Vol 30, No 2 (2026): PHISIOLOGY. EXPERIMENTAL PHYSIOLOGY

Relevance. Angiotensin converting enzyme 2 (ACE 2) is recognised as a significant regulator of cardiovascular and pulmonary homeostasis owing to its involvement in the renin-angiotensin system (RAAS). This extensive review addresses ACE 2’s conventional role in converting Angiotensin II (Ang II) to the Angiotensin-(1-7) to its broader implications in cardiovascular illness, pulmonary pathology, metabolic diseases, and cancers. Conclusion. Recent research has shed light on ACE2’s significance beyond its enzymatic capabilities, specifically as a cellular receptor of various pathogens. Furthermore, recent evidence shows that ACE2 is involved in inflammation, glucose metabolism, and gut microbiome modulation. The tissue distribution patterns, regulatory mechanisms, and therapeutic possibilities show its dual role as a protective factor in and a possible entryway for the viral infections. Understanding these multiple processes in health and disease state serves to be essential in establishing tailored treatments for the diseases. This review outlines the existing understanding of ACE 2 and emphasizes areas for further research, notably its potential as a therapeutic target. Furthermore, we have discussed the challenges and future directions in ACE2-based therapeutics.

The aim of this study was to investigate the features of heart rate variability during postural changes in women, depending on the excitability of parasympathetic centers and of the menstrual cycle phase. Material and Methods. 47 female students from Ivanovo State Medical University participated in the study. The average age of participants was 19.2±0.16 years. The study took place during the follicular and luteal phases of menstrual cycle, lasting an average of 29.3 ± 0.4 days. The features of parasymphathetic center excitability were assessed using the K30:15 ratio during the transition to an upright position. The electrocardiogram was recorded for 5 minutes using a computer electrocardiographic system Poly-spectrum (NeuroSoft, Ivanovo, Russia) both in the horizontal position and during active orthostasis, passive orthostasis and passive antiorthostasis. Results and Discussion. Based on the analysis of the dynamics of HRV indicators, it was found that the transition from a supine position to an upright body position was accompanied by a decrease in the influence of the vagus nerve on the heart. With active orthostasis, this does not depend on the excitability of the parasympathetic system and the phase of the menstrual cycle. While with passive orthostasis and reduced excitability of the parasympathetic centers, this is manifested in both phases of the cycle, and with normal excitability - only in the follicular phase. Antiorthostasis initiates an increase in parasympathetic activity in women with normal excitability only in the follicular phase, whereas in women with reduced excitability, there is a decrease in the influence of the vagus nerve in both phases of the cycle. Conclusion. The nature of circulatory system responses to changes in body position in women depend not only on type of posture but also on excitatory characteristics of parasympathetic nerves and menstrual cycle phases.

Relevance. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of acute lung injury with a high mortality rate. In severe cases, pathological changes extend to the systemic level and manifest as cytokine storm syndrome. The lack of effective treatment options underscores the importance of exploring therapeutic approaches, including cell therapy. Interest in this treatment option increased during the SARS-CoV-2 pandemic, as evidenced by the numerous clinical trials registered for the use of cell preparations to treat ARDS. The aim of the study: Thus, this review summarizes preclinical and clinical studies on using highly differentiated cells, including immune system cells, to treat ARDS. To this end, we will describe key points in the pathogenesis of ARDS, including etiologic subtypes and stages, as well as the key cells involved and the results of their use in ARDS therapy. This review highlights the potential of using alveolar cells type 1 and type 2, as well as epithelial cells, for rapid lung regeneration after ARDS. Currently, there are no data describing the use of neutrophils, which trigger primary pathological changes in the lungs, for ARDS treatment. The use of macrophages, which play a key role in ARDS pathogenesis, is limited by their ability to quickly repolarize. Natural killer cells (NK cells), regulatory T cells (Tregs), and invariant natural killer T (iNKT cells) have shown high efficacy in treating ARDS in preclinical and clinical studies. Conclusion. Thus, using NK cells, Tregs, and iNKT cells for ARDS cell therapy seems promising. However, the lack of standardized protocols for preparing and administering cell therapies, as well as small sample sizes, indicate the need for additional studies.

Relevance. Uveal melanoma is a rare form of cancer that originates in the eye, most frequently arises in the choroid (90%). BAP1 is a tumor suppressor gene, mutations in this gene were found in 40-84% of primary UM. Given many investigators have proven the association of mutations in the BAP1 gene with UM. Aim: our study aims to figure out UM associated polymorphisms by sequencing DNA in exon 10, exon 11, exon 15, exon 16, and exon 17 as well as to assess the role of BRCA1 mutations in risk of UM development. Materials and Methods. A total of 95 individuals recruited in the study, out of them 42 as a patient group, 23 as a risk group, and 30 as a control group. The target regions of BAP1 gene amplified by PCR were sequenced by Sanger method and BRCA1 was genotyped by real-time PCR using commercially produced kits. Results and Discussion. This study did not demonstrate presence of any polymorphisms in the sequenced regions of the BAP1 gene or the genotyped specific BRCA1 sites that are correlated with an increased risk of uveal melanoma development. Our findings do not deny the published strong association between BAP1 inactivating mutations and the UM disease. This study’s findings instead propose that within this targeted population, the molecular mechanisms for BAP1 loss-function may include aberrations other than changes in the examined exons. Conclusion. Consequently, we recommend future research that includes sequencing the entire BAP1 gene in larger sized samples and studying of other candidate genes.

Relevance. Obtaining reliable data on the levels of cardiovascular morbidity and mortality among patients with rheumatoid arthritis remains important. These aspects of patient management are very important; they determine further therapeutic tactics and are aimed at reducing the risks of complications. Target - to analyze cardiovascular pathology in the structure of comorbidity and mortality of patients with RA in the cohort of patients of the Center for Responsible Rheumatology ″Induction″ LLC in the period 2015-2022. Materials and Methods. A sample of 1020 patients with a reliable diagnosis of RA, established according to the classification criteria (ACR/EULAR, 2010), who were treated at the LLC Center for Responsible Rheumatology ″Induction″, was made. The average age was 55.3 ± 1.8 years, women predominated (88.8%). Comorbid status was assessed on the basis of lifetime consultations and analysis of medical documentation of the examined patients according to a developed chart, including a specified cardiovascular disease, as well as the fact of death. A systematic review of scientific works (2019-2024) on rheumatoid arthritis in the aspect of cardiovascular pathology was carried out. Results and Discussion. The incidence of cardiovascular pathologies in patients with RA, according to numerous studies (2019-2024), varies widely. Hypertension, coronary artery disease, heart failure, cardiac rhythm and conduction disorders, and atherosclerotic cardiovascular diseases occupy the leading place in prevalence. Patients with RA in the study cohort were characterized by a complex comorbidity structure. Cardiovascular pathology is the most common (42.29%). Respiratory diseases (23.07%), COVID-19 (11.53%), and Blastomatosis (7.69%) follow it. Acute pancreatitis complicated by pancreatic necrosis, bronchial asthma, lymphocytic leukemia, hypothyroidism, autoimmune thyroiditis, diabetes mellitus were recorded in no more than 3.85% of the cohort. Cardiovascular disorders included ischemic heart disease (30.76%) and hypertension (11.53%). The three main causes of death in patients with RA included cardiovascular, respiratory diseases, and sepsis. The leading position was occupied by cardiovascular events (47.83%), predominantly acute myocardial infarction (30.43%). Conclusion. An analysis of new data on the place of cardiovascular diseases in the structure of comorbidity and mortality of patients in the Stavropol Territory of the LLC “Center for Responsible Rheumatology ″Induction″ cohort with an established diagnosis of RA was carried out. The information obtained is useful for a better understanding of the clinical portrait of RA patients with cardiovascular pathology, and can be taken into account by rheumatologists to optimize management tactics for RA and the risk of cardiovascular events.

Relevance. According to experimental data, administration of the drug cisplatin into the tumor during radiation therapy can increase its effectiveness. To date, there is no model that can predict the effectiveness of such therapy. The development of such a model is an important task for planning therapy. The goal of this work is to find analytical relationships for the survival of cells exposed to the combined effect of radiation and cisplatin in vitro. Materials and methods. Based on digitized experimental data on cell survival from a number of publicly published works, the corresponding linear-quadratic (LQ) approximation coefficients for survival were found for irradiation without the drug \( \alpha_R , \beta_R \), and for combined exposure to radiation and cisplatin \( \alpha_{RC} , \beta_{RC} \). Next, a regression analysis of the resulting set of coefficients and cell survival when exposed to cisplatin alone \( S_C \)  was performed. Results and Discussion.\( \alpha_{RC} \)  was found to be statistically dependent on \( \alpha_R, \beta_R \) and \( S_C \). This dependence could be described by several models, the best of which in terms of a number of indicators was \( \alpha_{RC} = \alpha_R + \alpha_R \ln S_C \), where \( \alpha = -4.27 \pm 0.57 \) is a parameter that is the same for all cell types and experimental conditions. It was found that \( \beta_{RC} \) is statistically dependent on \( \beta_R \). No signs of dependence of \( \beta_{RC} \) on \( \alpha_R \) and \( S_C \) were found. The best model for \( \beta_{RC} \) was \( \beta_{RC} = \beta_R \). These models are simple, but they allow predicting the value of cell survival under the combined effect of radiation and cisplatin \( S_{RC} \) from the values \( \alpha_R , \beta_R \) and \( S_C \) only approximately. The obtained models are collated with kinetic equations and a mechanistic interpretation is given, which is based on the hypothesis of a decrease in the rate of recovery of cells from potentially lethal lesions r , with an increase in the radiation dose and cisplatin concentration. Conclusion. The type of statistical dependence of LQ coefficients \( \alpha_{RC} \) and \( \beta_{RC} \) on \( \alpha_R , \beta_R \) and \( S_C \) has been found. In the case of high toxicity of cisplatin (low values of \( S_C \)), the combination of the above-mentioned models for \( \alpha_{RC} \) and \( \beta_{RC} \) allows to make a useful for practical application prediction of cell survival \( S_{RC} \). The results of this work will help for the future construction of more complex models of the combined effects of radiation and cisplatin, and may also have practical application in the case mentioned above.

Relevance. The Far Eastern Federal District is a territory of advanced development, requiring a large number of specialists. Healthcare work is one of the most complex and demanding jobs, with high psychological stress, requiring attentiveness, endurance, and a high work ethic. Medical education has its own specifics; even in their first years, at least 80 % of students face a range of challenges: stress, sleep deprivation, fatigue, and other factors, which have negative consequences for learning, behavior, and communication, and impact their health. Building a motivational system is one of the most important steps in studying at medical universities. A highly motivated student will be engaged in the learning process, and therefore will study voluntarily and actively master the curriculum. Therefore, studying the motivation of medical students at medical schools is relevant. The aim of this study was to conduct a comparative analysis of the interaction between motivation to learn and the health status of medical students at medical universities in the Far East. Materials and Methods. Within the framework of the educational, scientific and industrial cluster «Far Eastern» on the basis of cooperation agreements, within the framework of social partnership of educational organizations of higher education and interaction of universities of the Far Eastern region, the following universities participated in the study: Far Eastern State Medical University (FESM), Amur State Medical Academy (ASMA), North-Eastern Federal University named after M.K. Ammosov (NEFU), Far Eastern Federal University (FEFU), Pacific State Medical University (TSMU). The health status of 2,676 first- to fifth-year students aged 17-24 was studied. The study utilized health group data obtained as a result of medical examinations and preventive checkups, the academic motivation scales (AMS) questionnaire, and self-assessment using a developed individual questionnaire. Students from Tver State Medical University, Far Eastern Federal University, and Far Eastern State Medical University completed the survey in the university classroom using printed questionnaires, while students from North-Eastern Federal University and Altai State Medical Academy participated in the survey using Google forms online. The Statistica 12.0 software package and the analytical functions of Microsoft Office Excel were used for mathematical and statistical processing. Results and Discussion. The conducted comparative characteristics of motivation for learning of students in medical specialties in medical universities of the Far East revealed a high intrinsic motivation for learning from 3.4 to 4.9. The highest values in assessing the motivation to achieve were among students of NEFU - 4.07, in TSMU and ASMA this criterion was 4.0. A relationship between the level of external and internal motivation with the health status of students was revealed. Students with health group 3 showed significant (group 3B p = 0.55) cognitive motivation, strong, almost absolute (p = 0.9) - external motivation and high motivation for achievement. Introjected motivation was weak (from p = 0.2 to p = 0.344) and did not depend on the health group. Conclusion. The relationship between extrinsic and intrinsic motivation for learning and health status among medical students at medical universities was identified and studied.