Aim. To examine the pattern of morphological changes, RNA quality number, and gene expression in mouse tissues sampled at autopsy under controlled experimental conditions.

Materials and methods. Balb/c mice were euthanized and subsequently subjected to necropsy at 0, 3, 12, 24, 48, and 72 hours of the postmortem period. During the first three hours following euthanasia, the mice were maintained at room temperature, after which they were transferred to a refrigerator (4 º С). Total RNA was extracted from tissue samples taken from the kidney, liver, and brain; the integrity of the RNA samples was assessed by capillary electrophoresis, and the RNA quality number (RQN) was calculated. The expression levels of Actb, Epas1, and Rps18 housekeeping genes were evaluated by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) with original primers and probes using the TaqMan assay. The histologic examination was performed according to standard techniques.

Results. Degradation of RNA extracted from mouse kidney tissues appeared to be greater than that of RNA taken from the liver. In the meantime, a negative linear correlation was observed between RQN and the duration of the postmortem interval for liver and kidney samples. In contrast, no significant changes in the RQN score were observed for brain RNA samples at any of the time points. The expression of the Epas1 and Rps18 genes was significantly decreased in mouse kidney and liver tissues. However, the level of Epas1 and Rps18 gene expression in the brain remained stable at all time points and did not exhibit a significant decrease at 72 hours after euthanasia. No obvious morphological changes were detected by the histologic examination, which does not exclude the presence of ultrastructural pathological changes.

Conclusion. RQN in autopsy tissues serves as a crucial predictor of sample quality for molecular biology studies, including gene expression analysis.

Aim. To establish the features of structural and functional changes in the brain in patients with schizophrenia.

Materials and methods. A morphometric analysis of the brain using MRI scans was performed, along with a clinical assessment of the electroencephalogram (EEG) of 35 patients with schizophrenia (20 men and 15 women). The control group included 18 healthy sex- and age-matched individuals (10 men and 8 women). Statistical processing was carried out using the χ2 test, the Fisher’s exact test, and the Spearman’s rank correlation coefficient.

Results. Compared to the control group, patients with schizophrenia were significantly more likely to show signs of ventricular dilation (p = 0.039), asymmetry of the lateral ventricles (p = 0.041), periventricular edema (p < 0.001), and enlargement of the subarachnoid space of the cerebellum (p = 0.004). Changes (class >1A) in the functional activity of the brain in the group of patients with schizophrenia were detected in 65.7% of the cases. In more than half of the cases, patients with schizophrenia showed decreased bioelectric activity of the brain (class 2 in 48.6% and class 3 in 11.4%); at the same time, EEG signs of paroxysmal activity were detected in a few patients (class B in 11.4% and class C in 5.7%) (p < 0.001). A statistically significant direct correlation was found between the enlargement of the subarachnoid space of the cerebellum and paroxysmal EEG activity in patients with schizophrenia (r = 0.377; p = 0.044).

Conclusion. The findings of our study highlight that the combined use of MRI and EEG can provide important information about brain pathology in schizophrenia. The data obtained are also important for testing the hypothesis on the association between vascular and functional disorders of the brain in patients with schizophrenia.

Background. Many studies have shown that neutrophil extracellular traps (NETs) in the form of web-like structures are present in the peripheral blood of patients with inflammatory diseases. In our research, in addition to traditional web-like NET structures, several anomalous forms were identified, including NETs with cloud-like appearance.

Aim. To investigate morphological and functional transformation of NETs under the influence of Klebsiella pneumoniae and immunoglobulin G (IgG).

Materials and methods. The study included 42 patients of Moscow City Clinical Hospital No. 51: 28 patients with acute inflammation in the abdominal cavity (appendicitis, cholecystitis, pancreatitis, peritonitis), 6 patients diagnosed with ulcerative colitis, and 8 patients with hernias. Neutrophils were isolated using gradient-density centrifugation. To calculate NETs, we used SYBR Green I-induced fluorescence microscopy (Evrogen, Russia), with the dye specifically interacting with double-stranded DNA. The functional activity of NETs was determined in the Klebsiella pneumoniae (ATCC 700603) capture test.

Results. In patients with inflammatory diseases of the abdominal cavity in the postoperative period, the functional activity of NETs was several times lower than in healthy individuals. NETs in these patients capture and bind no more than 20 cells of the microorganism. Under the effect of IgG, neutrophil networks transform into loose cloud-like structures, which can hardly capture and bind the pathogen, binding only 8.46 ± 0.44 cells of the microorganism. Spontaneous enzymatic degradation of cloud like NETs may be accompanied by the production of secondary alteration factors.

Conclusion. The results of the study provide the grounds for the development of new approaches to elaborating vaccination regimens and using immunobiologics that require preliminary monitoring of the state of innate immunity, in particular, neutrophil networks in the patient’s body.

Aim. To develop a model of chronic thromboembolic pulmonary hypertension (CTEPH) in rats by embolization of the pulmonary vascular bed with microencapsulated fibrin (MF).

Materials and methods. Microencapsulated fibrin (MF) was prepared by encapsulating fibrin particles smaller than 71 μm in sodium alginate. Non-encapsulated fibrin with a particle size of 71–200 µm was used as an alternative embolic particle. Modeling was performed on male Wistar rats. The animals were divided into 4 groups. Intact (INT) animals (n = 7) were administered normal saline intravenously. In the NF8 group (n = 14), non-encapsulated fibrin was injected as embolic particles 8 times every 4 days. In the MF5 group (n = 14), 0.5 ml MF (9,047 ± 430 particles) was administered intravenously 5 times every 5 days. In the MF8 group (n = 14), MF was administered 8 times every 4 days. Six weeks after the last injection of embolic particles, cardiac catheterization with manometry and histologic examination of the lungs were performed.

Results. According to cardiac catheterization, right ventricular systolic pressure (RVSP) in the MF8 group was significantly higher compared to rats from the INT and NF8 groups (p < 0.05). The hypertrophy index and the percentage of collagen fibers in the structure of the vascular wall of the pulmonary artery branches were significantly higher in the MF5 and MF8 groups than in the INT and NF8 groups (p < 0.01). There were no significant differences between the MF5 and MF8 groups.

Conclusion. A representative CTEPH model in rats was developed, characterized by a stable increase in RVSP and pronounced structural changes in the branches of the pulmonary artery.

Aim. To conduct a comparative assessment of parameters and dynamics of pulmonary congestion according to lung ultrasound and remote dielectric sensing (ReDS) in patients hospitalized with decompensated chronic heart failure (CHF).

Materials and methods. The pilot single-center study included patients hospitalized with decompensated CHF. Lung ultrasound and ReDS were simultaneously performed within 24 hours from the moment of hospitalization and at discharge. Eight-zone lung ultrasound was performed with the calculation of the sum of B-lines. Pulmonary congestion was confirmed with the sum of B-lines ≥ 5. ReDS was performed according to the manufacturer’s protocol. Congestion was confirmed at the value of more than 35%. To determine ReDS interoperator variability, each patient was examined by two operators who were blind to each other’s findings with a 20–30-minute interval.

Results. Thirty-five patients were included in the study: 40% (n = 14) men, the average age was 71 (65.5; 78.5) years, the median NT-proBNP was 1,379 (470; 4,277) pg / l. Hydrothorax at admission was observed in 31,4% (n = 11) of patients. The incidence of pulmonary congestion according to lung ultrasound was 57.1% (n = 20): 31.4% (n = 11) of patients had mild congestion, 22.9% (n = 8) – moderate, and 2.9% (n = 1) – severe congestion. ReDS data revealed pulmonary congestion in 62.9% (n = 22) of cases, of which 37,1% (n = 13) of cases were characterized by mild, 22.9% (n = 8) – by moderate, and 2.9% (n = 1) – by severe congestion. A moderate correlation was found between ReDS (%) and lung ultrasound (sum of B-lines) findings at admission (Spearman’s rank correlation coefficient = 0.402; p = 0.017). No correlation between the two methods was found at discharge (p = 0.613). The frequency of agreement between lung ultrasound and ReDS on signs of congestion at admission was 77.1% (p = 0.004) with an average Cohen’s Kappa coefficient (κ = 0.53). The average interoperator variability in ReDS was 9.9%.

Conclusion. A moderate correlation was revealed between ReDS (%) and lung ultrasound (sum of B-lines) in detecting pulmonary congestion (Spearman’s rank correlation coefficient = 0.402; p = 0.017). No correlation between the two methods was found at discharge (p = 0.613).

Aim. To evaluate the expression of VEGFR1 and VEGFR2 and the maturity of endothelial cells in neurogenic niches in the model of Alzheimer’s disease.

Materials and methods. The study was carried out on 6-month-old male C57BL/6 mice. The experimental group (n = 15) received 2 µl of 1 mM Aβ25-35 solution in the CA1 hippocampal region, while the control group (n = 15) received normal saline. Brain plasticity was assessed at day 10, 17, and 38 after surgery by the passive avoidance test. The expression of VEGFR1, VEGFR2, and CLDN5 was assessed by immunohistochemistry and the Image ExFluorer imaging system.

Results. In the control group, cognitive training stimulated angiogenesis in the neurogenic niches of the brain, which was accompanied by the formation of microvasculature with fully mature endothelium. In the experimental group, an early and pronounced increase in the VEGFR1 expression was observed by day 7 after cognitive training, which was followed by impaired barrier formation and high VEGFR2 expression by day 28 after cognitive training. These changes were associated with the formation of small vessels with structural incompetence of endothelial cells.

Conclusion. Angiogenesis in neurogenic niches of the animals with the model of Alzheimer’s disease is characterized by incompetent mechanisms regulating the subpopulation composition of endothelial cells, impaired stabilization of the endothelial layer, and a decrease in the maturation rate of endothelial cells in newly formed microvessels by the time of cognitive deficit manifestation. This may contribute to microcirculatory dysfunction and impaired neurogenesis in neurogenic niches as well as to the development of pathological permeability and neuroinflammation. On the whole, the disruption of angiogenesis in neurogenic niches observed in the animal model of Alzheimer’s disease suggests a potential contribution of this mechanism to the development of aberrant brain plasticity.

Aim. To identify the features of the subpopulation composition of blood monocytes and tumor macrophages in relation to the plasma concentration and intratumoral expression of galectins 1 and 3 in patients with colorectal cancer.

Materials and methods. A total of 23 patients with colorectal cancer (ICD C18-20) were examined – 5 men and 18 women (average age 63.8 ± 9.4 years). The control group consisted of healthy volunteers; the comparison group encompassed age- and sex-matched patients with colon adenomas. The study materials included whole blood and tumor biopsies. The concentration of galectins 1 and 3 in the blood was determined by enzyme-linked immunosorbent assay, the content of tumor galectin-1⁺ and galectin-3⁺ cells – by immunohistochemistry. Subpopulations of blood monocytes were evaluated by flow cytometry; the macrophage immunophenotypes M1 (CD68⁺ CD80⁺ ) and M2d (CD68⁺ CD206⁺ ) in tumor tissues were determined using immunofluorescence staining. Statistical processing of the research results was performed by the Jamovi 2.3.21 software package for Windows.

Results. In patients with colorectal cancer (CRC), a positive relationship was identified between high plasma concentrations of galectins 1 and 3 and an imbalance of blood monocytes manifested by a decrease in the relative count of classical CD14⁺⁺CD16^- monocytes and, conversely, an increase in the number of non-classical CD14⁺CD16⁺⁺ and intermediate CD14⁺ CD16^- cells. The relative numbers of M1 (CD68⁺CD80⁺) and M2d (CD68⁺CD206⁺) macrophages in CRC tissue samples turned out to be comparable and did not depend on the level of galectins 1 and 3 in the blood and tumor. In patients with colon adenomas, the M2d subpopulation of tumorassociated macrophages was predominant (p = 0.031).

Conclusion. In patients with CRC, galectins 1 and 3 have a modulating effect on the ratio of non-classical CD14⁺CD16⁺⁺, intermediate CD14⁺CD16^- , and classical CD14⁺⁺CD16^- monocytes in the blood and do not affect the M1/M2d expression profile of tumor-associated macrophages.

Aim. To determine clinical and laboratory factors associated with a severe course and lethality in hospitalized patients with COVID-19.

Materials and methods. A retrospective comparative study included data of 745 adult patients hospitalized with COVID-19 from 16.05.2020 to 30.09.2020 (Tomsk, Russia). The intergroup comparison of indices, ROC analysis, and determination of odds ratio to assess the association between risk factors and the outcome were performed.

Results. Age > 62 years, pneumonia within a year before COVID-19, and the presence of ≥3 comorbidities were associated with a fatal outcome (FO). Negative predictors of the outcome at the time of hospitalization included dyspnea, diastolic blood pressure ≤ 80 and pulse pressure > 48 mmHg, SpO2 < 94% (and/or a decrease to ≤ 89% throughout hospitalization). Laboratory predictors of FO at admission were platelets ≤ 183 × 109 / l, neutrophils > 4.57 × 109 / l, lymphocytes ≤ 1.08 × 109 / l, neutrophil-to-lymphocyte ratio > 4.8, aspartate aminotransferase > 39 U / l, urea > 6.75 mmol / l, lactate dehydrogenase > 219 U / l, blood albumin ≤ 38 g / l, C-reactive protein (CRP) > 47 mg / l. When threshold values were reached during any of the hospitalization periods, FO was associated with CRP > 38 mg / l, ferritin > 648.6 µg / l, D-dimer > 731.11 ng / ml, white blood cells > 14.27 × 109 / l, lymphocytes ≤ 0.73× 109 / l, duration of oxygen therapy > 3 days, need for non-invasive and invasive ventilation ≥ 1 day, need for glucocorticoid administration > 1 day, reaching a total course dose > 6 mg for dexamethasone.

Conclusion. The factors associated with FO in hospitalized patients with COVID-19 were identified.

Aim. To identify predictors of the development of pulmonary hypertension (PH) in the subacute period of myocardial infarction (MI) in young and middle-aged males to improve preventive measures.

Materials and methods. We studied the results of treatment of male patients aged 32–60 years with a verified diagnosis of MI. Based on echocardiography findings and detection of PH at the end of the third week of MI, the patients were divided into the study group (patients with PH) and the comparison group (patients with a normal pressure in the pulmonary artery). In the studied groups, a comparative assessment of various parameters was performed, and an analysis of the risks of developing PH using the Pearson’s chi-squared test was conducted.

Results. We found that the risk of developing PH in the subacute period of MI was significantly affected by certain parameters of peripheral hemodynamics, the presence of bradycardia, and the calculated value of total pulmonary resistance. The main parameters of the lipid profile were found to be significant predictors of PH in the subacute period of MI, along with some parameters of electrolyte metabolism (sodium and magnesium in the first 48 hours of MI, potassium and calcium at the end of the third week of the disease). We established the presence of a reliable relationship between several parameters of the structural and functional state of the myocardium both in the first 48 hours of MI and the end of the third week of the disease with the risk of developing PH in the subacute period of MI.

Conclusion. The identified predictors make it possible to determine patients with MI who are at an increased risk of PH to timely diagnose and treat the disease and improve the prognosis.

Aim. To study the effect of forced treadmill exercise on lipid and carbohydrate metabolism parameters in liver and skeletal muscle tissues of mice with a model of type 2 diabetes mellitus, taking into account age and biological rhythm characteristics.

Materials and methods. To create a model of type 2 diabetes mellitus (T2DM), a high-fat diet was used. Physical activity in the form of forced treadmill exercise was carried out for 4 weeks. Parameters of lipid and carbohydrate metabolism in muscle and liver tissues were determined by Western blotting.

Results. A decrease in glycogen content in the muscles in T2DM was associated with activation of its breakdown rather than with its reduced synthesis. Significant and multidirectional changes were recorded in the content of glycogen phosphorylase in the liver and skeletal muscle tissues. These changes were significantly influenced by both the nature of diet and physical activity. The development of T2DM in mice was accompanied by a decrease in high-density lipoprotein (HDL) content in the liver along with an increase in low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) levels. It is worth noting that physical activity provided partial normalization of the ratio of lipid fractions, despite the fact that the exercises were performed in the context of a high-fat diet. In the T2DM group, metabolic changes caused by both T2DM modeling and physical exercises were not only quantitative, but in some cases also qualitative. The effects of physical exercises performed at different times of the day on metabolic processes in the liver and muscle tissues varied significantly.

Conclusion. Physical activity can help prevent not only metabolic disorders (obesity and insulin resistance), but also associated complications on the part of the liver and cardiovascular system.

Aim. To characterize parameters of neutrophil extracellular trap (NET) production in the leukocyte culture and citrullinated histone H3 (citH3) level in peripheral blood to assess the features of NETosis in children with tuberculosis.

Materials and methods. The study included 20 children with active pulmonary tuberculosis (TB group) and 20 clinically healthy children without signs of sensitization to Mycobacterium tuberculosis antigens (control group). The ability of neutrophils to form NETs under ex vivo exposure to a non-specific immune stimulant and the concentration of citH3 in peripheral blood were investigated.

Results. Neutrophils in children with tuberculosis formed filamentous NETs (Me = 21.0 and Me = 16.0, respectively; p = 0.0474) and cloud-like NETs (Me = 10.5 and Me = 4.0, respectively; p = 0.0068) more frequently than the controls. Filamentous NETs prevailed in both groups. However, cloud-like NETs were registered in all patients in the TB group (100%) and only in 15 of 20 children in the control group (χ² = 16.01; p < 0.0068). The concentration of citH3 in the blood was 18.9 times higher in the TB group than in the control group (Me = 26.5 and Me = 1.4, respectively; p = 0.0041). A strong positive correlation was found between the citH3 concentration and the generation of filamentous (r = 0.86; p = 0.0137), but not cloud-like NETs (r = 0.95; p = 0.0008) in both groups.

Conclusion. The high level of citH3 in the TB group can reflect its NETosis-induced release and be caused by increased NETosis in vivo. This may be due to the previously formed potential of neutrophils to generate NETs (a proNETotic phenotype), which is consistent with our observation of an increased ability of isolated neutrophils to form extracellular traps ex vivo in children of the TB group.

Aim. To study the presence and severity of insomnia in patients with comorbid coronary heart disease (CHD) and depressive disorder (DD).

Materials and methods. The study included 132 patients with CHD (class II–III exertional angina after myocardial infarction experienced more than 6 months ago): 58 patients with DD and 74 patients without depression. The Beck Depression Inventory (BDI) was used to diagnose DD. The diagnosis in all cases was confirmed by a therapist. Sleep disturbances were assessed using the Sheehan Patient-Rated Anxiety Scale (ShAS). The data were presented as M ± SD; n (%); and Me [25%; 75%]. The differences were considered significant at p < 0.05.

Results. Insomnia in the general group of patients was registered as follows: none or clinically not significant – in 62 patients (54.9%), clinically significant – in 51 patients (45.1%). Night awakenings in the general group of patients were detected as follows: none or clinically not significant – in 66 patients (58.4%), clinically significant – in 47 patients (41.6%). Disturbances in falling asleep and night awakenings were significantly pronounced in patients with CHD with identified DD compared to patients without mental disorders: disturbances in falling asleep – 2 [1; 3] vs. 1 [0; 2] (p = 0.0001), night awakenings – 2 [1; 3] vs. 1 [0; 2] (p = 0.00002), respectively. In the group of CHD with DD (n = 58), 2 people (3.4%) did not complete the scale. Among those who did, 12 patients (21.4%) had no difficulty falling asleep, 9 patients (16.1%) had little difficulty, and 35 patients (62.5%) had clinically significant disturbances. In the group of CHD without DD (n = 74), 17 people (23%) did not complete the scale. Among those who did (n = 57), 21 patients (36.8%) had no difficulty falling asleep, 20 patients (35.1%) had little difficulty, and 16 patients (28.1%) had clinically significant problems. In patients with comorbid CHD and DD who completed the ShARS (n = 56), 7 patients (12.5%) had no night awakenings, 17 patients (30.4%) had few night awakenings, and 32 patients (57.1%) had clinically significant disturbances in maintaining sleep. In the group without DD, among those who completed the ShARS (n = 57), 18 patients (31.6%) had no night awakenings, 24 patients (42.1%) had few night awakenings, and 15 patients (26.4%) had clinically significant disturbances in maintaining sleep. Significant differences were noted for all test questions (p < 0.0005).

Conclusion. In patients with comorbid CHD and DD, changes in the circadian rhythm are detected in the form of significant disturbances in falling asleep and awakening, which can aggravate the clinical course of CHD and the prognosis of patients with cardiovascular diseases.

Aim. To develop a new method to determine the viability of Opisthorchis felineus in vitro using the MTS reagent and to evaluate its applicability for analyzing the efficacy of anthelmintic agents in the treatment of opisthorchiasis.

Materials and methods. Golden hamsters were used to create a model of O. felineus infection. The animals were infected with metacercariae obtained from fish of the Cyprinidae family. Three months after infection, adult parasites were extracted from the hepatobiliary system. Their viability was assessed using the motility scale and a new method based on the modified MTS test protocol. To account for differences between the size and number of adult parasite cells, the results were normalized with respect to protein content. To evaluate the feasibility of the new approach in the study of pharmacological activity against opisthorchiasis, the viability of adult parasites in the presence of praziquantel was tested.

Results. During incubation of adult flukes in a medium with the addition of the MTS reagent, colored watersoluble formazan was accumulated. Thermal inactivation of parasites significantly decreased the production of this compound. Since the studied adult parasites differed in size and number of cells, the obtained data on their viability were normalized to protein content. The results correlated with the data on parasite viability obtained by the traditional method using the motility scale. Evaluation of praziquantel efficacy at different concentrations using two independent methods (the MTS test and the motility scale) showed that the results of the MTS test were consistent with literature data and comparable with the results obtained using the motility scale.

Conclusion. A new method for in vitro evaluation of anti-opisthorchiasis activity of drugs was developed. It is based on the assessment of water-soluble formazan production by adult O. felineus flukes in the culture medium using the MTS reagent for screening anti-opisthorchiasis activity of new anthelmintic drugs.

The aim of this study was to examine the public reaction to the implementation of quarantine measures through a personality-oriented discourse.

Materials and methods. Text data were collected from a microblogging platform, resulting in a dataset of 86,750 texts related to the topics of “pandemic” and “quarantine measures”. The lexical conceptualization of the pandemic and quarantine measures represented in the texts was analyzed through the lens of a personality-oriented discourse. Text lemmatization was conducted using the “snowball” library. A data feature matrix was then created based on the lemmatized tokens, which included 53 tokens with a frequency of use exceeding 1,300 times. The Social Network Analysis (SNA) method was used to create a keyword co-occurrence network consisting of undirected graphs. This analysis was performed using the free software R version 4.4.1, with the assistance of the Quanteda library, built-in “base” packages, and the gsub function.

Results. The resulting network consisted of 53 key lexemes, which actors used to respond to quarantine measures in the personality-oriented discourse. The central node of the network was “coronavirus”, which was used 79,838 times between March 1 and April 30, 2020. The nearest nodes were “test” (used 4,663 times) and “Russia” (used 5,848 times). This network had high centrality, indicating that despite strict restrictive measures, the focus of the general public was on the pandemic itself and its impact on society rather than on the restrictions imposed.

Conclusion. The implementation of these anti-epidemic measures has created a unique sociolinguistic world view, reflecting the interaction between society and the outside world in a time of uncertainty and health risks, affecting the analysis of information and the behavioral strategies chosen by society.

The aim was to study the rate and changes in the incidence (by uptake) of age-related diseases (ARDs) in 2018– 2022 through the example of a municipal hospital in Saint Petersburg.

Materials and methods. The study was carried out on the basis of records and reports for the period of 2018–2022 for the main statistical age groups (adult population (AP), working age population (WAP), persons over working age (POWA)). The incidence was analyzed for the most common ARDs (hypertensive diseases; coronary heart disease; type 2 diabetes mellitus; senile cataract, and glaucoma). The assessment of the incidence rate was carried out both for ARDs in general and for particular diseases.

Results. A long-term observation revealed that the incidence of ARDs has been increasing. In WAP, the rate of the increase in the incidence of ARDs was more pronounced compared to the same indicator in the general population surveyed (16.1 versus 5.4%). Moreover, in the post-COVID period, the incidence rate of a number of ARDs increased. In addition, a regular sequence was found in the manifestation of ARDs: hypertensive diseases, coronary heart disease, type 2 diabetes mellitus, senile cataract, glaucoma.

Conclusion. The incidence rate of age-related diseases has been increasing, which is especially pronounced among WAP. In the post-COVID period, these diseases were found to develop much faster. ARDs are characterized by a sequence of manifestations as patients get older, which in the future will allow to develop clearer approaches to the prevention, diagnosis, and treatment of ARDs depending on the age of the patient.

Aim. To carry out in silico screening of interactions of synthetic glucocorticoids with TRPM8.

Materials and methods. Information on the structure of the ligands was obtained from the PubChem chemical database in sdf format. The TRPM8 protein model was downloaded from the AlphaFold Protein Structure Database (AlpahaFold ID: AF-Q7Z2QW). Prediction of molecular cavities and coordinates of their centers was carried out on the PrankWeb web server. Modeling of molecular interactions was carried out using AutoDock (generation of 100 epochs) and MOE (generation of 300 poses) software.

Results. The study revealed that the ligands formed stable complexes with TRPM8, but all of them, except for beclomethasone dipropionate, did not interact with the Tyr745 amino acid residue (the key binding site for channel activation). Thus, it can be assumed that glucocorticoids are most likely inhibitors of this ion channel. Of all glucocorticoids, special attention was paid to prednisolone, flunisolide, and budesonide, since the results of molecular docking of these molecules using AutoDock and MOE showed comparable data.

Conclusion. The results obtained provide an insight into the therapeutic potential of these drugs in terms of their use in the treatment of cold-induced airway hyperresponsiveness and also expand the potential for their personalized use in the treatment of bronchial asthma and COPD.

Three-dimensional (3D) bioprinting is rapidly proliferating across many medical disciplines and is making strides towards manufacturing intricate human organs for clinical application. One of the most promising areas in 3D bioprinting is development of bioinks with certain composition and designed properties.

The aim of this systematic review was to assess current biomedical research evidence regarding the efficacy of 3D bioprinting for skin regeneration and wound healing. A comprehensive search for all applicable original articles was conducted according to pre-established eligibility criteria. The study employed PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect databases.

Of the retrieved articles, eighteen satisfied the inclusion criteria, while twenty-three were excluded. A total of 159 animals that had wound defects were considered in all animal-based research. Collagen and gelatin hydrogels were the most commonly employed bioinks. In relation to cellular composition, allogeneic fibroblasts and keratinocytes were predominant. The observation period ranged from one day to six weeks. Complete wound closure was achieved within 2–4 weeks in most animal studies. In vitro and in vivo animal studies have shown a positive effect of printed bioengineered constructs in accelerating wound healing. Notably, the research where bioprinting was performed directly in the wound in situ was of particular interest. Further studies are required to enhance the tissue bioprinting technique to address skin wound healing in animal models. The utilization of standardized parameters may pave the way for human clinical studies.

Oncolytic viruses (OVs) are a new class of targeted anticancer drugs with unique mechanisms of action. Oncolytic virotherapy has evolved from the use of in vitro-passaged strains (first generation) to genetically engineered viruses with increased selectivity (second generation) and, ultimately, to recombinant OVs expressing a transgene (third generation).

The aim of the review was to analyze and summarize data on the current state of clinical research on OVs.

A PubMed search identified 182 articles from 1997 to 2024 with 154 studies reporting data on 4,850 patients. We found that adenovirus (n = 44) is the most common OV in clinical trials with more than two-thirds (n = 108) using modified or recombinant viral backbones, and granulocyte-macrophage colony-stimulating factor (GM-CSF; n = 40) was the most common transgene. The most common tumors targeted were melanoma (n = 1,997) and gastrointestinal (GI; n = 916) cancers with the most common monotherapy received by intratumoral (n = 3,003) or intravenous (n = 1,318) delivery routes. The most common combination included chemotherapy (n = 54).

Treatment-related adverse events included low-grade constitutional symptoms and local injection site reactions. Measurements of virus shedding were frequently performed, but many studies were limited to blood and tumor tissue analysis, using only polymerase chain reaction (PCR). Although most studies reported antiviral antibody titers (n = 101), only a few reported virus-specific T-cell responses (n = 23). Objective responses were recorded in 458 (9.4%) patients and disease control was achieved in 1,141 (23.5%) patients, although standard reporting criteria were used in only 60.4% of cases.

These data provide an insight into the current state of clinical research on OVs and highlight potential areas requiring further investigation to better define the role of OVs in cancer treatment.

Angiogenin is a small polypeptide consisting of 123 amino acids involved in the processes of angiogenesis and tumorigenesis. This protein plays an important role in various physiological and pathological processes through the regulation of cell proliferation, survival, migration, invasion, and differentiation.

The lecture presents data on angiogenin production and interaction with various proteins, describes mechanisms of its action, and shows its biological role in angiogenesis and oncogenesis. The literature search was carried out in the PubMed, Medline, Elibrary, Scopus, The Cochrane Library, and RSCI search engines.

The lifestyle of people nowadays and poor diet are factors affecting the increasing incidence of digestive diseases in people all over the world. The search for new methods of early diagnosis of the disease is an urgent issue of modern medicine. In the last decade, much attention has been paid to various biological markers that can be used to assess the risk of disease development, the response to therapy, and the possible development of complications. Biomarkers in clinical medicine can be used as additional tools not only to improve early diagnosis of gastrointestinal diseases but also to assess the effectiveness of therapy.

The aim of this lecture was to analyze and systematize biomarkers in various gastrointestinal diseases.

The lecture analyzes the results of research on the role of humoral and cellular mediators, their interaction, as well as the imbalance of angiogenic factors in psoriatic arthritis. The information is presented with identification of the leading typical pathological processes: inflammation and microcirculation disorders, formed due to the activation of protein cascades and interaction of molecular proinflammatory mediators and angiogenic factors. It is known that the clinical phenotypes of psoriatic arthritis are diverse. A deeper understanding of the pathogenesis and changes in the predominant pathological process can become the basis for the development of a personalized treatment strategy based on the pathogenesis to minimize iatrogenic complications and economic costs, as well as for the introduction of modern diagnostic methods for verification, differentiation, and monitoring of psoriatic arthritis in order to timely correct drug treatment.

Bronchial asthma (BA) remains one of the most common chronic respiratory diseases in childhood. BA develops with a combination of genetic predisposition and environmental factors. Epidemiological data on the development of BA emphasize the role of early-life microbiota in the formation of immune responses and susceptibility to the development of BA. In recent years, enough data has been accumulated to suggest that an imbalance in intestinal and airway microbiota during early life may predispose a child to the development of BA. In turn, the biodiversity of the environment influences the colonization of various biotopes in the human body by microorganisms. The study of the mechanisms of interaction between microbiota communities of the environment and humans will pave the way for the development of new strategies for the prevention of BA.

The aim of this review was to analyze current research aimed at assessing the importance of biodiversity of human microbiota and environment in the susceptibility to the development of BA in children.