卷 23, 编号 3 (2025)

Purpose of the review. The purpose of this review was to summarize the available relevant data on pathogenetic mechanisms in the formation of steroid resistance in severe bronchial asthma.

Material and methods. The analysis of domestic sources on the CyberLeninka and e-Library scientific electronic libraries, and the search for published foreign full-text articles, reviews, systematic reviews, meta-analysis data and randomized clinical trials in PubMed/Medline were conducted to summarize relevant material on the pathophysiology of steroid-resistant asthma. In addition, a reverse search was conducted for links to relevant studies. Publications from 2020 to 2024 were considered for consideration. The analysis included full-fledged articles and the results of clinical trials containing information on key cytokines of neutrophilic asthma: IL-33, IL-17, TNF, IFNγ. A search for the term “steroid-resistant asthma” for the specified period (2020–2024) initially revealed a list of 93 articles. 62 articles presented in the form of abstracts or not corresponding to the target topic were excluded from the general list. A total of 31 publications from an electronic search in the PubMed database and 17 articles additionally found using a manual search were included in the analysis.

Results. Bronchial asthma (BA) is an extremely heterogeneous respiratory disease characterized by airway obstruction, bronchial hyperreactivity, and airway inflammation. About 3-10% of asthma patients suffer from uncontrolled severe asthma. The main difference between patients with severe form of the disease and patients with mild and moderate asthma is resistance to basic therapy drugs – glucocorticosteroids. Severe bronchial asthma is heterogeneous and includes different immunophenotypes: Th2-high (eosinophilic inflammation), Th2-low and Th17-high (non-eosinophilic inflammation accompanied by neutrophilic inflammation of the respiratory tract), mixed Th1/Th17-mediated inflammation.

Conclusion. The paper provides information for determining common points of interaction between different immune mediators and related mechanisms related to respiratory tract inflammation and the immunobiology of steroid-resistant asthma.

Introduction. Allergic bronchial asthma (BA) is accompanied by activation of histamine H₁/H₄ receptors and variable response to antihistamines.

The aim of this review is to analyze the molecular mechanisms of action of second- and third-generation antihistamine drugs, their pharmacokinetic features and pharmacogenetic aspects of application in bronchial asthma, as well as prospects for developing new drugs with improved characteristics.

Methods. Narrative review of the literature (PubMed/Scopus, 2019–2024), including data from cryo-EM structures of the H₄ receptor, single-cell RNA-seq profiles of bronchial epithelium and clinical pharmacogenetic studies of the CYP family (41 sources).

Results. Key signaling pathways (FcεRI–MAPK/NF-κB, IL-13/STAT6) indirectly targeted by H₁ blockers have been identified. Increased HRH4 expression in IL-13^high Th2 clusters has been shown to correlate with asthma severity. Modern cryo-EM models of H₄R have allowed us to refine the architecture of binding sites and optimize the design of promising ligands. CYP2D6 and ABCB1 polymorphisms account for up to 30–50% of interindividual variability in plasma concentrations of loratadine/desloratadine and bilastine according to clinical cohort data.

Conclusion. Integration of omics data and pharmacogenetic testing opens the way to targeted and personalized asthma therapy with antihistamines.

Introduction. Thanks to advances in modern medicine, it has been possible to significantly increase life expectancy. With the high effectiveness of methods for diagnosing and treating many chronic pathologies, a sharp increase in the number of elderly patients is expected. This cohort of patients has features including polymorbidity; polypharmacy, and low compliance. Taking direct oral anticoagulants (DOACs) is associated with a risk of hemorrhagic complications, which can be difficult to predict in elderly patients, especially those with impaired renal function.

Objective. To evaluate factors that increase the risk of taking direct oral anticoagulants in elderly patients with polypharmacy and chronic kidney disease based on the analysis of molecular and genetic markers.

Material and methods. For this study, a database was collected that included 503 patients observed at the Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department” for the period from April to September 2023 with atrial fibrillation and stage 2C–4C kidney disease. The questionnaire method was used, as well as the collection of clinical and laboratory data to evaluate DOAC-dependent complications – cases of bleeding, duration of DOAC administration. Additionally, molecular markers of endothelial dysfunction and inflammation were determined, as well as genetic polymorphisms associated with DOAC metabolism in kidney tissues.

Results. DOAC administration increases bleeding risks with a significant decrease in creatinine clearance (less than 45 ml/min/1.73m²), especially with dabigatran. This observation regarding dabigatran applied to patients in CKD stages C2 and C3a; with creatinine clearance less than 45 ml/min/1.73 m², this drug was rarely used. The use of apixaban and rivaroxaban does not have a statistically significant increase in the incidence of hemorrhagic complications as renal failure progresses. A correlation was found between the level of molecular markers of endothelial dysfunction (eNOS, VEGF) and the risk of developing DOAC-dependent bleeding. Patients with the rs2032582 single nucleotide polymorphism of the ABCB1 (MDR1) gene had an increased risk of hemorrhagic complications when taking dabigatran.

Conclusion. The study of drug interactions and the association of DOAC intake with various endpoints in larger samples will help identify molecular and genetic predictors of adverse outcomes and adjust therapy. A personalized approach to DOAC prescription based on the assessment of kidney function, molecular markers of endothelial dysfunction, and the patient's genetic profile can significantly reduce the risk of hemorrhagic complications in geriatric patients.

Relevance. Iron deficiency anemia is a disease present all over the world and maintaining a high incidence rate of both general and primary morbidity despite various options for correction and prevention of this pathology. Molecular genotyping opens up new possibilities for understanding the pathogenetic mechanisms of disease development, as well as for finding a more targeted and personalized approach to therapy.

The aim of the study was to determine genetic markers of the risk of iron deficiency anemia by assessing polymorphic variants of rs235756 of the BMP2 gene, rs855791 of the TMPRSS6 gene, rs104894696 of the HAMP gene, rs4820268 of the TMPRSS6 gene and rs3817672 of the TFR1 gene.

Material and methods. The study included 97 patients with mild iron deficiency anemia and 120 people in the control group. Genotyping was performed by real-time polymerase chain reaction using primers and probes selected using the open online resource PrimerBlast (https://www.ncbi.nlm.nih.gov/tools/primerblast/).

Results. Genetic markers of the risk of developing IDA were identified: rs235756 of the BMP2 gene, rs855791 of the TMPRSS6 gene and resistant course of IDA: rs4820268 of the TMPRSS6 gene. This allows us to recommend determining these genetic markers when examining patients with iron deficiency anemia who do not respond to therapy with iron-containing drugs.

Conclusion. The identified marker profiles of IDA genotypes can optimize the approach to diagnosis, treatment and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease.

Introduction. It is assumed that in degenerative diseases of the retina, photostimulation with fractal dynamics signals activates neuroplasticity, increasing the effectiveness of visual rehabilitation. Previously, we demonstrated the positive effect of fractal optic stimulation (FS) on the intraocular synthesis of neurotrophins in rabbits without ophthalmopathology and proved the safety of long-term courses of photostimulation for the retina.

Purpose of the study: to evaluate changes in the intraocular production of neurotrophic cytokines against the background of the use of low-intensity fractal optical therapy in the model of retinal pigment epithelium (RPE) atrophy in an in vivo experiment.

Material and methods. The study material was vitreous body (VH) samples of 38 (76 eyes) Soviet Chinchilla rabbits with a model of RPE atrophy.

Depending on the type of exposure used, animals with RPE atrophy were divided into groups: the main group – 18 animals (36 eyes – FS), the control group – 18 animals (36 eyes – exposure to light from an incandescent lamp). The comparison group consisted of 2 rabbits (4 eyes) with RPE atrophy without exposure. Photostimulation sessions were carried out daily. The duration of each FS session was 20 minutes. The duration of FS courses ranged from 7 to 90 days. The concentrations of BDNF, CNTF, IL-6, NGF, and PEDF were determined in the CT samples using enzyme immunoassay. The results were recorded using a Cytation 5 multifunctional photometer.

Results. PEDF, BDNF, and NGF were detected in 100% of the CT test samples from the main and control groups of animals. IL-6 was detected only in 1 case, and CNTF was not detected in the samples. For the first time, the dynamics of intraocular production of neurotrophic factors was determined under the influence of fractal photostimulation on a model of RPE atrophy. Under the influence of FS, the level of BDNF production statistically significantly increased in the eyes of animals with RPE atrophy and indicated the initiation of reparative mechanisms in the retina in response to RPE damage. With an increase in the duration of the course of light stimulation in the main and control groups, a gradual weakening of the intraocular BDNF synthesis was noted, more rapid in the control group. Of particular interest were the changes in intraocular PEDF production under the influence of FS courses of different durations: individual analysis demonstrated an increase in intraocular cytokine production in 16.7% of eyes after a 1-week course of therapy with a maximum level of 58.7 pg/ml, an increase in the number of therapy sessions led to a significant decrease in its concentration in the CT in 80% of cases.

Conclusion. The results of the study allow us to conclude that FS affects the production of neurotrophic factors in RPE atrophy in the experiment: the most noticeable effects were found in relation to PEDF and BDNF. Individual analysis of changes in local PEDF synthesis indicates the advisability of prescribing a 1-week FS course lasting 1 week in the treatment of macular pathology associated with impaired RPE function, photoreceptors (for example, in AMD). The data obtained seem important for the development of the FS method and its translation into the clinic for visual rehabilitation of patients with neurodegenerative diseases of the retina.

Introduction: Studying the relationship between functional dyspepsia and gut microbiota will provide insight into the role of individual microorganisms and their metabolic products in the development of this pathology. The aim of the study was to analyze the microbiota of patients diagnosed with functional dyspepsia.

Materials and methods: Using the Ion Torrent PGM platform, sequencing of the V3 region of the 16S rRNA gene was performed.

Results: Differential analysis of the abundance showed that patients with dyspepsia have Corynebacterium jeikeium and Eggerthella lenta bacteria in the intestines, which have previously been associated with a number of inflammatory diseases. A relationship was established between Erysipelotrichaceae UCG-003 bacterium, Fusicatenibacter saccharivorans and Turicibacter sanguinis and dyspepsia.

Conclusion: The fecal microbiota characteristics of patients with dyspepsia were studied. The results showed a relationship between individual species and this pathology. For the first time, the relationship between the species Erysipelotrichaceae UCG-003 bacterium, Fusicatenibacter saccharivorans and Turicibacter sanguinis and functional dyspepsia was demonstrated.

Introduction. Studying the effect of the nitric oxide (II) donor, S-nitrosoglutathione, on the relative amount of selectin P in HUVEC cell lysates in vitro may contribute to fundamental understanding of the effect of the nitric oxide system on the adhesive function of the endothelium.

Objective: To evaluate the effect of nitric oxide (II) donor S-nitrosoglutathione (GSNO) on the activity of mitochondrial endotheliocyte oxidoreductases, the relative amount of selectin P and nitric oxide metabolites in HUVEC cell lysates, and the absolute amount of sP-selectin (soluble) in a conditioned medium.

Material and methods. The mitochondrial dehydrogenase activity of HUVEC cells was evaluated using an MTT test. The relative amount of P-selectin in endotheliocyte lysates was determined by the Western blot method, the absolute amount of the soluble selectin fragment (sP) in the cellular supernatant was determined by the sandwich ELISA method, the level of persistent nitric oxide (II) metabolites was determined by the method based on the reduction of nitrates to nitrites in the presence of vanadium chloride and subsequent spectrophotometric detection using Griss reagent.

Results. The study found that upon joint incubation of the primary HUVEC cell line with nitrosoglutathione solutions in various concentrations, the development of nitrosative stress is noted, as evidenced by an increase in its markers – persistent nitric oxide (II) metabolites in cell lysates. Under conditions of nitrosative stress, there is a decrease in the activity of mitochondrial endotheliocyte oxidoreductases, which may be due to the negative effects of excess nitric oxide or its toxic products. With a three-hour exposure of nitrosoglutathione to endotheliocytes at a low concentration of 10 mkM, there is a statistically significant increase in the relative amount of P-selectin; at high concentrations of 100-500 mkM, there is a statistically significant decrease in the relative amount of P-selectin.

Conclusion. The results obtained in this study indicate the effect of nitric oxide (II) on the functional response of the endothelium by quantifying the cell adhesion molecule P-selectin.