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卷 18, 编号 2 (2020)
- 年: 2020
- 文章: 11
- URL: https://journals.eco-vector.com/1728-2918/issue/view/5766
- DOI: https://doi.org/10.29296/молмед.v18i2
Articles
ON THE POSSIBLE USE OF EXOGENOUS HISTONES AND CATIONIC PEPTIDES IN MOLECULAR BIOTECHNOLOGY
摘要
The prospect of developing transport systems using histones for delivery of therapeutic agents possessing poor penetration characteristics through cellular membranes and tissue barriers has been investigated. A review of the literary, as well as proper data, are presented concerning of mucoadhesive protein therapeutic agents. Delivery systems have been designed to obtain entrapment of protein therapeutic agents into nanoshperes during nanosphere preparation from dextran. Such mucoadhesive delivery systems containing histones immobilized on nanospheres for site-specific delivery of protein therapeutic agents to target (organ or tissue) for intranasal delivery. An increase in the mucoadhesive properties of dextran nanospheres with diameter of100-200nm coated by histones is due to electrostatic interaction of positively charged histones with negatively charged mucins of sialic acid, which leads to the formation of mucus layer and nanospheres associations over a long period of time. Moreover, the release of protein during nanospheres resorption can occur in mucus layer due to the fact that the protein will be absorbed paracellular or transcellular in the underlying epithelium of the mucous membrane. Further protein intake can be carried out along the olfactory epithelial route by means of axoplasmic transport along of olfactory neurons into the olfactory bulbs and from them using neuronal pathways in central nervous system. Histones immobilized on nanospheres can also be used to modify surfaces intended for cell cultivation. They can be applied as components to three-dimensional pore matrices that are designed for producing tissue-like structures in vitro.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):3-10
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PROTEASOME FUNCTIONING IN PRETUMORAL AND NEOPLASTIC HUMAN EPITHELIUM
摘要
The review describes the characteristics of the ubiquitin-proteasome system involved in proteins degradation and its role in the transition of pretumor changes of the epithelium to cancer. According to modern concepts, the ubiquitin-proteasome system is actively involved in the regulation of numerous intracellular processes, such as proliferation, apoptosis, differentiation, which play an important role in the development of tumors. Main target proteins which have been shown to be cleaved in proteasomes, can participate in carcinogenesis. Detailed research of the ubiquitin-proteasome system will reveal the specific mechanisms involved in the transition of precancerous diseases to malignant neoplasms.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):11-16
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COMPUTATIONAL TOOLS AND METHODS FOR THE IMPLEMENTATION AND ELABORATION OF MOLECULAR DOCKING FOR ENZYMES OF THE MEDICAL DESTINATION
摘要
At present biomedical research is based on joint fulfillment of theoretical and experimental investigations of various derivatives of potential therapeutic destination. Well-balanced combination of noted studies is provided for the high reliability of ensemble for obtained results. The implementation of molecular docking of high-molecule pharmacological compounds with different ligands of their natural microenvironment is notably important among such investigations. It should be noted the perspectives of such results for study of enzymes. The investigations of such kind are directed on ascertainment of mechanism of the action of these agents in biological systems and grounding of productive manners for obtaining of the high efftcacy of drug preparations of the enzyme nature. The implementation of molecular docking was conduced the lead-in of glycosaminoglycans (components of endothelial glycocalyx of the protective layer of the vessel wall) to circle of research interest. The implementation of molecular docking with elaboration of its data by methods of molecular dynamics became a productive approach for development of theoretical models of protein-glycosaminoglycan complexes. Algorithms of docking and scoring functions, conformational alterations of enzyme structure (on short /ps and ns/ more continual scale of time) were considered. The ponderable challenge of molecular docking progress was demonstrated as using of notion of the enzyme structure flexibility due to a mode of molecular dynamics with modeling of all freedom degrees in enzyme-ligand complex.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):17-22
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MESENCHYMAL STEM CELL TRANSPLANTATION IN NEURODEREGENERATIVE DISEASES
摘要
Neurodegenerative diseases are a group of pathologies of the nervous system, which are characterized by progressive death of nerve cells and gradually increasing atrophy of the corresponding parts of the brain or spinal cord. In developed countries, an increase in average life expectancy is observed. The frequency of neurodegenerative diseases also has a pronounced upward trend. Currently, the treatment of neurodegenerative diseases is ineffective, especially at the advanced stages. Pathology of the nervous system is included in the list of global problems facing humanity in the 21st century. To solve such problems, funded programs are organized around the world. The development of regenerative medicine will allow developing in the near future new technologies for the diagnosis and treatment of neurodegenerative diseases. The review provides priority data on the prospects of using mesenchymal stem cell transplantation as replacement therapy for the treatment of neurodegenerative diseases.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):23-26
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COLLAGEN EXCHANGE AND CONTENT OF MINERAL SUBSTANCES IN BONE TISSUE OF ANIMALS WITH EXPERIMENTAL DIABETES
摘要
Introduction. The risk of bone tissue disturbance leading to a disability of diabetes mellitus patients brisks up the study of the mechanisms of diabetic osteopathy. The aim of the study. To study the indices of collagen exchange, the content of components of a mineral matrix of compact and spongy bone tissue in rats with alloxan diabetes. Methods. In the diaphysis of the femur and the body of the second lumbar vertebra of rats have been determined: the level of carboxyterminal telopeptide of collagen type I using the method of enzyme-linked immunosorbent assay (β-CrossLaps; ELISA); the amount of total collagen, as well as neutral salt-soluble collagen basing on the concentration of hydroxyproline applying in colorimetric method; the content of calcium and phosphorus using the method of atomic emission spectroscopy with inductive bind plasma. All the readings mentioned above were studied on the 7h, 14th, 21st and 28th day after injecting alloxan tetrahydrate. Results. A decrease in a quantity of neutral salt-soluble collagen was noted in the bone tissue of experimental rats, that points out the synthesis of a given biopolymer inhibition. The concentration of β-CrossLaps - the marker of collagen decay - was increasing in the tissues studied since the 14h day of the research. Total collagen content in the femur was reduced at the 21st and 28th days of the experiment, and in the vertebra during the whole period of observation. The processes of collagen catabolism activation were accompanied by diminution of calcium and phosphorus content both in the femur and vertebra. Conclusion. In the bone tissue of alloxan-induced rats, the processes of degradation prevailed. It resulted in the decrease both of total collagen content and mineral matrix components.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):27-32
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DETERMINATION OF FcγRIIIb (CD16) EXPRESSION ON THE SURFACE OF BLOOD NEUTROPHILS IN ANTI-PLAGUE VACCINATED PEOPLE
摘要
Aim. Comparative evaluation of FcγRIIIb (CD16) expression level on the surface of blood neutrophils in vaccinated and unvaccinated people before and after the interaction of cells in vitro with the plague microbe allergen (pestin). Materials and methods. Blood samples of 25 healthy donors not vaccinated against the plague were examined, as well as 40 volunteers who were vaccinated once and several times with the plague vaccine alive, before and during different periods (1, 6 months) after the vaccination. The expression of CD16 on the surface of neutrophil granulocytes was determined by flow cytometry before and after incubation of blood samples for 4 hours with pestin. Results. After vaccination in all subjects there was registered a significant increase in the expression level of the CD16 molecule on the surface of blood neutrophils. After in vitro contact with pestin, the expression level of the FcγRIIIb molecule (CD16) decreased on the surface of neutrophils only in blood samples of people vaccinated against the plague. Conclusion. The change in the neutrophil phenotype from CD16bright to CD16dim, revealed by in vitro interaction with blood pestin grafted against the plague of people, mimics the response of these cells in anaphylactic shock mediating with specific IgG, and apparently represent the result of the functioning of the FcγRIIIb (CD16) as a trigger for netosis.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):33-38
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STRUCTURALLY FUNCTIONAL ORGANIZATION OF THE GENOME OF A CLINICALLY SIGNIFICANT STRAIN HELICOBACTER PYLORI HP42K ISOLATED FROM THE PATIENTA HOSPITAL IN THE BELARUS REPUBLIC
摘要
Introduction. The use of genomic approaches allows a detailed studying of the pathogenetic potential of H. pylori bacteria. The aim of the study. To investigate the genome structural and functional organization of the H. pylori isolated in the Republic of Belarus. Methods. Using next-generation sequencing with the Ion PGM System genome analyzer, a genomic analysis of the clinically significant H. pylori isolate was performed. Results. The study of the structural and functional organization of the H. pylori HP42K isolate genome can identify the pathogenetic and antigenic determinants as possible predictors of the clinical properties. The loci: five DNA motifs AATAAAGATA and EPIYA-ABC motifs in the structure of the cagA gene, as well as the oipA gene, and alleles s1 and m1a of the vacA gene were identified to be not related to carcinogenesis. Three circular sequences represented by chromosomal and plasmid DNA of H. pylori were identified and deposited in GenBank NCBI with identification numbers CP034314.1, CP034313.1, and CP034312.1. Conclusion. The analysis of the H. pylori HP42K isolate genome showed its pathogenetic features to be associated with the development of gastroduodenal pathology but not associated with stomach cancer risk.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):39-43
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IMMUNOHISTOCHEMICAL STUDY OF TRANSCRIPTION FACTORS NEUROD1, PROX1, FOXM1, SOMATOSTATIN, AND CXCR4 RECEPTORS, CD38 IN GLIOBLASTOMAS TO DEVELOP NEW APPROACHES FOR THE TARGETED THERAPY
摘要
Currently, glioblastoma is an extremely malignant tumor, for which treatment only temozolomide is relatively effective. Aim to study the expression and variants of coexpression of transcription factors NeuroD1, Prox1, FoxM1, somatostatin receptors of the 2nd and 5th type, CD38 and CXCR4 receptors in glioblastoma. The methods included an immunohistochemicalstudy with antibodies to Neuro1l, CXCR4, Prox1, FoxM1, CD38, SSTR2, SSTR5and morphometric analysis of glioblastoma fragments from 22 patients (surgical material). Results. A high level of expression (>50% of the cells) of FoxM1 was detected in 85,7% of glioblastomas samples. The average expression level of FoxM1 accouned of 82,8±5,5%. NeuroD1 was expressed in the nuclei of glioblastoma cells in l00% of cases, the average level of its expression was 95,4±0,7%. High levels of CXCR4 expression were detected in l6 tumors (76,2%). The average expression level of CXCR4 was 76,2±6,1%. Proxl was expressed in 57,l% of cases with an average expression level of 58,4±7,0%. All of the above proteins were found in the tumor cells and the walls of its vessels. SSTRs of the 2nd and 5th types were expressed in the cells of the vascular walls in all cases, the expression level was 2,2±1,1 and 6,7±1,2%, respectively. Marked expression of CD38 was observed in only 9,5% of cases. The average level of expression of CD38 - l0,8±3,4%. When analyzing combinations of marker expression, FoxM1+/NeuroD1+/Prox1-/CXCR4+/ CD38- immunophenotype was most often found (in 38,1% of cases). Conclusion. As a result of the study, the expression of CD38 was detected for the first time in glioblastoma cells. High levels of expression of the studied proteins were recorded in the tumor cells and in walls of its vessels. The immunophenotypic heterogeneity of glioblastoma was determined, the most common variant of protein combination in one tumor, FoxM1+/NeuroD1+/Prox1-/CXCR4+/CD38-, was revealed. According to the data obtained, a new personalized approach to treatment is required with the definition of targets for exposure and the corresponding spectrum of drugs in each individual case.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):44-50
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PROTECTIVE IMPACT OF BIOREGULATOR PEPTIDES BY EFFECT OF CONSTANT GEOMAGNETIC FIELD ON ORGANOTYPIC TISSUE CULTURE OF VARIOUS GENESIS
摘要
Introduction. The investigations of the magnetic-biological effects are actual because the modern technical works are related to the constant magnetic field (CGF) Purpose of the study was the investigation of impact of (CMF) on the tissues of various genesis - ecto-, meso- and entodermal. Method of organotypic culture of tissues of Wistar line rats was used. Results. CMF with 200 mTl induction had no effect on the tissues of meso- and entodermal genesis (liver, kidney, prostate gland, myocardium). However CMF inhibited CMF cell proliferation in the nervous tissue of brain cortex and in the spleen immune tissue. The introduction in the cultural media of bioregulator peptides MNN-1 and MNN-2 delated the inhibitory CMF effect and the cell proliferation was as in the control explants. Conclusion. The data obtained the protective effect of bioregulator can be used for the normalization of the proliferation potential of tissues, and also for the elaboration of the scientific recommendations for the reglament norms by exploitation of magnetic-levitation transport systems and for the passenger and workers protection from the technogenic effect
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):51-53
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ANALYSIS OF HERMINAL MUTATIONS IN ONCOGENES AND TUMOR SUPPRESSOR GENES IN WOMEN WITH MULTIPLE PRIMARY MALIGNANT NEOPLASMS
摘要
Introduction. Multiple primary malignant neoplasms (MPMN) most often develop in individuals with a hereditary predisposition to oncological diseases. There are inherited allelic variants of oncogenes, tumor suppressor genes and their combinations which disrupt the functional activity of the corresponding proteins. This leads to the development of certain tumors and is clinically manifested as familial oncological syndromes. Materials and methods. Fifty key genes associated with carcinogenesis were sequenced for 8 women, developed MPMN and have a family tumor history. Results. A total of 26 polymorphic variants were identified in l8 genes. Ten of them are located in introns, one - in the regulatory region of the gene, ten of them are silent-mutations, five - are missense-mutations. Each patient has from 9 to l7 such variants. Probably the polymorphism RET rsl800863 in the existing genomic context in Patient № l predetermined the development of medullary thyroid cancer in her and her daughter. Family of patient №2 shows a picture typical of Li-Fraumeni-like syndrome. We assume that due to either the single homozygous TP53 rsl800372 polymorphism, or its combination with TP53 rsl042522 polymorphism, determines the presence of Li-Fraumeni-like syndrome in this family. Conclusion. The frequency of rs55986963, rsl050l7l, rsl2628 polymorphisms in the sample exceeds that in the population. It is necessary to expand the sample at the expense of MPMN-patients and healthy women for further discussion.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):54-59
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THE STATE OF THE PROTEOLYSIS SYSTEM IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA ON THE BACKGROUND OF DIABETES MELLITUS TYPE 2
摘要
Ntroduction. The progression of inflammation in community-acquired pneumonia is associated with the activation of proteolytic enzymes, involved in eliminating the pathogenic agent, removing damaged structures. Proteinases are controlled by a-proteinase inhibitor. It is known that in diabetes mellitus (DM) patients as a consequence of microangiopathy, the target for damage is pulmonary tissue, which is accompanied by the risk of developing bronchial asthma, pneumonia. In pneumonia on the background of type 2 diabetes there are poorly expressed symptoms or atypical course of the disease is shown. Therefore, it is promising to search for biochemical indices allowing to identify the features of the course of community-acquired pneumonia on the background of DM type 2. The aim of the study is to evaluate the level of elastase -, trypsin-like proteases and а-PI in the blood plasma of patients with community-acquired pneumonia, DM type 2, as well as in the group of patients with combined pathology of pneumonia and DM type 2. Results: level of α1-PI was maximal in community-acquired pneumonia and amounted to 43.9 МE/ml. The maximum increase of elastase-and trypsin-like proteinases level is observed in the group with combined pathology of pneumonia with DM type 2 and accounts for 145.3 nmol BANE/min·ml and 151.6 nmol BAEE / min·ml, respectively. Conclusion. Pneumonia on the background of DM type 2 occurs most acutely with pronounced destructive processes of the lung tissue, due to a violation of the balance of «proteolysis-anti-proteolysis».
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(2):60-63
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