Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU’s occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9–7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.

© 2018 Media Sphera Publishing Group. All rights reserved. In-depth study of the function and structure of the lymphoid tissue of the gastrointestinal tract and respiratory tract opens wide opportunities for the use of mucosal vaccines to improve immunity to various infectious agents. One such drug is The immunovac-VP4 vaccine containing pathogen-associated molecular structures (PAMSs) of microorganisms. They are the antigens of Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus. Discovered in many studies and experiments, the ability of the vaccine to induce innate immunity provides opportunities for prevention and treatment of both infections and allergic diseases, because it promotes the switching of Th2 immune response to Th1. The aim of the study was to study the effectiveness of the complex use of bacterial therapeutic vaccine Immunovac-VP4 and allergen-specific immune therapy (ASIT) in pollinosis in children and adults. Materials and methods. Bacterial therapeutic vaccine Immunovac-VP4 was used annually, nasal and oral administration in patients before the course of ASIT standardized aqueous-salt solutions of allergens. Results. The therapeutic application of bacterial vaccines, Immunoac-ÂÏ4 before the course ASIT has helped to reduce the frequency of acute respiratory infections in 8,5 times in comparison with the control group. Clinical efficacy of complex treatment according to the results of the survey of patients in 7 years after the start of therapy was 90%. There was a significant decrease In IgG4 to causally significant allergens, General immnunoglobulin E (IgE) and a tendency to decrease IgE. Conclusion. The use of bacterial therapeutic vaccine Immunovac-VP4, which is a natural ligand of toll-like receptors in combination with ASIT, seems to be an effective and promising direction in the treatment of allergic diseases.