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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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 1868

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 1753

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 1540

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 1646

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 1575

Pavlenko VB, Kaida AI, Klinkov VN, Mikhailova AA, Orekhova LS, Portugalskaya AA

One of the subjects being discussed by the professional community currently is the role possibly played by the mirror neuron system (MNS) in the violation of social behavior of children with autism spectrum disorders (ASD). The MNS is known to shape the perception of emotions of others and understanding and imitation of their actions. Mu rhythm desynchronization in EEG is considered to be the indicator of the MNS activation. The purpose of this study was to identify the features of reactivity of the EEG mu rhythm within an individually determined frequency range in preschoolers with ASD in situations requiring instrumental, emotional and altruistic helping behavior (HB). The study involved children 4–7 years old with ASD (n = 26) and their normally developing peers without the condition (n = 37). Although in most cases, HB was more pronounced in the group of normally developing children, the differences between the groups are significant only for altruistic HP (p < 0.01), and for the situation requiring complex altruistic and emotional HP it approaches significance (p = 0.09). Evaluation of the mu rhythm reactivity indices showed that the tasks invoking complex altruistic and emotional HB bring this indicator down significantly in children with ASD compared to the group of normally developing participants, as shown by the central leads of the left and right hemispheres and the parietal lead of the right hemisphere (C3: p = 0.02 ; C4: p = 0.03; P4: p = 0.03). It is assumed that the detected features stem from the impaired functioning of the MNS and the downstream regulation to the MNS from prefrontal cortex and other areas of the neocortex. The data obtained can be used in development of EEG biofeedback training protocols for children with ASD.

Received: 2023-02-19

Published online: 2023-03-31

DOI: 10.24075/brsmu.2023.009

Comments 0

VIEWS 1774

Egiazaryan KA, Ratjev AP, Miroschnikova EA, Zhavoronkov EA, Abilemets AS

Severe complex deformities of the forefoot in elderly patients with no rheumatoid arthritis result in the pronounced decrease in quality of life, chronic pain, reduced mobility, failure to get shoes for everyday use, exacerbation of the concomitant somatic diseases. The use of conventional joint preservation techniques in such patients often leads to the deformity relapse, persistent pain, and the need for revision surgery that is often impossible due to worsening of the patients' general somatic status and local functional status. The study was aimed to improve surgical outcomes in elderly patients with no rheumatoid arthritis who had severe forefoot deformities. The prospective cohort study that involved allocation to the retrospective group for comparison of surgical outcomes in 65 patients was carried out in 2016–2019. The results obtained before and after surgery were assessed using the FFI, AOFAS Hallux, and AOFAS Lesser Toes scores. The Maryland scores were used to assess the outcomes during the postoperative period. The study revealed significant differences in treatment outcomes based on the AOFAS Hallux (p = 0.0001), AOFAS Lesser Toes (p = 0.0001), FFI (p = 0.0001), and Maryland (p = 0.0001) scores. In view of the elderly patients' specific nature, the radical surgical techniques that do not ensure joint preservation may be considered as effective and predictable methods of correction aimed at reducing the rate of revision surgeries. These techniques represent a one-step method to improve the quality of life of elderly patients.

Received: 2023-02-02

Published online: 2023-02-28

DOI: 10.24075/brsmu.2023.008

Comments 0

VIEWS 1545

Gaydin TY, Geller EV, Rozhnova SA, Gaydina TA

Due to the changes in the modern world, it is necessary to develop the domestic pharmaceutical industry, which is a task especially important in the context of implementation of the import substitution policy. The article classifies the main measures the state industrial policy has for the pharmaceutical industry; these measures cover informational and consulting aspects, research and technical parts, innovations and economic matters. Practical actions and their possible consequences are considered for each group of the industrial policy measures: encouragement of domestic consumption, regulation of imports, stimulation and support of exports, stimulation of technological development, public-private partnerships, support of the development of intersectoral territorial production complexes (clusters), direct state support of investment activities, tax incentives for investors.

Received: 2023-01-30

Published online: 2023-02-28

DOI: 10.24075/brsmu.2023.007

Comments 0

VIEWS 1660