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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Ershova ES, Veiko NN, Kostyuk EV, Poletkina AA, Rozhnova TM, Nizyaeva NV, Muzaffarov DU, Klimenko PA, Kostyuk SV

Pregnancy requires the cells of the woman’s body to ensure increased ribosomal biogenesis in order to enhance the protein synthesis intensity. The number of ribosomes depends on the copy number of ribosomal genes (rDNA) in the genome. The study aimed to test the hypothesis about the association of the rDNA copy number in the woman’s genome with the course of normal and complicated pregnancy. The sample of 488 pregnant women (25–39 weeks) included the following groups: 1) normal pregnancy (control); 2) impaired uteroplacental blood flow and fetoplacental insufficiency; 3) congenital malformations; 4) isthmic-cervical insufficiency; 5) early placental maturation; 6) dichorionic diamniotic twins; 7) polyhydramnios; 8) macrosomia. The rDNA copy number was determined by the quantitative hybridization method in the DNA extracted from peripheral leukocytes. The rDNA copy number varied between 226 and 800 (n = 488). DNA samples with the rDNA copy number below 290 were lacking in groups 3–8. Groups 5–8 included no samples with the rDNA copy number exceeding 520; these in total differed from group 1 by low rDNA copy number values (the average values were 360–381 for groups 3–8 and 452 for group 1; p < 10–7). The rDNA copy number range of 290–520 in the woman’s genome (the adaptive norm typical for long-lived individuals) is optimal in terms of successful completion of pregnancy in the presence of pregnancy complications. The low rDNA copy number (200–290) in the genome is associated with the failure to complete embryogenesis when there are some fetal abnormalities/ features. A high rDNA content (over 600 copies) indicates the presence of genetic variants in the woman's genome that can interfere with the complicated pregnancy course. Determining the rDNA copy number in the genome of married couples may be useful for planning and predicting the course of pregnancy.

Received: 2025-10-23

Published online: 2025-12-12

DOI: 10.24075/brsmu.2025.075

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Petrash EA, Yunina-Pakulova NYu, Kuryishina SA, Karpenko AS, Kuznetsova AA

Memory in all the variety of the types and processes ensuring its functioning has a psychotherapeutic resource that is realized when working with manifestations of post-traumatic stress disorder (PTSD). One of these is obsessive repetitive memories with traumatic content. The study aimed to look into reconsolidation of early memories in reliving the traumatic experience of participation in combat. The total sample size was 62 individuals (males aged 21–46 years). The experimental group included 31 respondents with combat experience having the status of war veterans (the average period of participation was 1 year and 5 months). The control group consisted of 31 respondents with no combat experience. The Mini-Mental State Examination (MMSE) scale, set of functional neuropsychological tests (“10 Words” by A.R. Luria, "Pictograms" method by A.R. Luria, "Difficult-to-Verbalize Figures" by T.V. Akhutina, "Rhythm Reproduction Test" by A.R. Luria), analysis of the transcripts of audio recordings of early memories were used. It has been reliably found that the early memory of a positive, negative or neutral modality resulting from the influence of combat experience is changed through the reconsolidation mechanism, which is reflected in the linguistic and semantic parameters. The linguistic and semantic structure of the combat veterans’ early memories is characterized by the event-based model, with a predominance of verbs and adverbs. The semantic core of the combat veterans’ early memories is more often negatively colored, despite the general ambivalent or positive modality.

Received: 2025-10-25

Published online: 2025-12-11

DOI: 10.24075/brsmu.2025.069

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Khokhlova AN, Vavilov MV, Chepurnykh TV, Rodionova NS, Petushkov VN, Yampolsky IV, Dubinny MA

Traditional medicine has been using earthworms to treat a wide range of pathological conditions for many centuries. Current research focuses primarily on the isolation and characterization of biologically active compounds, including notable examples such as glycoprotein G90, which exhibits thrombolytic and antitumor properties; the enzyme complex lumbrokinase; and the extracellular oxygen transport protein erythrocruorin, regarded as a potential basis for blood substitute development. Model organisms such as Caenorhabditis elegans, which are used to study the mechanisms of aging, neurodegenerative diseases, and evaluate the effectiveness of medicines, also play an important role. Bioluminescent systems of annelids are of particular interest because they exhibit a variety of chemical mechanisms of luminescence and unique cofactors that hold promise for applications in biomedicine. The combination of these properties and abilities underscores the importance of worms as a source of enzymes, proteins, and metabolites, as well as model systems for finding solutions to both fundamental and applied biomedical problems.

Received: 2025-10-21

Published online: 2025-12-10

DOI: 10.24075/brsmu.2025.067

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VIEWS 283

Kulinich TM, Kukoleva EA, Goncharov SV, Kudinova EA, Puchkov IA, Goncharova OI, Kaminsky VV, Bozhenko VK

Peritoneal carcinomatosis remains one of the most challenging forms of dissemination in gastric and colorectal cancer. It directly determines the disease prognosis and is highly resistant to treatment. The use of the existing therapeutic approaches is often limited by low benefit-risk ratio. It is necessary to develop innovative strategies aimed at overcoming the molecular mechanisms of tumor progression associated with RAS mutations, which play a crucial role in the carcinogenesis of both colorectal and gastric cancer. The study aimed to estimate safety and preliminary efficacy of the novel peptide RAS-GTPase inhibitor «Ing-Ras» when included in the treatment regimen of patients with stage III–IV gastric and colorectal cancer, including patients with peritoneal carcinomatosis. A total of 35 patients with the confirmed diagnosis of stage III–IV gastric and colorectal cancer were included in the study. The «Ing-Ras» drug was administered at a dose of 1.8 mg/kg twice with a 7-day interval using the Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) technique. Primary efficacy was assessed by comparing the overall survival (OS) and progression-free survival (PFS) rates of the clinical trial patients with historical control groups. The OS and PFS rates for patients in the clinical trials were 92.1% and 84.22%, respectively, which significantly (p < 0.05) exceeded the values of these rates for the historical control group (50.8% and 65.25%). Thus, the use of «Ing-Ras» can significantly improve the treatment results for patients with advanced forms of colorectal and gastric cancer.

Received: 2025-10-23

Published online: 2025-12-09

DOI: 10.24075/brsmu.2025.065

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VIEWS 328

Grigoryeva ES, Tashireva LA, Savelieva OE, Zavyalova MV, Cherdyntseva NV, Perelmuter VM

It is known that chemokine receptors CXCR4 and CXCR7 in primary tumor cells are associated with tumor growth progression; however, the significance of their expression in circulating tumor cells (CTCs) remains insufficiently studied. The objective of this study was to investigate the expression of chemokine receptors CXCR4 and CXCR7 in subpopulations of CTCs with positive (EpCAM+) and negative (EpCAM−) EpCAM expression in breast cancer patients, as well as assessed their correlation with clinicopathological parameters and prognostic relevance.The study methods included protein expression analysis and transcriptome profiling of CTCs obtained from peripheral blood. This study comprehensively characterized CXCR4 and CXCR7 expression across EpCAM+ and EpCAM− CTC subsets and assessed their clinical relevance through protein-level detection, transcriptomic profiling, and long-term patient follow-up. CXCR4 and CXCR7 receptors were predominantly expressed in EpCAM+ CTCs, whereas EpCAM− cells were largely negative. Importantly, an increased number of EpCAM− CTCs, irrespective of CXCR4/7 status, was associated with disease progression over a six-year period (p = 0,0007). Prognostic significance was specifically attributed to EpCAM−CXCR4/7− CTCs, with counts exceeding 1.25 cells/ml predicting progression with high sensitivity and specificity. Distinct CTC subpopulations were further characterized by stemness and epithelial-mesenchymal transition (EMT) markers, underscoring the aggressive phenotype of EpCAM− cells exhibiting EMT traits. Transcriptomic analysis of EpCAM−CXCR4/7− CTCs revealed upregulation of genes involved in ferroptosis (p = 3.315 × 10⁻⁷) and androgen receptor signaling pathways (p = 8.0 × 10⁻⁵), alongside identification of progression-associated genes (HBB, IGLC2, and IGHM). Conversely, MALAT1 was overexpressed in patients without progression, indicating a potential metastasis-suppressive function (p = 1.52 × 10⁻²). These findings highlight the pathogenetic importance of EpCAM− CTCs in breast cancer progression and support a paradigm shift in CTC research towards this subpopulation. Further investigations are warranted to elucidate the functional roles of these cells and their utility as prognostic biomarkers.

Received: 2025-10-24

Published online: 2025-12-08

DOI: 10.24075/brsmu.2025.064

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VIEWS 338

Perina EA, Buyko EE, Kaidash OA, Efimova LF, Diksas EB, Krivoshchekov SV, Ivanov AA, Ivanov VV, Udut EV

The problem of opisthorchiasis caused by Opisthorchis felineus requires a search for alternative treatments, because the trematode can develop drug resistance and the existing drugs, such as praziquantel, may have undesirable side effects. This study aimed to identify the anti- opisthorchiasis and hepatoprotective properties of Populus tremula L. bark extract using in vitro methods. The PGF-PT active fraction with a high content of phenol glycosides was obtained though extraction. PGF-PT showed a dose-dependent anti-opisthorchiasis effect: the relative mobility index of maritae decreased from 98.2% at 250 µg/ml to 54.5% at 2000 µg/ml (p < 0.05), and the proportion of immobile specimens at 2000 µg/ml was 30% (p < 0.05). The probable mechanism of action is focal damage to the cells of the parasite’s superficial epithelium (tegument). PGF-PT exhibited a pronounced hepatoprotective effect in a lipotoxicity model based on HepG2 cells, as evidenced by normalized intracellular lipid accumulation and reduced oxidative stress. A high antioxidant activity of PGF-PT was shown in the model system (IC50 = 79.3 ± 1.0 µg/ml). Thus, the PGF-PT fraction has a complex effect — eliminating parasites and correcting metabolic disorders in the liver — which makes it a promising basis for new effective anthelmintic drugs.

Received: 2025-10-17

Published online: 2025-12-02

DOI: 10.24075/brsmu.2025.063

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VIEWS 282

Ponomarev GYu, Shlykov AG, Gorin IO, Voronina MM, Potanina AYu, Petrov VA, Koshel SM, Adamov DS, Balanovska EV

An urgent problem of the role of Slavic expansion in shaping gene pools of the population of Europe is being analyzed actively using various methods to study ancient and current populations. However, it is difficult to solve due to the lack of consolidated data on the Y-haplogroups in Slavic-, Finnish-, and Turkic-speaking populations of European Russia. The study aimed to look into genetic portraits of Mordovian populations and Russians of the Ryazan Region relative to the surrounding populations of indigenous peoples of Central Russia. For the first time the Y-gene pool of the Volga–Oka region (10 populations, n = 1136 individuals) was assessed in a broad context of our own data on the gene pools of European Russia (based on a single panel of 35 Y-haplogroups, 80 populations, n = 9712). The analysis was performed by multidimensional scaling (MDS) and computed cartography (GeneGeo). The produced series of 35 maps of the Y-gene pool of Central Russia and maps of genetic distances from peoples of the Volga–Oka region describe the gene-geographic landscape of the region in detail. It has been shown that all the assessed Russian populations belong to the common “Slavic” cluster that also includes representatives of Western Slavs. The cluster of populations of the Ural–Volga region including three Finnish-speaking populations of Mordovia (Erzya, Moksha, Shoksha) and 7 Turkic-speaking populations of the Chuvash and Mishar turned out to be the most genetically close to the Russian populations of Central Russia. It has been hypothesized that this group of populations can be traced back to the gene pool of the ancient indigenous Finnish-speaking population of the Volga–Oka region.

Received: 2025-10-16

Published online: 2025-12-01

DOI: 10.24075/brsmu.2025.062

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VIEWS 287

Besedovskaia ZV, Korobov AY, Kudriashova NI

Quantitative processing of optoacoustic angiograms is an important task, the solution of which will potentially enable the early diagnosis of vascular diseases. The aim of this study is to refine and conduct biomedical validation of a software tool for the analysis of optoacoustic angiograms, focusing on the application of machine learning methods. The work was conducted on an open dataset containing three-dimensional optoacoustic angiograms of an experimental animal (mouse) in three temperature conditions: cold temperature (16 °C), room temperature (23 °C), and body temperature (30 °C), as well as a dataset with basic vascular features obtained by processing using Amira/Avizo (Thermo Fisher Scientific), a general-purpose software for visualization and analysis of scientific and industrial data. Various vascular features missing from previous work were developed and calculated, after which basic methods of unsupervised/supervised clustering and supervised classification were applied to determine different temperature conditions of vessel segments. Supervised classification methods demonstrated high overall accuracy: CatBoost — 98.9%, SGDClassifier — 95.7%, and logistic regression — 99.7%. The results are consistent with existing descriptions of vascular changes during temperature tests. The applied methodology is universal, meaning with minor modifications it can be adapted to patients. Therefore, the results of this study may potentially improve the diagnosis of vascular pathologies.

Received: 2025-10-07

Published online: 2025-11-27

DOI: 10.24075/brsmu.2025.060

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VIEWS 365