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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Fokin VF, Ponomareva NV, Shabalina AA, Konovalov RN, Medvedev RB, Boravova AI, Lagoda OV, Krotenkova MV, Tanashyan MM

Cognitive reserve (CR) is characterized by the ability to engage neural networks for adaptive reorganization of brain functions in response to damage or stress. This study aimed to identify the structural and functional organization of neural networks in patients with chronic cerebral ischemia (CCI) having different CR. The study involved 137 women aged 50–85 years suffering from CCI without diabetes. The average duration of CCI was 10.1 ± 0.7 years. CCI patients were divided into two groups: with secondary (SE) and higher (HE) education. Salivary cortisol levels were measured before and after cognitive load, along with the differences in brain connectivity organization based on fMRI data in two patient groups. Connectivity patterns were primarily found in the auditory areas, different in two groups after applying multiple comparison correction (FDR) and were responsive to cortisol levels. Patients with greater CR developed CCI later, showed significantly more positive connectivity values, had lower baseline cortisol levels, and displayed larger shifts in cortisol levels during cognitive load.

Received: 2024-11-28

Published online: 2025-01-31

DOI: 10.24075/brsmu.2025.002

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VIEWS 1810

Pisklova MV, Baulina NM, Matveeva NA, Favorova OO

The role of miRNAs (small non-coding RNAs) in regulation of gene expression is reported. By binding with target mRNAs miRNAs control expression of the genes encoding these mRNAs at post-transcriptional level taking part in physiological and pathological processes, from embryogenesis to neoplastic disorders. Various research teams have been studying the miRNA functions and mechanisms of action since the discovery of these molecules in 1993. The paper reports miRNA biogenesis pathways, modes of interaction between miRNAs and target mRNAs, and the mechanisms underlying suppression of translation and mRNA degradation. The results of numerous studies have shown that miRNAs can be used in medicine as biomarkers for diagnostic and prognostic purposes. Developments in miRNA therapeutics hold promise for the treatment of diseases, in which gene dysregulation plays a key role.

Received: 2024-11-24

Published online: 2025-01-28

DOI: 10.24075/brsmu.2025.001

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VIEWS 2433

Valieva YM, Popov KV

Gene therapy is subdivided into in vivo and ex vivo according to the tactics of delivery of therapeutic constructions. In vivo therapy, a vector containing a therapeutic construction is injected into the patient. In ex vivo therapy, cells are removed from the patient's body, genetically modified, and then returned. In ex vivo therapy for inherited diseases, hematopoietic stem cells are most often subjected to modification. Despite the advantage of in vivo therapy, which consists in the possibility of scale-up of production and convenience of use of ready-to-use drug, therapy based on transplantation of genetically modified hematopoietic stem cells remains relevant for a number of genetic diseases.

Received: 2024-12-25

Published online: 2024-12-31

DOI: 10.24075/brsmu.2024.074

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VIEWS 1650

Bayramova GR, Trofimov DYu, Andreev AO, Burmenskaya OV, Asaturova AV, Piven VD

Currently, testing for human papillomavirus (HPV) DNA is more and more often used as a primary diagnosis method when conducting screening for cervical cancer. However, HPV genotypes reported when assessing cervical smears can differ from the results of testing cervical biopsy specimens. The study aimed to assess the features of detecting HPV DNA in the paired cervical canal epithelium samples and cervical biopsy specimens. HPV-positive patients (n = 99) underwent targeted cervical biopsy. The HPV DNA was detected 175 times in biomaterial obtained from the cervical canal and 111 times in histologic blocks. In the group of patients with chronic cervicitis, the rate of HPV DNA testing results match was 28.3%, in the group with LSIL it was 45%, and in the group with HSIL it was 67.7%. When the HPV viral load was low, the results were matched in 27.1% of cases, when the viral load was moderate in 35.4%, and when the viral load was high these were matched in 82.3% of cases. We revealed a relatively strong correlation between the viral load and the probability of the HPV test results match: the percentage of HPV DNA test results match between paired samples increases by 9.3% with the increase in the HPV viral load by 1 lg.

Received: 2024-12-13

Published online: 2024-12-31

DOI: 10.24075/brsmu.2024.073

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VIEWS 1585

Naberezhnaya ER, Soboleva AV, Vorobyev PO, Vadekhina VV, Yusubalieva GM, Isaeva IV, Baklaushev VP, Chumakov PM, Lipatova AV

Immunotherapy with oncolytic viruses (OVs) becomes a full-fledged neoadjuvant therapy method in the paradigm of evidence-based medicine for the growing number of cancers. The use of OVs for immunologically “cold” tumors causing minimal immune response and having the clearly immunosuppressive tumor microenvironment is especially relevant. Recombinant OVs carrying the sequences of proteins activating the immune system can be used to stimulate antitumor response. The study aimed to assess oncoselectivity and antitumor activity of the recombinant OV designed based on the LIVP vaccinia virus strain showing expression of human and murine interpheron alpha sequences (hIFNα and mIFNα, respectively). The in vitro experiments showed that the recombinant OVs designed showed oncoselectivity in relation to tumor cell lines of appropriate species. The ability to effectively infect human adenocarcinoma and glioblastoma cell lines was reported for LIVP-hIFNα. LIVP-mIFNα showed selectivity in relation to glioma Gl261 and melanoma B16 in vitro. The in vivo experiment involving the C57Bl/6 mice with subcutaneous melanoma В16 showed the ability of the intravenously administered LIVP-mIFNα to reduce the size of the subcutaneous tumor allograft and increase tumor infiltration with the CD8+ and NK cells. The recombinant virus designed can be a potential platform for the development of oncolytic virotherapy of human melanoma and glioblastoma.

Received: 2024-11-26

Published online: 2024-12-30

DOI: 10.24075/brsmu.2024.072

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VIEWS 1953

Adrianov MA, Bobrov M, Mamedov I, Manskih V, Rachkova AA, Shelekhova AM, Eldarov CM, Averina OV, Vyssokikh MYu

Enrichment of habitat of the captive rodents Heterocephalus glaber (naked mole rats) allowing them to implement the innate behavioral pattern of digging through hard soil somehow led to the emergence of unusual animals showing signs of cachexia in the colony; these differed from other animals by the reduced body mass index associated with subcutaneous fat reduction. Furthermore, the animals itself showed aggressive eating behavior, but showed no weight gain even after stopping digging due to detachment of the camera with soil. The study aimed to clarify the pathogenetic mechanism underlying the reported phenomenon. For that animals showing signs of cachexia (one female and two males aged 4–5 years) were withdrawn from the colony, along with the animals showing no such signs (two females and one male aged 4–5 years) as controls. Histologic assessment of tissues revealed cardiac hypertrophy and hyperlipofuscinosis of the liver. Cardiac hypertrophy was also suggested by the results of the animal heart microRNA sequencing bioinformatics analysis that revealed elevated levels of microRNA responsible for the increased cell division activity and reduced apoptotic activity in the heart. These data suggest that the animals living in the habitat with the increased oxygen content (21% vs. 8% in the natural habitat, underground) experienced severe oxidative stress during physical activity, which resulted in dysfunction of body’s regulatory systems, increased metabolism at rest, cardiovascular system overload, and damage to organs and tissues. Thus, naked mole rats can have normal physical activity only under conditions of low oxygen content.

Received: 2024-12-11

Published online: 2024-12-30

DOI: 10.24075/brsmu.2024.071

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VIEWS 1732

Gautier MS, Degtyareva AV, Degtyarev DN, Ushakova LV, Filippova EA, Albegova MB, Bavykin AS, Savilova AM, Zhdanova SI

The review is focused on exploring the etiology, pathogenesis, clinical manifestations, and primarily the contemporary treatment methods for Crigler–Najjar syndrome type 1. It considers relevant data regarding the efficacy and safety of the currently existing therapeutic strategies. Effective management of this condition relies on early diagnosis and prompt initiation of treatment, which are crucial for preventing disabling neurological complications associated with bilirubin encephalopathy in patients with Crigler–Najjar syndrome type 1. Prolonged phototherapy is the key treatment method, while liver transplantation represents a radical approach. Recent advances in gene therapy and the use of mesenchymal multipotent stromal cells present novel opportunities for developing alternative, less invasive treatment modalities aimed at improving the quality of life in such patients and reducing their dependence on long-term phototherapy, along with post-transplantation risk.

Received: 2024-12-06

Published online: 2024-12-30

DOI: 10.24075/brsmu.2024.070

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VIEWS 1720

Eldarov CM, Starodubtseva NL, Shevtsova YuA, Goryunov KV, Ionov OV, Silachev DN

Hypoxic ischemic encephalopathy (HIE) is a severe neonatal condition causing various neurological disorders and one of the main causes of mortality among full-term babies. Therapeutic hypothermia (TH), i.e. the newborn’s body temperature decrease that significantly reduces the risk of fatality and contributes to improvement of long-term outcomes in infants with HIE is the key treatment method for moderate-to-severe HIE. However, the timely diagnosis and disease severity determination are crucial for this method to be used, and the method has a number of limitations and requirements. Assessment of the mechanism underlying the effects of TH and the search for the major metabolic pathways and potential targets for HIE therapy are relevant. The study aimed to assess metabolome of dried blood spots by HPLC-MS, since it is the least invasive to patients test for the search for markers and metabolic pathways most active in TH that are likely to mediate its positive effects. As a result, alterations in the class of phosphoglycerolipids were found, which suggests an important role of endocannabinoid metabolism in protection of the body against HIE. Furthermore, metabolic pathways of ubiquinone, certain fatty acids, and bile acids were altered. The targeted quantitative studies of these metabolites will make it possible to optimize HIE diagnosis and treatment based on the potential targets identified.

Received: 2024-12-03

Published online: 2024-12-29

DOI: 10.24075/brsmu.2024.069

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VIEWS 1848