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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Pinaev SK, Venevsky S, Chakov VV, Tian L, Gong P, Kaprin AD, Starinsky VV, Chizhov AYa, Pinaeva OG

Russian Federal Far East District is a continental scale area where wildfires are frequent. We aimed to a) determine whether wildfires are related statistically to cancer for children and adults in the Russian Federal Far East District (FFED); b) to estimate time lags of such relationships and c) to find out which age groups are most vulnerable for wildfires. Annual number of fires (NF) in administrative units (AUs), normalized to the maximum value for all AUs in observation period 1992–2019, was taken as a characteristic of wildfires in our analysis. Annual cancer incidence (CI) for five cancer types for children up to 14 years and the entire population, normalized similarly to NF, was compared to normalized NF. ARIMA models were used for time series analysis for the period 1992–2019. Linear statistical analysis was done for NF and CI for short time series (10–12 years) for the central AU of FFED for “children up to 4 years”; Three additional embryonal types of cancer and five benign types of tumors were also focused in linear statistical analysis. ARIMA analysis revealed 27 associations between NF and CI with a lag from 0 to 3 years for two age groups, and five cancer types (p-values between 0.002 and 0.1). Linear statistical analysis for “children up to 4 years” revealed correlations for two from three embryonal types of cancer and three from five benign tumors (0.002 < p < 0.046). Incidences of hematopoietic, lymphoid, vascular, and soft tissue neoplasms, as well as CNS tumors had associations with wildfires for “children up to 4 years”, for “children up to 14 years” and “the entire population” age groups in many cases. Entire population and children up to 4 years in the central AU of FFED are most sensitive to wildfire — cancer interactions. Associations “number of fires — cancer incidence” as a rule have time lags from 0 to 3 years.

Received: 2023-04-25

Published online: 2023-08-26

DOI: 10.24075/brsmu.2023.028

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VIEWS 1064

Nosova MA, Latif II, Kraeva LA, Khamdulaeva GN, Sharov AN, Kopetskiy IS, Eremin DA, Postnikova EV, Postnikov MA

Periodontitis is a problem urgent in Russia and throughout the world in general. Because of the dynamically changing flora causing this diseases, the treatment methods designed against it should be adapted on a regular basis. The classic approach to arresting development of the acute process relies on 0.2–0.12% chlorhexidine, a chemical antiseptic, but after 3 weeks of use, its efficacy drops drastically because pathogenic flora adjusts thereto. In the recent years, plantbased complexes with antiseptic properties have shown their capacity to challenge the classic approach. Obviously, efficacy of active ingredients depends on the form of the final product. The marker of periodontitis in the oral cavity is Staphylococcus aureus. Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii have virulence markers that are copathogens for periodontitis. This study aimed to find plant-based preparations capable of eliminating the said microbes and Streptococcus mitis, Streptococcus oralis, Streptococcus salivarius, Enterococcus faecalis. We compared antibacterial, adhesion and biofilm formation preventing properties of Phytodent plant-based products in various forms: water solution, water-alcohol solution, oil solution, gel. Long exposure form — gel — proved to be the most effective in terms of the properties tested. Products with synthetic and plant-based antiseptics, as well as those with plant-based antiseptics in maximum concentration (elixir), had comparable efficacy. Water and oil solutions are less effective because of the lower active ingredient concentration and relatively brief exposure. Our results support the results of clinical studies dedicated to the use of Phytodent products as oral care products in the context of periodontitis prevention and treatment. We recommend conducting further studies comparing compositions, cross- and comparative studies investigating the effect of frequency of application and time of exposure, such studies registering titers of active ingredient concentrations, and with subjects thereof including mixed biofilms.

Received: 2023-06-16

Published online: 2023-08-24

DOI: 10.24075/brsmu.2023.029

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VIEWS 796

Shatova OP, Gaponov AM, Grigoryeva TV, Vasilyev IYu, Stoletova LS, Makarov VV, Yudin SM, Roumiantsev SA, Shestopalov AV

The signaling role of tryptophan and its catabolites is well known. However, their effects on the potential microbiota metabolic activity is still poorly understood. The study was aimed to assess concordance between changes in the predicted gut microbiome enzyme-encoding gene abundance and the tryptophan catabolites. The study involved 109 healthy volunteers and 114 obese patients. Quantification of tryptophan catabolites in the feces was performed by HPLC. Bacterial DNA was extracted from fecal samples, and the 16S rRNA gene V3-V4 region was sequenced. Primary processing of the sequencing data was performed using the QIIME v.1.9.1 tool. The alleged metabolic role of microbiota members was explored via reconstruction of unobservable states using PICRUSt. The maximum number of significant correlations between the unobservable states and the predicted gut microbiome enzyme-encoding gene abundance in obese individuals was reported for indole-3-lactate. A significant correlation between indole-3-lactate and the abundance of genes encoding the enzymes involved in metabolism of fructose, amino sugars, nucleotides, amino acids, polyamines, and sulfosaccharides was revealed. It has been found that obese patients show a threefold increase in the indole-3lactate-producing microbiota. It has been shown that in obese individuals microbial population of the intestine is represented by the totally different genera and species of microorganisms. It is concluded that indole-3-lactate has a significant effect on the predicted gut microbiome enzyme-encoding gene abundance in obese patients.

Received: 2023-06-21

Published online: 2023-08-07

DOI: 10.24075/brsmu.2023.027

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VIEWS 823

Pavlenko VB, Vlasenko SV, Orekhova LS, Biryukova EA

As explained earlier, neurorehabilitation sessions involving the use of the non-invasive “brain – computer – hand exoskeleton” interface reduce hand muscle spasticity and improve motor skills in children with cerebral palsy (CP). However, the changes in the patients’ speech functions and their relationship with the upper limb mobility have not been analyzed. The study was aimed to assess the correlation between the motor and speech functions of children with CP, as well as to detect the changes in motor realization of speech production following complex treatment of patients including sessions of neurorehabilitation. The study involved children with CP aged 6–15. The index group (n = 40, 16 girls, 24 boys) received complex resort treatment with the course of neurorehabilitation, while the comparison group (n = 20, 10 girls, 10 boys) received standard resort treatment. A significant (р < 0.001) correlation between the total ABILHAND-Kids score and the indicators of speech production motor realization was revealed. In patients of the index group, complex treatment with the course of neurorehabilitation resulted in the significant (р < 0.001) decrease in hand spasticity and the increase in the total ABILHAND-Kids score and speech scores. No significant changes of these indicators were revealed in children of the comparison group. Beneficial effects of neurorehabilitation may be based on the enhanced plasticity of the neural circuits responsible for planning and execution of complex hand movements, as well as speech processes. The findings can be used to develop new methods for correction of motor and cognitive spheres in children with CP.

Received: 2023-06-17

Published online: 2023-07-28

DOI: 10.24075/brsmu.2023.026

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VIEWS 770

Nazarov VD, Cherebillo CC, Lapin SV, Sidorenko DV, Devyatkina YA, Musonova AC, Petrova TV, Nikiforova AI, Ivanova AV

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive skeletal muscular weakness and atrophy. The newborn screening for spinal muscular atrophy should define all molecular forms of SMA. The aim of this study is to compare a PCR-based test for detection of homozygous SMN1 loss with multiple ligation probe amplification (MPLA) in patients with spinal muscular atrophy and other numerical changes of the SMN1 gene. PCR-based test was used to detect exon 7 of SMN1 gene homozygous loss. The study included 341 samples of patients with clinical suspicion of SMA from Biobank of Centre of Molecular Medicine of Pavlov State Medical University (Saint-Petersburg, Russia). Group 1 included 206 whole blood samples and Group 2 included 135 dried blood spot (DBS) samples. Copy number of the SMN1 and SMN2 genes had been evaluated with MLPA as a reference method. The results showed that kit was able to detect homozygous SMN1 loss in all samples from group 1 and 2 (Group 1: n = 67; 33%; Group 2: n = 19; 14%). At the same time in all samples with 1–3 copies of the SMN1 gene, the results of the kit were negative for homozygous loss of SMN1 gene (Group 1: n = 139; 67%; Group 2: n = 116; 86%). Kit showed high effectiveness in the detection of homozygous loss SMN1 gene. The kit detects all possible molecular forms of homozygous SMN1 gene loss in both DNA samples extracted from the whole blood and DBS.

Received: 2023-05-30

Published online: 2023-06-30

DOI: 10.24075/brsmu.2023.025

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VIEWS 1007

Vasileva OO, Tereschenko VP, Krapivin BN, Muslimov AR, Kukushkin IS, Pateev II, Rybtsov SA, Ivanov RA, Reshetnikov VV

Development of the new tuberculosis vaccines that would be effective in adults is an urgent task: worldwide, the annual death toll of this disease exceeds 1.5 million. In the recent decades, the matter has been addressed in numerous studies, but none has yielded an effective vaccine so far. There are many factors to resistance against tuberculosis; this study focuses on the T-cell response, a mechanism that enables elimination of intracellular pathogens, such as M. tuberculosis. We aimed to develop an mRNA vaccine capable of triggering a pronounced T-cell response to the M. tuberculosis antigens. The in silico analysis allowed us to select epitopes of the M. tuberculosis secreted protein ESAT6 (Rv3875) and design a multi-epitope mRNA vaccine thereon. We assessed the intensity of T-cell response in mice immunized with mRNA vaccines that encode a full-length or multi-epitope antigen. The results of this study in mice show that immunization with a multi-epitope mRNA vaccine produces twice as many IFNγ-secreting splenocytes in response to specific stimulation than immunization with an mRNA vaccine encoding the full-length protein. Thus, the developed multi-epitope mRNA vaccine can be an effective M. tuberculosis prevention agent the mode of action of which involves formation of a pronounced T-cell response.

Received: 2023-04-24

Published online: 2023-06-29

DOI: 10.24075/brsmu.2023.021

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VIEWS 1285

Batyrova ZK, Bolshakova AS, Kumykova ZKh, Kruglyak DA, Uvarova EV, Chuprynin VD, Mamedova FSh, Sadelov IO, Trofimov DYu

Two forms of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome are recognized: isolated uterovaginal agenesis and associated with extragenital malformations, including several well-recognized syndromes. Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant condition characterized by facial dysmorphism, ectodermal and skeletal features. TRPS comprises TRPSI (caused by a heterozygous pathogenic variant in TRPS1), TRPSII (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Genital anomalies occur particularly in TRPSII. We present a case of rare combination TRPSII with MRKH syndrome. Delayed diagnosis resulted to prolonged pain syndrome and repeated surgery. Recognition of genital anomalies in TRPS allows timely referral diagnosis and appropriate care by paediatrician and adolescent gynaecologists.

Received: 2023-06-17

Published online: 2023-06-27

DOI: 10.24075/brsmu.2023.022

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VIEWS 770

Guselnikova VV, Razenkova VA, Sufieva DA, Korzhevskii DE

Arterial hypertension is one of the most significant medical and social problems, being widespread and associated with the risk of renal failure, cardiovascular and cerebrovascular complications. The aim was to investigate the morphofunctional state of microglia in different regions of the rat brain in the setting of arterial hypertension. Brain samples from spontaneously hypertensive SHR rats aged 3–8 months (n = 4) were used as study material. Normotensive WKY rats of the same age (n = 3) were used as the control group. The work was performed using immunohistochemical analysis and confocal laser microscopy. During the quantitative analysis, we were seeking to determine the number of microgliocyte bodies and the area occupied by the bodies and processes of these cells per 1 mm2 of the nervous tissue. An immunohistochemical reaction for calcium-binding protein Iba1 revealed that in rats with arterial hypertension, microglia in the cerebral cortex, striatum, subcortical white matter and subfornical organ showed morphological signs of activation: increased body size and thickening of the processes of these cells. The strongest activation is demonstrated by microglia of the subfornical organ, which is in a preactivated state in normotensive rats. The performed statistical analysis revealed a trend towards an increase in the amount of microglia in the brain in SHR rats compared to animals in the control group. The Iba1/CD68 double immunofluorescence reaction showed no changes in the amount and/or distribution of lysosomal CD68 protein in spontaneously hypertensive rats compared to control group. The results obtained indicate chronic activation of microglia in the brain of spontaneously hypertensive rats. Activation of microglia in this case is not accompanied by an increase in the phagocytic activity of these cells.

Received: 2023-06-05

Published online: 2023-06-27

DOI: 10.24075/brsmu.2023.024

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VIEWS 806