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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Shadrin VS, Kozhin PM, Shoshina OO, Luzgina NG, Rusanov AL

The search for the optimal cell model for studying the pathogenesis of pathological scars is a pressing challenge. This study aimed at evaluating the feasibility of using telomerized fibroblasts for the in vitro 3D modeling of pathological hypertrophic scars. NF and Fb-hTERT cells were cultured as monolayers and spheroids in the absence and in the presence of TGFβ1. The metabolic activity of the cultured cells was assessed using the MTT assay. Cell migration was estimated using the scratch assay. The expression of genes associated with fibrous scar tissue growth was measured by qRT-PCR. Fb-hTERT cells were more metabolically active than NF cells in the presence of TGFβ1 (for 1 ng/ml: 179 ± 12% vs. 135 ± 13% respectively; p < 0,05). Spheroids grown from Fb-hTERT cells were significantly larger than those derived from NF cells. In the presence of TGFβ1, the expression of proteins associated with extracellular matrix production (COL1A1, COL3A1, FN1) was lower in Fb-hTERT cells than in NF cells (more than 25, 20 and 2-fold, respectively; p < 0.05). Intact NF cells were more active in closing the scratch than Fb-hTERT cells: on day 2, the gap closure rate was 2.28 times higher in NF cells (p < 0.05). Exposure to TGFβ1 stimulated Fb-hTERT, unlike NF cells, to close the gap 2 times faster on day 2 (p < 0.05). Thus, telomerized fibroblasts have a few phenotypic traits observed in keloid fibroblasts; still there are some limitations that should be accounted for when using Fb-hTERT cells for the modeling of pathological hypertrophic scars.

Received: 2020-08-28

Published online: 2020-09-27

DOI: 10.24075/brsmu.2020.057

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VIEWS 2597

Iazeva EG, Legostaeva LA, Bakulin IS, Poydasheva AG, Abaimov DA, Suponeva NA, Shabalina AA, Ryabinkina YuV, Piradov MA

Transcranial magnetic stimulation (TMS) is one of rehabilitation approaches for patients with chronic disorders of consciousness (DOC). The aim of our study was to assess neurotrophic factors and the changes of those after TMS course in patients with chronic DOC. We enrolled 26 patients with chronic DOC of various etiology and 21 heathy volunteers. Blood serum and cerebrospinal fluid (CSF) were collected from all patients before and after the TMS course, the levels of BDNF, NSE, NGF, РDGF, GDNF and NT3 were assessed in the biomaterial. The blood BDNF, NSE, PDGF, GDNF and NT3 in patients with chronic DOC were higher compared to healthy volunteers (p < 0.05). We found no correlations between the type of DOC and neurotrophic factors concentrations in blood and CSF. The CSF level of BDNF in patients after traumatic brain injury (TBI) was higher compared to patients with non-traumatic chronic DOC (p < 0.05). We also found the increase of CSF BDNF after the TMS course in patients after TBI (p < 0.05). No other significant differences between groups and another blood and cerebrospinal fluid biomarker levels were detected. Thus, the serum BDNF, NSE, PDGF, GDNF and NT3 levels in patients with chronic DOC were higher compared to healthy volunteers. The BDNF level in CSF was higher in patients with traumatic DOC, and it also increased after the course of high-frequency TMS in this group. This fact may indicate the long-term neuronal plasticity processes in patients after TBI, as well as more favorable rehabilitation prognosis.

Received: 2020-08-19

Published online: 2020-09-24

DOI: 10.24075/brsmu.2020.056

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VIEWS 2404

Kaida AI, Eismont EV, Mikhailova AA, Pavlenko VB

One of the currently assumed causes of impaired social interaction exhibited by children with autism spectrum disorders (ASD) is dysfunction of the mirror neuron system (MNS), which is responsible for imitation, understanding the intentions and emotions of other people. Desynchronization of sensorimotor rhythms is considered to be the indicator of MNS activation. This study aimed to analyze the specific patterns of reactivity of the μ-rhythm in an individually determined frequency range and β-rhythm on the EEG in children with ASD during independent movements, observation, imitation and auditory perception of similar movements performed by another person. The data collected were compared to those describing normally developing children. The study involved right-handed children with ASD aged 5–10 (n = 10) and normally developing children (n = 10). In the independent movements exercise, β-rhythm desynchronization was more pronounced in children with ASD, with difference becoming significant in the P4 locus (p = 0.03). In the movements imitation exercise, the groups showed significant differences in the EEG μ-rhythm in the locus C3 (p = 0.03). Auditory perception of movements revealed significant differences in the ranges of both μ-rhythm (loci F3 and Fz (p = 0.02), F4 (p = 0.04), Cz (p = 0.009)) and β-rhythm (loci Fz (p = 0.01), F4 (p = 0.02)). In these situations, children with ASD exhibited synchronization of sensorimotor rhythms, while normally developing children showed desynchronization. The assumption is that the specific patterns revealed are the consequences of disruption of functions of MNS and anti-mirror system. The data obtained can be used in development of EEG biofeedback training protocols for children with ASD.

Received: 2020-08-19

Published online: 2020-09-22

DOI: 10.24075/brsmu.2020.055

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VIEWS 2290

Kazimirskii AN, Salmasi JM, Poryadin GV

Antiviral system of innate immunity includes two main components: the mitochondrial antiviral sensor — the mitochondrial outer membrane protein and peripheral blood neutrophils capable of forming neutrophilic extracellular traps. Depending on the activation pathway of the mitochondrial antiviral sensor (MAVS), two possible variants of cells death, apoptosis or cellular degeneration with necrotic changes, develop during cell infection with an RNA-containing virus. The development of virus-induced apoptosis of infected cells causes the formation of neutrophilic extracellular traps, the secretion of inflammatory cytokines, ROS generation, tissue damage, hemocoagulation and the development of an acute inflammatory process with the development of COVID-19 pneumonia. Violation of the prion-like reaction of MAVS in response to viral infection of the cell triggers an alternative pathway for activating autophagy. Cells under conditions of prolonged activation of autophagy experience necrotic changes and are eliminated from the organism by monocytes/macrophages that secrete anti-inflammatory cytokines. This type of reaction of the antiviral system of innate immunity corresponds to the asymptomatic course of the disease. From the most significant aspects of the pathogenesis of the coronavirus infection COVID-19 given, recommendations for the prophylactic treatment of this dangerous disease follow. The proposed treatment can significantly decrease the severity of COVID-19 disease and reduce mortality.

Received: 2020-08-31

Published online: 2020-09-21

DOI: 10.24075/brsmu.2020.054

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VIEWS 2467

Chernevskaya EA, Meglei AYu, Buyakova IV, Kovaleva NYu, Gorshkov KM, Zakharchenko VE, Beloborodova NV

The term “chronic critical illness” (CCI) refers to patients with prolonged dependence on intensive care. In most patients, CCI is triggered by severe brain injury. Ever more studies researching the microbiota in pathologic conditions are published every year, but a lot is yet to be elucidated about the composition of the gut microbiota in CCI. The aim of this study was to investigate possible correlations between changes in the taxonomic abundance of the gut microbiota, levels of proinflammatory and neurological serum biomarkers and the severity of central nervous system injury in patients with CCI. Our prospective observational pilot study included 29 patients with CCI. Using real-time PCR allowed us to detected changes in the taxonomic abundance of the gut microbiota. The correlation analysis of serum biomarkers and the taxonomic composition of the gut microbiota revealed statistically significant correlations between cortisol levels and the abundance of F. prausnitzii (r = ‒0.62; p < 0.05) and B. thetaiotaomicron (r = ‒0.57; p < 0.05) in vegetative state patients; between the CRP/albumin ratio and the abundance of S. aureus (r = 0.72; p < 0.05); between the abundance of B. fragilis group/F. prausnitzii and S100 levels (r = 0.45; p <0.05) in conscious patients; between Glasgow coma scale scores and the abundance of Enterococcus spp. (r = ‒0.77; p <0.05) in both groups. Thus, the association between the changes in the taxonomic composition of the gut microbiota and the severity of neurologic deficit can be evaluated using PCR-based diagnostic techniques and blood serum biomarkers. This approach will help to optimize antibacterial treatment regimens and/or develop alternative strategies to minimize the aggressive effect of antibiotics on the gut microbiota.

Received: 2020-08-20

Published online: 2020-09-17

DOI: 10.24075/brsmu.2020.053

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VIEWS 2502

Tanashyan MM, Shabalina AA, Roitman EV, Vavilova TV, Kuznetsova PI

Thrombogenicity and its causes in patients with ischemic stroke (IS) and pre-existing polycythemia vera (PV) is a significant clinical concern. The aim of this study was to identify the range of factors associated with increased thrombogenicity in patients with IS and pre-existing PV. We performed a physical examination and laboratory tests on 127 patients in the hyperacute stroke stage and 16-18 months after. Of them, 68 patients had PV (the main group) and 59 did not have this condition (the comparison group). Laboratory tests were conducted to evaluate blood rheology, hemostasis, endothelial function, angiogenesis, proinflammatory cytokine levels; we also tested patients for the presence of the V617F mutation in the JAK2 gene and analyzed the contribution of all studied parameters to the development of thrombotic and hemorrhagic complications. We found that the neurological picture did not differ between the groups: mean NIHSS scores were 12 and 13 points, respectively. Morphological and functional characteristics of red blood cells and platelets, hemostasis and cytokine profiles were compared between patients with IS and pre-existing PV and the comparison group. One of the key elements in potentiating thrombotic complications in patients with IS and PV was JAK2 V617F allele burden. The obtained data suggest the cumulative effect of the identified factors promoting thrombus formation in post-stroke patients with PV and overpowering the effect of antiplatelet therapy.

Received: 2020-08-11

Published online: 2020-09-01

DOI: 10.24075/brsmu.2020.052

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VIEWS 2332

Rybakova PA, Koroleva YuI, Ivanova GE, Zarubina TV

Currently, the new model of stroke care is actively implemented. There is a number of problems thereby related to digitalization. The study was aimed to work up the information model of the post-stroke rehabilitation at the first stage. The following basic objects of the rehabilitation system information model were identified and described using system analysis and business process modelling, based on studying laws, regulatory and legal acts, clinical guidelines, the “Development of the System of Medical Rehabilitation in Russia” pilot project protocol, and the problem area experts’ findings: patient, health information system (HIS) of a healthcare organization, document management. The objects’ properties and interaction are discussed, the information model is been constructed, main directions are described.

Received: 2020-07-25

Published online: 2020-08-31

DOI: 10.24075/brsmu.2020.051

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VIEWS 2252

Andreevskaya SN, Smirnova TG, Antonov EN, Chernousova LN, Bogorodsky SE, Larionova EE, Popov VK, Ergeshov A

Sustained-release drugs against tuberculosis are a promising approach to therapy since they positively affect patient compliance with long regimens, especially when it comes to the multidrug-resistant form of the disease. Conventional UV-visible spectroscopy does not work well with multicomponential culture media used for growing M. tuberculosis. The aim of this study was to develop a method for evaluating the kinetics of anti-tuberculosis drug released from bioresorbable polymeric carriers suitable for screening a wide range of encapsulated prolonged-release drugs and identifying the best performing candidate. While studying the growth dynamics of the laboratory susceptible strain M. tuberculosis H37Rv in the presence of different levofloxacin concentrations (from 0.03 to 0.4 μg/ml), we developed a model, which is essentially a set of 2 parallel experiments evaluating the kinetics of drug release into the culture medium. The results of these 2 experiments conducted on 3 encapsulated forms of levofloxacin loaded onto bioresorbable polymeric PLGA carriers (particles sized 50 μm and 100 μm and the matrix) revealed that release kinetics of the drug largely depended on the type of polymeric carrier. The best encapsulation of the antibiotic and its gradual release into the culture medium was observed for the matrix. All experiments were run in 3 replicates. The obtained data were analyzed using descriptive statistics.

Received: 2020-08-06

Published online: 2020-08-30

DOI: 10.24075/brsmu.2020.050

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VIEWS 2202