Preview

Proceedings of the National Academy of Sciences of Belarus, Medical series

Advanced search
Vol 21, No 2 (2024)
View or download the full issue PDF (Russian)
https://doi.org/10.29235/1814-6023-2024-21-2

CLINICAL AND EXPERIMENTAL MEDICINE

95-103 266
Abstract

The high biological potential of the developed genetically engineered plasmid construct pcDNATM3.1(–) VEGF165 has been established. It has been proven to induce a significant increase in the expression of the gene VEGF165 in mesenchymal multipotent stromal cells and human endothelial cells and to increase the production of the VEGF165 protein by cells. The identified temporary functional activity of the genetically engineered construct in cells and the absence of genotoxic effects minimize the likelihood of oncotransformation.

The created genetically engineered vector construct pcDNATM3.1(–) VEGF165 can be used to develop a gene therapy drug model that promotes angiogenesis in vivo in ischemic tissues.

104-115 356
Abstract

The genomes of the bacteria Streptococcus mutans and Streptococcus sobrinus, which cause dental caries, currently have been fully sequenced. However, the secondary and tertiary structures of the full-size surface proteins of these microorganisms, by which they attach to the surface of teeth covered with saliva, have not been instrumentally determined at the moment. There are a number of experimental studies on the use of these proteins in the process of developing a dental caries vaccine. However, there is currently no commercially available dental caries vaccine.

The aim of the study was to choose an antigen for subsequent molecular modeling of a unique peptide for the development of a dental caries vaccine.

To develop an effective and safe dental caries vaccine, it is necessary to perform a number of experiments in silico, preceding experiments in vitro and in vivo. Today, this approach is not only generally recognized, but also allows to significantly reduce the cost of experiments and time at the preclinical and clinical studies. According to our hypothesis, as an antigen for the development of a dental caries vaccine, it is necessary to use a short fragment of the surface protein (a peptide) of Streptococcus mutans and/or Streptococcus sobrinus, whose homology in amino acid sequence is 84.8  %, the spatial structure of which should correspond to the spatial structure of the corresponding fragment in a full-sized protein. In addition, the selected protein fragment, which will be part of the vaccine peptide, must be available to antibodies, i. e. located on the surface of the protein and defined as a B-cell linear and spatial epitope. Also, according to our hypothesis, the vaccine peptide may consist of the most stable fragments of alanine and proline rich regions of the surface protein of Streptococcus mutans and/or Streptococcus sobrinus for mutual stabilization of the spatial structure.

116-124 180
Abstract

A new system of targeted delivery of tissue plasminogen activator tenecteplase for restoration of coronary blood flow in acute myocardial infarction in animal experiments was developed.

The new system of targeted delivery of fibrinolytic consists of native (“free”) and encapsulated (“bound”) tenecteplase in liposomes, in the percentage ratio (60 and 40 %, respectively), which are conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies Fnl-3C.

The physicochemical characteristics of the obtained liposomes conjugated with fibrin-specific monoclonal antibodies (immunoliposomes) with tenecteplase were determined: immunoliposomes have a hydrodynamic diameter of ~76‒77 nm, a zeta potential of ~(‒33) mV, a polydispersity index of ~0.55. Modification of liposomes with fibrin-specific monoclonal antibodies does not alter thrombolytic activity.

When using immunoliposomes the survival rate of animals with acute myocardial infarction is ~90 %, liposomal and native form of the drug ‒ 80 %.

The use of immunoliposomal delivery system in animals with acute myocardial infarction leads to an increase in the free lumen of the infarct-related artery (p < 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with>< 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with immunoliposomes decreases (p < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase. The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment> < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase.

The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment.

125-137 186
Abstract

Informatization in transfusiology and hemostasiology is a relevant and modern direction that allows for organizational and methodological support, planning of therapeutic measures, distribution of components and blood products, taking into account the level and volume of medical care in the country, region, healthcare institution and also the provision of medical care in emergency situations.

Information and analytical systems (IAS) are developed taking into account legal, administrative, methodological and clinical and laboratory criteria in order to record, analyze, generate reports and plan medical events, as well as make production decisions using the international standard for the exchange of medical data HL7 FHIR, Web-applications and assume privacy, real-time operation.

At present, several IASs have been developed and implemented in the Republic of Belarus. Along with the blood donor registration system (AIS Donor), which has been functioning for many years, they form the basis of the transfusion-hemostasiology cluster, which contributes to ensuring the high quality of medical care and is implemented through interregional and interstructural cooperation aimed at ensuring the timeliness, safety and efficiency of patient care.

138-148 143
Abstract

The aim of the study was to assess the distribution of polymorphic variants G681A (*2) of the CYP2C19 gene, H1/H2 of the P2RY12 gene, T1565C of the ITGB3 gene, C807T of the ITGA2 gene, and T786C of the eNOS3 gene in the population of the Grodno region, and to study their associations with myocardial infarction (MI). The study of the population consists of 493 people, including 400 patients with MI aged 31 to 74 years and 93 people of the control group aged 32 to 60 years. Research data (clinical and genotyping performed by polymerase chain reaction) were analyzed using STATISTICA 10.0 software. The prevalence of carriage of genotypes associated with high residual platelet reactivity and variability in response to dual antiplatelet therapy among patients with MI was 25.2 % for the G681A polymorphic locus of the CYP2C19 gene (GA + AA), and for the H1/H2 polymorphic locus of the P2RY12 gene (H1/H2 + H2/H2) – 40.0 %, for the C807T polymorphic locus of the ITGA2 gene (CT + TT) – 65.8, for the T1565C polymorphic locus of the ITGB3 gene (TC + CC) – 25.5, for the polymorphic locus T786C of the eNOS gene (TC + CC) – 69.2 %. Among the individuals of the control group, the frequency of occurrence of these genotypes was 18.3, 46.2, 60.2, 37.6, 48.4 %, respectively. In patients with MI, compared to the control group, the TT genotype of the eNOS gene was less common (χ2   =  13.6, p  =  0.0002), the CC genotype of the eNOS gene (χ2 = 5.4, = 0.02) and the allele 786C of the eNOS gene (χ2 = 15.1, p = 0.0001) were more often detected. The carriage of the 786C allele of the eNOS gene increased the risk of MI in the studied population (OR = 2.0, 95 % CI: 1.41‒2.82, = 0.0001). Gender differences were not found in the distribution of genotypes and alleles within the studied groups. There were no differences in carriage by the number of combinations of minor alleles between the control group and patients with MI. The most common combinations of minor alleles in both groups were comparable.

149-155 160
Abstract

One of the promising directions for development of new pharmacological drugs for analgesia and other consequences of peripheral nerve damage is the study of the physiological effects of fatty acid amides. The potential selectivity of G-protein receptor antagonists has been evaluated using molecular docking and quantum chemistry methods, and its complexes with fatty acid amides have been constructed. As a result of docking, it was found that PSB-CB5 is a selective antagonist for GPR18 receptors, and O-1918 is a selective antagonist for GPR55. It was found that stable complexes are formed between fatty acid amides (REA, SEO) and orphan receptors (GPR 18, GPR55). Numerous van der Waals contacts and hydrogen bonds play a major role in the interaction of these compounds with receptors.

156-167 148
Abstract

The paper analyzes the results of virus detection in patients of different age at the time of sporadic and group morbidity of acute gastroenteritis (AGE). Enteric viruses were detected in the biological material of 1864 patients with sporadic cases of AGE in 2020‒2022 and in the biological material of 443 patients from 52 episodes of AGE group morbidity in 2009‒2021.

Among enteric viruses found in 53.7 % of patients with sporadic AGE cases rotaviruses A were predominated (27.0 %), followed by genogroup 2 noroviruses (13.8  %), adenoviruses F (5.3  %), enteroviruses (2.5  %), genogroup 1 noroviruses (0.4 %). Mixed virus–virus infection was detected in 7.4 % of patients. In AGE group morbidity, genogroup 2 noroviruses were the main etiological agents ‒ they caused 63.5 % of episodes, whereas genogroup 1 noroviruses ‒ 11.5 %, rotaviruses A ‒ 5.8 %, enteroviruses and sapoviruses ‒ 3.9 % of each. Prevailing age group among people with the sporadic cases of AGE were children ≤5 years old, while the main part of the AGE group episodes was registered among children aged 6‒17 years and adults. Depending on the age of patients, the frequency of detection of various enteric viruses had significant differences: among children ≤5 years old with sporadic AGE, the main etiologic agents were rotaviruses A, whereas genogroup 2 noroviruses were detected 2.5 times less often (p <0.001), among children aged 6‒17 years and adults, rotaviruses and genogroup 2 noroviruses were detected with equal frequency. Adeno- and enteroviruses were found more often in children from 0 to 17 years old than in adults.

The presented results indicate a significant contribution of enteric viruses to the incidence of AGE in our country. Moreover, this contribution is not limited by rotaviruses A only, but is largely formed by other enteric viruses, especially genogroup 2 noroviruses.

168-176 181
Abstract

The cytoskeleton is a participant in key cell events in oncogenesis and the reaction of cancer cells to therapeutic factors. The state and structure of the actin cytoskeleton contributes significantly to the mechanical behavior of cancer cells, forming the main features of their mechanical phenotype.

In the work, using atomic-force microscopy and fluorescent microscopy, we studied the changes in the structure of the actin cytoskeleton and parameters of the mechanical properties of breast cancer cells of different molecular biological subtypes (hormone-sensitive, line ZR-75, and triple-negative, BT-20 line, subtypes) when cells interact with the CD109 antigen, a TGF-β signaling pathway inhibitor. The use of antibodies for immobilizing the CD109 antigen has been shown to cause significant changes in the spatial organization of the actin cytoskeleton, stiffness and adhesive properties of the cell surface of both cell lines. Because of differences in the structure of the actin cytoskeleton, changes in the mechanical properties of the cells of different molecular biological breast cancer subtypes and the implementation of the TGF-β signaling pathway in these cells when binding to antibodies against the CD109 antigen occur in different ways. The obtained data open new perspectives for the development and evaluation of the effectiveness of anticancer drugs.



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1814-6023 (Print)
ISSN 2524-2350 (Online)