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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Baranova NS, Gris MS, Baranov AA, Spirin NN, Artyuhov AS, Shakirova KM, Nasonov EL

There are persistent infections that contribute to the emergence and development of multiple sclerosis (MS) exacerbations; they are triggered by the Epstein–Barr, herpes type 6, herpes simplex types 1 and 2, varicella-zoster viruses. Cytokines are crucial to arresting the spread of a herpes infection in a body. If their production is out of balance, MS can progress faster. This study aimed at determining the level of cytokines in the blood serum of MS patients, assessing their clinical significance and how they affect reactivation of herpes infection. We examined 36 patients (12 male and 24 female) with confirmed MS (McDonald criteria) in remission. In 18 of them, we diagnosed reactivation of peripheral herpes virus. Serum levels of 15 cytokines (IL1ß, IL4, IL6, TNF-a, INF-γ, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, sCD40L) were determined with the help of xMAP multiplexing. Compared to the control group, MS patients had increased levels of IL10, IL33 (p < 0.001), with high IL33 identified most often (20 patients; 52.8%). During exacerbations, the average level of IL10 grew up (p < 0.01), as did that of IL31, the high levels of which were detected significantly more often (42.8 and 6.9%, respectively; p = 0.04). In addition, a prevailing scenario was the increased levels of IL33 and other cytokines (IL17A, IL17F, IL21, IL31) (57.1 and 6.9% of cases, respectively; p = 0.008). Reactivation of herpes translated into higher levels of IL1ß, IL23 and IL33 compared to cases without reactivation (p < 0.05 and p < 0.01, respectively). High levels of IL33 were significantly more frequently recorded in this group of patients (77.7 and 33.3%; p = 0.008). We discuss involvement of IL10, IL31, IL33 and other cytokines in the pathogenesis of herpes-associated MS.

Received: 2023-07-24

Published online: 2023-08-31

DOI: 10.24075/brsmu.2023.032

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VIEWS 2045

Lisitsyna OI, Ekimov AN, Atapina EE, Syrkasheva AG, Goryainova EG, Makarova NP, Trofimov DYu, Dolgushina NV

To date the world community is actively working to optimize the approaches to determining chromosomal abnormalities in embryos. The study was aimed to assess the possibility of using noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) through analysis of cell-free DNA in spent culture medium (SCM). We conducted niPGT-A of aneuploid embryos by analysis of cell-free DNA in SCM. All blastocysts were considered to be aneuploid based on the results of previous preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy. The study involved 11 embryos from seven couples. All the embryos were warmed and individually cultured in the 10 µL drops for 9 h. All SCM was collected and analyzed by niPGT-A. The results obtained were tested for concordance with previous PGT-A data. A total of 12 SCM samples were assessed: 11 samples, in which the embryos were cultured, and one control sample. Chaotic niPGT-A results not allowing the karyotype diagnosis were obtained in one case (9.1%) out of 11. Full concordance of the PGT-A and niPGT-A results was revealed in seven cases out of 10 (70%), while clinical concordance was found in nine cases out of 10 (90%). In one case (10%), the blastocyst was considered to have euploid karyotype based on the niPGT-A data. It has been concluded that niPGT-A can be a promising method of preimplantation embryonal chromosomal status diagnosis that requires no biopsy.

Received: 2023-06-18

Published online: 2023-08-30

DOI: 10.24075/brsmu.2023.034

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VIEWS 1801

Kolomiets KV, Isaev IV, Kovalev VV, Grishchenko NV, Kokovihina DI, Morozova AA, Torosyan AR, Shashkova VV, Snegireva PV

In 85% of patients worldwide, gastric cancer (GC) metastasizes from the very beginning or within three years. In 30–50% of cases, metastases, both synchronous and metachronous, grow into liver. Multifocal liver metastases translate into an unfavorable prognosis: the median survival period is 10–15 months, with less than 10% of the patients surviving past three years. In such cases, the palliative treatment option is systemic chemotherapy. Combined with immunotherapy, transarterial chemoembolization (TACE), a relatively new method of local treatment of metastatic foci, offer new options of combating liver metastases. This work presents a clinical case of application of this combination coupled with chemotherapy to treat a patient with unresectable liver metastases spawned by HER2+ gastric adenocarcinoma. From the day of diagnosis, the patient's life expectancy was 42 months.

Received: 2023-06-27

Published online: 2023-08-29

DOI: 10.24075/brsmu.2023.031

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VIEWS 1897

Gusyakova OA, Smirnov SV, Kuznetsova OYu, Apergenova AR, Albikova AR

Parkinson's disease (PD) is a chronic neurodegenerative disease associated with specific neurological deficits in patients, it mainly affects dopaminergic neurons in the substantia nigra causing accumulation of the neurotoxic amounts of aggregated α-synuclein protein in the neuronal cell bodies. The paper reports the authors' view of certain pathochemical and biochemical aspects of the Parkinson’s disease development in terms of interplay between the metabolic pathways of catecholamines and pigments, particularly the possible pathway of neuromelanin synthesis in the neuronal cell bodies and its importance in the life of cells. Assessment of the use of certain neurodegenerative disorder biomarkers, which are of direct pathognomonic value, in the laboratory diagnosis of the disease is provided. It is suggested to use the results in the field of deeper understanding of biochemical patterns underlying neuronal death for early diagnosis of PD in individuals of different age groups, as well as for further study of pathogenesis based on fundamental biochemistry and pathobiochemistry of intracellular processes.

Received: 2023-07-24

Published online: 2023-08-29

DOI: 10.24075/brsmu.2023.030

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VIEWS 1697

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 2066

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 1808

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 1901

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 1886