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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Fadeeva AA, Osipova ZM, Chepurnykh TV, Myshkina NM

Rodent neoplastic process models are extensively used in pre-clinical practice to assess the dynamics of tumor development and test anti-cancer drugs, which ensures flexibility of choosing both basic and advanced personalized tumor development models for researchers. Various modern model tumor imaging methods are considered, including fluorescence and bioluminescence imaging, which enable comprehensive assessment, from qualitative evaluation to in vivo monitoring. We believe that the development of autonomous bioluminescent systems in mammalian cells will provide new possibilities for noninvasive imaging of animal physiological processes, including long-term monitoring of tumor progression.

Received: 2025-03-04

Published online: 2025-03-27

DOI: 10.24075/brsmu.2025.015

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VIEWS 84

Kalinchuk AYu, Tsarenkova EA, Loos DM, Mokh AA, Rodionov EO, Miller SV, Grigoryeva ES, Tashireva LA

The clinical significance of programmed cell death protein 1 (PD-1) expression in the tumor microenvironment (TME) of lung cancer, particularly in the context of immunotherapy, remains poorly understood. This study aimed to evaluate PD-1 expression in tumor-infiltrating immune cells and its association with clinical outcomes in lung cancer patients. In a study of 20 patients (17 men and three women, average age 56 ± 6.9 years) with lung cancer, four key immune cell populations involved in the immunotherapy response were analyzed using multiplexed in situ immunofluorescence. The focus was on PD-1 expression patterns and their correlation with progression-free survival (PFS). Our findings revealed that PD-1 expression was predominantly observed on CD8+ lymphocytes, albeit at low levels (~5%), suggesting a state of T-cell exhaustion. Notably, PD-1-expressing immune cells were rare in both non-small-cell and small-cell lung cancer microenvironments, indicating that most immune cells remain functionally active. This deficit of PD-1+ cells may explain the limited therapeutic efficacy of antiPD-1 antibodies. Furthermore, we identified CD20+ B-cell infiltration as an independent predictor of poorer PFS (HR = 0.17, 95% CI: 0.02–0.65, p = 0.0454), highlighting a previously underappreciated role of B cells in lung cancer progression. Additionally, the presence of distant metastases (stage M1), a high proportion of PD-1+CD163+ macrophages, and a low proportion of PD-1+FoxP3+ lymphocytes were associated with shorter PFS, underscoring the complex interplay between immunosuppressive and immunostimulatory cell populations in the TME. These findings suggest that PD-1-expressing immune subsets, particularly cytotoxic lymphocytes and regulatory T cells, may serve as prognostic markers and potential therapeutic targets.

Received: 2025-03-04

Published online: 2025-03-24

DOI: 10.24075/brsmu.2025.014

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VIEWS 89

In issue 6 (November–December 2024) of the Bulletin of RSMU a few errors were made: https://vestnik.rsmu.press/archive/2024/6/18/abstract?lang=en Aktanova AA, Bykova MV, Skachkov IP, Denisova VV, Pashkina EAImpact of tumor on the cell cycle and differentiation of hematopoietic stem cellsBulletin of RSMU. 2024; (6): 27–33. DOI: 10.24075/brsmu.2024.065 The following corrections should be applied: Published text: p. 27, item “Funding” Funding: the study was supported by the Russian Science Foundation, project No. 23–25-10099. Correction: Funding: the study was supported by the Russian Science Foundation in cooperation with the Government of the Novosibirsk Region, project No. 23–25-10099. Published text: с. 29, пункт "Финансирование" Финансирование: исследование выполнено при финансовой поддержке Российского Научного Фонда, проект № 23–25-10099. Correction: Финансирование: исследование выполнено при финансовой поддержке Российского Научного Фонда совместно с Правительством Новосибирской области, проект № 23–25-10099.

Received: 2024-12-02

Published online: 2025-03-12

DOI: 10.24075/brsmu.2025.013

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VIEWS 144

Petrash EA, Lisichkina AA, Karpenko AS, Nikishina VB, Polonets AI

The relevance of the proposed study is due to the need to find solutions in reducing the vulnerability of elderly and seniors to deception and fraudulent actions. The purpose of the study is to assess the cognitive correlates of deception recognition in the elderly and seniors. The sample size was 87 elderly and senile subjects (60–89 years old) — 38 men and 49 women. Research methods: MoCA (Montreal Cognitive Assessment); Sally–Anne test; Pragmatic intervention short stories Winner's Task; experimental method Read the Mind in the eye (RMET); Dembo–Rubinstein self-esteem scale; trust self-esteem scale. Based on the findings of the study, the cognitive correlates of deception recognition in the elderly and seniors were identified. It is reliably found that with age, as ageing progresses regardless of education level, there is a decline in cognitive level, which, in general, is natural in the process of normative ageing. These changes lead to a decrease in the level of understanding of the mental model, which in turn makes it more difficult to recognise emotions and increase trust. The empirical study supported the hypothesis that there is a correlation between cognitive level and the ability to recognise deception. The lower the general cognitive level, the worse the deception is recognised and the more trusting a person becomes.

Received: 2025-02-13

Published online: 2025-02-28

DOI: 10.24075/brsmu.2025.010

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VIEWS 229

Vlasenko SV, Lyovin GV, Osmanov EA

Assessment of muscle functional state in children with cerebral palsy (CP) is an important aspect of developing personalized rehabilitation programs. The combined use of bioelectrical impedance analysis (BIA) and electromyography (EMG) makes it possible to optimize the diagnosis methods and improve therapy efficacy. The study aimed to compare groups of patients with CP (n = 91) and healthy children (n = 94) using BIA and EM. Based on the BIA data the patient were divided into four categories: A — increased body fat percentage (BFP), reduced skeletal muscle mass (SMM); B — decreased BFP, increased SMM; C — increase in both indicators; D — decrease in both indicators. The analysis considered gender and average age of each group. Patients with CP (M: BFP p = 0.0001, SMM p = 0.0015; F: BFP p = 0.0003, SMM p = 0.0009), regardless of gender, showed similar distribution: the majority belonged to categories C (М — 50%; F — 46.9%) and D (М — 32.5%; F — 28.1%). The group of healthy people (М: BFP p = 0.0005, SMM p = 0.0004; F: p = 0.0013, p = 0.0008) showed the opposite trend: the majority of patients belonged to categories А (34%) and В (34%). In the group of females, the majority of patients belonged to group B (40.4%), group C ranked second based on the number of patients (27.6%), which was considerably lower, than in the group of children with CP. The phase angle values were also traced: there were significant differences (p < 0.05) with superiority of categories А and В, regardless of the group and gender. The EMG data also showed superiority of categories А and В when considering turn amplitudes. A conclusion was drawn about the skeletal muscular function differences in the specified categories of patients.

Received: 2024-12-19

Published online: 2025-02-27

DOI: 10.24075/brsmu.2025.012

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VIEWS 221

Bilyalov AR, Piatnitskaia SV, Rafikova GA, Akbashev VN, Bikmeyev AT, Akhatov ISh, Shangina OR, Chugunov SS, Tikhonov AA

The choice of the sterilization method for ceramic implants is critically important, as it can affect the chemical and physico-mechanical properties of the material and its biocompatibility. Higher cytotoxicity, which is a possible side effect of sterilization, hinders osseointegration. This study aimed to determine the cytotoxicity of porous ceramic samples after sterilization using the most common methods. Samples of hydroxyapatite (HA), tricalcium phosphate (TCP), and aluminum oxide (AO) were prepared by stereolithography, and bone allograph samples were made using the DLP method. The annealing lasted for 4 hours, with a peak temperature of 800 °C and the temperature increment of 3 °C per minute; the sintering temperature was up to 1200 °C. We used the following sterilization methods: autoclaving at 1 atmosphere, 120 °C, for 45 minutes; radiation sterilization, 25 seconds with an absorbed dose of 25 kGy; plasma peroxide sterilization, 42 minutes; dry heat sterilization at 180 °C, for 60 minutes. Cytotoxicity was determined with the help of an MTT assay (24-hour exposure in a CO2 incubator). The results of the study: for HA, high porosity means growth of values in transition from autoclaving (0.1115) to plasma peroxide sterilization (0.2023). Medium and low porosity show similar results, with peaks in dry-heat sterilization (0.4954 and 0.4505). As for for AO, it exhibited high viability when subjected to this method. The TCP samples have shown stable results, but their low-porosity variation had the values growing after autoclaving (0.078 to 0.182, dry-heat sterilization). The study forms the basis for optimizing the ceramic implants manufacturing technology and sterilization methods to ensure their high biocompatibility.

Received: 2024-12-14

Published online: 2025-02-27

DOI: 10.24075/brsmu.2025.009

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VIEWS 225

Osikov MV, Efros LA, Zhuravleva LYu, Fedosov AA

Chronic kidney disease (CKD) represents one of the most common complications of type 1 diabetes mellitus (T1D). Oxidative stress (OS) can be considered as a key link of pathogenesis of CKD associated with T1D, therefore, identification of the redox status markers is important for prevention of the development and progression of this disorder. The study aimed to assess the substances generated during oxidative destruction of proteins and their correlation with glomerular filtration rate (GFR) in patients with T1D and stage 1–3 CKD. The study involved healthy individuals (n = 14), patients with T1D showing no signs of CKD (n = 30), as well as patients with T1D and stage 1 CKD (n = 60), stage 2 CKD (n = 38), and stage 3 CKD (n = 31). Healthy participants were matched to the index group by age and gender: 42.9% were males, 57.1% were females, the average age was 30.6 ± 4.2 years; body mass index, systolic and diastolic blood pressure, lipid profile were within normal. It has been found that patients with T1D and stage 1–3 CKD demonstrate plasma accumulation of early and delayed neutral and base products of oxidative protein modification (OPM): spontaneous 157% based on median, metal-induced 143% based on median relative to healthy individuals. We have revealed a decrease in overall antioxidant status (OAS) of plasma in 51% of patients with T1D and stage 3 CKD compared to patients with T1D without CKD. Estimated GFR, the integral indicator of renal function, decreases with increasing plasma levels of OPM products, decreasing OAS. The data obtained allow us to consider plasma levels of OPM products, OAS as affordable and informative methods to assess progression of early stage CKD in patients with T1D.

Received: 2025-01-27

Published online: 2025-02-26

DOI: 10.24075/brsmu.2025.011

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VIEWS 169

Radaeva OA, Simbirtsev AS, Kostina YuA, Iskandiarova MS, Negodnova EV, Solodovnikova GA, Yeremeev VV, Krasnoglazova KA, Babushkin IO

Today, the analysis of the risk of developing cardiovascular complications in patients with essential hypertension (EH) following recovery from novel coronavirus infection (COVID-19) is relevant. The value of leukemia inhibitory factor (LIF) and its soluble receptor (sLIFr) in EH progression has been shown, along with the relevance of circadian approaches to assessment of the contribution of pro-inflammatory cytokines to the pathogenesis of acute cerebrovascular accidents (CVA). The study aimed to compare alterations of the LIF and sLIFr levels during reconvalescence after COVID-19 and influenza in patients with stage II EH, to determine the features that are important for the development of acute CVA, and to analyze the associations with circadian rhythms. The study was conducted in four phases (n = 180; age 55–60 years): (1) 6–8 months before COVID-19; (2–3) on day 10–14 after primary or recurrent COVID-19; (4) on day 10–14 after influenza. In each phase blood levels of LIF and sLIFr were determined by enzyme immunoassay at 7.00–8.00 h and 19.00–20.00 h, in 12 patients in four phases — at 7.00–8.00 h, 12.00–13.00 h, 19.00–20.00 h, 23.00–1.00 h throughout three days. It has been demonstrated that patients with EH show elevated LIF and sLIFr levels relative to healthy individuals in all time points (р ˂ 0.001) and significantly elevated levels at 19.00–20.00 h (р ˂ 0.001). The analysis of the relationship between circadian rhythms and blood levels of LIF, sLIFr in patients with stage II EH post COVID-19 and influenza has revealed similar changes in the form of the larger increase in sLIFr levels at 19.00–20.00 h (the ROC analysis data has shown predictive value for developing acute CVA within a year after СOVID-19 in cases of the value increase above 7100 pg/L at 19.00–20.00 h). The principles revealed actualize further investigation of the effects of the LIF/sLIFr complex associated with the EH progression after acute infectious diseases.

Received: 2024-11-28

Published online: 2025-02-26

DOI: 10.24075/brsmu.2025.005

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VIEWS 222