ISSN Print 2500–1094    ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
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Original research Prospects of gene therapy with hematopoietic stem cells
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 172
Original research Comparative analysis of the results of testing cervical epithelial samples and cervical biopsy specimens for HPV
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 185
Original research Interferon type I-expressing recombinant vaccinia virus as a platform for selective immunotherapy of glioblastoma and melanoma
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 235
Original research Increased physical activity under conditions of normoxia causes idiopathic cachexia in Heterocephalus glaber
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 203
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Original research Effectiveness of enriching drug treatment with systemic ozone therapy in patients with post-COVID asthenic syndrome
Soldatenko AA, Gumenyuk LN, Berdieva DM, Ponomarchuk EI
Post-COVID asthenic syndrome (PCAS) is still the subject of active study. The study was aimed to assess the effects of systemic ozone therapy used to complement drug therapy on plasma levels of TNFα, IL1β, IL6 and parameters of mental status in patients with PCAS. Two randomized groups of patients with PCAS (n = 140, age 18–45) were assessed and treated: patients of the index group (n = 70) received systemic ozone therapy in addition to drug therapy; patients of the comparison group (n = 70) received drug therapy without systemic ozone therapy. Plasma levels of TNFα, IL1β, IL6 were measured and the patients’ mental status was assessed using the MFI-20, MoCa, ISI, HARS, and CGI-S scores before and after treatment. After the end of therapy (on day 30) the TNFα, IL1β, IL6 levels reported for the index group showed no significant differences from the values reported for the control group (р > 0.05) and were lover, than the values of the comparison group by 39% (р = 0.003), 33.3% (р = 0.022), and 36.1% (р = 0.012), respectively. The changes in mental status were also more pronounced in the index group, than in the comparison group: the average final MFI-20 score was lower by 36.7% (р = 0.001), ISI by 50.5% (р < 0.001), HARS score by 45.8% (р = 0.001), while MoCa score was higher by 10.9% (р = 0.046), respectively. In the index group, the number of patients with “no disease” based on CGI-S was 94.2%, while in the comparison group it was 62.9% (р = 0.001). In our study adding systemic ozone therapy to drug therapy in patients with PCAS allowed us to achieve normalization of the TNFα, IL1β, IL6 levels and complete reduction of PCAS clinical manifestations in 94.2% of cases. Thus, the use of systemic ozone therapy can be considered as one of the effective and pathogenetically substantiated strategies for combination treatment of patients with PCAS in outpatient settings.
Received: 2024-07-02
Published online: 2024-08-27
DOI: 10.24075/brsmu.2024.034
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VIEWS 676
Original research Association of local bioimpedance analysis of the abdominal region with morphological and biochemical traits
Bondareva EA, Leonov GE, Parfenteva OI, Arutiunian AA, Bevziuk NA, Kovaleva ON, Gadzhiakhmedova AN, Shemyakov SE, Kulemin NA
Quantification of the subcutaneous and visceral fat depot in the abdominal region is a promising method to assess individual risk of cardiometabolic disorders and estimate the efficacy of certain drugs. The local bioimpedance analysis (BIA) represent a new promising method for separate quantification of two fat depots in the abdominal region. The method combines high accuracy, low cost, and noninvasiveness. The study was aimed to analyze the relationships between the impedance estimates obtained in the local BIA lead and the complex of anthropometric and biochemical characteristics in males and females. A total of 147 females and 42 males aged 18–73 years were assessed. To estimate subcutaneous fat, we used the local BIA lead (АВС-02 Medass) in accordance with the earlier proposed electode placement scheme. Local impedance (Z50sc, Ohm) was recorded using the АВС-02 Medass software. The correlation analysis revealed significant correlations of Z50sc with the waist-to-height ratio, insulin concentration, body fat percentage, and HOMA-IR. Markers of the risk of cardiometabolic diseases (abdominal obesity, insulin resistance, and body fat percentage) are associated with the increased Z50sc values. The results of ROC analysis with the insulin resistance index (AUC 0.79 [0.72; 0.84], p < 0.000) make it possible to consider Z50sc a promising marker of the risk of cardiometabolic diseases. The differences between subgroups are confirmed by both statistical significance and large effect size.
Received: 2024-05-31
Published online: 2024-08-07
DOI: 10.24075/brsmu.2024.030
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VIEWS 671
Special Project Author's Work
Dear researcher!
At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.
Richard FEYNMAN Cargo cult science
American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.
Ivan PAVLOV On the Russian mind
In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.
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