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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Ashkhatsava TI, Kalinin VA, Yakunina AV, Poverennova IE

In recent decades, scientific research on tumor-associated epilepsy has increasingly focused on the study of the biochemical and molecular mechanisms of the brain tumor and peritumoral tissues, opening up new and unprecedented perspectives in understanding the glioma-associated epilepsy pathogenesis and treatment. Evidence suggests that neurons play a central role in tumor growth and cancer cells, in turn, can reconfigure the nervous system and its functions. Extracellular glutamate levels in the tissue around the glioma are up to 100 times higher than those in the healthy brain, as detected. At the same time, the available data support the idea that the excitatory neurotransmitter glutamate is the most significant mediator of the seizures related to glioma. The article reports some aspects of the cerebral glioma pathogenesis. The authors believe that modern antiepileptic drugs can affect the neoplastic process course. A number of antiepileptic drugs having the antitumor potential are presented.

Received: 2025-09-18

Published online: 2025-10-27

DOI: 10.24075/brsmu.2025.051

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VIEWS 782

Yurchenko DA, Markova ZhG, Petukhova MS, Matyushchenko GN, Shilova NV

The formation of recombinant chromosomes in the offspring of inversion and insertion carriers constitutes a significant challenge in clinical genetics due to the high risk of chromosomal abnormalities in children. Here, we present a clinical case. The aim of this study was to characterize the structure and origin of a chromosomal imbalance in a female patient presenting with delayed motor and speech development, craniofacial anomalies, and sensorineural hearing loss through molecular cytogenetic analysis of a recombinant chromosome 22. Chromosomal microarray analysis of the proband, who exhibited psychomotor delay and dysmorphic features, revealed three interstitial duplications: 22q11.21, 22q12.3–q13.1, and 22q13.2. Fluorescence in situ hybridization (FISH), using both commercial and homemade DNA probes, demonstrated that the mother carried a complex intrachromosomal rearrangement comprising an initial paracentric inversion of 22q11.21–q12.3, followed by an interstitial insertion of the 22q11.21 and 22q12.3–q13.1 segments into the nucleolar organizer region at 22p12. Accordingly, the recombinant chromosome identified in the proband resulted from meiotic segregation of the maternal complex intrachromosomal inversion and insertion. These findings highlight the diagnostic value of an integrated cytogenomic approach for the precise delineation of complex chromosomal rearrangements, determination of their origin, and assessment of genetic risk in clinical genetic counseling.

Received: 2025-09-16

Published online: 2025-10-26

DOI: 10.24075/brsmu.2025.050

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VIEWS 872

Timofeev AV, Galimov RR, Kolesnikova EA, Artyuhov AS, Skoblov YuS, Taktarov SV

Insulin autoantibodies (IAA) represent the major serological marker of type 1 diabetes mellitus (T1D), the disease resulting from autoimmune damage to β-cells in the pancreatic islets. Testing for IAA is used in early and differential diagnosis of T1D, as well as to perform screening for this disorder. The best foreign diagnostic labs perform IAA tests using different radioimmunoassay (RIA) formats. The RIA performance characteristics, i. e. diagnostic sensitivity (DSe), diagnostic specificity (DSp), and diagnostic accuracy (DA), are on average equal to 44%, 100%, and 81%, respectively. Unfortunately, in Russia RIA has not been used to determine IAA for a long time. All Russian labs use the enzyme-linked immunoassay (ELISA)-based test systems for this purpose. DSe, DSp, and DA of ELISA systems are on average 24%, 87%, and 62%, respectively, i.e. considerably lower compared to RIA systems. Our study aimed to reproduce IAA RIA in the diagnostic lab of the RCCH. The method is based on IAA competitive binding to insulin and 125I-labeled insulin. Serum samples from patients with new onset T1D and patients without diabetes were tested for IAA. DSe, DSp, and DA were 43%, 100%, and 73%, respectively. Thus, performance characteristics of the reproduced IAA RIA are close to those of RIAs used in foreign labs and are significantly superior to the characteristics of ELISA-based tests.

Received: 2025-09-16

Published online: 2025-10-26

DOI: 10.24075/brsmu.2025.049

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VIEWS 791

Chepeleva EV, Kozyr KV, Borodin VP, Khakhalkin VV, Vladimirov SV, Makhmudov MA, Badoian AG, Baranov AA, Krestyaninov OV

Currently the development of the production of domestic medical devices is of special importance in the context of ensuring the healthcare system sustainability. Leveraging international experience in developing embolic coils, while considering the capabilities of Russian production, will enable the creation of devices that meet global standarts. The study aimed to conduct systematic evaluation of six endovascular coil models from leading foreign manufacturers and perform comprehensive assessment of the design features of the metal coil frames, including analysis of geometrical dimensions, materials used, and engineering solutions. Based on our findings and a comparison with clinical and experimental literature data we determined the optimal parameters for creating the coil prototype: the wire diameter 0.07–0.12 mm, coil-core type interlock mechanism, and atraumatic polymer tip. These solutions ensure the optimal combination of performance characteristics and manufacturability. The findings provide the basis for the development of domestic analogues meeting the today’s clinical requirements, considering the available production capacity.

Received: 2025-09-15

Published online: 2025-10-23

DOI: 10.24075/brsmu.2025.048

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VIEWS 894

Shagina IA, Turchaninova MA, Golovina OA, Bufeeva LS, Zhurina TI, Saifullin RF, Myshkin MYu, Mutovina ZYu, Britanova OV

Systemic scleroderma (SS) remains a disease with a high mortality rate; validated biomarkers for stratification and disease monitoring are still lacking. The study aimed to assess the expression of the developed panel of IFN-I-induced genes (IFI27, IFI44, IFIT3, ISG15, XAF1) in peripheral blood and affected skin of patients with SS. We tested samples of 48 SS patients and 31 healthy donors. Gene expression was analyzed using RT-qPCR (ΔΔCt) method (with normalization to the reference housekeeping gene TBP). The SFRP4 gene expression was used as a marker of skin fibrosis. Expression values of the IFN-I-induced genes were significantly (p < 0.1) increased in both blood and skin of SS patients compared to healthy donors. Comparison between compartments revealed that the expression levels of XAF1, IFI44, IFIT3, ISG15 in the patients’ blood are higher (p < 0.01), than those in skin samples. The IFI27 gene expression, in contrast, is higher in the skin (p < 0.01). The findings show that the test system developed for interferon signature assessment can potentially be used as a noninvasive tool for stratifying SS patients by analysis of RNA from peripheral blood samples, to substantiate the prescription of therapy with the IFN-I receptor blockers.

Received: 2025-09-06

Published online: 2025-10-21

DOI: 10.24075/brsmu.2025.047

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VIEWS 929

Shatalova RO, Shevyrev DV

Cellular senescence is associated with the accumulation of senescent cells characterized by functional alterations, telomere shortening, cell cycle arrest, resistance to apoptosis, and metabolic dysregulation. In recent years, senescence has been extensively investigated not only in the context of aging but also in relation to cancer therapy, as senescence induction in various tumor cell types may differentially influence disease progression. The aim of this study was to comparatively evaluate commonly used chemotherapeutic agents with respect to their ability to induce senescence and their effects on mitochondrial and lysosomal compartments in primary dermal fibroblasts isolated from C57BL/6 mice. Cellular senescence was assessed using both chromogenic and fluorescent assays for β-galactosidase (β-Gal) activity. Mitochondria were labeled with the potential-sensitive dye MitoTracker® Orange, and lysosomes were stained with LysoTracker® Red. Flow cytometry analysis was performed using a BD LSRFortessa cytometer. Our results revealed a significant decrease in mitochondrial membrane potential and an increase in lysosomal fluorescence intensity in cells undergoing chemotherapy-induced senescence. Using an integrative senescence induction index developed in our laboratory, we demonstrated that doxorubicin exerts a more pronounced effect on senescence induction and on mitochondrial and lysosomal compartments compared to cisplatin, bleomycin, and etoposide.

Received: 2025-09-06

Published online: 2025-10-19

DOI: 10.24075/brsmu.2025.045

Comments 0

VIEWS 1103

Kalinchuk AYu, Patskan IA, Stadelman MM, Grigoryeva ES, Tashireva LA

Understanding subtype-specific variability of functional programs in FAP+ tumor-associated fibroblasts (TAFs) is fundamental for developing effective therapeutic strategies targeting stromal components. The aim of this study was to identify subtype-specific signaling pathways, markers, and molecular features of FAP+ TAFs. Using spatial transcriptomic analysis, we demonstrated that FAP+ TAFs in luminal breast cancer exhibit a phenotype characterized by extracellular matrix organization (GO:0030198, FDR q-value = 0.0307) and expression of genes associated with metastasis (COL10A1, MMP13, CXCL14, TSPAN8). In contrast, FAP+ TAFs in triple-negative breast cancer display a pronounced immunomodulatory phenotype with overexpression of immunosuppressive genes (CD36, PLA2G2A, CHI3L1) and enrichment of immune response-related pathways (immune response (GO:0006955, FDR q-value = 7.85e-17), inflammatory response (GO:0006954, FDR q-value = 2.79e-11), regulation of cytokine production (GO:0001817, FDR q-value = 3.39e-10)). We also identified subtype-specific gene signatures related to radioresistance: luminal A and B subtypes showed activation of DNA repair pathways (IGF1R, ERBB3, CRIP1), while triple-negative tumors demonstrated enrichment of epithelial-mesenchymal transition and stemness markers (ZEB2, NOTCH4, FOXM1). These findings emphasize that FAP+ fibroblasts are not a homogeneous population but functionally specialize depending on tumor subtype — acting as stromal architects in luminal breast cancer and as regulators of immune response in triple-negative breast cancer.

Received: 2025-09-10

Published online: 2025-10-16

DOI: 10.24075/brsmu.2025.046

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VIEWS 1237

Chepeleva EV, Kozyr KV, Vaver AA, Khakhalkin VV

The materials used to restore bone defets have a number of systemic limitations. The metal implants showing high mechanical strength have an insufficient osseointegration capability, while ceramic and polymer materials have better biocompatibility, but do not meet the requirements of mechanical reliability in the zones of considerable load. In this regard, the study of new classes of materials combining the strength characteristics with the osseogenic potential seems to be a promising area. The study aimed to assess cytocompatibility of the boron carbide (B4C)-based porous ceramic material to confirm the possibility of its use for bone defect replacement. The B4C semi-finished products were manufactured by pressureless sintering at 1900–2100 °C; ultrastructure of the resulting sample surface was examined by atomic force and scanning electron microscopy. Citotoxicity of the B4C samples was estimated by an indirect method relative to human mesenchymal stem cells. The following cell survival rates were reported: 102.1% (24 h) and 99.1% (72 h) for the samples autoclaved; 110.0% (24 h) and 94.4% (72 h) for those treated with ethylene oxide. No significant intergroup differences were revealed (Mann–Whitney U-test). The findings allow us to consider B4C ceramics as a promising solution for bone grafting. However, further research is required to assess its clinical potential, including the development of sterilization protocols for larger and complex-shaped samples.

Received: 2025-09-10

Published online: 2025-10-12

DOI: 10.24075/brsmu.2025.044

Comments 0

VIEWS 904