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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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 92

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 84

Plotnikova MA, Oleynik VA, Klotchenko SA

Abstract has not been added yet...

Received: 2025-11-27

Published online: 2025-12-26

DOI:

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VIEWS 160

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

The diversity of epidemiologically significant enteroviruses (EVs) and their tendency to regularly change the currently prevalent strain result in a naturally unstable clinical picture and morbidity. This study aimed to investigate cases of enterovirus infection (EVI) in hospitalized children during the recovery phase of the epidemic process following the COVID-19 pandemic. We collected clinical samples from 156 EVI patients across a range of ages. Virus genotyping was performed using the Sanger sequencing method; we analyzed the 5′UTR–VP2 and VP1 fragments of the genome. Sixteen types of enteroviruses have been identified. For one, we established the type only (EV-C). The dominant type of EV 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. CV-A6 most often caused skin lesions (vesicular exanthema and enterovirus vesicular stomatitis with exanthema) and was associated with respiratory infections. 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 cases of EVI were associated with ECO6 ― four out of 11 patients were diagnosed with meningitis, the rest showed neurological symptoms (meningism, intense headache, vomiting) against the background of fever. We observed a large number of EVI cases accompanied by the presence of other infectious agents in biological samples, which may result from immune weakening during EVI 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 facilitate future epidemiological analyses 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 201

Semikina EV, Azarova YuE, Panichev SA, Basareva OI, Dzhanchatova NV, Alferova EJ, Polonikov AV

Diabetic nephropathy (DNP) is a serious complication of type 2 diabetes mellitus (T2D), leading to early disability and mortality from end-stage renal failure. Experimental and clinical studies have shown the leading role of oxidative stress-induced damage to macromolecules, including DNA, in the development and progression of DNF against the background of hyperglycemia. On the contrary, repair of these DNA lesions serves as a signal to end ongoing oxidative stress. The key DNA repair enzyme is 8-oxoguanine DNA glycosylase, encoded by the OGG1 gene. The aim of this study was to analyze the associations of five polymorphic variants (rs2072668, rs1052133, rs293795, rs2304277, and rs6443265) of the OGG1 gene with the risk of developing DNF in patients with type 2 diabetes. The study included 1461 patients with type 2 diabetes, 577 of whom were diagnosed with DNF. DNA genotyping was performed by real-time polymerase chain reaction using allele-specific fluorescently labeled probes. Associations were established between the rs293795-G/G genotype (OR = 1.97, 95% CI = 1.23-3.16, p = 0.007) and the rs2072668C-rs1052133C-rs293795G-rs2304277G-rs6443265C haplotype (OR = 1.30, 95% CI = 1.06-1.60, p = 0.012) of the OGG1 gene with a predisposition to DNF in the background of T2D. Moreover, six OGG1 diplotypes associated with an increased risk of DNF and one diplotype associated with a reduced risk of DNF in patients with T2D were identified. Thus, in our study, we presented for the first time data on the association of the OGG1 gene polymorphism with DNF, which creates a scientific foundation for further research on the contribution of disturbances in the DNA oxidative damage repair system to the development of microvascular complications of T2D.

Received: 2025-12-01

Published online: 2025-12-24

DOI: 10.24075/brsmu.2025.084

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VIEWS 190

Grigorova IL

Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play critical roles in inducing and controlling B cell responses, including the generation of high-affinity humoral immunity, the antibody class-switching, and the prevention of autoreactivity. Successful Tfh responses are linked to robust vaccine-induced neutralizing antibody production and efficient clearance of various pathogens. Conversely, dysregulation of follicular T cells is often linked to autoimmune diseases and allergic reactions. Furthermore, these cells are implicated in the formation of ectopic lymphoid structures (ELS), contribute to certain vascular pathologies, and hold prognostic value in several cancers. Consequently, the analysis of follicular T cell subpopulations in human peripheral blood is increasingly utilized to investigate the mechanisms underlying various diseases. In this opinion article, the current understanding of follicular T cell subsets, their functions, and the evolving methods for analyzing their circulating counterparts in human blood are discussed. In the author's opinion, the central unresolved questions remaining in the field are the precise phenotypic definition of circulating Tfr cell subpopulations, the elucidation of their developmental trajectory from precursors cells to mature regulatory forms, and the identification of their anatomical differentiation niches. The collection and translation of these essential data into reliable cellular signatures for peripheral blood analysis are critical for advancing personalized patient prognosis and developing tailored therapies.

Received: 2025-12-10

Published online: 2025-12-23

DOI: 10.24075/brsmu.2025.076

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VIEWS 224

Shamovskaya DV, Gordukova MA, Smertina MA, Galeeva EV, Oscorbin IP, Khrapov EA, Boyarskikh UA, Filipenko ML

Abstract has not been added yet...

Received: 2025-11-23

Published online: 2025-12-22

DOI: 10.24075/brsmu.2025.066

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VIEWS 173

Zhulai GА, Kurbatova IV, Dudaniva OP

Experimental studies have demonstrated the protective role of ectonucleotidases — particularly CD39 and CD73 — in limiting inflammation connected to a liver pathology. However, their expression in metabolically associated fatty liver disease (MAFLD) has not been thoroughly investigated. This study aimed to evaluate the mRNA levels of the ENTPD1 and NT5E genes, which encode CD39 and CD73, respectively, in patients with different forms of MAFLD (liver steatosis (LS) and metabolically associated steatohepatitis (MASH)), and to assess the expression of CD39- and CD73-positive cells following immune cell activation in vitro. The sample included 29 healthy donors and 56 MAFLD patients. We measured the mRNA levels of the ENTPD1 and NT5E genes, pro-inflammatory cytokines (IL-6, TNFα), fragmented cytokeratin-18, and the blood content of CD39+ cells. Another parameter measured in vitro was the effect of immune cell activation on the proportion of CD39+ and CD73+ cells in patients with MASH and healthy donors. The expression of the ENTPD1 gene (p = 0.007 vs. control group; p = 0.010 vs. LS group) and the proportion of CD39+ cells among monocytes (p = 0.004 vs. control group; p = 0.003 vs. LS group) and lymphocytes (p = 0.034 vs. control group) were lower in the MASH group compared with both the control and LS groups. Activation of cells from MASH patients increased the proportion of CD39+ lymphocytes, but not that of CD14+ monocytes. It also increased the proportion of CD73+ cells among both lymphocytes and CD14+ monocytes. Thus, further investigation into the roles of CD39 and CD73 in the context of MAFLD progression represents a promising avenue for future research.

Received: 2025-11-11

Published online: 2025-12-21

DOI: 10.24075/brsmu.2025.079

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VIEWS 223