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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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 22

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 99

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 120

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 133

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 116

Blokhina AE, Palkina KA, Shakhova ES, Malyshevskaia AK, Osipova ZM, Myshkina NM

Medicines play an indisputable role in life extension and improvement of the quality of life. To obtain medicinal compounds, researchers traditionally rely on natural sources and chemical synthesis, however, currently developing biotechnological methods allow one to introduce the group of genes encoding new metabolic pathways into the genomes of heterologous hosts and regulate activity of the hosts' intrinsic metabolic pathways. Such an approach makes it possible to reproduce biosynthesis of bioactive substances in heterologous hosts, the approach combines the benefits of conventional methods and works around the shorcomings of those. In our view, the use of metabolic engineering to obtain medicinal compounds is becoming increasingly important for their production.

Received: 2023-04-05

Published online: 2023-04-26

DOI: 10.24075/brsmu.2023.014

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VIEWS 90

Bakulin IS, Zabirova AH, Poydasheva AG, Sinitsyn DO, Lagoda DYu, Suponeva NA, Piradov MA

The study of the metaplasticity-based transcranial magnetic stimulation (TMS) protocols is an extensively studied approach to increase the effectiveness of stimulation. However, the effects of protocols with different intervals between the TMS blocks on cognitive functions are poorly understood. The study was aimed to assess the effects of two theta-burst transcranial stimulation (iTBS) protocols with short and long intervals between blocks on the working memory (WM) performance in healthy volunteers. A total of 16 participants were underwent a single TMS session of each protocol, which were applied in random order (iTBS 0–15 — two iTBS blocks over the left dorsolateral prefrontal cortex (DLPFC) iTBS with an interval of 15 min between blocks followed by stimulation of the vertex area in 60 min after the first block; iTBS 0–60 — iTBS block over the left DLPFC iTBS, block of the vertex stimulation after 15 min, and the second block of iTBS over the left DLPFC iTBS 60 min after the first one; iTBS 0 — one block of iTBS over the left DLPFC iTBS and two blocks of the vertex stimulation; control protocol — three blocks of the vertex stimulation with similar intervals). WM was assessed using the n-back test before the first block and after the second and the third stimulation blocks. No significant effects of protocols on WM or differences between protocols in alterations of test results and the responder rates to TMS between protocols were observed. The trend toward statistical signficance was reported for the protocol with short interval (iTBS 0–15). Furthermore, low reproducibility of individual iTBS effect was reported. The study of protocols with short intervals between blocks involving larger cohort of volunteers and taking into account the other factors potentially influencing the effect of the protocol (number of blocks and duration of a single block) seems to be promising.

Received: 2023-03-24

Published online: 2023-04-25

DOI: 10.24075/brsmu.2023.011

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VIEWS 109

Chaplin AV, Chagina IA, Pimenova AS, Gadua NT, Kargaltseva NM, Borisova OYu, Donskikh EE, Kafarskaya LI

Aerococcus genus bacteria are often associated with human urinary tract and bloodstream infections. The Aerococcus sp. 1KP-2016 strain isolated from the buffy coat had the 16S rRNA sequence that was a 98.7% (and less) match with the previously described members of this genus. The purpose of this study was to perform whole genome sequencing of Aerococcus 1KP-2016 followed by phylogenetic reconstruction. We have shown that Aerococcus 1KP-2016 belongs to the new species of the Aerococcus genus that is closest to Aerococcus viridans and Aerococcus urinaeequi. The genomic sequence, which consists of 2.042 million bps with GC content at 38.5%, was deposited in the DBJ/EMBL/GenBank under identifier NEEY00000000.

Received: 2023-03-22

Published online: 2023-04-25

DOI: 10.24075/brsmu.2023.012

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VIEWS 118