Molekulyarnaya Meditsina (Molecular medicine)

Introduction. Glutamate receptors are involved in modulating key T-lymphocyte functions, including proliferation, chemotaxis, and others. In the context of the immunopathogenesis of multiple sclerosis (MS), studying the mechanisms underlying these effects is of great scientific and practical interest.

The aim of the study. To investigate the molecular mechanisms underlying AMPA receptors (AMPARs) in T-lymphocyte adhesion in MS.

Material and methods. The study involved peripheral blood lymphocytes from healthy donors and MS patients. The effects of AMPAR glutamate agonists and antagonists on T-cell adhesion were determined using human umbilical vein endothelial cells as an in vitro model of the blood-brain barrier. The effect of glutamate AMPAR receptor ligands on the expression of the adhesion molecule VLA-4 (Very late antigen-4) by various T-helper cell subsets was studied using flow cytometry.

Results. According to the study results, cells from MS patients in the acute stage were most sensitive to the effects of glutamate AMPAR ligands. Their action resulted in changes in the level of T-cell adhesion to endothelial cells, as well as in the surface expression of the key adhesion molecule VLA-4. Importantly, the NBQX antagonist inhibited VLA-4 expression primarily in subsets of T-helper cells types 1, 17, and 17.1. The observed heterogeneity in the response of T-lymphocyte subsets likely reflects differences in sensitivity to the functional state of AMPA receptors or the involvement of cells in the adhesion process.

Conclusion. AMPA glutamate receptors have been shown to be involved in modulating the adhesion of T-lymphocyte subsets pathogenetically significant for MS. The importance of this glutamate receptor subtype increases during disease exacerbation. These identified functional features of glutamate neurotransmitter receptors contribute to our understanding of the pathogenesis of MS and the development of new approaches to pharmacotherapy.

Introduction. The incidence of eosinophilic esophagitis is 5.31 cases per 100,000 person-years. It is a multifactorial disease with a clear genetic predisposition, specifically involving the expression of the thymic stromal lymphopoietin and IL-33 genes. Eosinophilic esophagitis in the pediatric population is of scientific and clinical interest due to its distinct pathogenetic features. It is essential to emphasize the importance of comparative pathomorphological analysis of esophageal mucosal changes in children across different age groups, while also accounting for sex-based differences.

Purpose of the study. To determine the morphological criteria for eosinophilic esophagitis in children and evaluate their diagnostic significance for confirming the diagnosis and differentiating it from other inflammatory esophageal diseases.

Material and methods. This retrospective study included 76 children with eosinophilic esophagitis (ICD-10: K20; ICD-11: KB81.0) and 30 children in the control group without esophageal diseases. Inclusion criteria: age 1–18 years, confirmed EoE diagnosis with peak eosinophil count ≥ 15 cells per high-power field. Patients with other inflammatory gastrointestinal diseases were excluded. Methods: clinical examination, endoscopy with biopsy (≥ 6 samples), histological assessment using the EoEHSS scale (8 criteria), and statistical analysis.

Results. Morphological examination of esophageal mucosal biopsies in children with clinical signs of eosinophilic esophagitis revealed characteristic histological changes confirming the diagnosis. In all cases, there was an increase in eosinophil count in the epithelial layer – from 15 to 80 cells per high-power field. Most patients (approximately 70%) showed uneven infiltration with focal eosinophil accumulations and degranulation. In 62% of cases, eosinophil microabscesses were identified, predominantly in the superficial epithelium. In addition to eosinophilic infiltration, 58% of children exhibited signs of spongiosis and acanthosis of the epithelium, thickening of the basement membrane, and moderate interstitial fibrosis of the lamina propria. In isolated cases (about 20%), superficial erosions and mild neutrophilic infiltration were noted. Comparison of morphological data with clinical manifestations showed that the severity of eosinophilic infiltration correlated with disease duration and dysphagia severity. Children with recurrent EoE exhibited more pronounced epithelial structural changes, including basal layer hyperplasia and subepithelial fibrosis. Thus, the results confirm that morphological examination of esophageal biopsies is a key method for verifying eosinophilic esophagitis in children and should be considered a mandatory step in the diagnostic algorithm for this condition.

Conclusion. Eosinophilic esophagitis in children is characterized by pronounced inflammatory and structural changes in the esophageal mucosa, which progress with age. The data underscore the importance of comprehensive diagnostics using morphological assessment and biopsy, even in the absence of visible endoscopic changes.

Background. Pollinosis is a progressive allergic disease mediated by an IgE-dependent reaction associated with the activation of inflammatory processes, oxidative stress and lipid peroxidation, which affects, first of all, the membrane structures of various cells of the body, changing their structure and functional properties. This applies primarily to the most numerous and long–functioning group of blood cells, red blood cells. Studying the state of antioxidant and immune defense systems, free radical oxidation processes, and lipid peroxidation at the tissue and cellular levels, using serum and erythrocyte mass, opens up new prospects for understanding the mechanisms of metabolic shifts in hay fever and establishing the possibility of additional diagnosis and prevention of allergic diseases.

Aim. To study the direction of metabolic shifts in the antioxidant and immune defense system in residents of the Krasnodar Territory who suffer from pollinosis.

Material and methods. A blood test was performed on individuals suffering from hay fever (n = 100) and healthy volunteers (n = 100). The study group was divided into four subgroups: individuals with аllergic rhinitis caused by pollen of allergenic plants (AR) (n = 10); AR in combination with аllergic conjunctivitis (AC) (n = 57); bronchial asthma with a predominance of an allergic component (BA) (n = 13); AR+AC+BA (n = 20). The ELISA method was used to determine the level of total IgE in blood serum. Metabolic shifts in oxidative homeostasis were assessed by the activity of superoxide dismutase and the level of malondialdehyde in hemolysate.

Results. А pronounced imbalance in the antioxidant system of the body of patients with pollinosis, especially in its comorbid conditions (AR+AС; AR+AС+BA), was established. A significant increase in the level of malondialdehyde (2.8 times; p < 0.001), total IgE (8.6 times; p < 0.001), was observed compared to the control group. A moderate increase in superoxide dismutase activity indicates a compensatory reaction of antioxidant protection, but not sufficiently pronounced to suppress the developing oxidative process in pollinosis.

Conclusion. The data obtained highlight the relationship between IgE hyperproduction, oxidative stress, and insufficiency of the antioxidant defense systems in pollinosis. An integrated approach aimed at suppressing the hyperimmune response and correcting the oxidative imbalance can improve measures to control the development, course, and prevention of allergy complications.

Introduction. Ovarian cancer is characterized by high mortality. Despite available diagnostic and therapeutic methods, patient survival remains unsatisfactory, especially for high-grade tumors, necessitating the exploration of new molecular targets. Heat shock proteins Hsp27 and Hsp90, which regulate cellular stress and survival, are considered key factors in tumor progression.

Objective. To conduct a comparative assessment of the immunohistochemical detection of Hsp27 and Hsp90 in high- and low-grade serous ovarian carcinomas with separate evaluation of the nuclear and cytoplasmic localization of the reaction.

Material and methods. The prospective study (NCT04817501) included 58 patients with newly diagnosed ovarian cancer. Of these, serous cancer (FIGO stages I-IIIC) was verified in 49 patients: 36 HG cases and 13 LG cases. Paraffin-embedded tumor tissue blocks obtained before treatment were studied. The study material consisted of paraffin blocks from biopsy and surgical tumor specimens. The proportions of Hsp27- and Hsp90-positive cells in the tumor and stromal components were assessed by immunohistochemistry followed by digital analysis of scanned images (Aperio AT2, Leica; QuPath software).

Results. Significant differences were revealed in the tumor component between the HG and LG groups. The proportion of Hsp27-positive tumor cells with cytoplasmic and nuclear localization of the immunohistochemical reaction was significantly higher in the HG group than in the LG group (p = 0.02). No significant differences in Hsp90 were found between the groups in either the stromal or the tumor component.

Conclusion. Differences in the immunohistochemical detection of Hsp27 and Hsp90 in the tumor and stromal components of ovarian carcinoma, as well as a significant increase in the proportion of Hsp27-positive tumor cells in HGSC compared with LGSC, indicate the potential diagnostic and prognostic value of Hsp27. Furthermore, the obtained results indicate the potential of chaperone-targeted therapy as a promising direction that requires further research.

This review systematizes current data on branched-chain aminotransferases (BCATs). Their molecular structure, classification as fold type IV pyridoxal phosphate (PLP)-dependent enzymes, and catalytic features are discussed in detail. The differences between the two main isoenzymes — mitochondrial (BCATm) and cytosolic (BCATc) — their tissue specificity and functions are highlighted. The key role of BCATs in BCAA metabolism is outlined, including the regulation of protein synthesis via the mTOR pathway, glucose and nitrogen homeostasis. Particular attention is paid to the pathogenetic significance of BCATs: their involvement in the development of neurodegenerative diseases (via the synthesis of the neurotransmitter glutamate), oncological processes (glioblastoma, leukemias, gastric and breast cancer), as well as their association with insulin resistance and aging. The potential of BCATs as targets for pharmacological intervention, specifically the inhibition of BCATc by gabapentin, is discussed. The prospects for studying BCATs to develop new therapeutic strategies for metabolic, neurological, and oncological diseases are considered.

Relevance. Modern approaches to detecting circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) demonstrate high potential for improving the accuracy of molecular diagnostics of tumors and require a comprehensive analysis of all stages, from the biology of fragments to computational data processing methods.

Results. This review systematizes the key biological, preanalytical, laboratory, and bioinformatic factors that determine the sensitivity of a liquid biopsy. The parameters affecting the preservation and representativeness of cfDNA are considered in detail, including the size profile of fragments, the effects of apoptosis and necrosis, as well as the variability of DNA concentration depending on the type of tumor and the stage of the disease. Special attention is paid to strategies that can significantly improve the detection of low-fraction mutations even with minimal tumor burden. These include the optimization of nucleic acid extraction processes, the use of unique molecular identifiers, deep targeted sequencing, and the combination of data from different technology platforms. It is shown that progress in the methods of purification and stabilization of samples, the improvement of NGS platforms and the introduction of machine learning algorithms are critical conditions for improving the accuracy, reliability and reproducibility of the results. Additionally, approaches to the integration of multidimensional data and the use of advanced statistical models are discussed, allowing to reduce the level of background errors and increase the specificity of the analysis.

Conclusion. The findings emphasize the importance of the integrated implementation of these technologies to accelerate the translation of liquid biopsy into clinical practice, expand its diagnostic capabilities and earlier detection of tumor diseases.

Cardiovascular diseases remain one of the main causes of hospitalization, disability, and mortality. The usual monitoring model and rare face-to-face visits often do not keep up with the actual clinical dynamics. This partly explains the growing interest in wearable devices and telemedicine support formats. The doctor no longer has individual measurements at his disposal, but sequential physiological series of data on rhythm, heart rate, motor activity, sleep, and in some cases, electrocardiographic parameters. The scenarios related to the detection of atrial fibrillation, telemonitoring for heart failure, telerehabilitation for coronary heart disease, and assessment of functional status based on daily activity data are the best studied today. However, the clinical value of these technologies is determined not by the fact of their use, but by the degree of validation of the received signals, the quality of data inclusion in the treatment route, and the doctor’s ability to distinguish significant changes from digital noise. Within the framework of personalized medicine, wearable devices should be considered as a source of additional information about the patient’s phenotype, including reflecting the state of autonomous regulation, the inflammatory background, signs of endothelial dysfunction, processes of myocardial remodeling and neurohumoral shifts. However, the direct integration of digital parameters with molecular biomarkers is currently used mainly in scientific research, without proper development in clinical practice.