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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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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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

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VIEWS 302

Ivanov AS, Tananakina TP, Kashchenko SA, Pogorelova IA

MicroRNAs are resistant to RNases and are highly specific for various pathological conditions, particularly inflammation, allowing them to be considered inflammation biomarkers. They were detected in all body fluids, and miR146a plays a key role in the pathogenesis of inflammation. A total of 180 male white Wistar rats were selected for the study. All animals were 8–10 weeks old and weighed 200–250 grams. The animals were divided into five groups of 36 each. The first received saline solution intramuscularly, while the others underwent experimental modeling of obesity and knee arthrosis. The second group received 1.0 ml of saline solution intramuscularly, while the third, fourth, and fifth groups received dexamethasone at doses of 1 ng/ml, 10 ng/ml, and 100 ng/ml, respectively. Blood samples for the study were collected on days 3, 5, and 10. The obtained parameters were analyzed at the statistical significance level (p < 0.05). Increased miR146a levels were observed in animals in the second group compared to the others, due to the development of inflammation associated with obesity and concomitant gonarthrosis. In the third group, expression levels decreased slightly, remaining high. In the fourth group, with the use of 10 ng/ml dexamethasone, miR146a expression levels decreased most significantly on days 3 and 5. In the fifth group, virtually no changes were observed, with the parameter decreasing only slightly. The 10 ng/ml dexamethasone dose demonstrated the greatest efficacy during the experiment, possessing the greatest anti-inflammatory activity compared to the other doses.

Received: 2025-10-04

Published online: 2025-11-11

DOI: 10.24075/brsmu.2025.056

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VIEWS 458

Gamisonia AM, Rebrikov DV

The accumulation of scientific data can conflict with theoretical propositions, requiring their revision. Ptolemy's model of celestial motion was repeatedly "upgraded" until the paradigm fundamentally changed. Today, we not only understand the structure of the solar system but also see the universe across fourteen billion lightyears. Similarly, phenotype-based medical genetics still operates with concepts such as dominance, recessiveness, penetrance, expressivity, complementarity, epistasis, and so on. These are descriptive terms of limited accuracy, which are redundant and often confounding in clinical settings. This opinion article re-examines the relationship between molecular inheritance and its phenotypic manifestations in light of the growing role of gene editing and gene therapy. We believe that the use of the classical terms “dominant” and “recessive” in a medical context should be avoided as non-informative and possibly misleading in terms of clinical decisions and treatment choices.

Received: 2025-10-23

Published online: 2025-10-31

DOI: 10.24075/brsmu.2025.055

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VIEWS 382

Smirnova TG, Andreevskaya SN, Larionova EE, Zaytseva AS, Kiseleva EA, Ustinova VV, Chernousova LN, Ergeshov AE

The diseases caused by nontuberculous mycobacteria (NTM) are a public health problem all over the world due to increasing incidence and the associated mortality. Since it is difficult to treat mycobacteriosis, the search for drugs effective against NTM is relevant. Bedaquiline was approved in 2012 as a drug for tuberculosis treatment. The study aimed to determine susceptibility to bedaquiline of the main clinically significant NTM species that were common in the Russian Federation. In 2011–2024, a total of 345 NTM isolates were obtained: 289 isolates of slow growing NTM species (M. avium, M. intracellulare, M. chimaera, M. kansasii, M. xenopi) and 56 of the fast growing one (M. abscessus). Drug susceptibility testing for bedaquiline was performed by microdilution in a 96-well plate using the bedaquiline concentration range of 0.125–4 µg/mL. The minimum inhibitory concentration of bedaquiline inhibiting 50% (MIC50) and 90% (MIC90) of NTM strains of each spesies was determined. It has been shown that the bedaquiline MIC50 for M. avium, M. intracellulare, M. chimaera, M. kansasii is < 0.125 µg/mL, MIC90 — from < 0.125 to 0.5 µg/mL, for M. xenopi: MIC50 —4 µg/mL, MIC90 — > 4 µg/mL, M. abscessus: MIC50 — 1 µg/mL, MIC90 — 2 µg/mL.

Received: 2025-10-02

Published online: 2025-10-30

DOI: 10.24075/brsmu.2025.054

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VIEWS 382

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

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VIEWS 476

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

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VIEWS 426

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 420