Original research Development of the vascular condition classifier using supervised machine learning methods
Besedovskaia ZV, Korobov A, Kudriashova N
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 129
Original research Comparative imaging of the HAEE-CY5 and ЕЕАН-СУ5 tetrapeptide binding to the Aβ aggregates on the SH-SY5Y cells
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
Comments 0
VIEWS 140
Original research Perivascular mast cells and angiogenesis in the tumor microenvironment of synovial sarcoma
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
Comments 0
VIEWS 172
Clinical case Severe acute α-PVP poisoning complicated by systemic rhabdomyolysis syndrome: case report
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
Comments 0
VIEWS 154
Original research Features of the immune response to tumor alloantigens in the context of decreased clonal diversity of T cells
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 164
Original research Expression of microRNA miR146a in the blood plasma of rats with obesity and knee arthrosis after administration of dexamethasone
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
Comments 0
VIEWS 318
Opinion The terms "dominant" and "recessive" should be avoided due to gene therapy
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
Comments 0
VIEWS 271
Original research Susceptibility of the nontuberculous mycobacteria circulating in Russia to bedaquiline
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
Comments 0
VIEWS 273