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 6, 2025

Topic Anxiety and depressive disorders

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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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Issue 4, 2025

Topic Chronic cerebral ischemia

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Issue 5, 2025

Topic Age-related alterations in the immune system

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New articles

Lapshtaeva AV, Sychev IV, Adamchik AI, Puzakova DV, Marmuleva VS, Sychev DA

Anovulatory infertility remains a significant medical and social issue requiring the development of new approaches to personalized patient management in assisted reproductive technology programs. Pharmacogenetic testing of hormone metabolism gene polymorphisms can contribute to optimization of ovarian stimulation protocols and higher in vitro fertilization (IVF) efficacy. The study aimed to assess a possible association of polymorphic variants of CYP isoenzyme genes (CYP1A1, CYP1A2, CYP17А1, CYP19A1) with the IVF program clinical efficacy in patients with anovulatory infertility. A total of 18 polymorphisms of the CYP1A1, CYP1A2, CYP17A1, and CYP19A1 genes were analyzed by genotyping on the Illumina iScan platform. The CYP1A2 Т/Т rs2470890 and А/А rs762551 genotype carrier state is associated with the increased likelihood of getting pregnant (OR = 3.824; 95% CI: 1.150–12.713, p = 0.023 and OR = 4.030; 95% CI: 1.372–11.839, p = 0.009, respectively). As for other studied polymoprhisms, including rs1048943, rs1800031, rs4646903, rs2606345 (gene CYP1А1), rs2069514 (gene CYP1А2), rs743572, rs104894136 (gene CYP17А1), rs10046, rs936306, rs700518, rs749292, rs1062033, rs2470152, rs28757157, rs6493497, rs7176005 (CYP19А1), no significant differences in the abundance of genotypes between comparison groups were revealed (p > 0.05). The pilot study data obtained suggest the potential role of the CYP1A2 gene rs2470890 and rs762551 variants in modulation of the individual response to treatment and the IVF program efficacy in patients with anovulatory infertility.

Received: 2025-12-25

Published online: 2026-01-22

DOI: 10.24075/brsmu.2026.001

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VIEWS 23

Adrianov MA, Gautier MS, Degtyareva AV, Marey MV, Manukhova LA, Rastorguev SM, Simonov VS, Ushakova LV, Vyssokikh MYu

The most common biochemical defect in Leigh syndrome is aberrations in proteins involved in the assembly of the electron transport chain (ETC) complex IV subunits — cytochrome C oxidase (COX). Among these, mutations in the SURF1 gene are the most common. The SURF1 protein is embedded in the inner mitochondrial membrane and plays a crucial role in the COX complex assembly. All mutations in the SURF1 gene result in the truncated protein biosynthesis and damage to the COX complex. Adeno-associated viral vectors (AAV9), which carry the not mutated SURF1 gene (AAV9-SURF1), are being investigated for the treatment of this disease. The aim of this study was to evaluate the expression levels of SURF1 and MTCO1 proteins in whole blood from patients with Leigh syndrome compared to reference values obtained for a pool of patients without mutations, as well as to evaluate the expression of the MTCO1 cytochrome c oxidase subunit in skin fibroblast cultures from patients with Leigh syndrome treated with AAV9. To investigate the gene therapy efficacy, AAV9-SURF1 was added to fibroblasts derived from the skin of a patient with a mutation in the Surf1 gene and to control skin fibroblasts at an optimal dose that did not impair cell viability in the MTT assay. We used Western blot analysis and quantitative PCR to evaluate changes in the relative amounts of the studied proteins after the addition of AAV9-SURF1 to control cells and cells obtained from the patient and identified significant compensatory changes in skin fibroblasts from a patient with a SURF1 mutation.

Received: 2025-12-12

Published online: 2025-12-29

DOI: 10.24075/brsmu.2025.083

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VIEWS 222

Zhygmitova EB, Kosykh AV, Gurskaya NG

Diseases associated with limbal stem cell deficiency, such as chronic epithelial erosion and corneal scarring, require new therapeutic approaches rooted in regenerative medicine. This study aimed to develop a protocol for obtaining progenitor cells of the epithelium of the limb and cornea from induced pluripotent stem cells (iPSCs). We differentiated iPSCs toward eye organoids to obtain three-dimensional heterogeneous structures within three weeks. The resulting organoids contain corneal epithelial progenitor cells expressing keratin 3 and collagen 7, which confirms the possibility of generating functional epithelium in vitro. The protocol enables the generation of isogenic, patient-specific cell lines for treating limbal insufficiency and dystrophic epidermolysis bullosa, including applications following preliminary genome editing of iPSCs.

Received: 2025-11-25

Published online: 2025-12-27

DOI: 10.24075/brsmu.2025.070

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VIEWS 201

Plotnikova MA, Oleynik VA, Klotchenko SA

Monoclonal antibody therapy is one of the most promising approaches for effective influenza control. In this study, we evaluated the antiviral activity of exogenous mRNA-encoded single-chain variable fragment (scFv) antibodies, which are capable of binding viral antigens inside the cell with high affinity. Two influenza virus proteins, hemagglutinin (antibody FI6) and nucleoprotein (antibody 2/3), were chosen as targets. Each scFv encoded by mRNA was produced in two variants: one containing a signal peptide (SP) to direct secretion into the extracellular space (scFv-SP) and one lacking the signal peptide (scFv-WO) for cytosolic localization and function. These variants showed distinct intracellular localization patterns: scFv-SP localized to regions characteristic of the endoplasmic reticulum and the Golgi complex, whereas scFv-WO was distributed diffusely throughout the cytoplasm. mRNAs encoding scFv-FI6-SP, scFv-2/3-SP, and scFv-2/3-WO exhibited antiviral activity against influenza A virus in vitro. The scFv-FI6-SP mRNA showed the strongest antiviral effect, reducing viral load by approximately tenfold compared to the control. For influenza B virus, both scFv-2/3 mRNA variants, with and without the signal peptide, reduced viral load by an average of 50%. These findings highlight the antiviral potential of intracellular antibodies and point to new opportunities for targeting viral components that are not accessible to conventional antiviral therapies.

Received: 2025-11-27

Published online: 2025-12-26

DOI: 10.24075/brsmu.2025.077

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VIEWS 369

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Popular articles

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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VIEWS 922

Fokin VF, Abaimov DA, Ponomareva NV, Medvedev RB, Konovalov RN, Lagoda OV, Krotenkova MV, Shabalina AA, Tanashyan MM

The study of the role of catecholamines (CAs) in cerebral organization of functions in patients with chronic cerebral ischemia (CCI) is relevant, since their important role as neurotransmitters is well known, along with the association with stress severity and cortisol. The study aimed to assess the impact of stable combinations of dopamine (DA), norepinephrine (NA), and adrenaline (ADR) on the organization of cerebral functions. A total of 76 patients with CCI were assessed based on the fMRI data (n = 21) converted into a network structure using the SPM-12 and CONN-18 software tools. Significance level estimation involved adjustment for multiple comparisons. Stable combinations of CAs reflecting mutual positive correlation of DA, NA and BP significantly affected cerebral organization of patients with CCI. CA combinations were associated with salivary cortisol (F = 4.8; p = 0.038) and memory (F = 7.5; p = 0.011) indices: the CA level increase was associated with increased cortisol levels and worse memory indices. Based on fMRI data the differences were revealed in connectivity organization of CCI patients with high and low levels of all three CAs. Patients with the CA content below median are characterized by the presence of closed neural networks extending to both brain hemispheres, which contributes to information integration and retention. It is assumed that such networks may be associated with the long-term potentiation mechanisms playing an important role in memory processes and changes in the synaptic connection strength. Thus, the use of non-invasive biochemistry testing methods and fMRI has made it possible to obtain new data on the ring organization of brain neural networks associated with stable CA combinations. Such neural network organization is likely to affect cognitive functions. High catecholamine levels in CCI patients are associated with increased cortisol levels, memory deterioration, and decreased connectivity in neural network of the brain.

Received: 2025-07-29

Published online: 2025-08-21

DOI: 10.24075/brsmu.2025.038

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VIEWS 781

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.