ISSN Print 2500–1094    ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
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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: 2025-09-23
Published online: 2025-09-30
DOI:
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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
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Original research Determination of aging phenotype based on the changes in spontaneous and induced interleukin-6 and interleukin-10 production in vitro
Grechenko VV, Gromova TV, Ogurtsova AD, Muradyan TG, Zhuravleva ER, Gankovskaya LV
During the aging the immune system alterations are accompanied by developing the systemic, sterile inflammation: inflammaging. Successful and pathological aging phenotypes are distinguished. Inflammaging severity depends largely on the ratio of pro- and anti-inflammatory mediators, especially IL6 and IL10. The study aimed to conduct the analysis of IL6 and IL10 production in the cultures of the patients’ peripheral blood mononuclear cells (MNCs) as a possible approach to determining the aging phenotype. The data of elderly patients (n = 80), senile patients (n = 100), and centenarians (n = 30) were included in the study. Among those the groups were allocated with the successful and pathological phenotypes, along with the comparison group (young adults). The stimulation coefficient (SC) was assessed based on the ratio of the levels of stimulated and induced cytokine production. For the successful phenotype in elderly and senile individuals, as well as centenarians, a decrease in the IL6 SC to 5.3 [2.2–14.3] (p < 0.01), 5.3 [3.01–7.8] (p < 0.01), 6.5 [5.2–14.1], respectively, was reported, against the comparison group, where the value was 17.6 [13.7–31.1] (p < 0.05). With the pathological phenotype, the IL6 SC values of the studied age group showed no significant differences from that of the comparison group. For the successful phenotype in senile individuals, the increase in the IL10 SC to 6.9 [3.8–13.8] relative to the values of the group with the pathological phenotype — 3.3 [2.0–5.9] (p < 0.01) and the comparison group — 2.0 [1.9–2.2] (p < 0.001) was reported. In the group of centenarians with the pathological phenotype, there was a significant increase in the IL10 SC (11.2 [5.4–18.1] vs 2.7 [2.3–6.5] p < 0.001) in the group with successful aging, which can indicate the pronounced compensatory anti-inflammatory reserve being a factor of survival and long life in the context of the presence of a large number of age-related disorders in this group.
Received: 2025-08-03
Published online: 2025-08-30
DOI: 10.24075/brsmu.2025.041
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Original research Comparison of the efficacy of mRNA vaccines against M. tuberculosis based on linear and circular RNAs
Kirshina AS, Shepelkova GS, Khlebnikova AS, Maslov AA, Kozlova AV, Kunyk DA, Yeremeev VV, Ivanov RA, Reshetnikov VV
The success of mRNA-based vaccine formulations against viral infections motivated many researchers to develop mRNA vaccines against bacterial infections. The development of new anti-tuberculosis vaccine is an urgent task since the only approved BCG vaccine is not effective enough in terms of infection prevention, despite the fact that it reduces the risk of severe disease. The study aimed to compare two anti-tuberculosis mRNA vaccines based on the classic linear mRNA (mRNA-MTBmEp-5-1) and circular RNA (circRNA-MTB-mEp-5-1) by immunogenicity and the capability of protecting I/St mice against M. tuberculosis infection. The efficacy of mRNA vaccines in the formulations with lipid nanoparticles was compared with the BCG efficacy. The findings suggest that immunization with the mRNA vaccine based on the linear mRNA resulted in the cell-based and humoral immune response (OD IgG = 0.36 ± 0.12) that was less pronounced than after BCG vaccination (OD IgG = 0.54 ± 0.14). At the same time, immunization with the mRNA vaccine and BCG ensured comparable reduction of bacterial load in the lung and spleen of experimental mice (CFU in lung tissue for BCG: 4.00 × 105 ± 2.13 × 105, p = 0.0068; mRNA: 4.72 × 105 ± 3.44 × 105, p = 0.0059; LNP: 4.91 × 106 ± 3.89 × 106, ns; PBS: 4.01 × 106 ± 1.69 × 106) and increased survival of mice after getting infected with M. tuberculosis. Immunization with the vaccine based on the circular RNA resulted in developing humoral mmunity only (OD IgG = 0.52 ± 0.13) and did not ensure protection after getting infected with M. tuberculosis (CFU in the lung for circRNA: 2.12 × 106 ± 5.30 × 105, p = 0.85). Thus, in our studies, anti-tuberculosis vaccines based on circular RNAs are inferior in effectiveness to formulations based on linear RNAs.
Received: 2025-07-22
Published online: 2025-08-26
DOI: 10.24075/brsmu.2025.040
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Original research Prognostic value of procalcitonin rapid test in purulent inflammatory diseases of the maxillofacial region
Belchenko VA, Chantyr IV, Zavgorodnev KD, Pakhomova YuI
Dental diseases, which exhibit high prevalence within the population, are frequently complicated by odontogenic inflammatory processes in the maxillofacial region (MFR), posing a significant risk of systemic septic complications. Procalcitonin (PCT) is a promising biomarker for the diagnosis of sepsis showing high sensitivity and specificity. However, its prognostic value for purulent inflammatory diseases of the maxillofacial region (PID-MFR) is still understudied. The study aimed to evaluate the diagnostic value of the PCT semi-quantitative rapid test for predicting septic complications in patients with PID-MFR and to evaluate the relationship between PCT levels and clinical/laboratory parameters. The study involved 60 patients (73.3% males, 26.7% females) aged between 21 and 71 years with PID-MFR. Serum PCT levels were determined by a semi-quantitative method. Patients were stratified into two groups: group 1 with PCT > 0.5 ng/mL (23.3%), group 2 with PCT < 0.5 ng/mL (76.7%). Septic complications were observed in 28.57% of patients in group 1, whereas no complications occurred in group 2 (p = 0.001; OR = 0.025). There were no significant differences in clinical and laboratory indicators, number of cellular maxillofacial spaces affected (3.7 ± 1.7), disease duration (5.17 ± 3.39 days), and length of hospital stay (6.50 ± 2.41 bed-days) between groups (p > 0.05). Our findings demonstrate that measuring PCT levels via a semi-quantitative method is an effective and accessible approach to predict septic complications of PID-MFR.
Received: 2025-03-19
Published online: 2025-04-15
DOI: 10.24075/brsmu.2025.018
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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
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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.
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