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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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 1098

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 797

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: 2025-11-21

Published online: 2025-12-24

DOI: 10.24075/brsmu.2025.084

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VIEWS 918

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 769

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

Salmonellosis remains one of the leading causes of bacterial gastrointestinal infections in humans and animals. Molecular diagnostics has dramatically reshaped the diagnostic landscape for Salmonella infection; however, it remains time- and resource-intensive. Isothermal DNA amplification, for example loop isothermal amplification (LAMP), performed at a constant temperature, is the basis for the development of rapid diagnostic tests that can be adapted to the point-of-care (PoC) formats and implemented in resource-limited settings or remote from centralized laboratories. The aim of this study was to develop and validate a novel LAMP-based method for detecting Salmonella enterica in human stool samples, wherein amplification results are monitored using a loop primer labeled with a fluorophore and an internal quencher. The proposed method achieves a limit of detection (LoD95) of 250 copies per reaction, with a sensitivity of 86.84% (95% CI: 71.91–95.59%) and specificity of 96.49% (95% CI: 87.89–99.57%) relative to qPCR, and demonstrates increased robustness against DNA amplification inhibitors present in fecal samples. Incorporation of distinct fluorophores into loop primers for FLP-LAMP targeting different genes could potentially enable multiplexing and simultaneous detection of multiple pathogens, thereby expanding the diagnostic utility of isothermal amplification.

Received: 2025-11-23

Published online: 2025-12-22

DOI: 10.24075/brsmu.2025.066

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VIEWS 794

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 metabolic-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 metabolic-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 782

Poydasheva AG, Sinitsyn DO, Bakulin IS, Zabirova AH, Lagoda DYu, Suponeva NA, Piradov MA

Personalization of selecting a target for rTMS is a problem, solving which can significantly increase the method efficacy. Stimulation of the key hubs of individual-level resting-state networks represents an approach to personalization. The study aimed to develop an rTMS personalization method based on the selection of individual frontoparietal control network (FPCN) hubs and assessment of their localization variability. To determine the FPCN hubs, individual maps were built using the FPCN group mask as a seed. The searchlight algorithm with the sphere radius of 5 mm was used to select targets within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). The target spatial localization variability and correctness of using the routine “5 cm rule” for the DLPFC localization were analyzed. In 24 healthy volunteers (9 males, average age 29±7 years), high interindividual variability of targets was demonstrated. In no area is there a universal position of the stimulation coil that would effectively stimulate targets in all volunteers. Spatial dispersion of points is higher in the DLPFC (volumes of the polyhedra containing the point sets are 2095 mm3 in the DLPFC and 739 mm3 in the PPC). All individual targets in the DLPFC are located within the FPCN mask, while in the PPC some targets are outside this mask. The average distance between the М1 zones and DLPFC is 64±13 mm. In 75% of the subjects, this exceeds 5 cm, which confirms that it was incorrect to use the routine “5 cm rule” for coil positioning in the majority of subjects. An algorithm to select personalized targets for rTMS based on the resting-state fMRI data in the DLPFC and PPC being the key FPCN hubs has been developed.

Received: 2025-11-14

Published online: 2025-12-20

DOI: 10.24075/brsmu.2025.081

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VIEWS 958

Solovyova NV, Chuprova NA, Kochergina KV, Mitrofanov AA, Chausova SV, Kichuk IV

In psychiatric practice, there is a need to develop simple, pathogenetically substantiated biomarkers for prediction of the patient’s current affective status and his/ her status short-term perspective. The study aimed to analyze the association of the affective status of patients with mood disorders with the peripheral blood catecholamine and serotonin levels. The Hospital Anxiety and Depression Scale (HADS) was used for affective status evaluation. Concentrations of catecholamines (adrenaline, norepinephrine, and dopamine) in blood plasma and serotonin in blood serum were assessed by high-performance liquid chromatography (HPLC). The study included 114 individuals with affective disorders, the average age was 34.57 (SD = 10.36) years, the share of females was 64%. We revealed no significant prognostic effects of peripheral blood neurotransmitter levels relative to the current affective status. The serotonin/norepinephrine ratio, the increase in which significantly decreases the risk of clinical depression according to HADS-D considering the patient's sex and age (p = 0.059), turned out to be the only marker at the level of trends. In patients diagnosed with recurrent depressive disorder or depressive episode, a slight decrease in serotonin levels (p = 0.068) compared to the patients diagnosed with the disorders beyond the category of mood disorders is reported. In the same group a negative correlation has been found between the HADS-A scores (anxiety) and norepinephrine levels (Rs = ‒0.410, p < 0.05). The findings suggest that it will be possible to confirm the preliminary results obtained and acquire new data in the expanded clinically homogenous samples.

Received: 2025-10-30

Published online: 2025-12-19

DOI: 10.24075/brsmu.2025.080

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VIEWS 787