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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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 269

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 223

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 226

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 307

Ivanova AV, Chmelyuk NS, Kuzmichev IA, Shilyaeva MI, Abakumov MA

Due to high diagnostic value of β-amyloid aggregates, the target ligands capable of specific binding to abnormal Aβ aggregates are of special interest. The study aimed to perform comparative characterization of the HAEE-Сy5 (Ac-His-Ala-Glu-Glu-Gly-Gly-Gly-Gly-Lys(ε-Cy5)-NH2) and EEAH-Cy5 (Ac-Glu-Glu-Ala-His-GlyGly-Gly-Gly-Lys(ε-Cy5)-NH2) tetrapeptide capability of binding to the Aβ aggregates in the SH-SY5Y human neuroblastoma cell line by confocal microscopy. It has been shown that the HAEE-Cy5 tetrapeptide demonstrates specific binding yielding typical cytoplasmic clusters and clear co-localization with the amyloid aggregates, while the EEAH-Cy5 peptide with the inverted sequence totally loses the binding capability. Quantification has confirmed high specificity of the HAEECy5 binding to the Aβ aggregates (Manders' colocalization coefficient 0.58 ± 0.03). It has been found that the histidine N-terminal position is a critical determinant of the interaction specificity. The findings offer the prospects of using the HAEE peptide as a platform for the development of targeted disgnostic systems for amyloid disorder imaging.

Received: 2025-10-15

Published online: 2025-11-24

DOI: 10.24075/brsmu.2025.061

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VIEWS 365

Bulanov DV, Makhachev DR, Suntsov MA, Gubich DS, Filippova YD, Krutilina AA, Svoyak AV, Ivannikova AA, Ghabibullaev RM

Synovial sarcoma is characterized by marked histological and molecular heterogeneity, and angiogenesis as well as innate immune cells are considered potential sources of prognostic markers and therapeutic targets. This study aimed to evaluate the relationship between the quantitative and spatial characteristics of mast cells and angiogenesis in the tumor microenvironment of synovial sarcoma, as well as their prognostic significance. Using immunohistochemistry (tryptase/ CD117, CD31/CD34, VEGF-A, α-SMA, CD3/CD8, CD68/CD163) and digital morphometry normalized to 1 mm2, we analyzed 140 cases of synovial sarcoma. The intrathumoral, peritumoral, and perivascular (≤50 µm from CD31+/CD34+ vessels) zones, as well as the mastocyte degranulation index, were evaluated separately. Mast cells were detected in all observations; their density and signs of degranulation were greatest in the perivascular zone. Perivascular mast cells were positively correlated with both microvascular density and VEGF-A expression, and inversely correlated with α-SMA pericyte coverage; these relationships remained significant even after accounting for CD163+ macrophages. A high microvascular density and increased perivascular mast cell counts were associated with an unfavorable survival prognosis, while pronounced CD8+ infiltration predicted better outcomes. The developed integral Mast-Angio Score, which combines perivascular density, mast cell degranulation, microvascular density, and VEGF-A expression, improves the accuracy of prognostic stratification and can serve as a morphological basis for justifying combined antiangiogenic and immune therapy.

Received: 2025-10-07

Published online: 2025-11-21

DOI: 10.24075/brsmu.2025.059

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VIEWS 376

Makarovskaya NP, Lodyagin AN, Batocyrenov ChB, Razamasova SYu, Antonova AM, Narzikulov RA, Sokolova ES

Today, acute poisoning with modern psychoactive substances and narcotic drugs is among the major causes of emergency admissions to toxicology units. There is a clear upward trend in the number of life-threatening complications of poisoning with psychoactive substances, one of which is rhabdomyolysis. Here we report a clinical case of severe acute α-PVP poisoning complicated by systemic rhabdomyolysis, describe the features of the clinical course and intensive care for this disorder. The early diagnosis, timely and effective treatment by conducting aggressive detoxification infusion therapy made it possible to prevent progression to the anuric phase of acute kidney injury, as well as to avoid invasive procedures of extracorporeal detoxification methods and probably avoid the adverse outcome of the acute α-PVP poisoning complicated by systemic rhabdomyolysis.

Received: 2025-10-02

Published online: 2025-11-19

DOI: 10.24075/brsmu.2025.058

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VIEWS 291

Korotkova MS, Persiyantseva NA, Kalinina AA, Khromykh LM, Kazansky DB

A T cell receptor (TCR), an αβ heterodimer, recognizes peptide antigens presented by self molecules of the major histocompatibility complex (MHC). A significant number of T cell clonotypes are alloreactive: they can interact with various allelic variants of MHC and the associated peptides. Currently, it is unclear whether the effectiveness of the allogeneic immune response depends on the diversity of the TCR repertoire. Seeking to experimentally narrow the diversity of T cell clonotypes, we used mice with transgenic expression of the β-chain TCR (TCRβ) in this work. We analyzed how the TCRß-transgenic mice on the CBA/Lac (H-2k) background respond to EL-4 (H-2Kb) lymphoma cells in vivo with the aim to assess the effect of a narrower repertoire on the allogeneic immune response. The study has shown that transgenic mice develop a weak immune response to transplant antigens, and the formed pool of cytotoxic T cells is 1.5–1.7-fold smaller than that in wild-type animals. Consequently, the mice failed to reject the allogeneic tumor, leading to 100% mortality rate. The results of this work are consistent with the data from our earlier studies that employed another TCRß-transgenic model. They confirm that the decreased diversity of the TCR repertoire impairs the response to alloantigens, allowing the tumor to evade the immune response and progress in the allogeneic recipient.

Received: 2025-10-06

Published online: 2025-11-14

DOI: 10.24075/brsmu.2025.057

Comments 0

VIEWS 293