Молекулярный докинг лигандов перспективных для сорбции IgG из биологических жидкостей

Hyperproduction of immunoglobulin G (IgG) is a major pathogenic factor in autoimmune diseases. Specific sorbents are used to eliminate the high level of IgG. Molecular docking can be used as a tool for theoretical search for sorbent ligands for the IgG removal from biological fluids. Using docking, modeling of amino acid interactions with IgG ligands was performed. Based on the docking results, active amino acids were identified and possible combinations of them were proposed for the creation of diand tripeptide sequences. As a result, aromatic amino acids (Tyr, Trp, Phe), di-and tripeptides based on them (Trp-DTyr, Phe-DTyr, Trp-Phe-DTyr, Phe-Trp-DTyr) were found to have high activity for IgG proteins, and three peptides (Trp-Phe-DTyr, Phe-Trp-DTyr) not only show high activity to total IgG, but can also be divided in their activity relative to subclasses of class G immunoglobulins.Гиперпродукция иммуноглобулинов класса G (IgG) является основным патогенным фактором при аутоиммунных заболеваниях. Для устранения высокого уровня иммуноглобулинов класса G применяются специфические сорбенты. В качестве инструмента для теоретического поиска лигандов сорбентов для удаления IgG из биологических жидкостей может применяться молекулярный докинг. С помощью докинга проведено моделирование взаимодействий аминокислот с IgG. Исходя из результатов докинга, были выявлены активные аминокислоты и предложены возможные комбинации из них для создания дии трипептидных последовательностей. В результате расчетов было выявлено, что лучшими по энергии взаимодействия в ряду аминокислот обладают ароматические аминокислоты (Tyr, Trp, Phe), созданные на их основе дии трипептиды (Trp-DTyr, Phe-DTyr, Trp-Phe-DTyr, Phe-Trp-DTyr) имеют высокую энергию связывания к белкам IgG, а трипептиды (Trp-Phe-DTyr, Phe-Trp-DTyr) не только демонстрируют высокую энергию взаимодействия с общим IgG, но и могут быть разделены в своей активности относительно подклассов иммуноглобулинов класса G

Spatial and temporal variation in Arctic freshwater chemistry—Reflecting climate-induced landscape alterations and a changing template for biodiversity

Freshwater chemistry across the circumpolar region was characterised using a pan-Arctic data set from 1,032 lake and 482 river stations. Temporal trends were estimated for Early (1970-1985), Middle (1986-2000), and Late (2001-2015) periods. Spatial patterns were assessed using data collected since 2001.Alkalinity, pH, conductivity, sulfate, chloride, sodium, calcium, and magnesium (major ions) were generally higher in the northern-most Arctic regions than in the Near Arctic (southern-most) region. In particular, spatial patterns in pH, alkalinity, calcium, and magnesium appeared to reflect underlying geology, with more alkaline waters in the High Arctic and Sub Arctic, where sedimentary bedrock dominated.Carbon and nutrients displayed latitudinal trends, with lower levels of dissolved organic carbon (DOC), total nitrogen, and (to a lesser extent) total phosphorus (TP) in the High and Low Arctic than at lower latitudes. Significantly higher nutrient levels were observed in systems impacted by permafrost thaw slumps.Bulk temporal trends indicated that TP was higher during the Late period in the High Arctic, whereas it was lower in the Near Arctic. In contrast, DOC and total nitrogen were both lower during the Late period in the High Arctic sites. Major ion concentrations were higher in the Near, Sub, and Low Arctic during the Late period, but the opposite bulk trend was found in the High Arctic.Significant pan-Arctic temporal trends were detected for all variables, with the most prevalent being negative TP trends in the Near and Sub Arctic, and positive trends in the High and Low Arctic (mean trends ranged from +0.57%/year in the High/Low Arctic to -2.2%/year in the Near Arctic), indicating widespread nutrient enrichment at higher latitudes and oligotrophication at lower latitudes.The divergent P trends across regions may be explained by changes in deposition and climate, causing decreased catchment transport of P in the south (e.g. increased soil binding and trapping in terrestrial vegetation) and increased P availability in the north (deepening of the active layer of the permafrost and soil/sediment sloughing). Other changes in concentrations of major ions and DOC were consistent with projected effects of ongoing climate change. Given the ongoing warming across the Arctic, these region-specific changes are likely to have even greater effects on Arctic water quality, biota, ecosystem function and services, and human well-being in the future

Тестирование экспериментальных образцов сорбентов на основе ароматических пептидов

By dynamic experiments, the purpose of which was to establish the time during which the saturation of sorbents occurs, as well as the maximum amount of total IgG bound, the saturation and capacity properties were revealed. Sorption dynamics data have been obtained for tripeptides: Phe-Trp-DTyr, Trp-Phe-DTyr, Phe-Ala-Tyr-OMe, Phe-Asn-Tyr-OMe, Phe-Asp (Bzl)-Tyr-OMe, Phe-Gln-Tyr-OMe and Phe-Gly-Tyr. Specific saturation was reliably confirmed for the Phe-Trp-DTyr sample and the Phe-Gln-Tyr-OMe sample. Other samples of sorbents show positive dynamics with episodic periods of desorption, with further alignment of the positive dynamics of the sorption process.В результате динамических экспериментов для установления времени, за которое происходит насыщение сорбентов, а также максимального количества связанного общего IgG, были выявлены свойства насыщаемости и емкости. Получены данные динамики сорбции для трипептидов: Phe-Trp-DTyr, Trp-Phe-DTyr, Phe-Ala-Tyr-OMe, Phe-Asn-Tyr-OMe, Phe-Asp(Bzl)-Tyr-OMe, Phe-Gln-Tyr-OMe и Phe-Gly-Tyr. Удельная насыщаемость достоверно подтверждена для образцов Phe-Trp-DTyr и Phe-Gln-Tyr-OMe. Другие образцы сорбентов показывают положительную динамику с эпизодическими периодами десорбции с дальнейшим выравниванием положительной динамики процесса сорбции

Селективность аффинных сорбентов на основе ароматических пептидов для связывания иммуноглобулинов класса G

Biospecific sorbents for the removal of IgG and subclasses from biological fluids based on oligopeptides that contain aromatic protein residues have been created. A functional assessment of high-quality experimental samples of sorbents and their preferences for IgG subclasses was carried out. It was found that each sorbent has good characteristics for removing IgG from biological fluids, but the sorbent based on Phe-Trp-DTyr is more effective in binding of total IgG. With respect to IgG subclasses, the best binding results are as follows: Phe-Gln-Tyr-OMe - IgG1 (86,53%), Phe-Ala-Tyr - IgG2 (60,2%), Phe-Trp-DTyr - IgG3 (59,52%) and IgG4 (55,05%).Созданы биоспецифические сорбенты для удаления IgG и подклассов из биологических жидкостей на основе олигопептидов, содержащих остатки ароматических аминокислот. Проведена функциональная оценка сорбционных качеств экспериментальных образцов сорбентов и их селективности к подклассам IgG. Обнаружено, что все сорбенты имеют хорошие характеристики по удалению IgG из биологических жидкостей, но сорбент на основе Phe-Trp-DTyr эффективней остальных связывает общий IgG. По отношению к подклассам IgG лучшие результаты связывания следующие: Phe-Gln-Tyr-OMe - IgG1(86,53 %), Phe-Ala-Tyr - IgG2(60,2 %), Phe-Trp-DTyr - IgG3 (59,52 %) и IgG4 (55,05 %)

Intraosseous infusion of medicines with autogenous thrombocytose gel in the therapy of chronic parodontal diseases

63 patients with parodontal diseases were divided into two groups. We used standard flap surgery in the first group (32 patients, 50,8%). Complex therapy of the second group (31 patients, 49,2%) were suppelmented with intraosseous infusion of natrium hypochlorite 0,03%. The results of our investigations allow us to speak about enhancement of efficiency in the complex treatment of parodontal disease

Efficiency of use intraosseus infusion of natrium hydrochlorite 0,03% in the therapy of chronic traumatic osteomyelitis of the lower jaw during the early period

45 patients with traumatic osteomyelitis of lower jaw were divided into two groups. We used standard surgical treatment in the first group (29 patients, 64,4%). Complex therapy of the second group (16 patients, 35,6%) were suppelmented with intraosseous infusion of natrium hypochlorite 0,03%. The results of our investigations allow us to speak about enhancement of efficiency in the treatment of chronoc traumatic osteomyelitis

Оценка селективности сорбентов для связывания IgG на основе трипептидных лигандов

Biospecific sorbents for the removal of IgG and subclasses from biological fluids based on oligopeptides, containing aromatic amino acid residues, were created. The selectivity properties of specific sorbents for IgM, IgE, and plasma proteins were evaluated. It was found that the created sorbents exhibit the low activity to the total plasma protein, albumin, IgM, IgE and are highly specific for IgG.Созданы биоспецифические сорбенты для удаления IgG и подклассов из биологических жидкостей на основе олигопептидов, содержащих остатки ароматических аминокислот. Проведена оценка селективности специфических сорбентов по отношению к IgM, IgE и белкам плазмы крови. Обнаружено, что созданные сорбенты прояв- ляют низкую активность к общему белку плазмы крови, альбумину, IgM, IgE и высоко специфичны к IgG