ISSN Print 2500–1094    ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
Scopus SCImago Journal & Country Rank

New articles

Original research Transcriptomic features of FAP+ cells across molecular subtypes of breast cancer
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
Comments 0
VIEWS 56
Original research Cytocompatibility of pressureless sintered porous B4C-ceramics assessed in vitro
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 70
Original research Age-related alterations in the immune system of aging mice
Matveeva KS, Sheverev DV
Accumulation of senescent cells in the tissues is associated with functional impairment and the development of age-related disorders. The key role in this process is played by the senescence-associated secretory phenotype (SASP) contributing to chronic systemic inflammation, which is associated with the increased risk of autoimmune disorders and cancer, as well as the decreased resistance to infections. Normally, the immune system eliminates senescent cells, but the effectiveness of this process decreases with age, including due to the immune system aging. The study aimed to assess age-related alterations in the main lymphocyte and myelocyte populations in the spleen and bone marrow samples of senile mice. The study involved groups of young (n = 8) and elderly (n = 4) С57BL/6 mice. Populations were tested by flow cytometry using the fluorescence-labeled antibodies. The aging phenotype was assessed based on the β-Gal enzyme activity with pre-treatment with bafilomycin А1, ensuring lysosomal alkalinization and allowing one to detect the increased enzyme activity typical for the aging cells (SA-β-Gal). As a result, the significantly increased levels of myeloid populations, CD11c+ B cells, double-negative T cells, along with the decreased levels of the CD8α+ dendritic cells, were reported in elderly mice. Furthermore, aging was associated with the significant increase in the levels of SA-β-Gal-positive cells, especially in the populations of myeloid cells. The data obtained suggest that the age-related alterations are of systemic nature and reflect the so-called myeloid shift, as well as accumulation of pro-inflammatory populations in the myeloid and lymphoid compartments.
Received: 2025-08-27
Published online: 2025-09-30
DOI: 10.24075/brsmu.2025.043
Comments 0
VIEWS 172
Original research Morphological, immunohistochemistry and molecular analysis of differentiated high-grade carcinoma
Makhachev DR, Bulanov DV, Shovkhalov MM, Bekmurziev BZ, Geroev IA, Netsvetova AM, Zhusupova AR, Gubich DS, Manovski AM
High-grade non-anaplastic (HGFC-NA) thyroid tumors belong to a rare and aggressive category of neoplasms that occupy an intermediate position between differentiated and anaplastic carcinomas. There are high mortality rate and limited standard treatment options, which usually include surgical tumor removal with subsequent radioiodine treatment and levothyroxine suppression therapy. Targeted tyrosine kinase inhibitors are additionally considered in radioiodineresistant forms, but the efficacy of those is limited. A clinical case of differentiated high-grade thyroid carcinoma (DHGTC) in a 62-year-old female patient post hemithyroidectomy is presented. Histological assessment, immunohistochemistry (TTF-1, PAX8, CK19, p53, Ki-67), and the key marker (TERT, TP53, BRAF) molecular testing methods were used. The tumor size was 3.4 × 2.8 × 2.5 cm; the tumor showed pronounced architectonic heterogeneity, focal necrosis, high mitotic activity — 8–10 mitoses per 10 fields of view at ×400 (corresponding to ≥ 5 per 2 mm2), and the Ki-67 proliferation index reached 35%. IHC was used to detect the TTF-1 and PAX8 expression, mutational p53 pattern of expression, suggesting the TP53 mutation. Molecular testing revealed no alteration of the TERT and BRAF genes. These characteristics made it possible to verify the diagnosis of DHGTC. A conclusion was drawn about the need for comprehensive morphological and molecular diagnosis of HGFC-NA tumors, since the mitotic activity quantitative parameters, Ki-67, and TERT/TP53 status determine the prognosis and the personalized therapy selection.
Received: 2025-09-02
Published online: 2025-09-24
DOI: 10.24075/brsmu.2025.042
Comments 0
VIEWS 287
View All
Submit Manuscript

Popular articles

Original research Intranasal lipopolysaccharide administration to Sprague-Dawley rats as a biomodel of acute respiratory distress syndrome
Kiseleva VV, Vishnyakova PA, Kosyreva AM, Kananykhina EYu, Emelianov II, Elchaninov AV, Fatkhudinov TH
High fatality rate and the lack of pathophysiological therapy are typical for acute respiratory distress syndrome (ARDS). Intratracheal lipopolysaccharide (LPS) administration is used to model ARDS in animals. The method has the limitation of requiring the use of equipment to perform intubation and control the animal’s state. The study aimed to assess the possibility of using intranasal LPS administration instead of intratracheal and determine the LPS optimal dose. A total of 150 mL of the E. coli O111:B4 LPS (7.5 mg/kg or 15 mg/kg) or 0.9% NaCl was administered to 21 Sprague-Dawley rats. After 48 h blood was collected from the tail vein to determine the white blood cell count and TNFa concentration. The lungs were retrieved to assess dry weight (wet/dry ratio) and to determine the expression of the genes encoding pro- and anti-inflammatory cytokines using real-time PCR. The relative counts of CD68-, CD86-, and MHC II-positive cells in the lung tissue were also evaluated using flow cytometry. The w/d ratio was higher when the dose of 15 mg/kg of body weight was used (p = 0.0228, ordinary one-way Anova). Вlood lymphocyte counts were decreased (p = 0.0019, ordinary one-way Anova), and neutrophil counts were increased (p = 0.0021, ordinary one-way Anova) upon administration of both doses. The counts of CD86- (p = 0.0014, ordinary one-way Anova) and MHC II-positive cells (p = 0.0050, ordinary one-way Anova) increased after LPS administration. The IL10 gene expression was significantly increased upon administration of the dose of 15 mg/kg (p = 0.0024, ordinary oneway Anova), while the IL4 expression (p = 0.0194, ordinary one-way Anova) was decreased upon administration of the dose of 7.5 mg/kg. Thus, intranasal LPS administration can be used to model ARDS in the Sprague-Dawley rats. Administration of the high dose leads to the rapid development of inflammation in the lung.
Received: 2025-04-21
Published online: 2025-05-20
DOI: 10.24075/brsmu.2025.027
Comments 0
VIEWS 841
Clinical case Two-step AAV8 gene delivery in a child with Crigler-Najjar syndrome type I
Rebrikov DV, Degtyareva AV, Yanushevich YuG, Gautier MS, Gorodnicheva TV, Bavykin AS, Ushakova LV, Filippova EA, Degtyarev DN, Sukhikh GT
Crigler–Najjar syndrome type I, an orphan UTG1A1 enzyme deficiency, manifests at birth with severe unconjugated hyperbilirubinemia. Here we describe sustained clinical response in a pediatric patient with Crigler–Najjar syndrome type I treated with two consecutive doses of AAV8 delivering the UTG1A1 coding sequence. Infusion I (6 × 1012 vg/kg) afforded sustained decrease in serum bilirubin, allowing substantial relaxation of the phototherapy from 12 h to 4 h daily. Infusion II at a double dose was made in 6 months; the decision was intended at complete elimination of phototherapy. However, the elimination led to a sharp increase in bilirubin levels necessitating resumption of phototherapy. The patient is currently stable on 4 h daily phototherapy for 80 weeks since the resumption and 107 weeks since the AAV8 therapy initiation. No toxic side effects were encountered. A slow incremental dynamics in serum bilirubin opens the issue of clinical advisability for subsequent infusions of the drug.
Received: 2025-04-25
Published online: 2025-04-30
DOI: 10.24075/brsmu.2025.025
Comments 0
VIEWS 787
Special Project Author's Work
Dear researcher!
At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.
Richard FEYNMAN Cargo cult science
American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.
Ivan PAVLOV On the Russian mind
In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.
All Workshops
All News