Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

Scopus

SCImago Journal & Country Rank

Log In Registration RU

Sokolova SR, Grigorova IL

In vitro B cell cutures are important for fundamental and applied science: these can be used to study antigenic specificity of B and T cells, as well as to produce monoclonal antibodies and other biopharmaceuticals. That is why the development of an optimal protocol for culturing of activated B cells, antibody-secreting cells (ASCs), and germinal center (GC) B cells in vitro remains an urgent task. The study aimed to find the conditions ensuring the following: high B cell expansion and survival rates, ASC accumulation, GC B cell production and accumulation. For that the CD27‒ and/or CD27+ B cells from human peripheral blood were cultured in the presence of the feeder 3T3-hCD40L line, various combinations of cytokines (IL21, IL4, BAFF), human serum components or under the control conditions throughout 7 days. Flow cytometry analysis of B cell cultures showed that the CD40L and IL21 co-existence was essential for achieving high B cell expansion, survival, and differentiation with the production of the CD27highCD38high ASCs and CD95highBcl-6+ GC-like cells. The highest expansion was observed in the cultures of CD27 naïve cells in the presence of human serum components. The IL4 supplementation moderately increased the share of GC-like cells. The maximum ASC accumulation was observed in the cultures of CD27+ memory В cells. The approach developed made it possible to find the optimal conditions for in vitro B cell culturing and clearly demonstrated the impact of both individual IL-21, IL-4, BAFF cytokines and their combinations on the B cell cultures of various subpopulations.

Received: 2025-09-26

Published online: 2025-10-30

DOI: 10.24075/brsmu.2025.053

Comments 0

VIEWS 342

Mokienko OA, Bobrov PD, Soloveva AA, Isaev MR, Kerechanin YaV, Ratnikova VYu, Kataitsev VA, Shagina ED, Nikishina VB

Neurophysiological mechanisms underlying the illusion caused by the mirror visual feedback are still poorly understood, despite the clinical use of mirror therapy for phantom pain and post-stroke hemiparesis. The study aimed to determine the mirror illusion neurophysiological correlates by the simultaneous use of electroencephalography (EEG) recording and near-infrared spectroscopy (NIRS). A total of 30 healthy volunteers (12 males, 18 females; average age 24 ± 8 years) were assessed. The experimental procedure consisted of three blocks: bimanual movement without a mirror; moving one hand with the mirror; tactile stimulation with the mirror. We analyzed the degree of EEG alpha rhythm (8–13 Hz) desynchronization in primary sensorimotor areas, supplementary motor area, and the posterior parietal cortex. Furthermore, changes in the concentrations of oxy- and deoxyhemoglobin (HbO and HbR) were assessed by NIRS. When moving the hand with the mirror, bilateral activation of primary sensorimotor areas occurred in both hemispheres: mu rhythm desynchronization, 9.71 [2.82; 16.20]% in the contralateral and 5.64 [2.84; 12.13]% in the ipsilateral hemispheres (p = 0.797), along with the HbO concentration increase by 6.88 [3.07; 17.20] nmol/L in the contralateral and by 4.91 [0.11; 14.59] nmol/L in the ipsilateral hemispheres (p = 0.094). The correlations between EEG and NIRS parameters were reported for the posterior parietal cortex only (rs = 0.527, p = 0.003). The illusion subjective characteristics were correlated to the emotional response, and only some of those showed a weak correlation with neurophysiological indicators. EEG and NIRS are complementary, rather than mutually exclusive, when used to study the mirror illusion resulting from the multi-level network organization of brain processes.

Received: 2025-09-29

Published online: 2025-10-28

DOI: 10.24075/brsmu.2025.052

Comments 0

VIEWS 299

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

Comments 0

VIEWS 279

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

Comments 0

VIEWS 264

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

Comments 0

VIEWS 264

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

Comments 0

VIEWS 251

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

Comments 0

VIEWS 340

Shatalova RO, Sheverev 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 417