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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Maltseva DV, Shkurnikov MYu, Nersisyan SA, Nikulin SV, Kurnosov AA, Raigorodskaya MP, Osipyants AI, Tonevitsky EA

The integrity of the intestinal epithelial cell lining is crucial for the normal intestinal function. As a rule, intestinal inflammation is associated with additional tissue hypoxia, leading to the loss of epithelial monolayer integrity. However, in the absence of visible damage to the epithelium, there still might be a risk of infection driven by changes in the intracellular transport of bacteria-containing vesicles. The aim of this study was to investigate the effects of hypoxia on transcytosis using a human intestinal enterocyte model. We found that hypoxia enhances transcytosis of the model protein ricin 1.8-fold. The comparative transcriptome and proteome analyses revealed significant changes in the expression of genes involved in intracellular vesicle transport. Specifically, the expression of apoB (the regulator of lipid metabolism) was changed at both protein (6.5-fold) and mRNA (2.1-fold) levels. Further research is needed into the possible mechanism regulating gene expression in intestinal erythrocytes under hypoxic conditions.

Received: 2020-08-08

Published online: 2020-08-28

DOI: 10.24075/brsmu.2020.049

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VIEWS 2257

Chagovets VV, Starodubtseva NL, Frankevich VE

Investigation of the triazole-derived drugs action mechanisms and understanding of their affinity and specificity molecular basis may contribute to the new drugs development. The study was aimed to investigate the triazoles class representative (fluconazole) complexes with amino acids using mass spectrometry, molecular dynamics and ab initio quantum chemistry calculations. During the experimental study, the fluconazole, alanine, lysine and threonine solutions were analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. The molecular dynamics modeling of the fluconazole–amino acid complexes was performed using the CHARMM force field. The quantum chemistry calculations of the complexes structure and energy parameters were carried out using the density-functional theory by B3LYP calculations (3-21G and 6-311++G** basis sets). Mass spectra indicated that fluconazole formed stable complexes with amino acids in the 1 : 1 stoichiometric ratio. In accordance with the tandem mass spectrometry with varying fluconazole–amino acid associates ion fragmentation energy, the following sequence was obtained: [Fluc + Ala + H]+ < [Fluc + Lys + H]+ < [Fluc + Thr + H]+. The fluconazole–amino acid interaction energy values resulting from the quantum chemistry calculations formed the sequence similar to that obtained by experiment. Thus, as seen in the case of fluconazole–amino acid complexes, it is possible to combine the experimental mass spectrometry studies with quantum chemical modeling for the complexes properties assessment.

Received: 2020-07-22

Published online: 2020-08-23

DOI: 10.24075/brsmu.2020.048

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VIEWS 2297

Bobrov PD, Biryukova EV, Polyaev BA, Lajsheva OA, Usachjova EL, Sokolova AV, Mikhailova DI, Dement'eva KN, Fedotova IR

Cerebral palsy (CP) is one of the most severe central nervous system diseases in childhood associated with motor impairment. The study was aimed to assess the efficiency of the complex comprising brain-computer interface (BCI) and hand exoskeleton as an instrument for the motor function recovery in patients with CP complementing the essential therapy. The Fugl-Meyer Assessment scale, ARAT test and Jebsen–Taylor function test were used in 14 children and adolescents for the motor function improvement assessment after the therapy complemented by 7–10 BCI-exoskeleton based procedures. The EEG mu-rhythm sources properties during the motor imagery BCI control were studied. After the procedures completion, the significant improvement of the Fugl-Meyer Assessment scale score (7 (2; 11) for hand active movements; 4.5 (1; 6) for proximal arm and 2.5 (0; 5) for hand), ARAT test score (7.5 (1; 31) for total score, 1.5 (0; 12) for grasp movement and 1.5 (0; 8) for grip movement), as well as significantly different from the zero execution time reduction in three out of seven Jabsen–Taylor function test items (–1 (–4.13; 0.25) for simulated feeding; –1 (–2; 0) for moving light and heavy cans) were identified. The average BCI detection level was 0.51 (0.45; 0.54) (max = 0.70). In most EEG recordings the mu-rhythm sources were detected, both for intact and affected hemispheres. The mu-rhythm desynchronization associated with motor imagery was observed, significantly affecting the BCI accuracy. The results obtained indicate that the use of BCI-exoskeleton complex effectively complements the standard rehabilitation methods for children with CP, and suggest that its clinical effectiveness in individuals with CP may be proven by enrollment of more patients.

Received: 2020-07-31

Published online: 2020-08-20

DOI: 10.24075/brsmu.2020.047

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VIEWS 2881

Kovriguine DA, Nikitenkova SP

In the last decade of April 2020, the second coronavirus epidemic wave in Iran has bloomed. The new wave has started in the vicinity of the critical point, marked by approximately 44,000 infections, where the rate of increase of the primary epidemic that appeared in Iran in mid-February 2020 was the highest. Today, this secondary wave almost has doubled the peak of the primary, and, passing the epidemic threshold of about 70,000 total cases in early June, generated the new third epidemic wave developing unpredictably and dynamically. The purpose of this work was to call into use a simple dynamical system represented by the discrete logistic equation with unknown parameters to predict secondary waves using the official statistical data. The mathematical modelling reveals the secondary epidemic waves in Sweden, the United States, Ukraine, Serbia, Romania, Czech Republic, Portugal, Luxembourg, Poland, and Ecuador. Also, the second waves appear in Russia and other countries. Despite many individual differences in the epidemic spread in different countries, we have traced regularity in the rise of secondary waves. The beginning of each new wave, if focusing on the number of total cases, practically coincides with the time of the maximum growth rate of the previous early epidemic. Thus, the passing through the threshold of the current wave should be the most responsible for strict observance of the rules of self-isolation and other sanitary standards.

Received: 2020-07-13

Published online: 2020-08-13

DOI: 10.24075/brsmu.2020.046

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VIEWS 2742

Kiryanov SA, Levina TA, Kirillov MYu

SARS-CoV-2 is a RNA coronavirus of the β-CoVs family responsible for the pandemic of the severe acute respiratory syndrome (COVID-19). It is hypothesized that the viral genome of the contemporary predominant founder clones is likely to be evolving in geographic-dependent manner. Thus, strains of different origin may be characterized by different mutation patterns. The study was aimed to perform the mutational and phylogenetic analysis of the Russian SARS-CoV-2 genomes at different time periods and in various regions, as well as to characterize the mutational profiles of isolates using the bioinformatics approaches. The mutation accumulation was compared in 86 SARS-CoV-2 whole-genome sequences from Russia and 220 from Europe and North America in order to reveal the characteristic gene variations, the possible positive selection patterns. Along with the known mutation variants in the structural proteins genes, typical for isolates of European origin, several additional mutations including the synonymous mutation in gene M (C26750Т) characteristic for Russian isolates were revealed. Double mutation R203K and G204R in the nucleocapside gene which previously emerged in Europe began spreading and rapidly (within a month) became the dominant form in Russia. The results obtained indicate that the viral genome of most Russian isolates evolves with accumulation of new mutations associated with increased viral transmission. Data on the SARS-CoV-2 genome specific mutation patterns might be used for the detection of the virus, as well as for tracking and controlling of its spread.

Received: 2020-06-26

Published online: 2020-07-28

DOI: 10.24075/brsmu.2020.045

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VIEWS 3147

Kashtanova DA, Klimenko NS, Strazhesko ID, Tkacheva ON, Starikova EV, Glushchenko OE, Gudkov EA, Ilina EN

Demographic aging poses a challenge to the medical community, pressing for research into the biological factors promoting longevity and its features. Below, we look at the gut microbiota as one of such factors. The aim of this non-longitudinal study was to profile the gut microbiota of centenarians and to compare it with that of relatively healthy, younger Moscow residents. The study recruited 20 people aged 97–100 years (mean age 98 ± 1 year); the control group consisted of 92 individuals aged 53 ± 13 years. For each stool sample, the variable V3–V4 regions of the microbial 16S rRNA gene were sequenced. Primary analysis, read filtering and taxonomic identification were conducted in the QIIME 1.9 environment; reconstruction of metabolic pathways was aided by PICRUSt. Statistical analysis was performed by means of Python v. 3.2. A few differences were detected between the gut microbiota of centenarians and younger individuals: Bifidobacterium (р = 0.026) and Coprococcus eutactus (р = 0.026) were more abundant in centenarians, whereas Bacteroides (р = 0.003) and Prevotella (р = 0.002) were better represented in younger participants. The potential for butyric acid synthesis was higher in the group of centenarians (р = 0.048). Surprisingly, the gut microbiota of centenarians was more diverse and surprisingly beneficial for advanced age. Besides, the gut microbiota of centenarians might have more pronounced anti-inflammatory potential due to its ability to better synthesize butyric acid.

Received: 2020-07-01

Published online: 2020-07-27

DOI: 10.24075/brsmu.2020.044

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VIEWS 3373

Larina NV, Nacharova MA, Korsunskaya LL, Vlasenko SV, Pavlenko VB

It was demonstrated previously that neurorehabilitation with the noninvasive BCI-controlled robotic device combined with conventional therapeutic modalities resulted in significant motor improvement in children with cerebral palsy. However, EEG records were not analyzed in the previous study. The aim of this paper was to describe the reactivity patterns of the EEG α-rhythm during a series of 10 BCI-based neurorehabilitation sessions. The study was carried out in 32 boys and girls aged 10 to 18 years with right- or left-side hemiparesis. EEG was recorded from 21 electrodes at rest and during kinesthetic imagery of finger extension. During the first session, patterns of α-rhythm reactivity during motor imagery differed between patients with left- and right-side hemiparesis. The differences were statistically significant at Р2 during left hand movement rehearsal (F1, 30 = 5.10; p < 0.05). During the final session, the pattern of α-rhythm reactivity was different: synchronization was taken over by desynchronization at some electrode sites, suggesting increased activity of the neocortex. The most conspicuous EEG changes were observed in children with left-side hemiparesis (F20, 300 = 1.84; p < 0.05). By the end of the rehabilitation course, the differences between patients with left-and right-side hemiparesis became much less pronounced. Rearrangements in the EEG patterns in the α-frequency band can be regarded as signs of beneficial reorganization of neural circuits responsible for planning and executing complex hand movements.

Received: 2020-06-16

Published online: 2020-07-16

DOI: 10.24075/brsmu.2020.043

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VIEWS 2867

Moshetova LK, Usharova SA, Turkina KI, Sychev DA, Saburina IN

Since the discovery of microRNAs just a few decades ago, our knowledge of these molecules and their potential as diagnostic biomarkers and therapeutic targets has significantly expanded. There is an ongoing discussion in the scientific community about the possibility of using microRNA for the diagnosis of cardiovascular diseases. It has been shown recently that levels of some microRNAs vary in vascular eye disorders, such as age-related macular degeneration and diabetic retinopathy. However, despite serious advances in our understanding of microRNA’s role in eye pathology, we still do not know whether it is possible to use microRNA as a biomarker for central retinal vein occlusion. Perhaps, the discovery of such candidate microRNAs will help in making the timely diagnosis and improve the quality of medical care in patients with retinal vein occlusion.

Received: 2020-06-26

Published online: 2020-07-15

DOI: 10.24075/brsmu.2020.042

Comments 0

VIEWS 2697