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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Issue 4, 2025

Topic Chronic cerebral ischemia

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Issue 5, 2024

Topic Gut dysbiosis

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Issue 6, 2024

Topic Crigler-Najjar syndrome: approaches to therapy

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Issue 1, 2025

Topic microRNA

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Issue 2, 2025

Topic Salivary gland carcinoma

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Issue 3, 2025

Topic Delivery of anti-tumor pharmaceuticals

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New articles

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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Gamisonia AM, Rebrikov DV

The relationship between a genotype and phenotype is a key problem in genetics. Gregor Mendel called a parental trait that manifests in offspring - dominant, while one that disappears - recessive. Today we know that traits represent the realization of the function of proteins encoded in DNA. Mendel's original "phenotypic" terminology gradually migrated to "genotypes," where the more "active" allele (regardless of why: a strong promoter, methylation, antisense RNA activity, codon usage, enzyme activity/concentration, etc.) called dominant, while the "inferior" allele called recessive. However, with this transition, the concepts of "dominant" and "recessive" fundamentally changed. Pea color and enzyme activity are different things. A dominant phenotype can result from either increased or decreased protein activity/concentration; these are unrelated concepts. Traditionally, loss-of-function (LOF) mutations are associated with recessive inheritance, while gain-of-function (GOF) mutations are associated with dominant inheritance, which is fundamentally incorrect. This article analyzes the molecular mechanisms of various inheritance patterns, including haploinsufficiency and dominant-negative effects. A comparison of LOF and GOF mutations and their impact on cellular processes is provided, leading to a holistic understanding of the principles of genetic pathology.

Received: 2025-10-23

Published online: 2025-10-31

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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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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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Popular articles

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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VIEWS 972

Popova ES, Agbalyan AN, Titov VD, Moiseeva VP, Mashin SV, Anfimiadi VA, Zhukov GM, Bondarevskaya AO, Gavrilyuk LM

Currently, the occurrence of multiple primary malignant tumors is one of the complex and poorly understood issues of oncology. After the diagnosis of malignant neoplasm is established, the risk of a new primary, non-metastatic tumor increases in a patient. The paper presents a case report of the patient with four multiple primary malignant tumors in the duodenum and colon. Synchronous cancer of the cecum and rectosigmoid junction occurred after 9 months of the duodenal cancer pancreatoduodenal resection, photodynamic therapy, and 12 multiagent chemotherapy courses. The patient received 8 courses of chemotherapy with capecitabine, during which cancer progression was reported, and 16 multiagent chemotherapy courses. Two years later rectal cancer occurred, due to which rectal re-resection was conducted, along with 4 multiagent chemotherapy courses and target therapy. This clinical case emphasizes that it is necessary to perform additional assessment when treating patients with synchronous or metachronous multiple primary tumors to ensure the timely diagnosis and multidisciplinary approach to treatment of cancer patients.

Received: 2025-04-07

Published online: 2025-05-27

DOI: 10.24075/brsmu.2025.028

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Special Project Author's Work

Secrets of a quality research study and a good manuscript

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”.

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.

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.