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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Kubekina MV, Filatov MA, Silaeva YY, Sitnikov DS

Impaired hatching of the embryo from the zona pellucida (ZP), the specialized protective shell, immediately before implantation is one of the factors of infertility. Hatching impairment is often due to the ZP hardening or thickening. In such cases, the laser assisted hatching procedure is used to overcome infertility. During this procedure a hole is drilled in the ZP facilitating the embryo release. The question of the safe use of laser for assisted hatching remains open, since laser beam can heat the environment and cause thermal shock in embryos. The study was aimed to assess safety of the mouse embryo femtosecond laser exposure during the assisted hatching procedure using the embryo viability and HSP gene expression assessment methods. A new type of pulsed laser was used in the study for the ZP dissection — the femtosecond laser. The energy of such pulses was two orders of magnitude lower than the energy of laser dissectors currently used in the clinics. To assess the femtosecond laser exposure to the embryo, the house mouse (Mus musculus) embryos were stained with fluorescence dyes, and expression of the genes encoding heat shock proteins (Hsp90aa1 and Hspa5) was assessed. The embryonic cells remained viable after the laser assisted hatching procedure involving the use of a femtosecond laser, while expression levels of the genes encoding heat shock proteins were slightly increased compared to the negative control group (p = 0.408).

Received: 2023-11-07

Published online: 2023-12-26

DOI: 10.24075/brsmu.2023.046

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VIEWS 1760

Roumiantsev SA, Kirilina IV, Gaponov AM, Khusnutdinova DR, Grigoryeva TV, Teplyakova ED, Makarov VV, Yudin SM, Shestopalov AV

Adipose tissue, being a source of chronic low-grade inflammation, activates cells of the immune system by producing cytokines and chemokines. The balance between pro- and anti-inflammatory molecules and their relationship with blood bacterial DNA in obese children and adolescents has not been studied sufficiently. This study aimed to find patterns of interaction between fractions of bacterial families in healthy and obese children, analyze cytokine levels and their relationship with blood bacterial DNA content, evaluate alpha diversity of blood microbiome and similarities of blood and fecal microbiomes. We examined 163 individuals (children and adolescents), who were divided into 2 groups, obese (n = 80, obesity classes I through III) and healthy (n = 83). The material sampled and studied was venous blood. Only individuals that have not been taking antibiotics, pro- and prebiotics for at least 3 months before the study were included. The methods employed were multiplex ELISA (enzyme immunoassay) and 16S rRNA gene sequencing (region V3–V4). From the angle of bacterial families, we found differences in their content (fractions) in blood microbiome and the frequency of isolation of their DNA therein. Nineteen families accounted for over three quarters of all bacterial DNA identified in the blood. In obese children, one of the dominating roles was played by Ruminococcaceae, with their DNA a key part of the microbiome's alpha diversity, while in healthy participants this could be said about Bacteroidaceae. Analyzing beta diversity, we found that in obese children, fecal and blood microbiomes differed significantly, which indicates, mainly, extra-intestinal translocation of bacterial DNA. Obese children exhibited increased content of IL17A (p = 0.017) and PD-L1 (p = 0.021); there were differences in blood microbiome between groups. We identified the patterns of interaction between bacterial DNA fractions, and assessed cytokine levels.

Received: 2023-10-13

Published online: 2023-12-23

DOI: 10.24075/brsmu.2023.049

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VIEWS 1673

Goncharov SV, Bozhenko VK, Zakharenko MV, Chaptykov AA, Kulinich TM, Solodkiy VA

Progression assessment enables implementation of the colorectal cancer (CRC) tertiary prevention measures aimed at early detection and timely treatment of metastatic cancer. The study was aimed to develop a model of CRC progression using pathomorphological and molecular genetic characteristics of tumors. Relative expression of mRNAs of 63 genes from various functional groups was determined in the tumor specimens of 223 patients with stage T1–4N0–2M0 CRC. The median follow-up period was 42 months. Binary logistic regression models were constructed, in which likelihood of progression within 36 months after the CRC diagnosis was a target variable. Explanatory variables were as follows: tumor grade, angiolymphatic invasion, ratio of the number of metastatic lymph nodes to the total number of lymph nodes in the surgical specimen, patient’s age and tumor localization, as well as expression levels of genes CCNB1, Ki67, GRB7, IGF1, Il2, Il6, Il8, GATA3. Prediction accuracy of the model using clinical and morphological characteristics was 56.6%. Inclusion of CCNB1, Ki67, GRB7, IGF1, Il2, Il6, Il8, GATA3 expression profiles in the model increased accuracy to 80.6%. Thus, prediction of CRC progression for treatment personalization requires additional parameters beyond information acquired within the framework of conventional morphological TNM classification. The use of molecular markers as predictors significantly increases the CRC progression prediction accuracy. Further research is needed for validation and quality improvement of prognostic models.

Received: 2023-09-13

Published online: 2023-12-23

DOI: 10.24075/brsmu.2023.050

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VIEWS 1963

Kolomiets KV, Ponomareva ES, Posypina YaR, Mihailov II, Mandzhiev CB, Povetkina EV, Tuguz RR, Bulgakov SM, Repunova VI

Uveal melanoma (UM) is a rare primary malignant tumor originating from uveal melanocytes (choroid (90%), ciliary body (6%), iris (4%)) of the eye. According to the aggregate data, the tumor incidence is 5.2 cases per 1 million population. In Russia this value varies between 6.23–8 cases per 1 million adult population across the regions. UM most often spreads to the liver (89–93%). The clinical case of using transarterial chemoembolization (carboplatin) in combination with immunotherapy (nivolumab + ipilimumab) in patients with metastatic liver disease from UM is provided. The disease control within 12 months has been achieved, which, in turn, demonstrates the possibility and efficacy of multidisciplinary approach.

Received: 2023-10-22

Published online: 2023-12-22

DOI: 10.24075/brsmu.2023.051

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VIEWS 1665

Kulshan TA, Bugaeva IO, Soboleva EF, Allyanova MS, Popov DA, Shvidenko IG

Currently, multidrug resistance of bacterial infectious agents poses a serious threat to the global public health. The following Corynebacterium strains are of special importance for infections, including hospital-acquired ones: C. amycolatum, C. urealyticum, C. striatum, C. jeikeium, C. aurimucosum, C. genitalium that are resistant to the broad spectrum of antimicrobial drugs. The study was aimed to conduct bioinformatics analysis of the pool of antimicrobial resistance genes in the published genomes of some members of the genus Corynebacterium. The data on the whole genome nucleotide sequences of 22 Corynebacterium isolates readily available from NCBI GenBank were assessed. Bioinformatics analysis of the whole genome sequences conducted in order to search for antimicrobial resistance genes in the specified genomes was performed using the PATRIC online resource. It was found that the genomes provided comprised various combinations of 25 antimicrobial drug resistance genes. Amino acid substitutions in GyrA (positions 87, 88 and 91) were revealed in some Corynebacterium strains, through which quinolone/fluoroquinolone resistance could be realized.

Received: 2023-10-20

Published online: 2023-12-19

DOI: 10.24075/brsmu.2023.047

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VIEWS 1615

Zhurlova PA, Besedovskaia ZV, Sokolinskaya EL, Putlyaeva LV

Nucleolus plays a vital role in enhancing rRNA production and maintaining ribosome biogenesis in tumor cells, making the nucleolus a desirable target for genetic and oncological research. The most convenient method for nucleolus monitoring is fluorescent microscopy, combining high efficiency and accessibility. Nevertheless, currently available fluorescent visualization methods are unsuitable for live-cell monitoring of nucleolus because they require continuous labeling. To address this issue, we have developed a genetically encoded Light-Activated Nucleolus Sensing (LANS) system for real-time nucleolar visualization. The combination of eMags domains and reader domain of DPF3 protein, responsible respectively for the light-induced dimerization and targeting the nucleolus, allowed LANS system to efficiently target nucleolus in several cancer cell lines without affecting cell morphology. This system makes it possible to increase the representation of the LANS2 sample in the nucleolus by 1.5 times relative to the fluorescence intensity values obtained before irradiation of the nucleolus. LANS holds the potential to accelerate the search for new drugs and enhance the primary screening of drug compounds in in vivo models.

Received: 2023-11-27

Published online: 2023-12-17

DOI: 10.24075/brsmu.2023.048

Comments 0

VIEWS 1592

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

Theta-burst stimulation (TBS) is widely used due to induction of the long-lasting effects with short protocol duration. To reduce the variability of the effect, approaches to personalize it, such as using theta-gamma coupling frequencies (TGC), are being investigated. The study was aimed to develop the personalized protocol of navigated intermittent theta-burst stimulation (iTBS-ind) based on TGC, and to compare this protocol with the standard one (iTBS-5/50) and sham stimulation (iTBS-sham). The study involved 16 healthy volunteers (М — 7; 29.6 years), who were randomized to receive one session of each protocol of the left dorsolateral prefrontal cortex iTBS. The effects were estimated using the n-back test with simultaneous presentation of verbal and spatial stimuli (n = 2, 3), Digit Span test, Corsi blocks task, Tower of London test; testing was performed immediately before, immediately after and 60 min after stimulation. No severe adverse events were reported. Significant effect was obtained when performing assessment after 60 min for iTBS-5/50 in the n-back test with spatial stimuli (n = 3) (pcorr = 0.018), for all protocols in the Tower of London test (pcorr = 0.039 for iTBS-5/50, pcorr = 0.045 for iTBS-ind, pcorr = 0.003 for iTBS-sham). The iTBS-5/50 effect was significantly higher compared to iTBS-sham in the spatial n-back test (n = 3) (pcorr = 0.039), but lower compared to iTBS-ind and iTBS-sham in the Corsi blocks task (pcorr = 0.038 and 0.048, respectively). Thus, we failed to confirm the personalized protocol efficacy and superiority to the standard protocol and sham stimulation. Considering the effect of standard protocol, its further investigation can be promising.

Received: 2023-10-07

Published online: 2023-12-07

DOI: 10.24075/brsmu.2023.045

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VIEWS 1760

Poryadin GV, Eremin DA, Khelminskaya NM, Kravets VI, Zhitareva IV, Posadskaya AV, Krasnov NM, Shen PA, Gureshidze MA

The regenerative medicine methods are being actively developed both in Russia and abroad due to relevance of this direction, especially in the field of the jaw osteoplasty. Autologous, allogeneic and xenoplastic materials, as well as the calcium phosphate ceramics synthetic preparations are conventionally used to normalize and stimulate osteogenesis, however, the treatment outcomes are not always unequivocal. The study was aimed to substantiate the use of the biocomplex consisting of plasma rich in growth factors (PRGF) and xenoplastic material to improve the jawbone osteogenesis efficacy. The study involved 136 patients (105 females and 31 males aged 21–67) divided into four groups based on the method of bone defect restoration. In group 1, no osteoplastic material was used; in group 2, osteoplasty involved the use of the PRGF fibrin gel; in group 3, the Osteobiol Gen-Os material was used; in group 4, osteoplasty involved using the combination of the Osteobiol Gen-Os material and plasma rich in growth factors (PRGF). Computed tomography and digital densitometry were performed before surgery and 3, 6, 12 months after it to assess the dynamics of osteogenesis. A year later restoration of the lost bone tissue volume was reported in 100% of patients in group 4, 70.27% of patients in group 3, 43.47% of patients in group 2, 37.5% of patients in group 1; Fisher's exact test revealed significant differences in the osteoplasty outcomes in groups 3 and 4 (p = 0.00002). There were significant differences in bone density between patients of groups 1 and 2 twelve months after surgery (p = 0.044), between patient of groups 3 and 4 three (p = 0.004), six (p = 0.0001) and 12 (p = 0.0001) months after surgery. The findings show that the method proposed is effective.

Received: 2023-10-02

Published online: 2023-11-21

DOI: 10.24075/brsmu.2023.044

Comments 0

VIEWS 1625