1.38) %m/m for gallic acid in LfAE leaves. Treatment with LfAE at all doses significantly decreased the leukocyte influx into the synovial fluid (p < 0.001) and myeloperoxidase activity (p < 0.001), an important marker of neutrophils. LfAE at doses of 100 (p < 0.05), 200 and 300 mg/kg (p < 0.001) also reduced the levels of MDA. LfAE at doses of 200 and 300 mg/kg significantly decreased the levels of IL-1ß (p < 0.05) and TNF-α (p < 0.001). All doses of LfAE resulted in increased levels of total glutathione (p < 0.001). Histopathological findings confirmed a reduction of the inflammatory infiltrate in the rats treated with LfAE at a dose of 200 mg/kg (p < 0.05). CONCLUSION: LfAE has an important anti-oxidant and anti-inflammatory effect on intra-articular inflammation.

Oct-4 and CD44 in epithelial stem cells like of benign odontogenic lesions.

Benign epithelial odontogenic lesions are great clinical importance entities that develop in the jaws from the tissues that form teeth. It has been shown that benign and malignant tumors are present in a large number of tumor stem cells, which has great implications in the development of these lesions. Oct-4 and CD44 have been demonstrated as important markers for tumoral stem cells. The aim of this study was investigate the presence of stem cell markers Oct-4 and CD44 in benign epithelial odontogenic lesions. Twenty odontogenic keratocysts (OKC), 20 ameloblastomas (AMB) of the solid/multicystic type and 20 adenomatoid odontogenic tumors (AOT) were retrospectively analyzed for immunohistochemical detection of Oct-4 and CD44 in their epithelial component. All cases were positive for the two markers, with the majority exhibiting a high expression. Analysis of the expression of Oct-4 revealed no statistically significant differences (p = 0.406) between the lesions studied. Regarding CD44, there was a significant difference between the cases of AMB and AOT in relation with OKC, with the latter presenting a greater labelling (p = 0.034). No statistically significant correlation between Oct-4 and CD44 was observed in the lesions. In our findings, the presence of stem cell-like phenotype at various sites of the epithelial component of the odontogenic lesions was identified, suggesting its possible participation in histogenesis and differentiation without, however, exerting influence on the aggressiveness of the lesions.

Tumor-associated immune aggregates in oral cancer: Their cellular composition and potential prognostic significance.

There is growing evidence supporting the importance of immune microenvironment in cancer development and progression, especially with the rapid development of immunotherapy. Presence of immune cell aggregates in solid tumors has been associated with clinical outcomes, but little is known about the immune microenvironment in oral squamous cell carcinoma (OSCC), which has high morbidity and mortality. Based on our preliminary observation, we hypothesize that there is the presence of tumor-associated immune aggregates (TaIAs) during oral cancer development. Adapting to the dynamic change of the composition of cellular membership and co-evolving with the tumor at invasion fronts, these TaIAs, either pro-inflammatory or immune suppressive, are associated with clinical consequences. With the unique access to a set of prospectively collected, highly annotated OSCC surgical samples and the use of multi-color immunostaining of key immune cells, the confirmation of our hypothesis may shed light of the underlying biology related to OSCC and the knowledge learned can potentially be used to identify prognostic markers, response predictive markers for immunotherapies, as well as novel therapeutic targets.

Hyaline ring granuloma of vegetable: Report of two cases with histochemical and immunohistochemical study.

BACKGROUND: Peripheral hyaline ring granuloma is a rare lesion characterized by the presence of hyaline rings and multinucleated giant cells. Its pathogenesis is related to exogenous factors such as vegetal origin, resulting in foreign body reaction mediated by macrophages against cellulose particles. We report two cases: a 58-year-old male with a lesion in the maxillary alveolar mucosa measuring 1.0cm×1.0cm; and a 50-year-old female presenting a slight swelling in the alveolar mucosa, measuring 0.7cm×0.7cm and diagnosed as asymptomatic sessile nodule of fibrous consistency. Microscopic examination revealed a dense connective tissue with focal area of concentric hyaline collagen deposition and multinucleated giant cell granulomas of foreign body type. Immunohistochemical study was positive for anti-CD68/anti-α-SMA, confirming the foreign body reaction and vascular integrity. Histochemical analysis for PAS with and without diastase and van Gieson highlighted the vegetable exogenous origin of foreign material. Additionally, we performed a review of 7 cases published in the literature in the last 10 years.

Relationship between the epithelial expression of hMLH1, MDM2, and p63 and lower lip carcinogenesis.

OBJECTIVES: To evaluate the relationship between the epithelial expression of hMLH1, MDM2, and p63 in lower lip carcinogenesis, comparing the immunostaining of these proteins in cases of actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC). STUDY DESIGN: Forty cases of AC and 40 cases of SCC were studied, both lesions were of lower lip. Histological sections of 3 µm were submitted to immunoperoxidase method, and 1000 cells were counted for immunohistochemical analysis of lesions. The results were analyzed quantitatively, and expression was compared by the Mann-Whitney, Student t-test, or one-way ANOVA, adopting a level of significance of 5%. RESULTS: A higher percentage of epithelial cells expressing hMLH1 was observed in cases of AC without dysplasia or mild dysplasia (721.23 ± 88.116), whereas fewer positive cells were observed in lower lip SSCs (255.03 ± 199.47) when compared to the AC group (P < 0.001). Immunoexpression of MDM2 was higher in SCCs of the lower lip compared with AC (P = 0.019). For p63 protein, the expression was higher in AC than in SCC (P = 0.045). CONCLUSION: The present results showed changes in the immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant and malignant lip disease, supporting the hypothesis that these alterations are related to the process of lower lip carcinogenesis.