Effectiveness of selenium in maintaining morphological architecture of prostatic compartments in mongolian gerbil

Male prostate is a reproductive gland that is under steroid hormones influence, which is object of several studies related to proliferative lesions that may arise during the aging process. Selenium is a micro-nutrient that has been described as a toxic mineral if administered at high concentrations but can also be beneficial mineral exerting a protective action on various tissues used properly. This mineral can be found in some foods such as Brazil nuts, grains, cereals and some vegetables. Mongolian gerbil prostate have morphophysiological similarities between the human prostate and has been used for comparative studies. This work aims to analyze the morphology and stereology of Mongolian gerbil prostate after selenium supplementation, followed by testosterone injection. Animals were divided into 3 groups (5 per group): GC intact animals; TG testosterone injection (1 mg/kg) for 21 days; TSG, selenium administration and testosterone injection (1 mg/kg) for 21 days. After experimental phase, animals were euthanized and prostate was dissected, fixed in metacarn, embedded, and sections were stained with hematoxylin-eosin (HE) for morphological and morphometric/stereological analyses. Analyzes showed that prostate epithelium of TG showed points of stratification and higher columnar cells when compared to CG and TSG. Already stereological analysis showed that the volume of epithelium in TG and TSG was higher than in CG. Besides, non-muscular volume of TG stroma showed higher than in TSG and CG. In conclusion, selenium is, in this concentration, an important factor that acts in maintenance of prostate morphology, even under the influence of exogenous testosterone

Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling

Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular eventsand this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fed Univ Sao Paulo UNIFESP, Postgrad Struct & Funct Biol, BR-04023900 Sao Paulo, SP, BrazilSao Paulo State Univ UNESP, Dept Biol, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ UNESP, Inst Biociencias Letras & Ciencias Exatas, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilUCL, Northwick Pk Inst Med Res, Dept Surg Res, London HA1 3UJ, Middx, EnglandPost-Graduation in Structural and Functional Biology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, 04023-900, BrazilFAPESP: 2012/21603-2FAPESP: 2012/13041-4FAPESP: 2014/18557-4CNPq: 308144/2014-7CNPq: 245859/2012-8Web of Scienc

The essential role of annexin A1 mimetic peptide in the skin allograft survival

Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection. Studies have demonstrated the anti-inflammatory effects of the annexin A1 (AnxA1) in the regulation of transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograft model was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Mice were used for the skin allograft model and pharmacological treatments were carried out using either the AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3days before surgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expression of AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26 increased skin allograft survival related with inhibition of neutrophil transmigration and induction of apoptosis, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1 and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, the combination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared with the cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigations in vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphorylation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role in augmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration and enhancement of apoptosis. This effect may lead to the development of new therapeutic approaches relevant to transplant rejection. Copyright (c) 2013 John Wiley & Sons, Ltd.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPqFundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESPFed Univ Sao Paulo UNIFESP, Postgrad Struct & Funct Biol, Sao Paulo, BrazilUCL, Northwick Pk Inst Med Res, Dept Surg Res, London, EnglandSao Paulo State Univ UNESP, Inst Biociencias Letras & Ciencias Exatas IBILCE, Dept Biol, Sao Jose Do Rio Preto, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Struct & Funct Biol, Sao Paulo, BrazilCNPq: 302768/2010-6CNPq: 132871/2007-6FAPESP: 2012/13041-4Web of Scienc

The essential role of annexin A1 mimetic peptide in the skin allograft survival

Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection.Studies have demonstrated the anti-infl ammatory effects of the annexin A1 (AnxA1) in the regulationof transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograftmodel was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Micewere used for the skin allograft model and pharmacological treatments were carried out using eitherthe AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3 days beforesurgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expressionof AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26increased skin allograft survival related with inhibition of neutrophil transmigration and inductionof apoptos is, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, thecombination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared withthe cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigationsin vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphory-lation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role inaugmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration andenhancement of apoptosis. This effect may lead to the development of new therapeutic approachesrelevant to transplant rejection