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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Kildyushevsky AV, Kotov SV, Sidorova OP, Borodin AV, Bunak MS

Multiple sclerosis is an autoimmune disorder, the development of which involves humoral and cellular immunity. The disease-modifying drugs (DMDs) for multiple sclerosis slow down the disease progression, but the therapy prescribed is not always well tolerated by patients; allergy and other side effects are possible. In this regard, the development of new methods, including non-pharmacological ones, is relevant. These methods include extracorporeal photopheresis involving UV exposure of peripheral blood lymphocytes and its modification — transimmunization (involving incubation of lymphocytes after UV exposure). The study aimed to compare and within a year assess the transimmunization and glatiramer acetate efficacy in patients with relapsing-remitting multiple sclerosis. A total of 19 adult patients with relapsing-remitting multiple sclerosis, who had been prescribed transimmunization, were assessed. Patients over the age of 18, who did not receive treatment by other methods (DMDs for multiple sclerosis, etc.), were included in the study. The comparison group consisted of 48 adult patients with relapsing-remitting multiple sclerosis, who were prescribed subcutaneous glatiramer acetate 20 mg daily. Clinical assessment was performed using EDSS. Brain and spinal cord MRI was performed in the 3.0 and 1.5 T scanners. When performing transimmunization, the decrease in the median overall EDSS score from 2 to 1.5 points was reported. In the comparison group of patients receiving glatiramer acetate, the median EDSS score changed from 1.75 to 2 points. Therefore, transimmunization is comparable with first-line DMDs for multiple sclerosis and can be used to stabilize the disease course.

Received: 2025-04-02

Published online: 2025-04-29

DOI: 10.24075/brsmu.2025.023

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Ivanenko AV, Starodubova VD, Shokhina AG

Wilson’s disease is a rare hereditary disorder caused by the ATP7B gene mutations that leads to copper metabolism disturbances and toxic copper accumulation in the liver, brain, and other organs. The main manifestations include liver damage, neurological and psychiatric symptoms. The use of advanced treatment methods (D-penicillamine, trientine, zinc salts) improves the outcome, but is limited by side effects and complexity of adherence to therapy. Liver transplantation is used in severe forms, but it is limited by the donor shortage and the need for immunosuppression. In our opinion, promising areas include gene therapy involving the use of AAV vectors and CRISPR/Cas9, mRNA platforms, and cell technologies. However, these approaches require further research for the efficacy, safety, and accessibility improvement.

Received: 2025-04-02

Published online: 2025-04-28

DOI: 10.24075/brsmu.2025.022

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Nikishina VB, Petrash EA, Chausov AS, Kanimetov KK

The relevance of the study provided results from the need to search for the objectifying methods to assess self-identification phenomenon in early childhood. The study aimed to evaluate the diagnostic potential of the software-hardware complex for analysis of self-identification phenomenon in young children. The sample consisted of 136 subjects of early age (12–36 months): 57 boys and 79 girls. Assessment methods: functional neuropsychological tests for evaluation of facial and optical-spatial gnosis; test 22 — mirror image series of the Bayley-III cognitive scale; self-recognition mirror test; the developed software-hardware complex for analysis of self-identification phenomenon in early childhood (SHC). The study conducted has shown that self-identification emerges at the age of 18 months, which has been also confirmed by the earlier research. However, the response to one’s own reflection in the mirror as one sign of self-identification manifests itself in children at an earlier age and in some children turns out to be shaped by the age of 12 months, which is suggested by the facts of successful test execution in the group aged 12–17 months and low specificity of the method for self-identification. Thus, high SHC specificity for self-identification in early childhood is reported based on the findings.

Received: 2025-03-28

Published online: 2025-04-25

DOI: 10.24075/brsmu.2025.021

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VIEWS 341

Nuralieva NF, Yukina MYu, Bykova SV, Savvateeva EN, Nikankina LV, Kulagina EV, Shaskolskiy BL, Gryadunov DA, Troshina EA

The search for concomitant autoimmune disorders (ADs) in patients with celiac disease is a pressing issue. The study aimed to determine the rate of the carrier state for antibodies (Abs) being the markers of AD development in patients with celiac disease using various immunological approaches. Enzyme-linked immunoassay and hydrogel microarray-based multiplex immunoassay (MI) were used to determine Abs against thyroid peroxidase (TPO), thyroglobulin (TG), glutamate decarboxylase (GAD), pancreatic islet cells (ICA), tyrosine phosphatase (IA2), 21-hydroxylase (P450c21), Castle's intrinsic factor, tissue transglutaminase (TGM2) in blood serum of patients with celiac disease (group 1, n = 27) and healthy individuals (group 2, n = 16). The microarray also enables testing of Abs against interferons (IFN) alpha and omega, interleukin 22. In group 1, Abs against IA2 (30%), TPO (22%), TG (19%), GAD (19%) were detected by the enzyme-linked immunoassay, and in group 2 Abs against IA2 (38%), TPO (19%), GAD (19%) were detected. In group 1, Abs against TPO (11%), TG (11%), P450c21 (4%), IFN-alpha (4%), ICA (4%) were detected using the microarray, and in group 2 Abs against TPO (13%), ICA (13%), TG (6%), IFN-alpha (6%) were identified. No significant differences in the rate of elevated Abs in the groups were revealed (p > 0.05). Patients, in whom the Ab carrier state was established using microarrays, with negative results enzyme-linked immunoassay can develop the delayed ADs, which suggests prognostic value of MI. The lack of significant differences in the rate of elevated Abs in patients with celiac disease and healthy individuals can result from small size of the studied groups and can suggest high prevalence of potential AD forms in these cohorts.

Received: 2025-04-02

Published online: 2025-04-23

DOI: 10.24075/brsmu.2025.020

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VIEWS 385

Buzenkova AV, Grigoryeva ES, Alifanov VV, Tashireva LA, Savelieva OE, Pudova ES, Zavyalova MV, Cherdyntseva NV, Perelmuter VM

It is difficult to detect the circulating tumor cells (CTCs) being through the epithelial–mesenchymal transition (EMT) terminal phase, since these do not express epithelial markers or show weak expression of those. This hampers assessment of the CTC prognostic potential. It has been shown that the circulating cells (CCs) with the CD45–EpCAM–CK7/8–CD24+N-cadherin‒ phenotype are associated with the risk of metastasis in breast cancer (BC). The study aimed to test CCs based on the side scatter parameters considering the expression of epithelial cell markers and CD11b. CC phenotypes were assessed by flow cytometry within the regions with low (SSClow) and high (SSChigh) side scatter in 11 donors and 20 female patients with BC. All the CD45–EpCAM–CK7/8–CD24+N-cadherin– CCs were represented by the CD11b– and CD11b+ phenotypes found in both SSClow and SSChigh regions. Among eight CD45–mEpCAM–CK7/8–CD24+N-cadherin– CC phenotypes with different variants of co-expression of epithelial markers (E-cadherin, panCK, and icEpCAM) and CD11b found in patients, six showed signs of epithelial nature based on one of the markers, while another two showed no epithelial traits and predominated over other phenotypes (only these two phenotypes were found in donors). The differences in light scattering parameters of the CCs with the same phenotype is one more characteristic, the prognostic value of which remains to be uncovered. The E-cadherin and panCK expression in the absence of mEpCAM and presence of icEpCAM suggest that some CCs are tumor cells in the state of pronounced EMT. CCs showing co-expression of CD11b and epithelial markers can emerge due to hybridization with myeloid cells.

Received: 2025-03-11

Published online: 2025-04-18

DOI: 10.24075/brsmu.2025.019

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VIEWS 393

Belchenko VA, Chantyr IV, Zavgorodnev KD, Pakhomova YuI

Dental diseases, which exhibit high prevalence within the population, are frequently complicated by odontogenic inflammatory processes in the maxillofacial region (MFR), posing a significant risk of systemic septic complications. Procalcitonin (PCT) is a promising biomarker for the diagnosis of sepsis showing high sensitivity and specificity. However, its prognostic value for purulent inflammatory diseases of the maxillofacial region (PID-MFR) is still understudied. The study aimed to evaluate the diagnostic value of the PCT semi-quantitative rapid test for predicting septic complications in patients with PID-MFR and to evaluate the relationship between PCT levels and clinical/laboratory parameters. The study involved 60 patients (73.3% males, 26.7% females) aged between 21 and 71 years with PID-MFR. Serum PCT levels were determined by a semi-quantitative method. Patients were stratified into two groups: group 1 with PCT > 0.5 ng/mL (23.3%), group 2 with PCT < 0.5 ng/mL (76.7%). Septic complications were observed in 28.57% of patients in group 1, whereas no complications occurred in group 2 (p = 0.001; OR = 0.025). There were no significant differences in clinical and laboratory indicators, number of cellular maxillofacial spaces affected (3.7 ± 1.7), disease duration (5.17 ± 3.39 days), and length of hospital stay (6.50 ± 2.41 bed-days) between groups (p > 0.05). Our findings demonstrate that measuring PCT levels via a semi-quantitative method is an effective and accessible approach to predict septic complications of PID-MFR.

Received: 2025-03-19

Published online: 2025-04-15

DOI: 10.24075/brsmu.2025.018

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VIEWS 454

Familia Frias DR, Visaitova ZYu, Tigay YuO, Ivina AA, Babichenko II

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland consisting of three main histological components: mucocytes, intermediate and epidermoid cells. Various grading systems (AFIP, Brandwein, modified Healy, MSKCC) are difficult to use. The Ki-67 and GLUT1 markers associated with tumor aggressiveness can improve MEC diagnosis and classification. The study aimed to assess the correlation of the cell proliferative activity and glucose metabolism with the MEC grading systems. Tumors of a total of 40 patients with MEC were analyzed and determined in accordance with the following grading systems: AFIP, Brandwein, modified Healy, and MSKCC. Immunohistochemistry (IHC) was used to estimate Ki-67 proliferation indices and GLUT1 expression intensity. IHC showed high Ki-67 indices and GLUT1 values in epidermoid and intermediate cells, while mucocytes showed low or no expression. There were significant differences in Ki-67 and GLUT1 expression between epidermoid (p < 0.005) and intermediate cells (p < 0.01). Comparison revealed the increase between grades 1 and 2, 1 and 3, but no differences between grades 2 and 3. Spearman’s rank correlation test revealed moderate positive correlations with tumor grades for GLUT1 and Ki-67, and the AFIP system showed the highest correlation (Ki-67: rs = 0.55; GLUT1: rs = 0.50). Thus, GLUT1 and Ki-67 are most intensely expressed in epidermoid and intermediate cells showing a strong correlation with the tumor grade and aggressiveness, especially in low-grade and intermediate-grade MEC. These markers can improve the diagnosis of MEC malignancy degree. The AFIP system most closely matches these markers in epidermoid and intermediate cells.

Received: 2025-03-13

Published online: 2025-04-11

DOI: 10.24075/brsmu.2025.017

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VIEWS 437

Nazarenko RV, Irzhak AV, Gvasalia BR, Pushkar DYu

Despite widespread use of methods to assess structure and functional activity of spermatozoa, practical application of those in in vitro fertilization programs is currently rather limited. Limitations are primarily due to destructive nature of the methods. The study aimed to investigate the capabilities of confocal Raman spectroscopy in analysis of the human sperm organelle biochemical markers. Assessment of 176 spectra of spermatozoa collected from healthy sperm donors aged 18–35 years was performed using the Bruker Senterra confocal Raman microscope (Germany). Spectra were acquired from the sperm acrosome, nucleus, and midpiece. In addition, the spermatozoa suspension was exposed to a focused x-ray beam. As a result, bands were identified inherent to the sperm nuclear DNA — 1092 cm–1 and 780 cm–1, typical for the head — 748 cm–1 (mitochondrial DNA marker); changes of shape of the triple band 420 cm–1, 1445 cm–1 and 1486 cm–1 with predominance of the middle part 1445 cm–1 are typical for acrosomal spectra. No differences in the main Raman bands nherent to cells post DNA damage under exposure to x-ray radiation for 5 and 10 min relative to intact samples were reported. Confocal Raman spectroscopy is a promising noninvasive method to assess sperm ultrasctructure and biochemical processes.

Received: 2025-02-22

Published online: 2025-03-31

DOI: 10.24075/brsmu.2025.016

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VIEWS 532