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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Shestopalov AV, Ganenko LA, Grigoryeva TV, Laikov AV, Vasilyev IYu, Kolesnikova IM, Naboka YuL, Volkova NI, Roumiantsev SA

Today, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are distinguished. Adipose and muscle tissues can determine the obese phenotype due to adipokine and myokine production. Gut microbial community is also involved in MHO. The study was aimed to reveal the features of adipokine and myokine levels and their association with the gut microbiome alpha diversity in patients with MHO and MUO. A total of 265 subjects were divided into two groups: healthy individuals and obese patients. The latter were divided into two subgroups: patients with MHO and patients with MUO. Body mass index, waist circumference, HOMA-IR, adipokine and myokine levels, gut microbiome taxonomic composition, alpha diversity indices were defined in all the surveyed individuals, lipid and carbohydrate metabolism was also assessed. Significant differences in the adipokine and myokine levels and their association with the gut microbiome diversity indicators were revealed in patients with different obese phenotypes. Patients with MHO and MUO showed significantly lower adiponectin levels (р < 0.05) and significantly higher leptin and asprosin levels (р < 0.05) than healthy individuals. Patients with MUO had lower adiponectin and leptin levels (p < 0.05) than patients with MHO. Significantly higher FGF21 levels were observed in patients with MUO. Large-scale correlation analysis revealed the relationship between the glucose levels and the gut microbiome diversity indices that was missing in patients with MUO. This indicated the loss of the microbiota diversity effects on the blood glucose control in individuals with MUO, as well as different regulatory roles in the gut microbiome‒liver‒muscle/adipose tissue axes of individuals with MHO and MUO played by gut microbiota. The findings show the relationship between the gut microbiome diversity and the obese phenotype.

Received: 2022-12-19

Published online: 2023-02-17

DOI: 10.24075/brsmu.2023.004

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VIEWS 1250

Iulmetova LN, Kulemin NA, Sharova EI

Fuchs' endothelial corneal dystrophy is a socially significant hereditary disease. More than a half of cases in the European population are caused by the increased number of trinucleotude repeats in the TCF4 gene. The study was aimed to develop and test the approach of dividing patients into groups based on the chip-based genotyping and genome-wide association study (GWAS) results. The analysis was conducted using FECD Genetics Multi-center Study and AREDs project datasets containing the data of 1721 clinical cases and 2408 control patients. When analyzing the GWAS results, the patients and the control group were divided into two groups by means of hierarchical clustering suggesting that patients with the increased number of repeats in the TCF4 gene are carriers of specific combinations of genomic variants (haplotypes). It was shown that individual variants cannot be used for the molecular genetic stratification of patients with the increased number of repeats in TCF4 due to inconsistent results obtained for the variants. Furthermore, the haplotype-based approach outperformed the SNPs in terms of odds ratio. The paper proposes a method that enables further search for the biologically relevant combinations of genomic variants.

Received: 2022-12-12

Published online: 2023-02-12

DOI: 10.24075/brsmu.2023.001

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VIEWS 1223

Rogovaya OS, Alpeeva EV, Ruchko ES, Eremeev AV, Vorotelyak EA

Tissue-engineered constructs (TECs), the dermal equivalent (DE) and the skin equivalent (SE), are allogenic equivalents of the skin and derm used to treat critical skin loss. Selection of storage conditions that contribute to longer shelf life, thereby expanding the possibilities of logistics and use, is one of the major issues related to the TECs development. The study was aimed to determine the shelf life of the DE and SE TECs stored in normal saline at room temperature by assessing morphology and viability of the cells on their surface, along with the levels of endothelial growth factor (VEGF) secreted by these cells. Using the MTT assay and staining with vital dye, we discovered the following: when TECs of both types were stored in normal saline, the cells viability and metabolic activity decreased by more than 50% by days 3–4 of storage. Furthermore, these decreased faster in DEs than in SEs. Morphology of the cells isolated from DEs and SEs after the 3-day storage remained unchanged. Mesenchymal stem cells on the surface of TECs kept producing VEGF after TECs culture medium was changed for saline solution (confirmed by immunofluorescence assay), which could indicate that the cells retained essential secretory activity.

Received: 2022-12-16

Published online: 2023-01-30

DOI: 10.24075/brsmu.2023.003

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VIEWS 1562

Sitnikov DS, Ilina IV, Filatov MA, Silaeva YY

The zona pellucida (ZP) is a dynamically changing object that plays an important role during the preimplantation stage of embryogenesis. The ZP thickness may affect the implantation success and pregnancy rate, it is considered as a prognostic factor in a number of studies. The study was aimed to assess the dynamic changes in the mouse embryonic ZP thickness after laser assisted hatching (LAH) that involved breaching the ZP integrity at the blastocyst stage. Femtosecond laser pulses were used to perform the zona microsurgery. The zona thickness was measured both at the stage of blastocyst microsurgery (~Е3.5, i.e. 3.5 days of embryogenesis) and at the hatching stage (~Е5). Significant differences in the ZP thickness were revealed in the control group of embryos: from 6.21 µm (Е3.5) to 5.4 µm (Е5). The changes in thickness from 6.6 µm (Е3.5) to 6.2 µm (Е5) observed in the group subjected to LAH were non-significant. Tracing the ZP thickness of a particular embryo from the blastocyst stage to the hatching stage made it possible to estimate the thinning coefficients in the experimental and control groups. The findings that indicate lower tensile strength of the zona in case of LAH can provide the basis for further research on the ZP properties in case of using the embryo cryopreservation protocols.

Received: 2022-11-09

Published online: 2023-01-27

DOI: 10.24075/brsmu.2023.002

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VIEWS 1571

Postnikov MA, Butvilovsky AV, Alsharifi A AM, Madatyan AV, Kopetskiy IS, Eremin DA

Anatomical features of the teeth should be accounted for dental treatment plans. The need for constant monitoring of changes in the dentition system determines the relevance of this research. The study aimed to establish the size of anterior teeth with the help of odontometry. We made bi-layer single stage impressions and cast diagnostic models of the anterior teeth of 50 male and 50 female participants aged 18–24 years. The absolute sizes of crowns of incisors and canines were established. To assess the reduction of lateral incisors, we calculated the interincisor index (Ii) of teeth 22 and 21; sexual dimorphism was determined using the Garn–Lewis formula. It was discovered that there are no differences in the mesiodistal widths of crowns of contralateral teeth on the right and left sides (p > 0.05). The mesiodistal width of crowns of anterior teeth decreases (significant changes) in the following order: maxillary central incisors → maxillary canines → mandibular canines and maxillary lateral incisors → mandibular lateral incisors → mandibular central incisors. The degree of reduction of lateral incisors is low (Ii = 74.9) and more prominent in males than in females. In the examined patients, the greatest mean length of crowns of anterior teeth is that of upper central incisors and lower canines, while upper canines are shorter in length and upper lateral incisors, lower central and lateral incisors have the shortest mean crown length. Males have longer (mean length) crowns of lower canines, upper incisors and canines than females, the difference being significant (p < 0.001). The parameters of the crowns determined in this study showed that they have sufficient height and mesiodistal width, which, together with the low degree of reduction of the lateral incisors, justifies the possibility of direct fabrication of orthodontic fixed retainers. The data can also be used at the stage of dental treatment planning.

Received: 2022-11-11

Published online: 2022-12-31

DOI: 10.24075/brsmu.2022.069

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VIEWS 1312

Siniavin AE, Russu LI, Vasina DV, Shidlovskaya EV, Kuznetsova NA, Gushchin VA, Gintsburg AL

The COVID-19 disease pandemic remains a significant global problem, resulting in hundreds of millions of cases and millions of deaths. The search for specific inhibitors of SARS-CoV-2 for the treatment of this infection remains relevant. Drugs such as Favipiravir and Molnupiravir, which exhibit specific antiviral activity against SARS-CoV-2, are already being used to treat patients. However, there is limited evidence of their effectiveness, especially against novel genetic variants of the COVID-19 pathogen. The aim of this study was to investigate the antiviral effect of these drugs using an in vitro experimental model of SARS-CoV-2 infection in Vero E6 cell culture and an animal model of infection using Syrian hamsters. It has been established that Molnupiravir has an inhibitory effect against variants of the SARS-CoV-2 with IC50 values from 16.51 to 7.88 μM in vitro, and reduces the infectious titer of the virus in the lungs of animals by ~1.5 Log10 in vivo, in while Favipiravir shows lower activity and severe toxicity. Dose selection and frequency of use remain unexplored.

Received: 2022-12-05

Published online: 2022-12-31

DOI: 10.24075/brsmu.2022.071

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VIEWS 1529

Bormotov DS, Shamraeva MA, Kuzin AA, Shamarina EV, Eliferov VA, Silkin SV, Zhdanova EV, Pekov SI, Popov IA

The primary method of initial treatment of meningiomas is radical neurosurgical intervention. Various methods of intraoperative diagnostics currently in development aim to improve resection efficiency; we focus on methods based on molecular profiling using ambient ionization mass spectrometry. Such methods have been proven effective on various tumors, but the specifics of the molecular structure and the mechanical properties of meningiomas raise the question of applicability of protocols developed for other conditions for this particular task. The study aimed to compare the potential clinical use of three methods of ambient ionization in meningioma sample analysis: spray from tissue, inline cartridge extraction, and touch spherical sampler probe spray. To this end, lipid and metabolic profiles of meningioma tissues removed in the course of planned neurosurgical intervention have been analyzed. It is shown that in clinical practice, the lipid components of the molecular profile are best analyzed using the inline cartridge extraction method, distinguished by its ease of implementation and highest informational value. Analysis of oncometabolites with low molecular mass is optimally performed with the touch spherical sampler probe spray method, which scores high in both sensitivity and mass-spectrometric complex productivity.

Received: 2022-11-27

Published online: 2022-12-30

DOI: 10.24075/brsmu.2022.072

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VIEWS 1322

Kozhin PM, Romashin DD, Rusanov AL, Luzgina NG

The HaCaT cell line represents the spontaneously immortalized non-carcinogenic human keratinocytes that are used as a model for studying the function of normal human keratinocytes. There are two TP53 alleles in the HaCaT cell genome, which comprise two gain-of-function (GOF) mutations acquired through spontaneous immortalization (mutTP53). Mutations result in the increased proliferation rate and violation of the stratification program. The study was aimed to assess the effects of the mutTP53 gene knockout on the HaCaT keratinocytes capability of proliferation and migration in the in vitro model of epidermal injury and regeneration (scratch test), and on the ability to form stratified epithelium in the organotypic epidermal model. To perform the scratch-test, cells were cultured until monolayer was formed, then the standardized injury was created. The organotypic model was obtained by growing keratinocytes in the polycarbonate membrane inserts with the pore size of 0.4 μm at the interface between the phases (air-liquid). It has been shown that the mutant TP53 gene knockout results in the increased migration capability of the HaCaT keratinocytes: in the HaCaT with the mutTP53 knockout, the defect closure occurred faster than in the appropriate group of the WT HaCaT (p < 0.05), on day three the defect size was 12% ± 3% and 66% ± 5% of the initial size. There is evidence that mutant TP53 in the HaCaT cells is a negative regulator of the laminin 5 expression (LAMC2 expression was 9.96 ± 1.92 times higher in the cells with the mutTP53 knockout, p < 0.05), however, this does not promote normalization of the program of epithelial differentiation and stratification followed by formation of the stratum corneum in the organotypic model.

Received: 2022-12-12

Published online: 2022-12-30

DOI: 10.24075/brsmu.2022.070

Comments 0

VIEWS 1330