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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Darawsheh HM, Mellin RV, Akulinichev EA, Moiseev DA, Snezhko OV, Kopetskiy IS, Vasiliev YuL

Treatment of mandibular fractures remains a pressing issue in maxillofacial surgery. This paper presents a novel single-jaw splinting technique (RF patent No. 2735258) for the immobilization of bone fragments in fractures located within the dental arch. Mathematical modeling using the finite element method (FEM), based on computed tomography data from one volunteer, was performed to assess its biomechanical efficiency. A 3D model of the mandible with the fixation construct and an indenter (simulating occlusal load up to 50 N) was constructed. The modeling results showed that the relative movement between the fragments was approximately 25 µm, which is comparable with literature data for two-titanium-plate osteosynthesis. The maximum equivalent stress values in the metal splint reached 100 MPa, and in the splint these reached 3 MPa. The developed method ensures stable fixation without involvement of the maxilla. The analysis involved only a single model and no experimental validation; therefore, confirmation in further research is required. Nevertheless, the obtained data suggest that the method is promising as an alternative to existing immobilization techniques.

Received: 2026-03-03

Published online: 2026-04-23

DOI: 10.24075/brsmu.2026.015

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VIEWS 69

Khetagurov SK, Sadaeva AA, Shovkhalova RU, Murzabekov BI, Dovletmurzaev ZS, Ozkan Zh-M, Sugaipova DA, Betersultanova DI, Oleinik II

Drug-induced xerostomia is common among elderly patients taking multiple medications. The condition significantly affects dental health and quality of life. This study aimed to evaluate the clinical and laboratory characteristics of oral fluid (OF) in xerostomia patients taking xerogenic medications, and to assess associations between total xerogenic load, salivary flow rates, and OF composition. The study included 60 people aged 45–75 years. The treatment group consisted of 40 patients with at least 3 months of dry mouth history and routine intake of two or more medications with known xerogenic potential. The control group included 20 healthy individuals exhibiting no signs of xerostomia and not taking medications routinely. We used the Xerostomia Inventory questionnaire to collect data from the participants; they also underwent clinical dental examination and sialometry for unstimulated and stimulated oral fluid (OF). The fluid samples were examined in the laboratory to determine pH, buffer capacity, total protein content, alpha-amylase activity, glucose and lactate levels. Compared to the control group, patients in the treatment group showed marked hyposalivation, decreased OF pH and buffer capacity, increased total protein content and alpha-amylase activity, and tended more often to have multiple caries lesions, candidal stomatitis, and atrophic changes in the oral mucosa. Thus, drug-induced xerostomia is accompanied by pronounced quantitative and qualitative changes in OF as well dental health and quality of life deterioration. A comprehensive clinical and laboratory assessment of OF provides an objective measure of xerostomia severity and enables compilation of tailored prevention and treatment programs.

Received: 2026-03-19

Published online: 2026-04-22

DOI: 10.24075/brsmu.2026.016

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VIEWS 73

Tsyganov MM, Tsydenova IA, Loos DM, Ibragimova MK

Studying molecular mechanisms of carcinogenesis, including abnormalities of the homologous recombination (HR) system, is an important objective when studying malignization. Dysfunction of HR genes, such as BRCA1/2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens, such as dimethylbenz(a)anthracene (DMBA), allows one to simulate tumorigenesis processes and assess changes in expression of repair genes. It is important to study such changes to understand the mechanisms underlying adaptation of tumor cells to genotoxic stress and develop personalized approaches to cancer treatment. The study aimed to assess the expression of major HR genes in chemotherapy-induced carcinogenesis in mice. The study involved female outbred ICR laboratory mice (CD-1; n = 20). Two groups of animals were formed: the control group and the treatment group that was administered DMBA. Histological analysis of autopsy specimens was conducted to identify tumors. Gene expression levels were assessed using RT-PCR, and testing for chromosomal aberrations was performed using digital PCR. Tumors were found in four animals. Zero expression of the genes Brca1, Brca2, Cdk12, Chek2, Palb2, Bard1, Brip1 and Rad paralogues was observed in three tumor samples. One sample showed high expression of the genes Cdk12 (14.3), Chek1 (27.6), Rad51d (38.5). Predominance of deletions in the test genes was reported in the majority of cases. Thus, tumorigenesis is associated with the decrease in expression of major repair genes, chromosomal aberration formation, which can contribute to the emergence of more aggressive clones and increase sensitivity to chemotherapy drugs.

Received: 2026-03-17

Published online: 2026-04-19

DOI: 10.24075/brsmu.2026.014

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VIEWS 94

Zinoveva AA, Bakhchinian E, Kamenkov SS, Shcherbakova LN, Bugerenko AE, Ogay DS, Voloshin NS, Chechekhina ES, Kulebyakin KYu

The menopausal transition is accompanied by the decrease in estrogen levels and changes in the estrogen to androgen ratio, resulting in dysregulation of multipotent mesenchymal stem cell (MSCs) differentiation in the subcutaneous adipose tissue, reduction of their adipogenic potential, adipocyte hypertrophy, and metabolic disorder progression. Menopausal hormone therapy (MHT) is used to manage menopausal symptoms. However, the effects of exogenous hormones on MSCs are still poorly understood. The study aimed to assess adipogenic differentiation of the subcutaneous adipose tissue MSCs and their sensitivity to testosterone, 17β-estradiol, and parathyroid hormone (PTH) in postmenopause. A total of six patients with benign gynecological disorders were included in the study, among them two were of reproductive age, one was perimenopausal, and three were postmenopausal. The MSCs adipogenic differentiation was performed throughout 14 days with the addition of testosterone, 17β-estradiol, or PTH, 10 nM each, then the proportion of cells containing lipid droplets was assessed. The adipogenesis level in control samples was 26–30% in patients of childbearing age and 12–42% in postmenopausal ones, with the pronounced interindividual variability. Hormonal stimulation considerably suppressed MSCs adipogenesis in postmenopause: testosterone reduced adipogenesis to 46–56% of control levels, estradiol to 51–84%, PTH to 53–66%, while patients of childbearing age showed a less pronounced effect (65–85%). The obtained data demonstrate a shift in hormonal sensitivity of MSCs from subcutaneous adipose tissue in postmenopause and suggest that MHT may exert an additional inhibiting effect on adipogenesis through suppression of MSCs differentiation.

Received: 2026-03-09

Published online: 2026-04-16

DOI: 10.24075/brsmu.2026.013

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VIEWS 111

Balashova MS, Zhuchenko NA, Tuluzanovskaya IG, Glotov OS, Senina OS, Ignatova TM, Asanov AYu

For several decades, Wilson’s disease (WD) has remained the focus of attention for a wide range of specialists, including hepatologists, general practitioners, neurologists, geneticists, etc. However, despite significant advances in understanding its molecular basis, establishing clear correlations between the genotype and clinical phenotype of the disease remains a key unresolved issue. The study aimed to identify patterns between genetic variants in the ATP7B gene and the WD clinical manifestations using next-generation sequencing. The data from 81 WD patients, who were followed up between 2015 and 2019, were used in the study. Molecular genetic testing of biomaterial (blood) samples was performed by NGS. The analysis of the molecular genetic testing results using targeted NGS revealed 31 pathogenic variants. The following variants were the most frequent: c.3207C>A (p.His1069Gln) — 51.85% alleles, c.3190G>A (p.Glu1064Lys) — 8.64% alleles, and c.3402delC (p.Ala1135fs) — 6.17% alleles. A moderate correlation between genotype and phenotype was established: pathogenic variants (nonsense, frameshift, splicing) in the homo- or compound heterozygous state are associated with severe liver damage, severe degree of cirrhosis, and lower cholinesterase levels. The data obtained emphasize the importance of molecular genetic diagnosis for clarifying the diagnosis of WD and predicting the disease severity.

Received: 2026-02-24

Published online: 2026-04-01

DOI: 10.24075/brsmu.2026.012

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VIEWS 266

Kornilov DO, Simarzina VM, Bekhter AA, Maslakov GP, Nechaeva DM, Karyakina AE, Fadeev FA, Voroshilina ES, Zornikov DL

The PI3K/AKT/mTOR signaling pathway is a key regulator of cell growth, and its dysregulation is involved in oncogenesis. Existing methods for assessing mTOR activity have design flaws. The aim of this work was to develop and validate a novel multiplex RT-qPCR assay for relative quantification of mTOR gene expression normalized to RPLP0 and TBP. Primers and probes were designed in silico. Validation was performed using the human SCP-1 cell line. Specificity was assessed in 10 separate and 10 multiplex runs. Analytical sensitivity and efficiency were determined from 27 technical replicates using a protocol without an elongation step. Specificity of amplification was assessed by agarose gel electrophoresis, and quantitative analysis was performed in real-time PCR using FAM (mTOR), HEX (RPLP0), and ROX (TBP) fluorescence channels. The assay showed 100% specificity. Stable detection was achieved at 125,000 cells/mL. Amplification efficiencies were 73–81%. The variation of mTOR expression normalized to RPLP0 ranged from –21.5% to 26.4%, and normalized to TBP from –14.3% to 19.2%. Normalization to the geometric mean of both reference genes provided the best reproducibility, with an interquartile range from –9% to 23.4%. The developed assay demonstrates high specificity, sensitivity, and reproducibility, making it a reliable tool for subsequent clinical research.

Received: 2026-03-11

Published online: 2026-03-25

DOI: 10.24075/brsmu.2026.011

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VIEWS 346

Chichelnitsky AK, Savchenko DA, Kostina AS, Raklov DA, Zhuk ER, Buimova ES, Negodaeva AI, Ivanenko AO, Aduchieva VI

Hepatocellular adenoma is a rare benign liver tumor with the potentially unfavorable course due to the risk of hemorrhage and malignant transformation. Treatment depends on the mass subtype and size. Here we present a clinical case of hepatocellular adenoma in a woman of reproductive age developed against the background of the long-term use of oral contraceptives. The tumor sized 8 cm was detected accidentally during instrumental examination; morphological and immunohistochemistry assessment confirmed that it was a benign one without β-catenin mutation. Liver resection was performed. The case highlights the importance of careful monitoring of the patients during the long-term use of oral contraceptives, as well as of the timely surgical interventions in individuals with large hepatocellular adenomas to prevent hemorrhage and malignization.

Received: 2026-02-12

Published online: 2026-03-28

DOI: 10.24075/brsmu.2026.010

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VIEWS 273

Dementev IM, Gabitov MV, Timoshin SS, Kuzovlev AN, Grebenchikov OA

Hypoxic-ischemic encephalopathy remains a leading cause of neonatal mortality and disability. Experimental data suggest potential neuroprotective properties of xenon; however, the mechanisms and extent of its effect are not fully understood. The study aimed to evaluate the neuroprotective properties of a xenon-oxygen mixture in a neonatal ischemia-hypoxia rat model using MRI and follow-up neurological assessment. The experiment involved Wistar rat pups (n = 16). Neonatal ischemia-hypoxia was induced by the Rice–Vannucci method. Thirty minutes post-hypoxia, animals received the 60-min inhalation of either nitrogen-oxygen (control, n = 8), or 50/50 xenon-oxygen mixture (n = 8). Brain MRI was performed on day 7. In the xenon group, brain lesion volume was significantly reduced by 25% compared to controls on day 7 (p = 0.001). Neurological development was assessed from day 3 to 28 using a combination of behavioral tests. Xenon-treated animals demonstrated earlier formation of forelimb and hindlimb grasping reflexes (p = 0.025 and p = 0.005), better hindlimb placement and cliff avoidance on day 7 (p = 0.045 and p = 0.03), and better preserved auditory startle response on day 14 (p = 0.035). Thus, early administration of a xenon-oxygen mixture after ischemia-hypoxia exerts pronounced neuroprotection in newborn rats, confirmed by reduced brain damage and improved neurological outcomes.

Received: 2026-02-25

Published online: 2026-03-17

DOI: 10.24075/brsmu.2026.009

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VIEWS 305