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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Neznamov AN, Baykova YuP, Korshunov EN, Isaeva EM, Bruter AV, Kubekina MV

Atherosclerosis being the main cause of myocardial infarction and stroke remains a global medical and social problem. Despite the fact that it is recognized as a chronic inflammatory disorder, the intracellular molecular mechanisms that drive the disease progression are poorly understood. The CDK8 and CDK19 cyclindependent kinases being the key regulators of transcription and inflammation can potentially play an important role in the atherosclerosis pathogenesis. The study aimed to assess the impact of the Cdk8 and Cdk19 gene knockout on the development of atherosclerotic lesions in apolipoprotein E-deficient mice (ApoE⁻/⁻). It has been shown that both endothelium-specific and systemic Cdk8 knockout significantly reduce the area of atherosclerotic aortic lesions, and the total knockout has a more prominent anti-atherogenic effect. This suggests a pleiotropic role of CDK8 in the atherosclerosis pathogenesis mediated by its function not only in endothelial cells, but probably also in macrophages. In contrast to Cdk8, the systemic Cdk19 knockout had no significant effect on the development of atherosclerosis. Thus, CDK8, but not CDK19, has been identified as a pro-atherogenic regulator, which makes it a promising target for the development of novel therapeutic strategies.

Received: 2025-10-31

Published online: 2025-12-16

DOI: 10.24075/brsmu.2025.078

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VIEWS 385

Savelieva OE, Krivolesova TA, Zhigalina AS, Sigareva LP, Saburov AV, Reznik VA

Chronic endometritis (CE) is the most significant endometrial disease in terms of its impact on reproductive potential. Thus far, pathogenetically significant inflammatory markers — cytokines, inflammatory proteins, and hematological indices — have not been widely used in medical practice for the diagnosis of CE. This study aimed to evaluate indicators of systemic inflammation, including hematological parameters and inflammatory indices, in patients with infertility, and to determine their diagnostic significance for CE. We analyzed the data of examinations of 50 patients with infertility. The standard hematological method was used to determine the leukocyte count. Based on the blood cell composition, we calculated the inflammatory indices NLR, MLR, PLR, and SII. The concentration of CRP in the blood serum was determined by enzyme immunoassay. In patients with CE-associated infertility, the absolute and relative numbers of lymphocytes were lower (p = 0.0451 and p = 0.0089, respectively), whereas the relative numbers of monocytes and basophils were higher (p = 0.0469 and p = 0.0005, respectively) than in patients without CE. In the study group, the concentration of CRP in the blood was almost four times higher than in the control group (p = 0.0191), but all indicators remained within the normal range. A comparative analysis of the NLR, MLR, PLR, and SII indices revealed their significant growth in CE-associated infertility cases (p = 0.0387, p = 0.0058, p = 0.0335, and p = 0.0333, respectively). ROC analysis established the predictive significance of NLR (0.871 (95% CI: 0.767–0.974); p < 0.0001) and MLR (0.848 (95% CI: 0.737–0.958); p < 0.0001) indices for detecting CE in infertility patients.

Received: 2025-10-29

Published online: 2025-12-15

DOI: 10.24075/brsmu.2025.071

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VIEWS 482

Melamud MM, Ermakov EA, Tolmacheva AS, Sizikov AE, Klyaus NA, Nevinsky GA, Buneva VN

The high-mobility group protein B1 (HMGB1) belongs to alarmins — a group of molecules involved in inflammatory responses. HMGB1 is actively studied in the context of certain rheumatic diseases (RDs), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA), but the accumulated knowledge remains insufficient. HMGB1 can also act as an antigen, yet the level of anti-HMGB1 antibodies is poorly understood in RDs. The aim of this study was to investigate the concentrations of HMGB1 and anti-HMGB1 antibodies in four RDs. Using enzyme-linked immunosorbent assay (ELISA), plasma samples from patients with RA (n = 60), AS (n = 60), SLE (n = 24), PsA (n = 30), and healthy donors (HD) (n = 60) were analyzed. After adjustment for age and disease duration, it was shown that the concentration of HMGB1 was significantly increased in SLE (p < 0.01), RA (p < 0.01), and AS (p = 0.017), while a statistically non-significant increase in HMGB1 was observed in PsA (p = 0.07) compared to HD. Among the four diseases, the highest level of HMGB1 was found in SLE (p < 0.01). The concentration of anti-HMGB1 antibodies was also elevated in SLE (p < 0.01), RA (p = 0.026), and AS (p = 0.028). Using correlation and regression analysis, a strong direct association was established between the level of HMGB1 and the DAS28 index in RA (p < 0.01 for both analyses). The results of the study describe characteristic changes in HMGB1 and anti-HMGB1 antibody levels in RDs and indicate the involvement of HMGB1 in the pathogenesis of these diseases.

Received: 2025-10-29

Published online: 2025-12-14

DOI: 10.24075/brsmu.2025.074

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VIEWS 435

Zornikov DL, Bekhter AA, Kornilov DO, Simarzina VM, Nechaeva DM, Karyakina AE, Leshukova MA, Amineva PG, Voroshilina ES

The risk of contamination by cervical microbiota during transcervical sampling represents a fundamental methodological challenge in endometrial microbiome research. This study aimed to experimentally evaluate the efficacy of Pipelle and Endobrush endometrial sampling catheters in preventing this contamination. An in vitro cervix model with two anatomically distinct canal types (cylindrical and slit-like) was developed and filled with a synthetic cervical mucus containing a defined quantity of bacterial DNA. After catheter passage through the model cervical canal, a simulated ‘endometrial’ sample (sterile air) was collected and subjected to quantitative PCR analysis. Both catheter types facilitated substantial transfer of bacterial DNA from the cervical mucus into the endometrial sample. The median transfer of total bacterial DNA was 81.6% [54.4–107] for the Pipelle catheter and 29.8% [14.8–56.3] for the Endobrush catheter (p = 0.009), indicating that neither device provided sufficient protection for reliable characterization of the endometrial microbiota. Catheter efficacy was further dependent on cervical canal morphology and the specific microbial group analyzed. These findings demonstrate that transcervical sampling with either catheter type introduces a significant and variable degree of cervical contamination, thereby confounding the interpretation of endometrial microbiota data and underscoring the need to conceptualize and study a combined cervico-endometrial microbiota.

Received: 2025-11-18

Published online: 2025-12-13

DOI: 10.24075/brsmu.2025.073

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VIEWS 510

Ershova ES, Veiko NN, Kostyuk EV, Poletkina AA, Rozhnova TM, Nizyaeva NV, Muzaffarov DU, Klimenko PA, Kostyuk SV

Pregnancy requires the cells of the woman’s body to ensure increased ribosomal biogenesis in order to enhance the protein synthesis intensity. The number of ribosomes depends on the copy number of ribosomal genes (rDNA) in the genome. The study aimed to test the hypothesis about the association of the rDNA copy number in the woman’s genome with the course of normal and complicated pregnancy. The sample of 488 pregnant women (25–39 weeks) included the following groups: 1) normal pregnancy (control); 2) impaired uteroplacental blood flow and fetoplacental insufficiency; 3) congenital malformations; 4) isthmic-cervical insufficiency; 5) early placental maturation; 6) dichorionic diamniotic twins; 7) polyhydramnios; 8) macrosomia. The rDNA copy number was determined by the quantitative hybridization method in the DNA extracted from peripheral leukocytes. The rDNA copy number varied between 226 and 800 (n = 488). DNA samples with the rDNA copy number below 290 were lacking in groups 3–8. Groups 5–8 included no samples with the rDNA copy number exceeding 520; these in total differed from group 1 by low rDNA copy number values (the average values were 360–381 for groups 3–8 and 452 for group 1; p < 10–7). The rDNA copy number range of 290–520 in the woman’s genome (the adaptive norm typical for long-lived individuals) is optimal in terms of successful completion of pregnancy in the presence of pregnancy complications. The low rDNA copy number (200–290) in the genome is associated with the failure to complete embryogenesis when there are some fetal abnormalities/ features. A high rDNA content (over 600 copies) indicates the presence of genetic variants in the woman's genome that can interfere with the complicated pregnancy course. Determining the rDNA copy number in the genome of married couples may be useful for planning and predicting the course of pregnancy.

Received: 2025-10-23

Published online: 2025-12-12

DOI: 10.24075/brsmu.2025.075

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VIEWS 433

Petrash EA, Yunina-Pakulova NYu, Kuryishina SA, Karpenko AS, Kuznetsova AA

Memory in all the variety of the types and processes ensuring its functioning has a psychotherapeutic resource that is realized when working with manifestations of post-traumatic stress disorder (PTSD). One of these is obsessive repetitive memories with traumatic content. The study aimed to look into reconsolidation of early memories in reliving the traumatic experience of participation in combat. The total sample size was 62 individuals (males aged 21–46 years). The experimental group included 31 respondents with combat experience having the status of war veterans (the average period of participation was 1 year and 5 months). The control group consisted of 31 respondents with no combat experience. The Mini-Mental State Examination (MMSE) scale, set of functional neuropsychological tests (“10 Words” by A.R. Luria, "Pictograms" method by A.R. Luria, "Difficult-to-Verbalize Figures" by T.V. Akhutina, "Rhythm Reproduction Test" by A.R. Luria), analysis of the transcripts of audio recordings of early memories were used. It has been reliably found that the early memory of a positive, negative or neutral modality resulting from the influence of combat experience is changed through the reconsolidation mechanism, which is reflected in the linguistic and semantic parameters. The linguistic and semantic structure of the combat veterans’ early memories is characterized by the event-based model, with a predominance of verbs and adverbs. The semantic core of the combat veterans’ early memories is more often negatively colored, despite the general ambivalent or positive modality.

Received: 2025-10-25

Published online: 2025-12-11

DOI: 10.24075/brsmu.2025.069

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VIEWS 440

Khokhlova AN, Vavilov MV, Chepurnykh TV, Rodionova NS, Petushkov VN, Yampolsky IV, Dubinny MA

Traditional medicine has been using earthworms to treat a wide range of pathological conditions for many centuries. Current research focuses primarily on the isolation and characterization of biologically active compounds, including notable examples such as glycoprotein G90, which exhibits thrombolytic and antitumor properties; the enzyme complex lumbrokinase; and the extracellular oxygen transport protein erythrocruorin, regarded as a potential basis for blood substitute development. Model organisms such as Caenorhabditis elegans, which are used to study the mechanisms of aging, neurodegenerative diseases, and evaluate the effectiveness of medicines, also play an important role. Bioluminescent systems of annelids are of particular interest because they exhibit a variety of chemical mechanisms of luminescence and unique cofactors that hold promise for applications in biomedicine. The combination of these properties and abilities underscores the importance of worms as a source of enzymes, proteins, and metabolites, as well as model systems for finding solutions to both fundamental and applied biomedical problems.

Received: 2025-10-21

Published online: 2025-12-10

DOI: 10.24075/brsmu.2025.067

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VIEWS 407

Kulinich TM, Kukoleva EA, Goncharov SV, Kudinova EA, Puchkov IA, Goncharova OI, Kaminsky VV, Bozhenko VK

Peritoneal carcinomatosis remains one of the most challenging forms of dissemination in gastric and colorectal cancer. It directly determines the disease prognosis and is highly resistant to treatment. The use of the existing therapeutic approaches is often limited by low benefit-risk ratio. It is necessary to develop innovative strategies aimed at overcoming the molecular mechanisms of tumor progression associated with RAS mutations, which play a crucial role in the carcinogenesis of both colorectal and gastric cancer. The study aimed to estimate safety and preliminary efficacy of the novel peptide RAS-GTPase inhibitor «Ing-Ras» when included in the treatment regimen of patients with stage III–IV gastric and colorectal cancer, including patients with peritoneal carcinomatosis. A total of 35 patients with the confirmed diagnosis of stage III–IV gastric and colorectal cancer were included in the study. The «Ing-Ras» drug was administered at a dose of 1.8 mg/kg twice with a 7-day interval using the Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) technique. Primary efficacy was assessed by comparing the overall survival (OS) and progression-free survival (PFS) rates of the clinical trial patients with historical control groups. The OS and PFS rates for patients in the clinical trials were 92.1% and 84.22%, respectively, which significantly (p < 0.05) exceeded the values of these rates for the historical control group (50.8% and 65.25%). Thus, the use of «Ing-Ras» can significantly improve the treatment results for patients with advanced forms of colorectal and gastric cancer.

Received: 2025-10-23

Published online: 2025-12-09

DOI: 10.24075/brsmu.2025.065

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VIEWS 436