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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Ivanova EV, Naumenko VA, Garanina AS, Abakumov MA

The development of effective relief for cancer is one of the most urgent tasks of biomedicine. Despite the success of anti-tumor nanotherapeutics, low targeted delivery effectiveness remains a major limiting factor for widespread introduction of those into clinical practice. Tumor microenvironment is a complex, multicomponent system, the dynamic interaction of which with nanoparticles requires adequate analysis methods. Intravital microscopy presents a unique opportunity for in vivo assessment of drugs and body’s cells in the real-time mode. The review describes the possibilities and prospects of using intravital microscopy to study the nanotherapeutic biodistribution and delivery to tumor cells in preclinical animal models.

Received: 2025-06-04

Published online: 2025-06-30

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VIEWS 39

Butunts MA, Dyuzhina KA, Nifatova ES, Muradyan TG

Bone marrow transplant is the leading method to treat hematologic malignancies, immunodeficiency, and hereditary metabolic disorders. The Federal Bone Marrow Donor Registry effectiveness depends directly on public awareness of bone marrow donation and infrastructure development. A comprehensive approach to public awareness is necessary to increase the system effectiveness. The study aimed to investigate factors that influence joining the Federal Bone Marrow Donor Registry, with a focus on motivation, sources of information, impact of infrastructure, environment, and common myths. The respondents (potential donors registered in the Federal Registry; n = 3100) filled an online questionnaire of 24 questions aimed at studying and assessing the socio-demographic characteristics, motivation, sources of information, influence of the environment, awareness of bone marrow donation, and readiness to donate. It was found that young adults aged 18–36 (n = 1860) more often join the Federal Registry through informal channels, such as work/school events (n = 843; 27.2%), while respondents over the age of 37 (n = 1240) prefer healthcare institutions (n = 1590; 51.3%). Women make up the majority of potential donors (n = 2304; 74.3%), especially in Moscow (n = 1650; 74.5%), while higher prevalence of myths is reported for the regions (n = 1646; 53.1%). The findings emphasize the need for the differentiated approach to information policy, which will make it possible to increase the donor movement effectiveness nationwide. A key factor in scaling this work is partnership with commercial laboratories, which significantly expands the Federal Registry recruitment network and provides convenient conditions for donors to join.

Received: 2025-05-26

Published online: 2025-06-26

DOI: 10.24075/brsmu.2025.032

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Shishelova AYu, Guseva OYu, Kopetskiy IS, Ansari V

The chewing experience acquired during ontogeny may lead to developing functional asymmetry of the masticatory apparatus, adversely affecting the maxillofacial region functions. The study aimed to assess asymmetry of the masticatory muscle activity in healthy individuals showing no dentofacial system dysfunction. In 17 volunteers (6 males, 11 females aged 18–23 years), motor functional asymmetry of the brain was assessed using standard motor tests, and surface electromyogram (EMG) of the masseter (MM) and temporalis muscle (TMs) was recorded on the right and left sides: in the resting state, with the maximum voluntary bite force, during deliberate unilateral mastication (alternately on the left and right sides), and bilateral voluntary chewing. Three groups with various asymmetry manifestations were distinguished and characterized based on the asymmetry indices of standard EMG parameters (integrated EMG (AIint), average amplitude (AIav), and chewing bursts duration (AId)) of the right and left muscles: 1) showing stable unilateral asymmetry of the MM and TM activity; 2) showing the “dynamic asymmetry” that was different for the MMs and TMs; 3) showing the “adaptive control”, when the muscle activity asymmetry was manifested adequately to the chewing test, and AIint of the MMs and TMs reached 40 ± 18% and 97 ± 20% during chewing on the left side, 242 ± 39% and 127 ± 32% during chewing on the right side, 115 ± 12% and 115 ± 24% during bilateral chewing. The major significant between-group differences in AIint, AIav, and AId were reported for the MMs (the impact of the “group” factor on these indices was as follows: F = 11.0, p < 0.01; F = 5.72 and F = 3.73, p < 0.05; repeated measures ANOVA). Thus, in young adulthood, some people develop functional asymmetry of the masticatory muscles in the form of excessive predominance of electrical activity on one side of the face with changes in both amplitude and duration of the “chewing” EMG bursts.

Received: 2025-05-19

Published online: 2025-06-19

DOI: 10.24075/brsmu.2025.031

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VIEWS 130

Kopetskiy IS, Pobozhieva LV, Kopetskaya AI

Indices that reflect individual oral hygiene levels are widely used to determine microbial plaque of the tooth surface. When teaching patients how to take care about the oral cavity, dentists use visual demonstration of the dental plaque localization. The quantitative light-induced fluorescence (QLF) technique represents a modern method to diagnose individual oral hygiene, in which even minimal microbial plaque buildup shows up as red fluorescence. The study aimed to assess the oral hygiene status using the quantitative light-induced fluorescence technique. Dental deposits were detected using QLF; the Quigley Hein, Green-Vermillion, DMF indices were detected clinically. The findings show that Simple Hygiene Scores do not exceed 2, when the caries intensity is very low or low (p < 0.05). In these groups, the Green-Vermillion and Quigley Hein index values reach 0.5 ± 0.23 and 0.2 ± 0.14, respectively. When the caries intensity is medium, Simple Hygiene Scores vary between 1–5 points. Very high caries intensity is characterized by the Simple Hygiene Score between 3 and 5 points (maximum Green-Vermillion and Quigley Hein index values reach 2.3 ± 0.43 and 2.1 ± 0.35) (p < 0.05). Thus, the quantitative light-induced fluorescence technique can be used in clinical trials for objective oral hygiene assessment, visual demonstration of dental plaque buildup to patients, and assessment of the dynamic changes in these indicators.

Received: 2025-04-23

Published online: 2025-06-06

DOI: 10.24075/brsmu.2025.030

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VIEWS 193

Zinchenko RA, Tebieva IS, Zakharova EYu, Shchagina OA, Lotnik EE, Gabisova YuV, Khokhova AV, Bakin NV, Marakhonov AV

Mass screening of newborns for 36 hereditary diseases in the Russian Federation will enable the reduction of childhood disability and mortality from hereditary disorders, as well as the identification of all-Russian and regional population-genetic features of the screened disorders. The study aimed to assess the results of newborn screening (NBS), including expanded newborn screening (ENBS), in the Republic of North Ossetia-Alania obtained between January 1, 2023, and December 31, 2024, as well as to study clinical and population-genetic characteristics of the diseases screened in the region. In phase I of assessment, biochemical testing, tandem mass spectrometry, and DNA diagnostics were performed, and the TREС/KREС levels were determined in 14,994 newborns. In 355 cases (2.36%), positive values were revealed. In phase II, the necessary laboratory and subsequent confirmatory DNA diagnostics were carried out in 324 cases (91.2%): repeated analysis by MS/MS and DNA diagnostics (for hereditary metabolic diseases), immunophenotyping (for primary immunodeficiency states). During the 2-year study, a total of 37 diagnoses were established, which accounted for 0.25% of all children screened in phase I and clearly indicated the program's success and effectiveness. We managed to verify the specific spectrum of mutations characteristic of phenylketonuria (PKU) and medium-chain fatty acid acyl-CoA dehydrogenase deficiency (MCADD). The frequency of the disorder assessed within the framework of newborn screening was determined. The frequency of all PKU forms was 1 : 1153 newborns, and the frequency of MCADD was 1 : 789 newborns surveyed. All children are listed as sick in the medical genetic consultation of the Republic of North Ossetia-Alania; they receive treatment in accordance with the clinical guidelines.

Received: 2025-04-22

Published online: 2025-05-30

DOI: 10.24075/brsmu.2025.029

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VIEWS 246

Popova ES, Agbalyan AN, Titov VD, Moiseeva VP, Mashin SV, Anfimiadi VA, Zhukov GM, Bondarevskaya AO, Gavrilyuk LM

Currently, the occurrence of multiple primary malignant tumors is one of the complex and poorly understood issues of oncology. After the diagnosis of malignant neoplasm is established, the risk of a new primary, non-metastatic tumor increases in a patient. The paper presents a case report of the patient with four multiple primary malignant tumors in the duodenum and colon. Synchronous cancer of the cecum and rectosigmoid junction occurred after 9 months of the duodenal cancer pancreatoduodenal resection, photodynamic therapy, and 12 multiagent chemotherapy courses. The patient received 8 courses of chemotherapy with capecitabine, during which cancer progression was reported, and 16 multiagent chemotherapy courses. Two years later rectal cancer occurred, due to which rectal re-resection was conducted, along with 4 multiagent chemotherapy courses and target therapy. This clinical case emphasizes that it is necessary to perform additional assessment when treating patients with synchronous or metachronous multiple primary tumors to ensure the timely diagnosis and multidisciplinary approach to treatment of cancer patients.

Received: 2025-04-07

Published online: 2025-05-27

DOI: 10.24075/brsmu.2025.028

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VIEWS 284

Kiseleva VV, Vishnyakova PA, Kosyreva AM, Kananykhina EYu, Emelianov II, Elchaninov AV, Fatkhudinov TH

High fatality rate and the lack of pathophysiological therapy are typical for acute respiratory distress syndrome (ARDS). Intratracheal lipopolysaccharide (LPS) administration is used to model ARDS in animals. The method has the limitation of requiring the use of equipment to perform intubation and control the animal’s state. The study aimed to assess the possibility of using intranasal LPS administration instead of intratracheal and determine the LPS optimal dose. A total of 150 mL of the E. coli O111:B4 LPS (7.5 mg/kg or 15 mg/kg) or 0.9% NaCl was administered to 21 Sprague-Dawley rats. After 48 h blood was collected from the tail vein to determine the white blood cell count and TNFa concentration. The lungs were retrieved to assess dry weight (wet/dry ratio) and to determine the expression of the genes encoding pro- and anti-inflammatory cytokines using real-time PCR. The relative counts of CD68-, CD86-, and MHC II-positive cells in the lung tissue were also evaluated using flow cytometry. The w/d ratio was higher when the dose of 15 mg/kg of body weight was used (p = 0.0228, ordinary one-way Anova). Вlood lymphocyte counts were decreased (p = 0.0019, ordinary one-way Anova), and neutrophil counts were increased (p = 0.0021, ordinary one-way Anova) upon administration of both doses. The counts of CD86- (p = 0.0014, ordinary one-way Anova) and MHC II-positive cells (p = 0.0050, ordinary one-way Anova) increased after LPS administration. The IL10 gene expression was significantly increased upon administration of the dose of 15 mg/kg (p = 0.0024, ordinary oneway Anova), while the IL4 expression (p = 0.0194, ordinary one-way Anova) was decreased upon administration of the dose of 7.5 mg/kg. Thus, intranasal LPS administration can be used to model ARDS in the Sprague-Dawley rats. Administration of the high dose leads to the rapid development of inflammation in the lung.

Received: 2025-04-21

Published online: 2025-05-20

DOI: 10.24075/brsmu.2025.027

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VIEWS 397

Popov NS, Terekhov VM, Baranov MS, Balabanyan VYu, Kaurova DE, Myasnyanko IN, Terekhova EA

Assessment of pharmacologically active molecule biotransformation represents the most important phase of drug development, the results of which make it possible to identify active and toxic metabolites and provide a fundamental basis for the targeted design of new candidate drug molecules. The liver is the main organ involved in biotransformation of drugs. The currently widely used in vitro metabolism assessment methods do not allow one to identify products of extrahepatic drug molecule biotransformation. The study aimed to develop an in vivo approach to determination of the role of the liver in biotransformation of candidate drug molecules. The approach proposed is based on the vascular liver isolation performed surgically in laboratory rats. The organ involvement in biotransformation of pharmacologically active molecules is exemplified by the leader compound of the sydnone imine group possessing vasodilatory activity. It has been shown that elimination of the liver from systemic blood flow does not result in generation of the test compound metabolites identified by chromatography–mass spectrometry. The findings can provide the basis for prediction of drug pharmacokinetics, efficacy, and safety.

Received: 2025-04-16

Published online: 2025-05-15

DOI: 10.24075/brsmu.2025.026

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VIEWS 334