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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Guselnikova VV, Razenkova VA, Sufieva DA, Korzhevskii DE

The subfornical organ is an important regulator of water-salt metabolism and energy balance of the body, involved in the control of the cardiovascular system and immune regulation. The organ comprises several cell populations, among which microglia and macrophages remain uncharacterized. This study aimed at structural, cytochemical, and functional characterization of microglia and macrophages of the subfornical organ in rats. Brain specimens were collected from mature male Wistar rats (n = 8). Microglia and macrophages were revealed by immunostaining with poly- and monoclonal antibodies against calcium-binding protein Iba1 and lysosomal protein CD68; the slides were examined by light and confocal laser microscopy. The study provides a comprehensive morphological characterization of microglial cells and macrophages of the subfornical organ. We demonstrate that the majority of Iba1-expressing cells in this area of the brain are microglial cells, not macrophages. Pre-activated state of the subfornical organ microglia may reflect structural and functional features of this organ and specific functions of local microglia. Subependymal microglial cells, the processes of which penetrate into the third ventricle of the brain, constitute a distinct subpopulation among the Iba1-expressing cells of the subfornical organ. Apart from microglial elements, the subfornical organ contains few tissue macrophages with characteristic strong expression of CD68 accompanied by undetectable or weak expression of Iba1.

Received: 2022-03-27

Published online: 2022-04-28

DOI: 10.24075/brsmu.2022.020

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VIEWS 1926

Zakharova IA, Petrash EA, Nikishina VB, Razuvaeva TN, Shuteeva TV

Sensory impairments (visual and auditory) reduce quantity and quality of the information input. The associated memory loss can be classified as intrinsic decline in memory functionalities or mere physiological effect of sensory deprivation. This study aimed to specify this issue by analyzing memory consolidation and reconsolidation processes in older people with sensory deficits. The study enrolled 65–75 year-old individuals (n = 61) distributed into four groups: patients with unilateral sensorineural hearing loss (n = 17); patients with bilateral sensorineural hearing loss (n = 14); patients with visual impairment (n = 19); and patients with combined sensory deficits (n = 11). The methods included Luria’s auditory-verbal (“10 words”) and visual memory tests and Bartlett’s experimental procedure. A decrease in memory volume for auditory-verbal and visual-figurative short-term memories was observed in all groups. The results reveal significant adverse dynamics of qualitative and quantitative indicators for memory consolidation and reconsolidation processes, associated with decreased volume of short-term memories, both auditory-verbal and visual-figurative. Based on these findings, we conclude that consolidation and reconsolidation efficiency depends on proper accommodation of the newly incoming information to already memorized modules (previous experience) and requires dosing of the newly incoming information in order to preserve its integrity at the stage of consolidation.

Received: 2022-03-22

Published online: 2022-04-28

DOI: 10.24075/brsmu.2022.018

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VIEWS 1768

Kubekina MV, Kalinina AA, Korshunova DS, Bruter AV, Silaeva YY

Mitochondrial dysfunctions, which underlie many systemic diseases in animals and humans, may arise from accumulation of mutations in the mitochondrial genome. PolG-alpha enzyme encoded by Polg gene is crucial for replication and repair of the mitochondrial genome. The aim of this study was to assess the possible role of Polg mutations in mitochondrial dysfunctions using in vitro and in vivo animal models. The experiments involved transgenic mice with inducible expression of Polg mutant variant; the methods included cell culture, real time PCR assay, fluorescence flow cytometry, and skeletal muscle functional tests. The results indicate that mouse embryonic fibroblasts (MEFs) expressing Polg pathogenic mutant variant have decreased mitochondrial membrane potential and increased expression of mitophagy markers compared with control cultures. Transgenic animals with systemic expression of the pathogenic variant develop mitochondrial dysfunction which significantly affects muscular performance. In addition, systemic expression of mutated Polg in transgenic animals significantly inhibits expression of TCR subunit α and CD3 coreceptor complex subunits δ and ε in total splenocyte populations and significantly affects cellularity of the thymus without altering its CD4/CD8 subpopulation ratio. Thus, inducible expression of mutated Polg in transgenic animals provides a relevant model for studying mitochondrial dysfunction and its treatment in vitro and in vivo.

Received: 2022-04-14

Published online: 2022-04-27

DOI: 10.24075/brsmu.2022.021

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VIEWS 1955

Balanovska EV, Gorin IO, Ponomarev GYu, Pylev VYu, Petrushenko VS, Markina NV, Mamaeva AD, Larin AK, Agdzhoyan AT

Genetic contribution of pre-Slavic populations to gene pools of modern Russia is increasingly relevant, along with genetic footprints of the Golden Horde invasion. The novel genome-wide approaches enable advanced solutions in this field. The study aimed at searching for the footprints of genetic interaction among Finnicspeaking, Slavic and Turkic-speaking populations of Central Russia and Volga Region and their reflection in pharmacogenetic landscape. Modeling ancestral components by ADMIXTURE software and their mapping involved genome-wide genotyping data for 248 individual genomes representing 47 populations of 9 ethnic groups. Of specific ancestral components identified in each of the Finnic-speaking peoples, only Mordovian ancestral components are common for all populations within the studied geographic area, regardless of their linguistic affiliation. Gene pools of Russian populations include 80% of intrinsic component, 19% contribution from Finnic-speaking peoples, and 1% of Central Asian influence. The Tatar gene pool combines all identified ancestral components, including 81% contribution from Finnic-speaking peoples and only 12% of Central Asian influence, which prevents using it as a reference for the assessment of Golden Horde footprints in Russian gene pools. A map of genetic distances from Ryazan Russians based on a panel of 42 pharmacogenetic markers reveals a landscape strikingly independent from the selectively neutral ancestral genomic patterns. For instance, populations of Mordovia, Kaluga, Smolensk, and Kostroma regions are the closest to Ryazan Russians in pharmacogenetic status, whereas populations of Ryazan and Nizhny Novgorod regions have strikingly divergent pharmacogenetic status despite the similarity of the selectively neutral ancestral genomic patterns. These findings confirm the relevance of targeted pharmacogenetic characterization for gene pools of Russia.

Received: 2022-04-01

Published online: 2022-04-26

DOI: 10.24075/brsmu.2022.019

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VIEWS 2357

Milushkina OYu, Popov VI, Skoblina NA, Bokareva NA, Astashkevich EV, Zakharova AA, Skoblina EV

The problems of migration are becoming increasingly important and have primary impact on women’s and children’s health. The aim of the study was to evaluate the influence of migration factor on the establishment of menstrual function in girls. The study enrolled 1,222 female undergraduate students of Moscow universities, born in 1995–2000, of diverse ethnicity. The data were collected in 2015–2020 by questionnaire method. The main group included 322 students classified as migrants and the comparison group included 900 students of local origin (Muscovites). Statistical processing of the data was carried out using Statistica 10.0 package (StatSoft; USA). Mean age at menarche constituted 151.35 ± 1.20 months in migrants and 150.88 ± 1.06 months in Muscovites (p > 0.05). For all participants, menarcheal age fell within the range of 11–15 years (normal). Other parameters of menstrual function were also similar between the groups and comparable to corresponding data collected in other countries.

Received: 2022-03-24

Published online: 2022-04-24

DOI: 10.24075/brsmu.2022.017

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VIEWS 1883

Dovgan AA, Drapkina YuS, Dolgushina NV, Menzhinskaya IV, Krechetova LV, Sukhikh GT

Autoimmune mechanisms have been implicated in the negative effects of vaccines on female reproductive health. This study evaluates the endogenous levels of self-reactive antibodies and ovarian reserve-associated hormones before and after immunization with the domestically developed Gam-COVID-Vac combined vector vaccine to check for possible reproductive sequelae. The prospective study enrolled 120 women aged 18–49, subject to vaccination with Gam-COVID-Vac. Ovarian reserve was assessed prior to vaccination and 90 days after the first component injection. Profiles of specific antibodies to self-antigens, including phospholipids, nuclear antigens, FSH, progesterone, and also thyroid, ovarian, trophoblast, and zona pellucida antigens, were assessed at the same time points by enzyme immunoassay. Overall, the vaccination had no effect on the levels of ovarian reserve-associated hormones and autoantibodies, apart from a transient increase in positivity for antiphosphatidylethanolamine IgM and anti-dsDNA IgG. Seroprevalence of elevated serum autoantibodies constituted 70.8% before and 75% after vaccination. According to the results, immunization with Gam-COVID-Vac does not affect ovarian reserve or autoimmune status, thus being safe for the female reproductive potential.

Received: 2022-03-30

Published online: 2022-04-21

DOI: 10.24075/brsmu.2022.016

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VIEWS 2058

Burgasova OA, Dolinniy SV, Tetova VB, Ogarkova DA, Odnoralov MA, Bakalin VV, Smetanina SV, Antipyat NA, Taranova MV

Severe form of COVID 19 has been linked to the phenomenon of dysregulated inflammation with excessive cytokine release and elevated interleukin 6 (IL6) levels. Suppressive agents enabling specific inhibition of cytokines, notably monoclonal antibodies to IL6 and its receptors, have been applied as a rescue therapy in COVID 19 despite the underexplored clinical scope for these biologic medications. This study aimed to evaluate the clinical utility of IL6 receptor antagonist tocilizumab in moderate symptomatic COVID 19 prone to aggravation. The retrospective cohort study enrolled two groups of hospitalized patients (a total of n = 72) diagnosed with moderate COVID-19. The main group received a single 400 mg dose of tocilizumab (TCZ) on top of standard therapy. The comparative analysis included statistical evaluation for a number of clinical and laboratory parameters at reference time points and disease outcomes with regard to treatment strategy. Overall, TCZ administration provided no advantages in terms of oxygen supplementation status, disease progression, or survival. Lethal cases constituted 19.2% (10 pts) and 5% (1 pt) in TCZ and comparison groups, respectively. The results indicate that administration of monoclonal antibody drugs in hospital patients with COVID-19 must follow differential schemes with regard to the disease severity and comorbidities, as well as proper commencement schedules.

Received: 2022-03-10

Published online: 2022-04-15

DOI: 10.24075/brsmu.2022.015

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VIEWS 1897

Rakhmetova KK, Mishina ES, Vorvul AO, Bobyntsev II, Dolgintsev ME, Bezhin AI

Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p < 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.

Received: 2022-02-10

Published online: 2022-04-13

DOI: 10.24075/brsmu.2022.014

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VIEWS 2145