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 5, 2025

Topic Age-related alterations in the immune system

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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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Issue 4, 2025

Topic Chronic cerebral ischemia

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PUBLICATION FEES

New articles

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 134

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 111

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 217

Polyakova VA, Davydova EE, Luparev AR, Matsvay AD, Gnusareva NI, Gordukova MA, Galeeva EV, Tolokonceva AA, Shipulin GA

The diversity and succession of epidemiologically significant enteroviruses (EV) lead to constant changes in the clinical presentation and morbidity levels. The aim of the study is to investigate cases of EV infection in hospitalized children during the resurgence of the epidemic process following the COVID-19 pandemic. We collected clinical samples from 156 patients with EV infection across a range of ages. Virus genotyping was performed using the Sanger sequencing of the 5’UTR-VP2 and VP1 genome fragments. Sixteen types of enteroviruses were identified, with one additional case identified only to the species level (EV-C). The dominant EV type was Coxsackie CV-A6, with a share of 80.6% (95% CI: 66.7–95.5) in 2021 and 36.1% (95% CI: 27.5–44.6) in 2022. Most commonly, CV-A6 caused skin lesions (exanthema or HFMD) and respiratory manifestations. In 2022, the proportion of CV-A10 cases increased considerably to 27.0% (95% CI: 19.2–34.9) compared with 6.4% (95% CI: 0–15.1) in 2021. The most common clinical manifestation of CV-A10 was herpangina. The most severe EV infection cases were associated with ECHO 6 — four out of 11 patients were diagnosed with meningitis, while the remaining patients exhibited neurological symptoms (meningism, intense headache, vomiting) accompanied by fever. We observed a large number of EV cases accompanied by the presence of other infectious agents in biological samples, which may result from immune suppression during EV infection development. The most common of these agents was human herpesvirus 6 (HHV-6). The nucleotide sequences of the characterized enteroviruses have been deposited in the NCBI database to enable subsequent epidemiological analysis of enterovirus circulation in the Russian Federation.

Received: 2025-11-24

Published online: 2025-12-25

DOI: 10.24075/brsmu.2025.082

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VIEWS 268

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Popular articles

Ivanova AV, Lazareva PA, Kuzmichev IA, Vadekhina VV, Kosykh AV, Gurskaya NG, Abakumov MA

Due to the limited availability of advanced methods to diagnose Alzheimer's disease, small molecules and short peptides capable of specifically biniding β-amyloid are of special interest. The study aimed to perform comparative assessment of pharmacokinetics and biodistribution of two model peptides, HAEE (His-Ala-Glu-Glu) and HASS (His-Ala-Ser-Ser), as potential platforms for the development of diagnostic kits, as well as to determine the relationship between the peptide structure and organotropism. The study involving BALB/c mice (n = 10) was conducted using the fluorescence labeled compounds. We used in vivo IVIS imaging, ex vivo fluorescence microscopy, and pharmacokinetic analysis. The results showed fundamental differences: the negatively charged HAEE was accumulated mainly in the kidney (T½β = 4.39 h) due to tubular reabsorption, while neutral HASS was soon captured by the liver (T½β = 2.76 h). The data obtained demonstrate the key role of amino acid composition in determining organotropism and open prospects for the development of organ-specific peptide systems.

Received: 2025-07-10

Published online: 2025-07-31

DOI: 10.24075/brsmu.2025.036

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VIEWS 1064

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

Comments 0

VIEWS 856

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.