100 research outputs found

    Nitinol Carbofilm coated stents for peripheral applications: Study in the porcine model

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    Testing the safety and foreign body reaction (FBR) of a nitinol self-expandable carbon-coated stent system in the porcine animal model at different follow-up (FU) periods. Methods: Fifteen minipigs received 30 carbon-coated self-expandable nitinol stents in iliac arteries. Explants were carried out at 7 (3 animals), 30 (4 animals), 90 (4 animals) and 180 (4 animals) day FU, for evaluation of acute, sub-acute and chronic biological response to the implanted devices. Histological, immunohistochemical, histomorphometric and scanning electron microscopy (SEM) analyses were performed to assess inflammatory reaction, endothelialization process, neointimal growth and cellular composition. Results: Thirty stents were successfully implanted. No mural thrombi were observed at gross examination or by angiography. Histologically no significant inflammatory reaction was detected: the stents appeared covered by a thin monolayer of endothelial cells even at 7 day FU. The neointima presented homogeneous growth and moderate thickness after 30, 90 and 180 days explants (0.38 +/- 0.36 mm, 0.33 +/- 0.30 mm, 0.27 +/- 0.25 mm respectively). Internal and external elastic laminae were intact in 95% of stented arteries. Histological data validations of vessel endothelialization was obtained with SEM for the seven day follow-up group. Conclusions: This study showed good remarkable technical performances, minimal FBR and biocompatibility comparable with other available pre-clinical experimentations

    Structure based modeling of small molecules binding to the TLR7 by atomistic level simulations

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    Toll-Like Receptors (TLR) are a large family of proteins involved in the immune system response. Both the activation and the inhibition of these receptors can have positive effects on several diseases, including viral pathologies and cancer, therefore prompting the development of new compounds. In order to provide new indications for the design of Toll-Like Receptor 7 (TLR7)-targeting drugs, the mechanism of interaction between the TLR7 and two important classes of agonists (imidazoquinoline and adenine derivatives) was investigated through docking and Molecular Dynamics simulations. To perform the computational analysis, a new model for the dimeric form of the receptors was necessary and therefore created. Qualitative and quantitative differences between agonists and inactive compounds were determined. The in silico results were compared with previous experimental observations and employed to define the ligand binding mechanism of TLR7

    Anti-alpha enolase multi-antibody specificity in human diseases. Clinical significance and molecular mechanisms

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    Alpha-enolase (Eno) is an ubiquitary glycolytic enzyme playing multiple functions that go well beyond its principal metabolic role of energy supplier during glycolysis. Eno is localized in the cytoplasm, but also expressed on the cell membrane, where it binds plasminogen allowing its activation. Its shorter form, in the nucleus, acts as transcription factor. In inflammatory conditions, Eno undergoes post-translational modifications, such as citrullination, oxidation and phosphorylation. Eno is also an autoantigen in different disorders. In fact, autoantibodies to Eno have been detected in rheumatoid arthritis, lupus nephritis, primary glomerulonephritis, cancer, infections and other disorders, and in many cases they represent specific markers to be utilized in clinical practice. Anti-Eno antibodies in the different clinical conditions are not equal: they differ in isotype and often recognize different epitopes on the enzyme. IgG1 and IgG3 are prevalent in Rheumatoid Arthritis, IgG2 in Lupus nephritis and IgG4 in primary autoimmune glomerulopathy. This review analyzes the characteristics of anti-Eno autoantibodies in autoimmune disorders and cancer, describing their fine specificity and isotype restriction. The post-translational modifications that are target of autoantibodies are also discussed, as they represent the basis for elucidating the molecular mechanisms responsible for epitope generation. Despite an impressive amount of experimental work on anti-Eno antibodies, it is still necessary to validate the use of anti-Eno antibodies as biomarkers of selected diseases and extend the knowledge on the mechanisms of anti-Eno autoantibody production. Strategies that downmodulate the immune response to Eno may represent in the future novel approaches in the treatment of autoimmune disorders
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