Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious. The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angio­genesis, vascular tone, and permeability. Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction. Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endo­thelial dysfunction. Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology. Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described. Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.

Introduction: Tau proteinopathy is a pathology associated with the activation of post-translational modifications and interactions of pathophysiological cascades of neuroinflammation with hyperphosphorylation of Tau aggregates. Therefore, preference is given to agents that have properties in reducing or slowing down the processes of neuroinflammation and post-translational modifications in the brain. Materials and Methods: The study was conducted on male and female homozygous individuals of a transgenic murine line with overexpression of mutant human Tau gene (P301S) and a background wild mouse line C57Bl/6J. To assess the progression of Tau proteinopathy, behavioral tests were used at two control time points, and the last one measured the level of neuroinflammation markers and tau-proteinopathy. Results and Discussion: In the group of P301S mice treated with ARA-290, an improvement in the phenotypic picture of Tau proteinopathy was demonstrated compared with intact animals. In the Barnes circular maze test, mice showed a decrease in the total distance traveled and the latent time spent on the platform, which indicates a rapid entry into the shelter. In the O-shaped maze test, the group maintained a fairly high level of spontaneous exploratory behavior. In the vertical rod test, the animals recorded the best time indicators that they needed to turn and maintain balance compared to the intact group. A statistically significant decrease in the level of GSK-3β and an increase in CDK5 and PP2A were revealed, which indicates a dephosphorylating effect on Tau protein, as well as markers of neuroinflammation. NF-KB and TNF-α were significantly reduced by 57% and 32%, respectively, compared to the intact group. Conclusion: In the model of transgenic P301S murine line with overexpression of the mutant human Tau gene, the peptide agonist of the EPOR/CD 131 heteroreceptor demonstrated neuroprotective properties, which were confirmed by indicators of behavioral tests and markers of neuroinflammation and tau-proteinopathy. Введение. Таупротеинпатия – патология, связанная с активацией посттранляционных модификаций и за счет взаимодействия патофизиологических каскадов нейровоспаления с гиперфосфорилированием агрегантов Тау. Поэтому отдают предпочтения агентам, у которых есть свойства снижать или замедлять процессы нейровоспаления и посттрансляционные модификации в головном мозге. Материалы и методы: исследование проведено на самцах и самках гомозиготных особей трансгенной линии мышей с гиперэкспрессией мутантного гена Тау человека (P301S) и фоновой дикой линии мышей C57Bl/6J. Для оценки прогрессирования таупротеинпатии применялись поведенческие тесты в двух контрольно-временных точках и на последней измерялся уровень маркеров нейровоспаления и таупротеинпатии. Результаты и их обсуждение: в группе мышей P301S с лечением при помощи ARA-290 продемонстрировала улучшение фенотипической картины таупротеинпатии по сравнению с интактными животными. В тесте круговой лабиринт Барнса у мышей зарегистрировали снижение общего расстояния пройденной дистанции и латентного времени нахождения на платформе, что говорит о быстром заходе в «убежище». В тесте О-образный лабиринт группа сохранила достаточно высокий уровень спонтанного исследовательского поведения. В тесте вертикальный стержень, у животных зарегистрированы лучшие показатели времени, которые им требовались для поворота и для удержания равновесия относительно интактной группы. Статистически значимое снижение уровня GSK-3β и увеличение CDK5 и PP2A, что говорит о дефосфорилирующем действии на белок Тау, а также маркеры нейровоспаления (NF-KB и TNF-α), которые были значительно снижены на 57% и 32% соответственно по сравнению с интактной группой соответственно. Заключение: пептидный агонист гетерорецептора EPOR/CD131 на модели трансгенной линии мышей P301S с гиперэкспрессией мутантного гена Тау человека обладает нейропротективными свойствами, что подтверждается в показателях поведенческих реакций и в определении маркеров нейровоспаления и таупротеинпатии.

Introduction: Limiting the action of secondary injury factors can improve the prognosis in acute cerebral accidents. The aim of the investigation is to study the neuroprotective effects of 3-hydroxypyridine derivatives. Materials and methods: The study was performed in Wistar rats. An intracerebral hemorrhage (ICH) model was used. The animals were once administered intraperitoneally with the test drugs 1 hour before the surgery and on the 1st, 2nd and 3rd days. The registration of behaviors and condition of the animals on days 1, 3, 7 and 14 and the morphological examination of the brain were performed. Results and discussion: The use of the substances LKhT 4-97 and LKhT 11-02 in the treatment of experimental ICH had a positive effect on the survival rate of the animals and on the resolution rate of pathological signs (p<0.05). Clinical observations were confirmed by the results of analysis of the S100b brain damage marker and morphometry. The efficacy of LKhT 3-15 was largely comparable to that of the reference drug Mexidol. The efficacy of LKhT 01-09 was significantly inferior to that of the reference drug Mexidol. Differences in the neuroprotective effects of the studied substances are related to the metabolism of their various pharmacophores. A hypothetical mechanism for the induction of their neuroprotective effects has been proposed. Conclusion: Three of the four 3-hydroxypyridine derivatives under study have a neuroprotective effect, which is manifested in a more rapid resolution of pathological symptoms and less pronounced signs of neurodegeneration.

Background: Sex-related differences significantly impact biomedical research outcomes, yet female subjects are often excluded due to concerns about variability from the estrous cycle. This study aimed to investigate the sex-dependent differences in behavioral phenotypes and amyloid-beta plaque accumulation in the APPswe/PS1dE9/Blg transgenic mouse model of Alzheimer’s disease. Methods: Male and female APPswe/PS1dE9/Blg transgenic mice and wild-type (WT) controls were assessed at 7.5 and 10 months of age. A comprehensive behavioral test battery was employed, including the Open Field, Novel Object Recognition, Y-Maze, and Barnes Maze tests. Histological analysis of amyloid plaque was carried out. Results: Female transgenic mice displayed delayed accumulation of Aβ plaques and milder cognitive decline compared with males. At 10 months, plaque load in females corresponded to that of 7.5-month-old males, demonstrating a temporal lag in pathology. Behavioral impairments correlated negatively with cortical plaque burden (r = −0.4964, p = 0.0181), supporting its role as a structural biomarker of disease progression. Conclusions: This study identifies distinct sex-dependent trajectories of behavioral and histomorphometric biomarkers in APPswe/PS1dE9/Blg mice. Females exhibit delayed amyloid pathology and cognitive decline, suggesting intrinsic neuroprotective mechanisms that modulate biomarker expression over time. These findings emphasize the necessity of integrating both sexes in preclinical biomarker research and support the use of morphometric endpoints as translationally relevant indicators of Alzheimer’s disease progression.

Introduction: The purpose of this work is to review the main pathogenetic mechanisms of the development of PH, as well as modern established methods of treatment of various types of PH and to consider new, most relevant and promising possibilities of therapy for this pathology. Etiology, pathogenesis and epidemiology: In the modern structure of diseases, pulmonary hypertension plays a significant role, affecting about 1% of the population. However, each of its five main groups has its own characteristics. The causes of pulmonary hypertension can be a polyetiological violation of the processes of endotheliocyte apoptosis and angiogenesis, passive transmission of increased pressure from the left heart to the small circulatory system, chronic hypoxia, leading to vascular remodeling, and many others. In general, it is worth noting that, despite the multiplicity of etiological factors, the main pathogenetic link in the development of pulmonary hypertension is endothelial dysfunction. Treatment and promising areas of research: This article discusses the main established approaches to the treatment of pulmonary hypertension: general recommendations for patients, drugs used as supportive nonspecific therapy, as well as specific conservative and radical methods of treatment. In addition, the main modern directions of scientific research in the field of treatment of pulmonary hypertension are described. Such promising methods as the use of stem cells, gene therapy and epigenetic drugs are considered. Conclusion: Despite active research and many different drugs intended for the treatment of pulmonary hypertension, this pathological condition remains an urgent health problem. Thus, the search for new points of application of therapy and fundamentally new methods of treatment of pulmonary hypertension remains relevant to this day.

Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein.