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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Voronkov DN, Stavrovskaya AV, Gushchina AS, Olshansky AS

It is assumed that dysfunction of tanycytes could be one of the components of pathogenesis of both Alzheimer disease and type 2 diabetes mellitus. The study was aimed to assess alterations in the tanycyte morphology in the Alzheimer disease model. The 3 mg/kg streptozotocin dose was injected in the lateral ventricles of Wistar rats in order to model the Alzheimer disease. Alterations in hypothalamic tanycytes were assessed 2 weeks, 4 weeks, 3 months and 6 months after administration of the toxin. Immunohistochemistry was used to identify the protein markers of tanycytes (vimentin, nestin), astrocytes (GFAP, glutamine synthetase) and neurons (HuC/D), as well as to assess cell proliferation (with the use of Ki67 protein) and mitochondrial alterations (mitochondrial complex IV, PGC1a). Administration of streptozotocin lead to β-amyloid accumulation in hypothalamus and ventricular enlargement (p < 0.001). Streptozotocin damaged both α1/α2 tanycytes and β1 tanycytes. The intensity of vimentin staining in α1/α2 tanycytes decreased by week 4 (p = 0.003), and in β1 tanycytes it decreased in three months (p < 0.001). The same trend was observed for nestin. The number of Ki67+ nuclei decreased (p < 0.05), and the expression of proteins associated with mitochondria changed. The density of hypothalamic tanycytes decreased by week 4 after administration of the toxin. Moreover, astrocyte activation was revealed. However, no prominent damage to both astrocytes and neurons was observed within four weeks after administration of streptozotocin. The revealed high tanycyte vulnerability to streptozotocin is in line with the hypothesis of the role of damage to hypothalamic structures in both local and systemic metabolic disorders occurring in the Alzheimer disease models.

Received: 2021-10-07

Published online: 2021-10-29

DOI: 10.24075/brsmu.2021.050

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VIEWS 2102

Voroshilina ES, Zornikov DL, Ivanov AV, Pochernikov DG, Panacheva EA

The analysis of semen microbiota is difficult due to the lack of established criteria for interpretation of microbiological tests. The aim of the study was to determine the stable clusters of semen microbiota analyzed by real-time PCR in samples with normozoospermia. Semen samples of 227 men with normal spermiograms were included in the study. The quantity of total bacterial DNA and at least one group of microorganisms was more than 103 GE/ml in 107 (41.7%) samples. Four stable microbiota clusters with the prevalence of a specific microorganism group were distinguished in these samples: obligate anaerobes (OA) cluster (proportion in the centroid — 81.1%); Lactobacillus spp. cluster (proportion in the centroid — 64.3%); gram-positive facultative anaerobes (GPFA) cluster (proportion in the centroid — 92.5%); Enterobacteriaceae/Enterococcoccus (EE) cluster (proportion in the centroid — 80.8%). The clusters were ranked by frequency of occurrence: OA cluster was the most prevalent (43 (40.2%) of 107), second-most frequent were GPFA-cluster (27 (25.2%)) and Lactobacillus-cluster (22 (20.6%)). EE-dominated cluster was found in 15 (14.0%) cases.

Received: 2021-09-16

Published online: 2021-10-28

DOI: 10.24075/brsmu.2021.048

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Purtov KV, Petushkov VN, Rodionova NS, Chepurnykh TV, Kozhemyako VB, Zagitova RI, Shcheglov AS, Ziganshin RH, Tsarkova AS

The marine polychaete Chaetopterus variopedatus (Renier) (family Chaetopteridae) is a cosmopolitan species complex, consisting of distinct populations/ subspecies. The worms release glowing (460 nm) clouds of mucus when disturbed, and their parapodia often glow brightly. Currently, it is still unclear how exactly the bioluminescence system of these polychaetes functions. It has been previously assumed that the C. variopedatus luciferase may be used for detection of ferroptosis, the recently explored pathway of programmed cell death, resulting from accumulation of the ferrous ions. This study was aimed to extract and characterize the C. variopedatus luciferases, as well as to compare luciferases obtained from C. variopedatus of different populations. When extracting the enzyme responsible for bioluminescence from the frozen samples of Brazilian C. variopedatus using the improved method, two active luciferases, L1 and L2, were obtained. We assumed that one of the listed above luciferases was responsible for luminescence of the mucus and the other luciferase was responsible for luminescence in parapodia, and used the method for the distinct samples of mucus and parapodia of the living Far Eastern C. variopedatus. However, mucus of the latter turned out to be non-glowing. It is shown that luciferase L2 is responsible for luminescence in the parapodia of the C. variopedatus polychaete, since this luciferase has been found in the total biomass of Brazilian polychaetes and parapodia of Far Eastern polychaetes. Luminescence of the Brazilian C. variopedatus mucus is attributed to the functioning of luciferase L1, which is lacking in the mucus of the Far Eastern subspecies. The range of luciferase isoforms in polychaetes C. variopedatus depends on the place of origin.

Received: 2021-09-28

Published online: 2021-10-26

DOI: 10.24075/brsmu.2021.049

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VIEWS 2221

Kiblitskaya AA, Goncharova AS, Anisimov AE, Snezhko AV, Dimitriadi SN, Maslov AA, Gevorkyan YA, Kolesnikov EN

As a rule, esophageal adenocarcinoma develops in the lower esophagus. Life expectancy and survival rates depend on the cancer stage and the general health of the patient. Chemoradiotherapy is the most successful treatment approach to this type of cancer. The choice of optimal radiation doses for achieving the best possible therapeutic effect is still a challenge. The aim of this paper was to study effective radiation doses and assess response of human esophageal adenocarcinoma to radiation using a PDX model. The study was conducted in female Balb/c nude mice (n = 25). Fragments of the donor tumor were implanted into the cervical esophagus of immunodeficient mice. Effects of radiation on the obtained orthotopic xenografts were studied after each of 3 irradiation sessions (4, 6, 8, and 10 Gy in each of the experimental groups, respectively). First-passage xenografts reproduced the morphology of the donor tumor. The mean tumor volume differed significantly between the control group and the experimental groups exposed to 6, 8 or 10 Gy (р ≤ 0.01) after each irradiation session. Tumor growth delay was significant after exposure to the total dose of 18 Gy. The further radiation dose increase was ineffective. The reduction of tumor volume in the xenografts was correlated to the increase in the one-time radiation dose. The total dose over 18 Gy produced a detrimental effect on the hematopoietic system and blood biochemistry of the experimental mice.

Received: 2021-09-16

Published online: 2021-10-20

DOI: 10.24075/brsmu.2021.047

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VIEWS 1954

Kolobukhina LV, Burgasova OA, Kruzhkova IS, Bakalin VV, Generalova LV, Shagaev AV, Ogarkova DA, Nikiforova MA, Vasina DV, Gushchin VA, Smetanina SV

The COVID-19-associated mortality remains high. Studying the features of the COVID-19 course in vaccinated patients, who have got ill on different dates after vaccination, compared to unvaccinated individuals is relevant. The study was aimed to assess clinical and immunological features of the COVID-19 course, as well as to assess humoral immunity (virus neutralizing activity, VNA) and SARS-CoV-2 S protein RBD domain variation in the groups of patients, previously vaccinated with Sputnik V, and unvaccinated patients. A total of 251 patients with confirmed diagnosis of COVID-19 were enrolled, of them 116 individuals were previously vaccinated with one or two Sputnik V vaccine components, and 135 patients were not vaccinated (comparison group). Individuals over 50 years of age prevailed (82.8%). The patients, who received two vaccine components, had mild to moderate COVID-19 (92.1%). In the group of unvaccinated patients, 11 individuals received treatment in the ICU, 10 of them died. The viral load was significantly lower in vaccinated patients. Mutations of SARS-CoV-2, such as S477N, S477N+A522S, E484K and E484K+S494P, were identified both in vaccinated and unvaccinated patients. Assessment of the neutralizing activity of sera revealed no significant differences in VNA against different variants of SARS-CoV-2 mutations. The data obtained demonstrate that the lack of vaccination is an aggravating factor and is capable of increasing the risk of severe course and death in patients with COVID-19.

Received: 2021-09-29

Published online: 2021-10-17

DOI: 10.24075/brsmu.2021.046

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VIEWS 2350

Tumanova UN, Schegolev AI, Chausov AA, Shuvalova MP

In March 2020, the World Health Organization declared a COVID-19 pandemic. The aim of this study was to compare the causes of and statistics on neonatal mortality in Russia in 2020 and 2019 using the Rosstat A-5 forms that aggregate data from perinatal death certificates. In 2020, there was a 7.6% reduction in the absolute number of live births relative to 2019. In 2020, the overall early neonatal death rate (1.59‰) fell by 4.4% in comparison with 2019 (1.67‰). However, neonatal mortality in the Southern and Far Eastern Federal Districts rose by 20.5% and 6.1%, respectively. Respiratory diseases were the most common cause of early neonatal mortality across Russia (37.3% and 40.2% relative to the total number of neonatal deaths in 2019 and 2020, respectively). Congenital sepsis accounted for 43.6% and 46.6% of early neonatal deaths from infectious diseases and for 7.3% and 7.9% of all early neonatal deaths reported in 2019 and 2020, respectively. There was an increase in the proportion of respiratory diseases among neonates, including congenital pneumonia and other respiratory conditions, and infections, including congenital sepsis, which reflects the direct and indirect effects of SARS-CoV-2 infection on pregnant women and neonates.

Received: 2021-09-15

Published online: 2021-10-05

DOI: 10.24075/brsmu.2021.045

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VIEWS 2424

Golubinskaya EP, Sataieva TP, Fomochkina II, Kubyshkin AV, Makalish TP, Shkolyar NA, Galyshevskaya AA, Varghese DV

Tumor-associated macrophages are able to regulate the tumor cell proliferation and to affect the tumor cell dissemination. The study was aimed to assess the predictive potential of the macrophage population immunohistochemical phenotyping in early malignization of H. pylori-associated chronic gastritis. Gastic biopsy samples of male and female patients aged 48 ± 7.2 infected with Helicobacter pylori were used as the research material. The patients were divided into three groups: non-atrophic chronic gastritis (NACG, n = 10), atrophic chronic gastritis (ACG, n = 10), G1/G2 gastric adenocarcinoma (GAC, n = 10). The macrophage population was visualized using the CD68 pan-macrophage marker and the type 2 monocyte/macrophage marker CD163. Intensity of neoangiogenesis was defined using the CD31 endothelial marker by assessing the total cross sectional area of blood vessels. It was found that chronic gastritis was accompanied by the dynamic increase in the size of the general macrophage population with the progression of atrophic and metaplastic processes. According to immunohistochemical study of biopsies obtained from patients with NCG, the CD163 : CD68 ratio was 0.67 ± 0.02, and the total cross sectional area of blood vessels was 3590.92 ± 356.27 µm2. Atrophic gastritis and adenocarcinoma were characterized by vector redistribution of monocytes/macrophages into the 2nd functional phenotype. The CD163 : CD68 expression index in the group with ACG was 0.81 ± 0.04, and in the group with GAC it was 0.88 ± 0.03. Microvascular area was significantly increased in the groups with ACG and GAC, which reflected tumor neoangiogenesis intensification under the influence of М2 monocytes/macrophages. The increased expression of CD163 can serve as a predictor of chronic gastritis malignization together with evaluation of the glandular epithelium atrophy and metaplasia degree.

Received: 2021-08-19

Published online: 2021-09-14

DOI: 10.24075/brsmu.2021.044

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VIEWS 2168

Rubakova AA, Ivanova GE, Bulatova MA

A BCI-controlled hand exoskeleton activates neuroplasticity mechanisms, promoting motor learning. The contribution of perception to this phenomenon is understudied. The aim of this study was to assess the impact of sensorimotor integration on the effectiveness of neurorehabilitation based on the learning of a hand opening movement by stroke patients using BCI and to investigate the effect of ideomotor training on spasticity in the paretic hand. The study was conducted in 58 patients (median age: 63 (22; 83) years) with traumatic brain injury, ischemic (76%) or hemorrhagic (24%) stroke in the preceding 2 (1.0; 12.0) months. The patients received 15 (12; 21) ideomotor training sessions with a BMI-controlled hand exoskeleton. Hand function was assessed before and after rehabilitation on the Fugl–Meyer, ARAT, Frenchay, FIM, Rivermead, and Ashworth scales. An increase in muscle strength was observed in 40% of patients during flexion and extension of the radiocarpal joint and in 29% of patients during the abduction and adduction of the joint. Muscle strength simultaneously increased during the abduction and adduction of the radiocarpal joint (p < 0.004). Ideomotor training is ineffective for reducing spasticity because no statistically significant reduction in muscle tone was detected. Improved motor performance of the paretic hand was positively correlated with improvements in daily activities. Motor training of the paretic hand with a robotic orthosis activates kinesthetic receptors, restores sensation and improves fine motor skills through better sensorimotor integration.

Received: 2021-07-26

Published online: 2021-09-01

DOI: 10.24075/brsmu.2021.039

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VIEWS 2211