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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Bondorenko DV, Ivanov AS, Tananakina TP, Kashchenko SA, Pogorelova IA, Alexandrov IA

Nonsteroidal anti-inflammatory drugs (NSAIDs), one of which is diclofenac sodium, are widely used in clinical practice. This study aimed to assess the effect of diclofenac sodium on bone marrow cellularity, the population of hematopoietic stem and progenitor cells (Lin−Sca-1+ c-Kit+, LSK), as well as the levels of tumor necrosis factor — (TNFa) and interleukin-1b (IL1b) in laboratory mice with experimental dermatitis. The study was a randomized controlled trial; the experimental phase lasted 96 hours. Male BALB/c mice (n = 6, age 46 weeks, 18–25 g) were randomized into five groups: intact, untreated dermatitis, dermatitis + diclofenac 1.5 mg/kg, dermatitis + diclofenac 3 mg/kg, diclofenac 3 mg/kg without dermatitis. The drug was administered intramuscularly 2 times a day for 96 hours. Dermatitis was modeled using sodium dodecyl sulfate and Dermatophagoides farinae. Bone marrow was collected after 96 hours. The total number of cells was determined by an automatic counter, the LSK cell population by flow cytometry, and cytokine concentrations by ELISA. Statistical analysis was performed using ANOVA (p < 0.05). We observed a decrease in bone marrow cellularity in dermatitis groups (0.95 ± 0.12 versus 1.20 ± 0.15 × 106 ml; p < 0.05). Diclofenac 1.5 mg/kg decreased cellularity moderately (0.80 ± 0.10 × 106 ml) and an increased LSK cells (3.8 ± 0.5% vs. 2.1 ± 0.3%; p < 0.05). Diclofenac 3 mg/kg markedly brought down cellularity (0.60 ± 0.08 × 106/ml) and LSK cells (1.4 ± 0.3%; p < 0.01), and brought up IL1b (15.5 ± 1.2 pg/ml) and TNFa (82.1 ± 4.5 pg/ml). Our findings indicate a dose-dependent effect of diclofenac sodium on hematopoiesis and inflammatory response.

Received: 2026-05-15

Published online: 2026-06-30

DOI: 10.24075/brsmu.2026.038

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VIEWS 131

Parochkina EV, Rumiantseva AA, Semenova DK, Bormotov DS, Temnov AA, Stupnikova GS, Zavorotnyuk DS, Bocharov KV

Intraoperative determination of tumor margins reduces the volume of resected tissue while ensuring complete removal of malignant tissue without increasing the risk of recurrence. The existing approaches, including intraoperative histology or tomography, are highly effective, but they extend the time of the surgery. Therefore, real-time analysis methods are a particularly interesting avenue. One such solution is mass spectrometric profiling based on ambient ionization mass spectrometry. The molecular profile of the examined tissue is compared with a reference database of healthy and pathologically altered tissues. For many human organs, samples for this database can only be obtained from autopsy material. However, due to the unavoidable time delay between the moment of death and sample collection, tissue degradation may change the picture of pathological process. This experimental quantitative study investigated the stability of polar lipid profiles in the liver and brain tissues of healthy BALB/c mice (n = 23) during the early postmortem period (0–72 hours). It has been shown that lysolipids and free fatty acids correlate with the postmortem interval (r > 0.6 overall; r = 0.75 for FA 20:4 and FA 22:6); therefore, they cannot be used as molecular markers in diagnostic models based on autopsy samples. At the same time, the profile of phospholipids in tissue cell membranes remains largely unchanged in the early postmortem period, which preserves their value as biomarkers detectable in both biopsy and autopsy specimens.

Received: 2026-05-12

Published online: 2026-06-29

DOI: 10.24075/brsmu.2026.037

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VIEWS 146

Sorokina LE, Kokoeva DN, Kan NE, Fomochkina II

Preeclampsia (PE) is considered as one of the most severe pregnancy complications, an important role in pathogenesis of which is played by immunogenetic factors. The study aimed to assess the contribution of HLA-DR-dependent mechanisms to the immune response regulation in PE associated with the HLA-DRB1*01:01 allele carrier state in an in vitro experimental model. A comparative experimental in vitro study was conducted. Patients with PE (n = 7), who were HLA-DRB1*01:01 carriers, and women with the normal pregnancy course (NP; n = 10), who were not HLA-DRB1*01:01, -DRB1*04:01, -DRB1*10:01 carriers, were enrolled. The CD14+ and CD4+ cells, as well as placental tissue samples, from which the placental conditioned medium (PCM) was derived, were obtained from peripheral blood samples. The CD14+ and CD4+ cells were co-cultured in both groups. PCM was added to the culture to model the effects of placental factors. In the PE group, HLA-DR was blocked with the L243 monoclonal antibody; the IgG2a isotype antibody was used in the NP group. The share of Treg-cells in the cultures was determined by flow cytometry; the IL17, IFNγ, TNFα, IL10, and IL4 cocentrations were determined by ELISA. The direct CD14+ and CD4+ co-culture revealed no intergroup differences in the share of Treg and cytokine concentrations. The PCM supplementation in the PE group resulted in the decreased share of Treg and IL10 levels amid increasing IL17, TNFα, and IFN-γ. In the NP group, on the contrary, the increase in Treg counts, IL10 and IL4 levels, along with the decrease in IFN-γ levels was reported. The HLA-DR blockage in PE was associated with the decrease in IL17 and IFN-γ levels. The findings demonstrate the potential significance of placental factors and maternal immunogenetic features in the immune response regulation in PE.

Received: 2026-05-10

Published online: 2026-06-28

DOI: 10.24075/brsmu.2026.036

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VIEWS 140

Volkova AA, Gladkova AS

Diabetes mellitus (DM) is associated with systemic inflammation and neuroinflammation, but the role of β-arrestin 2 in these processes remains poorly understood. The experimental study aimed to assess the effect of β-arrestin 2 deficiency on the pro-inflammatory state of mice with streptozotocin-induced diabetes. Male C57BL/6J mice and mice with the global β-arrestin 2 gene knockout (Arrb2-/-) were divided into four groups: non-diabetic wild type mice (WT, n = 8), diabetic wild-type mice (WTd, n = 8), non-diabetic knockout mice (KO, n = 8) and diabetic knockout mice (KOd, n = 9). Arrb2 knockout delayed the development of hyperglycemia: on day 39, blood glucose levels were significantly higher in WTd mice than in KOd mice (22.3 ± 8.09 vs. 14.37 ± 7.65 mmol/L, p < 0.05). Arrb2-/- mice also showed increased systemic inflammatory markers: the baseline percentage of neutrophils in KO mice was 2.6-fold higher than in WT mice (p < 0.0001). Starting from day 18 KOd mice had significantly higher neutrophil counts compared to KO and WTd (p < 0.05). β-Arrestin 2 deficiency was associated with increased mRNA expression of the genes encoding pro-inflammatory cytokines and protease-activated receptors. The most pronounced changes included a significant increased Il6 mRNA expression in the hippocampus of KO compared to WT (2.9-fold, p < 0.01), increased Tnf expression in the cerebral cortex (4.3-fold for KO/WT and 2.0-fold for KOd/WTd) and the hippocampus (3.2- and 2.3-fold, respectively) of Arrb2-/- animals compared to appropriate wild type groups (p < 0.05), as well as the increased Par1 and Par4 expression in the cerebral cortex and hippocampus of Arrb2-/- mice (2.4–7.3-fold, p < 0.01). These findings suggest that β-arrestin 2 deficiency is associated with a pro-inflammatory phenotype in the CNS and may contribute to inflammation dysregulation in DM.

Received: 2026-04-14

Published online: 2026-06-27

DOI: 10.24075/brsmu.2026.035

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VIEWS 147

Baranova NS, Ostapenko YaS, Baranov AA, Ovsyanikova LA, Spirin NN, Rechkina OP, Zolotavkina SS, Vdovenko OV, Semechkin NV

Lyme borreliosis (LB) is a naturally occurring transmissible disease caused by Borrelia burgdorferi sensu lato. Some patients develop LB after effective treatment of the acute stage of the disease with antibiotics, which may suggest involvement of chemokines and cytokines in its pathogenesis. This study aimed to assess serum levels of chemokine (C–C motif) ligand 19 (CCL19) and interleukin-23 (IL-23) in patients with post-Lyme syndrome (PLS) and neurological involvement, and to examine their association with clinical manifestations and laboratory parameters. We examined 70 individuals (26 [37.1%] male and 44 [62.9%] female) with confirmed LB who presented with neurological symptoms persisting or recurring within 6 months following the recommended antibiotic treatment. The serum levels of CCL19 and IL-23 were determined using a solid-phase enzyme immunoassay; CCL19 was high in 12 (17.1%) participants, and IL-23 in 10 (14.3%). Significant positive correlations were established between the concentrations of CCL19 and IL-23 (r = 0.65, p < 0.0001) and their hyperproduction (r = 0.79, p < 0.0001). The likelihood of developing Lyme disease after treatment increased significantly in association with overproduction of CCL19 and, especially, IL-23: odds ratio — 5.00; 95% CI: 1.00–24.84, p = 0.04, and 22.42; 95% CI: 1.25–399.93, p = 0.03, respectively. No correlation was found between the concentration of CCL19, IL-23, and the levels CRP, IgM and IgG antibodies to B. burgdorferi, ass well as IgG antibodies to SARS-CoV-2. A subject matter being discussed in the paper is how CCL19, IL-23 and other mechanisms participate in post-treatment pathogenesis of Lyme disease with neurological damage.

Received: 2026-05-18

Published online: 2026-06-26

DOI: 10.24075/brsmu.2026.034

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VIEWS 145

Lobkarev AO, Muzhekhoev AA, Evloev MK, Dzhandigov RB, Korigov IA

Despite the successful practice of using the Russian-made original peptide complex (OPC), the complex pharmacodynamics is poorly understood. The study aimed to assess the effect of taking OPC on the prostate tissue oxygen consumption rate (OCR) in white outbred rats. The experiments involved 65 adult male white outbred rats (age 6 months, body weight 410.8 ± 2.7 g). The rats were kept under standard vivarium condition, each in a separate cage; the diet and drinking regime were standard. The difference in animal housing was that animals of the experimental group (n = 49) received OPC throughout 20 days before the day of the experiment: every day 0.35 mg (0.85 mg/kg) of the drug were dissolved in 20 mL of the drinking water the animals drank from the trough. The drug was not administered to the control group (n = 16). A prostatectomy was performed. The prostate tissue OCR was measured using the DKTP-03 optical dissolved oxygen sensor with a thermoelectric converter. The О2 concentration readings (ConО2) in mg/L were recorded every minute throughout 60 min. Significant intergroup differences in ConО2 values in the end of the experiment were found (р < 0.05). It has been shown that OPC increases the prostate tissue OCR in white outbred rats.

Received: 2026-05-19

Published online: 2026-06-21

DOI: 10.24075/brsmu.2026.033

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VIEWS 157

Svirin EP, Berdyshev DA, Shishkin SL

Quasi-movements (QMs), which are movement attempts minimized to the point of movement extinction, evoke EEG patterns similar to those of real movement. QMs can model attempted movement in healthy subjects and are therefore of interest as an alternative to motor imagery (MI) in rehabilitation brain–computer interfaces (BCIs), in which the attempted movement of the paralyzed limb is used as a control signal. Earlier QM studies were focused on thumb abduction. The study aimed to verify the feasibility of QMs based on more natural actions (pressing and pointing) and compare their EEG correlates with those of MI. In 11 healthy volunteers (6 women, aged 21–32), EEG recording was performed during execution of MI, non-goal-directed QMs (nQMs), goal-directed QMs (gQMs), and real movements. Both QM types caused more pronounced contralateral desynchronization of the 8–13 Hz mu rhythm than MI (0.63 dB, effect of movement type, p = 0.042), while nQMs and gQMs did not differ. There were no differences in ipsilateral desynchronization between the conditions (p = 0.216). Pairwise comparisons were significant in the upper-frequency mu rhythm sub-range (nQM–MI: 0.82 dB, p = 0.003; gQM–MI: 0.70 dB, p = 0.022). There was no effect of movement type in the parietal area of interest (p = 0.15). The contribution of residual movement was non-significant. The data obtained show that QMs based on natural actions are feasible and produce stronger sensorimotor activation than MI, which justifies further research focused on QMs in the context of rehabilitation BCIs.

Received: 2026-04-19

Published online: 2026-06-14

DOI: 10.24075/brsmu.2026.030

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VIEWS 206

Bobrakova AA, Salikhova NG, Panteleeva AN, Yasnetsov VV, Proskurina OV, Balabanyan VYu

In recent years, the number of emergencies, armed conflicts, and household injuries has increased, which has elevated the risk of thermal burns for a broad segment of the population. Design and testing of new, safe and efficient burn-healing drugs remains a relevant task. This study aimed to evaluate the burn — healing effects of a new cream containing polyprenols isolated from Ginkgo biloba L. in a rat thermal-burn model. The cream's active ingredient is a highly purified (≥ 95%) Ginkgo biloba L. polyprenols, and the excipients are lipids (phosphatidylcholine, phosphatidylserine) with tocopherol antioxidants. The experimental animals were 32 male Wistar rats weighing 280–320 g. We evaluated the effect of the new polyprenol cream and the reference preparations methyluracil and dexpanthenol on the dynamics of the skin lesion area in rats with grade III-B skin burns. The experiment showed that, on day 21 after the burn, the new cream reduced the wound area in rats by 2.3 times compared with the controls. Morphological examination showed that the new cream had a 1.3-fold better burn-healing effect than the comparison drug methyluracil (dioxomethyltetrahydropyrimidine). Further preclinical study of the cream as a potential burn and wound healing agent seems promising.

Received: 2026-05-12

Published online: 2026-06-18

DOI: 10.24075/brsmu.2026.032

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VIEWS 125