Molekulyarnaya Meditsina (Molecular medicine)

Introduction. This review is devoted to the study of the structure, properties, evolution of hemoglobins, biochemical and clinical aspects of the use of neuroglobin (Ngb) and fetal hemoglobin (HbF) in health and in ischemic hypoxia of the brain.

Material and methods. To search for relevant literature, we used the eLibrary, MedLine and ScienceDirect databases from 2000 to 2023. The data on Ngb and HbF are analyzed, mainly concerning the issues of diagnostics and treatment of hypoxic lesions of the central nervous system.

Results. The review begins with the structural organization of penta- and hexacoordinated hemoglobins. The evolution of hemoglobin genotypes from bacterial hemoproteins, currently represented by the Ngb protein, to the evolutionarily youngest HbF of placental mammals is presented. The diversity of hemoglobins allows us to assume that the transport function of vertebrate hemoglobins appeared relatively recently during adaptation to the increasing concentration of oxygen in the atmosphere, and the most ancient functions of hemoglobins should be enzymatic (utilization of NO and oxygen) and sensory (in relation to oxygen). Ngb is found in brain tissue, retina, some endocrine glands of mammals and humans. Functions of Ngb: participation in NO metabolism, detoxification of active oxygen species (ROS), protection from apoptosis, signal transmission, participation in lipid metabolism. As for HbF, the physicochemical properties of this hemoglobin have been studied for quite a long time, and a broader clinical study of Ngb and HbF in various pathologies is associated with the problem of diagnostic test systems for these hemoproteins.

Conclusion. Ngb is a promising drug for protecting cells from hypoxia and neuronal death, and Ngb-based drugs can find application in a variety of medical fields. As for HbF, the development of ELISA for HbF in blood hemolysates opens up new prospects for diagnosing hypoxic and ischemic central nervous system lesions.

Objective. To analyze the potential risks and technological limitations of using genome editing methods in neurodegenerative diseases, as well as to assess the prospects for their implementation in clinical practice.

Material and methods. A systematic analysis of the literature for the period 2014–2024 in the databases PubMed, Cochrane Library, ClinicalTrials.gov, SAGE Premier, Springer and Wiley Journals. The key risks of using genome editing technologies are considered, including inappropriate effects, immunological reactions, and long-term consequences of changes in the DNA of nervous tissue.

Results. The main technological limitations are analyzed, including problems of delivery across the blood-brain barrier, low editing efficiency in postmitotic neurons, and the complexity of long-term expression of components of editing systems. The prospects of introducing technologies into clinical practice are assessed, taking into account the current regulatory landscape in various countries.

Conclusion. Despite significant technological challenges and potential risks, the development of genome editing techniques opens up prospects for the creation of effective treatments for neurodegenerative diseases. Key areas of further research include improving the safety and specificity of editing, optimizing delivery systems, and developing methods for long-term monitoring of the effects of genetic modifications in the nervous system.

Introduction. Type 1 diabetes mellitus is a chronic autoimmune disease associated with severe complications of organs and systems, including complications of the course of dental diseases.

Material and methods. Results of 55 patients with type 1 DM became the material of laboratory-diagnostic studies. Patients with type 1 diabetes were divided into 2 groups depending on blood glucose levels: Group 1 (n=28) – patients with glucose levels ≥7 mmol/l; Group 2 (n=27) – patients with glucose levels ≤7 mmol/l; Control group – 28 patients. Periodontal tissues were evaluated by indices: PMA, SBI. OHI-S index reflected the state of oral hygiene. Mucosal immunity of oral fluid was studied using ELISA analysis of pro- and anti-inflammatory cytokines IL-8, IL-10, IL-1β, MCP-1, TNF-α, VEGF-А.

Results. The content in unstimulated oral fluid of IL-1β in patients with type 1 DM was 84.1 (95–74.6) pg/mL in the group with glucose ≤ 7 mmol/L, 80.1 (115.4–64.9) pg/mL in the group with glucose ≥7 mmol/L, 23.1 (28.2–18.6) pg/mL in the comparison group, VEGF-A was 1340 (1545–967.5) pg/mL, 1170 (1517.5–954.8) pg/mL in group 2, and 1655 (1860–1370.5) pg/mL in group 3. TNF-α was higher in group 1 – 9.8 (11.4–7.5) pg/mL than in group 2 – 8.3 (10.3–6.6) pg/mL and in group 3 – 1 (1.1–0.9) pg/mL (p < 0.05).

Conclusion. ROC curve analysis showed that these biomarkers have better sensitivity and specificity. The increase of IL-8, TNF-α, IL-1β content in mixed saliva up to 285.5 (339.8–214.5) pg/ml, 9.8 (11.4–7.5), 84.1 (95–74.6) pg/ml, respectively, was characterized by high medians of OHI-s, PMA and SBI indices, associated with high activity of inflammatory-destructive changes in periodontal tissues and impaired metabolic control of glucose level.

Introduction. Bronchial asthma is an inflammatory disease manifested by various phenotypes. The most studied phenotype of asthma is allergic. Molecular allergodiagnostics of allergic diseases using microchips makes it possible to determine the molecular profiles of sensitization of patients with allergic asthma, to identify priority molecules for personalized allergen-specific immunotherapy.

Objective: to conduct a molecular analysis of the sensitization of adult patients with allergic bronchial asthma with aeroallergens in the Rostov region of southern Russia

Methods. In a multicenter, retrospective, non-randomized cohort study, data from Allergy Explorer 2 (ALEX2) allergy chips were analyzed in 166 adult patients with an allergic phenotype of bronchial asthma. Statistical processing of the results was carried out using the Microsoft Office Excel 2010 and Statistica 10.0 for Windows software package.

Results. Molecular analysis of sensitization showed that pollen sensitization with a predominance of IgE-mediated reaction to ragweed pollen was most common in the studied cohort of patients – an increase in the level of IgE to the main allergen component Amb a 1 (pectate lyase) was registered in 73 (43.98%) patients, sensitization to the allergen of wormwood pollen Art v 1 (defensin) was noted 39 (23.49%). Sensitization to allergens of mold and yeast fungi was recorded, with a predominance to mold fungi – the main molecule Alternaria alternata (Alt a 1) in 27 (16.27%), less often the enolase protein family (Alt a 6) in 2 (1.20%), the molecule Cladosporium herbarum (Cla h 8) in 1.20% (n=2), rarely to Aspergillus fumigatus, a molecule of the superoxide dismutase family (Asp f 6) in 5 (3.01%) of the examined patients. Among yeast fungi, sensitization was rarely found to the allergens Malassezia sympodialis: molecules (Mala s 5) and (Mala s 6) in 1 (0.60%) of the examined adult asthma, respectively.

Conclusion. The method of molecular allergodiagnostics used made it possible to establish not only the spectrum and level of sensitization, but also to identify allergocomponents that play a causally significant role in the development of the allergic phenotype of asthma in adult patients. The simultaneous period of flowering of herbs and sporulation of fungi in the region increases the antigenic load, which contributes to an increase in sensitization in adult patients with asthma in the Rostov region of southern Russia, the transformation of asthma into more severe forms, the expansion of causally significant allergens and mixed sensitization.

Introduction. In general, the physiological response of tissues to external stresses is not linear in accordance with Hooke's law. Biological tissues are known to exhibit a nonlinear relationship between stress and strain, although the origins of this nonlinearity remain incompletely understood. In the literature, authors over the years have proposed many forms of σ-ε correspondence, but this question is still open.

The aim of the study. The article formalizes the characteristics of the elastic properties of soft biological tissues. Elastic behavior is considered within the framework of a two-phase elastin-collagen bilinear model with a variable elastic modulus and its detailed statistical analysis is performed.

Methods. Calculations were performed using the computer algebra system Mathcad 15.0 using the built-in fitting functions linfit, genfit, pwrfit and corr. The residual parameters of the experimental and model data were assessed using descriptive statistics.

Results. The correlation range of empirical and model data was R=0.8696–0.9845, the median of the correlation coefficient was 0.9616, the coefficient of variation was CV=0.03, which indicates a strong connection between the studied random variables and the homogeneity of the calculation procedures. The critical value of deformation ε=ε_cr, at which the mechanism of tissue deformation changes from elastin to collagen in the tissues of living organisms (median 0.38) is quite variable (CV 1.06). The median of the bilinear model parameters E₁ and E₂ were set to 0.02 MPa and 8.0 MPa, the CV was 0.35 and 0.79, respectively. Data outlier points have been identified. Based on the calculations performed, it was concluded that the Young’s modulus of collagen fibers in the tissues of the studied organs is a significant number of times (greater than the elastic modulus of elastin structures; average value 3071.36, median 160.00, CV 0.29), which is consistent with the literature data. The stress-strain relationships of phenomenological models alternative to the bilinear one are obtained. As a numerical example, the tissues of the periodontal ligament of the human central incisor are considered.

Conclusion. To describe the mechanism of evolution of the deformation properties of biological tissues, the terminology of the physics of phase transitions, accompanied by a change in symmetry, is used. It is proposed to consider as an order parameter the measure of «involvement» of collagen structures in the overall resistance of tissues to deformation, which is determined by the degree of «linearization» of the branched collagen network in the direction of the action of uniaxial load.