Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Koniaeva AD, Varakuta EYu, Leiman AE, Rafiev DO, Bolbasov EN, Stankevich KS

Wound defects of the oral mucosa are a common pathology the treatment of which often involves synthetic membranes. Development of varieties of such membranes is an ongoing process. This study aimed to register morphological features of the oral mucosa regeneration process in the presence of one of the varieties, the polymer piezoelectric membranes. The study involved 45 Wistar rats divided into 3 groups: 1) animals with an open wound defect; 2) animals with a wound defect covered with a copper-coated polymer membrane; 3) intact animals. The samples for morphometric study were collected on the 3rd, 7th and 12th days. On the 3rd day, rats of group 1 had the specific area of granulation tissue 1.4 times greater than that in group 2 (p = 0.033). In group 1 rats, endotheliocytes expressed more VEGF than in the animals of group 2. In group 2, the defect was ultimately completely covered with the epithelial layer, which was not the case in group 1. On the 7th day, the epithelium in rats of group 2 was twice as thick as the layer registered in group 1 (p = 0.019). Granulation tissue was replaced by loose fibrous connective tissue. In group 1, the specific area of inflammatory infiltration was greater than that of loose fibrous connective tissue, and the VEGF expression level was lower than in group 2. On the 12th day, the predominant tissue in group 2 was the loose fibrous connective tissue, the VEGF expression level equaled that of group 3, and peripheral nerves began to grow. In group 1, the specific area of dense fibrous tissue was 3.9 times greater than that in group 2 (p = 0.012), the epithelium had pathological changes and the VEGF expression was below control values. Thus, a polymer piezoelectric membrane had a positive effect on the post-wound restoration of the oral mucosa tissues.

Received: 2023-05-18

Published online: 2023-06-20

DOI: 10.24075/brsmu.2023.020

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VIEWS 1304

Rogova LN, Lipov DS, Perfilova VN, Kustova MV, Mukhina AV, Churzin DA

Granulosa cells feed the oocyte during its maturation and protect it. Aberrant apoptosis in these cells is known to ultimately impair oogenesis. The current knowledge of how extragenital inflammation affects apoptosis in granulosa cells is incomprehensive, which is the root of an urgent problem connected to the spread of inflammatory diseases and the growing level of female infertility. This study aimed to assess the intensity of granulosa cell apoptosis in women with impaired reproductive function that suffer from chronic respiratory and/or digestive system diseases of inflammatory origin, and to identify the link, if any, between the studied factor and dysfunction of the reproductive system in the test group. The group included 60 women with a history of respiratory and/or digestive system inflammatory pathology that underwent IVF in 2021–2022. The women were donors of the granulosa cells from the follicular fluid collected through transvaginal puncture of preovulatory follicles. We studied the apoptosis process with the help of flow cytometry. For statistical analysis, we used the Fisher's F-test and the Kruskal–Wallis test. Twenty participants without extragenital pathology in their medical histories, the first subgroup, had the level of apoptosis in granulosa cells at 0.0088 ± 0.0062%, which is significantly lower than in twenty donors with a history of chronic inflammatory digestive system diseases, the second subgroup (granulosa cell apoptosis at 0.0140 ± 0.0099%, p = 0.015), and the subgroup of women suffering from inflammatory diseases of the respiratory system (granulosa cell apoptosis at 0.0650 ± 0.0391%, p = 0.033); the efficacy of IVF was higher in the first subgroup.

Received: 2023-05-12

Published online: 2023-06-17

DOI: 10.24075/brsmu.2023.019

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VIEWS 1097

Gumenyuk LN, Zemlyanaya IA, Rami A, Badula ES, Ismailov AR, Seroshtanov NA, Kokareva SS, Cheremisova AA, Kupreichyuk YuR

Today, the association of gut microbiota with external genital endometriosis (EGE) is of special scientific interest. The study was aimed to assess alterations of the gut microbiota taxonomic composition and explore their correlations with plasma levels of IL6, IL8 and TNFα at the species level in patients with EGE. The crosssectional comparative study involved 50 patients with EGE (index group) and 50 healthy women (control group). The changes in the gut microbiota taxonomic composition and plasma levels of IL6, IL8 and TNFα were assessed. A significant decrease in the abundance of such species, as Coprococcus catu (р = 0.009), Turicibacter sanguinis (р = 0.008) and Ruminococcus gnavus (р < 0.001), along with the increase in the abundance of Eubacterium ramulus (р = 0.040), Bacterioides dorei (р = 0.001), Prevotella divia (р = 0.008) and Shigella flexneri (р < 0.001) were found in the gut microbiota taxonomic composition in patients with EGE. Significant correlations between the IL6 levels and the abundance of Turicibacter sanguinis (r = –0.92; р = 0.001), IL8 levels and the abundance of Shigella flexneri (r = 0.72; р < 0.001), TNFα levels and the abundance of Prevotella divia (r = 0.77; р = 0.001) were revealed. The findings add to the available literature data on the features of gut microbiota alterations and their association with some inflammation biomarkers in individuals with EGE, which can justify further research in this area and probably open up new approaches to treatment of the disease.

Received: 2023-01-13

Published online: 2023-06-15

DOI: 10.24075/brsmu.2023.018

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VIEWS 1269

Balanovska EV, Gorin IO, Petrushenko VS, Ponomarev GYu, Belov RO, Pocheshkhova EA, Salaev VA, Iskandarov NA, Pylev VYu

Eastern Caucasus is home to more than 30 peoples speaking Caucasian, Iranian and Turkic languages. Fusion of multiple migration flows together with the complex population structure of the Eastern Caucasus make it more difficult to analyze its gene pool: this is the most poorly studied one among all regions of the Caucasus. The study is aimed to identify the main patterns of the autosomal gene pool variation in this region. A total of 356 genomes of 29 ethnic groups were studied using the large panels of SNP markers: 243 genomes of 22 peoples of the Eastern Caucasus and 113 genomes of 7 peoples living in adjacent regions. The bioinformatics analysis involved the use of the ADMIXTURE ancestral component method and the gene pool variability principal component analysis (РСА). The hypothesis of three genetic strata, the interaction of which forms the structure of gene pool of the Eastern Caucasus, was put forward. The “Dagestan” stratum carries information about the gene pool of the ancient autochthonous population of the Eastern Caucasus. The “Iranian” stratum represents the legacy of ancient and middle-aged migrations surges of the Iranian-speaking population: it constitutes three quarters of the gene pool of modern Azerbaijan and about one third of the Dagestan peoples' gene pool. The “Steppe” stratum represents a negligible influence of the Eurasian steppe. Interaction of three genetic strata is only indirectly related to the peoples' linguistic affiliation, however, the association with linguistics is more obvious in the Caucasian-speaking peoples. Four genetically distinct groups of indigenous population of the Eastern Caucasus have been identified, the combination of which should be included in the characteristics of its autosomal gene pool: 1) Dargins, Laks; 2) Avars, Lezghins, Tabasarans, Aghuls, Rutul people, Tsakhur people; 3) Kumyks, Tat people and Azerbaijanis living in Dagestan; 4) Azerbaijanis and Talysh living in Azerbaijan. The directions of further research have been defined.

Received: 2023-04-26

Published online: 2023-05-29

DOI: 10.24075/brsmu.2023.017

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VIEWS 2357

Takhchidi KhP, Takhchidi NKh, Mahno NA

Rhegmatogenous retinal detachment complicated by macular hole is a rare disorder that is the most challenging in terms of vitreoretinal surgery, and good anatomical outcome is not always associated with high visual functions. Today, vitrectomy, involving macular hole closure with autologous platеlet-rich plasma, sealing peripheral retinal tears, and subsequent vitreal cavity tamponade with vitreous substitutes, is considered to be the most effective method for surgical treatment of this disorder. Despite variability of surgical approaches to treatment of rhegmatogenous retinal detachment complicated by macular holes, the search for safe and effective surgical technique, allowing one to achieve benificial morphological and functional outcome with minimal damage to the retinal structures and to minimize the patient's rehabilitation period, is still relevant. The clinical case reported demonstrates the possibility of performing single-stage endovitreal treatment of retinal detachment complicated by macular hole using the autologous conditioned plasma in combination with the short-term perfluorocarbon tamponade. The results of using this technique show its reliability and superior efficiency and ensure good morphological and functional outcome in the postoperative period: restored macular architectonics, macular hole closure, anatomic retinal adhesion, and improved visual functions.

Received: 2023-03-27

Published online: 2023-04-28

DOI: 10.24075/brsmu.2023.016

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VIEWS 1342

Ganin IP, Vasilyev AN, Glazova TD, Kaplan AYa

In the brain-computer interface based on the P300 wave (P300 BCI), the selection of the command by the user becomes possible due to focusing the user's attention on the external stimulus/command and extraction of the response to this stimulus in the form of the event-related potential (ERP) components from EEG. To obtain the ERP signal, stimuli should be repeated many times, however, in view of the existing variability in latency of the response to certain stimuli, the averaged ERPs may give a distorted view of the nature of such responses and reduce accuracy of the interface. The study was aimed to develop an effective method for identification of the effects of the ERP components' latency variability and for accounting these effects in the P300 BCI, as well as to identify the possible impact of psychophysiological factors on the nature of ERP variability. We have conducted a BCI-based study of 19 healthy subjects involving extraction and adjustment of latency in the N1 and P300 spatial components, which play a key role in the command classification in the P300 BCI, to explore the mechanisms underlying variability. Such an approach ensured higher accuracy compared to the use of conventional EEG leads, and the highest increase of 10% was observed when using the minimum number of the stimulus repetitions. Furthermore, modifications of the interface allowing one to ensure a higher level of the user's focus on the task and a more accurate visual fixation on the target objects contributed to the increase in the amplitude of the ERP components by reducing variability of the responses to single stimuli. The findings emphasize the important role of the processes underlying the ERP components' variability and provide an effective tool for scientific exploration of such processes and the development of advanced BCI systems.

Received: 2023-04-14

Published online: 2023-04-28

DOI: 10.24075/brsmu.2023.013

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VIEWS 1379

Shakiba Y, Naberezhnaya ER, Kochetkov DV, Yusubalieva GM, Vorobyev PO, Chumakov PM, Baklaushev VP, Lipatova AV

Among oncolytic viruses, modified vaccinia virus Ankara (MVA), a highly attenuated vaccinia virus (VV) is a well-studied variant with promising results in preclinical and clinical trials. The Lister VV strain from the Moscow Institute of Viral Preparations (LIVP) has been studied to a lesser extent than MVA and has a different oncolytic property from MVA. The aim of this work was to compare the oncolytic efficacy of LIVP and MVA strains against solid tumors. We developed recombinant variants LIVP-RFP and MVA-RFP; to enhance onco-selectivity thymidine kinase (TK) gene was inactivated by insertion of red fluorescent protein (RFP) gene to the TK locus. The replication kinetics and oncolytic activity of the obtained recombinant strains were evaluated in vitro and in vivo on tumor cell lines and mouse syngeneic tumor models of metastatic mouse 4T1 mammary adenocarcinoma, CT26 colon adenocarcinoma, and B16 melanoma. Both MVA-RFP and LIVP-RFP showed high replication efficiency in tumor cells and pronounced oncolytic activity against B16 melanoma and 4T1 breast adenocarcinoma allografts. In relation to 4T1, which is a model of triple negative human breast cancer, LIVP-RFP showed more than 50% increased cytotoxicity in in vitro tests compared to MVA-RFP, as well as a significant slowdown in the progression of 4T1 allografts and an increase in animal survival in experiments in vivo. Thus, the LIVP strain may be more promising than MVA as a platform for the development of recombinant oncolytic viruses for the breast cancer treatment.

Received: 2023-02-20

Published online: 2023-04-28

DOI: 10.24075/brsmu.2023.010

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VIEWS 1538

Panacheva EA, Kudryavtseva EV, Zornikov DL, Plotko EE, Petrov VM, Voroshilina ES

Obtaining enough good and excellent quality embryos is one of the key factors for achieving pregnancy using assisted reproductive technologies. This work was aimed at developing a mathematical model for predicting good and excellent quality embryos based on semen microbiota assessment in normozoospermia. The study included 127 men whose semen was used for in vitro fertilization (IVF). Patients were divided into 2 groups depending on the proportion of good-quality blastocyst developed on the 5th day of culturing (good-quality blastocyst development rate, GBDR). The 1st group included 57 patients with GBDR ≥ 40%, the 2nd group included 70 patients with GBDR < 40%. All patients’ semen was assessed at the day of fertilization. Semen parameters were evaluated in accordance with the WHO standards and semen microbiota composition was determined by means of real-time PCR. Discriminant analysis was used for development of the prognostic model. We developed a method for predicting efficiency of the embryological IVF stage in normozoospermia: EGO-Pro-N prognostic index (Embryos of GOod and Excellent quality Prognosis in Normozoospermia). If the EGO-Pro-N value is greater than 0.212, the probability of receiving GBDR ≥ 40% is low. Conversely, if the EGO-Pro-N value is less than or equal to 0.212, the probability is high. Sensitivity and specificity of the method were 71.9% and 70.0% respectively, accuracy was 70.9%. The developed model allows us to predict good and excellent quality embryos based on comprehensive semen microbiota assessment in normozoospermia before IVF.

Received: 2023-03-23

Published online: 2023-04-26

DOI: 10.24075/brsmu.2023.015

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VIEWS 1450