Original research Changes in expression of homologous recombination genes in chemotherapy-induced tumors in vivo
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 222
Original research Postmenopausal change in MSCs sensitivity to testosterone, 17β-estradiol, and PTH are associated with impaired adipogenesis
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 316
Original research NGS technology as a tool for the Wilson’s disease diagnosis and severity assessment
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
Comments 0
VIEWS 373
Original research A reliable and reproducible multiplex RT-qPCR assay for mTOR gene expression analysis
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: 2026-03-31
DOI: 10.24075/brsmu.2026.011
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VIEWS 499
Clinical case Large hepatocellular adenoma of the liver in a woman of reproductive age
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
Comments 0
VIEWS 357
Original research Early administration of xenon-oxygen mixture in neonatal hypoxic-ischemic encephalopathy
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
Comments 0
VIEWS 418
Original research Assessing functional activity of microglia and macrophages in barrier-associated brain areas of spontaneously hypertensive rats
Razenkova VA, Korzhevskii DE
The cerebrovascular disorder associated with arterial hypertension results in neuroinflammation, in which microglia and macrophages of the brain are actively involved. The study aimed to assess functional activity and immunophenotype of microglia and macrophages in the areas of brain barriers in spontaneously hypertensive rats (SHR). Specimens of the brain of male Wistar rats and SHR (age 3–4 months, n = 10) were used. The study involved the use of immunohistochemistry analysis and confocal laser microscopy. The presence of М2 activation (CD206) and phagocytic activity (CD68) markers in the population of microglia and macrophages was assessed. It was shown that the CD206 protein was present in perivascular cells, the counts of which were considerably increased in SHR (40.69 ± 4.87 cells per 1 mm2 vs. 28.73 ± 1.39 in Wistar rats; t-test, р = 0.0007). The quantitative analysis conducted allowed us to identify the upward trend of the share of phagocytic cells in the brain of SHR compared to Wistar rats. No changes in the CD68 protein distribution were found in SHR, therefore, activation of microglia and macrophages is not accompanied by the phagocytic activity increase. The findings suggest alternative activation of brain macrophages in neuroinflammation caused by arterial hypertension.
Received: 2026-02-04
Published online: 2026-02-28
DOI: 10.24075/brsmu.2026.008
Comments 0
VIEWS 417
Original research Linguo-semantic descriptors of painful sensations as a mirror therapy effectiveness criterion in trauma-related amputation
Petrash EA, Nikishina VB, Yunina-Pakulova NYu, Minaev AS, Melkonyan GG, Lytkina KA, Karpenko AS
Assessment of phantom pain linguosemantic descriptors in patients with traumatic amputation during the use of mirror visual feedback is conditioned by the need to find criteria for the psychological phantom pain adjustment effectiveness. The study aimed to assess the dynamic changes in linguosemantic pain descriptors in patients with traumatic amputation showing manifestations of phantom pain syndrome as a criterion for evaluating the effectiveness of mirror visual feedback. The total sample size was 87 males post traumatic amputation of one lower limb (age 23–55 years). The research methods were as follows: Mini Mental State Examination (MMSE), original form for registering linguosemantic descriptors of phantom painful sensations, Visual Analog Scale (VAS) for phantom pain. The detected dynamic changes in linguosemantic descriptors of phantom painful sensations in patients with traumatic amputation of the limb showing manifestations of phantom pain syndrome during treatment involving the use of mirror visual feedback makes it possible to consider the following as effectiveness criteria: an increase in the number of pain descriptors represented mainly by concrete and tangible nouns (makes it possible to reduce phantom pain severity rated using a 10-point scale), as well as the increase in the number of descriptors that characterize non-painful unpleasant sensations at the linguosemantic level.
Received: 2026-01-29
Published online: 2026-02-26
DOI: 10.24075/brsmu.2026.007
Comments 0
VIEWS 453