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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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 350

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 415

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 352

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 346

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 336

Agdzhoyan AT, Adamov DS, Potanina AYu, Voronina MM, Gorin IO, Shtrunov-Shlykov AG, Koshel SM, Balanovska EV, Ponomarev GYu

It has been shown that Y-haplogroup N3a1-B211 is common in the Finnish-speaking peoples of the Ural-Volga region. The study aimed to investigate gene geography and phylogeography of the westernmost variant of this haplogroup: the N3a1-Y23475 branch. Comprehensive genotyping of 395 haplogroup N3a1-B211 carriers from 29 populations of Eastern Europe, Ural-Volga region, and Siberia revealed 78 carriers of its western branch reaching its maximum frequency in Mordovia’s populations (8% in Moksha, 9% in Erzya, 25% in Tengushevsky Erzya-Shoksha). Low N3a1-Y23475 frequencies in the Turkic-speaking and Slavic populations suggest the role of the Finnish-speaking substrate in their gene pools. According to the phylogenetic analysis data, the N3a1-Y23475 branch emerged 2.3–2.7 thousand years ago, but active accumulation of its current diversity took place mainly in the populations of Mordovia during the last millennium. We performed DNA genotyping in 74 haplogoup N3a1-Y23475 carriers using the 37 Y-STR panel. The Y-STR haplotype phylogenetic network created suggests two periods of population growth in ancestors of Mordovia’s indigenous population: about 1000 years ago in the populations of proto-Erzya and proto-Shoksha, about 500 years ago in the populations of Moksha and Shoksha. The fact of finding haplogroup N3a1-Y23475 in the Northern and Southern Altaians requires further research. Position of Northern Altaians-Kumandins in the phylogenetic network presumably reflects migration of Mordovia’s population to Altai in the 19th–20th centuries. The age estimates reported for Southern Altaians-Telengits can indicate the association with the haplogroup N3a1 ancestral homeland in South Siberia before resettlement of its ancient carriers in the Ural-Volga region about 1.7 thousand years ago.

Received: 2024-12-10

Published online: 2024-12-29

DOI: 10.24075/brsmu.2024.066

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VIEWS 484

Roubalsky EO, Abdrakhmanova RA, Baeva GR, Rubalskaya TS, Lazko MV, Poroisky SV, Shcheblyakov DV, Favorskaya IV, Gushchin VA

The solid-phase immunocapture with antibodies is an important tool used in immunology studies, but conventional polystyrene plates are prone to deformation during thermal cycling and cross-contamination of samples, which reduces accuracy and reproducibility, when molecular genetic testing methods are included in the study. The development of alternative solutions, such as modified polystyrene-coated polypropylene tubes, makes it possible to eliminate these limitations. The study aimed to create a new approach to SARS-CoV-2 immunocapture involving the use of modified test tubes and to assess its efficacy. Monoclonal antibodies P2C5 and R107, as well as inactivated strains GК2020/1 (Wuhan) and hCoV-19/Russia/MOW-PMVL-51/2021 (Omicron) were used for analysis. Immobilization of antibodies, sorption of viral particles, and RNA extraction were accomplished using modified test tubes, standard plates, and uncoated test tubes. The key findings showed that the polystyrene-coated modified test tubes ensured better immunocapture compared to the plates (p < 0.0001), especially when using the P2C5 antibody effective against various SARS-CoV-2 lineages, including Omicron. The R107 antibody showed limited specificity, not exceeding that of the control group with bovine serum albumin. The cross-contamination analysis revealed contamination of 14 samples out of 288 in the plates, while no contamination of samples was reported for modified test tubes. Thus, modified test tubes used for high-precision molecular testing have some advantages, since these decrease the risk of cross-contamination and improve immunocapture efficacy.

Received: 2024-11-29

Published online: 2024-12-28

DOI: 10.24075/brsmu.2024.068

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VIEWS 333

Aktanova AA, Bykova MV, Skachkov IP, Denisova VV, Pashkina EA

Today, there is a theory that proliferative potential of hematopoietic stem cells is depleted, and the balance of committed precursor cells shifts towards suppressors during the development of cancer. However, differentiation of hematopoietic stem cells can vary depending on the tumor type, localization, and microenvironment specifics. The study aimed to assess the impact of tumors of various origins on the CD34+ hematopoietic stem cells (n = 10). Assessment of the cell cycle and cell differentiation via both direct contact with the tumor and exchanging humoral factors only in transwells was conducted by flow cytometry. In the co-culture with К562, the number of hematopoietic stem cells being in their synthesis phase was 2.1%, while in the control it was 11.2% (p = 0.01); in the co-culture with SK-mel37, the number of hematopoietic stem cells being in the G2‒M cell cycle phase was reduced to 0.3% (p < 0.05). 1301 and К562 directed the hematopoietic stem cell differentiation towards granulocyte-macrophage precursor cells (p < 0.05), while 1301 and SK-mel37 directed it towards common multipotent progenitor cells. It is interesting that the number of pluripotent hematopoietic stem cells significantly increased (2-fold) compared to control after incubation with К562 in transwells (24.17% and 10.19%, respectively). Thus, properties of hematopoietic stem cells can vary depending on both tumor type and the way of interacting with these cells.

Received: 2024-12-02

Published online: 2024-12-27

DOI: 10.24075/brsmu.2024.065

Comments 0

VIEWS 1011