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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Balanovsky OP, Gorin IO, Zapisetskaya YuS, Golubeva AA, Kostryukova ES, Balanovska EV

This study explored the gene pools of Russian and Karelian populations of Tver region. Forty-one samples representing Tver Karels (n = 11) and Russians residing in the Western, Central and Eastern districts of Tver region (n = 30) were genotyped using a genome-wide panel of 4,559,465 SNPs. In order to investigate the phenomenon of genetic admixture between Slavic and Finnish-speaking populations, the obtained results were compared to the data on the Russian populations inhabiting the neighboring territories, Karels from Karelia and other North Eastern Europeans. Studying the gene pools of Russian populations with a genome-wide SNP panel is essential for cataloging their genetic diversity and identifying the distinct features of regional gene pools; in addition, it provides valuable data for practical pharmacogenomics and forensics. Using the principal component analysis, the ADMIXTURE method and D- and f3-statistics, we demonstrated that the gene pool of Tver Karels is closest to the gene pool of Karelian Karels, despite a long (300 to 500 years) history of living among the larger Russian population and the twentyfold population decline during the 20th century. At the same time, the gene pool of Tver Karels exhibits more pronounced similarity to the gene pool of the studied Russian populations than does any other Karelian population. The genetic admixture between Tver Russians and Tver Karels occurred due to a more intense gene flow from Russians to Karels whereas the gene flow from Karels to Russians was much weaker: Tver Russians turned out to be as genetically different from Karels as Pskov Russians. The genetic similarity of Tver Karels to Karelian Karels assessed with the autosomal SNP panel exhibits a slight shift towards the Russian gene pool and is consistent with the previously published analysis of Y-chromosome lineages in these populations that detected no admixture between Tver Karels and Russians.

Received: 2020-10-10

Published online: 2020-11-26

DOI: 10.24075/brsmu.2020.072

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VIEWS 3032

Elezarov AA, Kucheryavyy AS, Gumenyuk LN, Sorokina LE, Arifdzhanova SR, Gerbali OYu

Dyssomnic disorders (DD) associated with juvenile rheumatoid arthritis (JRA) are some of the most common conditions that are difficult to endure and that lead to deconditioning. This study aimed to assess prevalence and structure of DD, their relationship with clinical picture peculiarities and contribution to deterioration of the quality of lives of JRA patients. At the 1st stage, we assessed prevalence of DD in a continuous sample of JRA patients and healthy children aged 8–16 years. At the 2nd stage, we assessed DD structure, features associated with gender and age, connections to the key clinical characteristics of JRA and quality of life of the patients. In the context of the study, we used the SDSC sleep quality scale, the PedsQL 4.0 quality of life model, and the Ritchie index. DD develop in JRA patients 3.3 times more often than in healthy children (in 178 (72.3%) and 93 (22.2%) children, respectively). The DD registered were sleep initiation and maintenance disorders (54 cases, 22.0%), respiratory disorders (32 cases, 13.0%), sleep-to-wakefulness transition disorders (31 cases, 12.6%), excessive sleepiness disorders (38 cases, 15.4%), combinations thereof (23, 9.3%). Girls had sleep initiation and maintenance disorders more pronounced (p = 0.003), boys were more prone to excessive sleepiness (p = 0.008). The severity of DD increases with patients' age (r = 0.69; p = 0.001) and JRA onset age (r = 0.71; p = 0.001); they are also more severe in polyarticular JRA patients (r = 0.32; p = 0.048). We have clarified the relationship between DD and indicators of inflammatory (r = 0.56; p = 0.001) and Ritchie indices (r = 0.44; p = 0.005), duration of morning stiffness (r = 0.49; p = 0.029). The proven connection between DD and JRA entails the need for routine checks for DD in such patients, and, when discovered, DD should call for personalized therapeutic and diagnostic approach rather than be regarded as one of the JRA syndromes.

Received: 2020-10-05

Published online: 2020-11-14

DOI: 10.24075/brsmu.2020.071

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VIEWS 2566

Osikov MV, Simonyan EV, Ageeva AA, Ageev YuI, Fedosov AA, Sinitsky AI

Oxidative stress (OS) escalation associated with thermal trauma (TT) and pleiotropic effects of melatonin (MT) suggest a study of protective properties of the latter when applied as part of a novel dermal film (DF) to skin burns. This work aimed to assess the content of OS markers in the skin subjected to experimental TT and treated with DF with MT. Third A degree TT (area of 3.5%) were modeled by immersing a patch of skin in boiling water. Twelve cm2 of DF with 5 mg/g of MT were applied daily for 5 days. The parameters calculated were wound's area and epithelializatiohon rate. The products monitored in the burn wound were lipid peroxidation (LPO) products in heptane and isopropanol phases of the lipid extract and protein oxidative modification (POM) products, the modification being spontaneous and metal-dependent. With TT in the wound, the content of secondary and end LPO products in heptane and isopropanol phases increased on the 5th and 10th days; the total content of POM products grew on the 5th day (primary products, neutral) and on the 10th day (primary and secondary products, neutral). Application of DF to a TT wound reduced the burn area, increased the epithelialization rate (by the 10th day, the median went from 1.90% to 6.57%; p < 0.05), reduced the content of secondary and end LPO products in isopropanol phase (by the 10th day, the median went from 0.007 to 0.004 u.o.i; p < 0.05), reduced the total content of OMP products, namely that of primary neutral products — on the 5th day, of primary and secondary neutral products — on the 10th day. With TT present in the context of MT application, the burn area showed presence of secondary LPO products in heptane and isopropanol phases, LPO end products in isopropanol phase, POM products in the wound (basic and neutral primary/secondary POM products).

Received: 2020-10-03

Published online: 2020-11-11

DOI: 10.24075/brsmu.2020.070

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VIEWS 2552

Isaeva MKh, Belova VA, Korostin DO, Degtyareva AV

Biliary atresia (BA) is a cholestatic disorder of infancy that is fatal if untreated. Despite years of study the etiology of BA remains unknown. Three etiopathogenic mechanisms may be involved, such as immune dysregulation, environmental factors and genetic susceptibility. Genetic predisposition is being actively studied. Candidate genes associated with BA in certain populations, genes affecting the cholangiocyte cilia function, as well as genes involved in stress responses have been identified. However, the long-term follow-up of twins with BA suggests that genotype is not of paramount importance for the disease development. Both epigenetic patterns and postzygotic somatic mutations may contribute to etiology of the disease. Recently, some evidence is being accumulated on the possible genetic predisposition to certain outcome of Kasai portoenterostomy performed in patients with BA. However, the presence of a number of factors contributing to the development of the disease makes it difficult to identify the genetic markers.

Received: 2020-10-08

Published online: 2020-11-07

DOI: 10.24075/brsmu.2020.069

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VIEWS 2752

Kravchenko YuE, Chumakov SP, Frolova EI

Most triple negative breast cancers (TNBC) are characterized by elevated expression of mesothelin (MSLN), a cell surface antigen and one of the preferred targets for the therapy of solid tumors. Most continuous TNBC cell lines are MSLN-negative, which obstructs the development of MSLN-targeted therapy for TNBC. The aim of this study was to identify TNBC cell lines with MSLN hyperexpression and to obtain single-domain antibodies (nanobodies) capable of recognizing MSLN in TNBC cells. Mesothelin expression levels were measured in the panel of TNBC cell lines by real-time reverse-transcription PCR. PCR results were verified by measuring concentrations of the megakaryocyte potentiating factor (the secreted fragment of the mesothelin precursor) using sandwich ELISA. Immune phage-display VHH fragment libraries were prepared from mononuclear cells of Vicugna pacos using a modified library enrichment protocol. Two nanobody variants with high specificity for the target and Kd of about 140 and 95 nmol, respectively were obtained. Two MSLN+ and three MSLN– cell lines were identified in the TNBC cell lines panel. The nanobodies demonstrated the ability to recognize the target antigen in MSLN+ cells and had the low ability to bind to MSLN– cells. Thus, we found a convenient MSLN+ TNBC cell model for MSLN-targeted therapy testing. The new single-domain antibodies can be used as targeting components of chimeric antigen receptors.

Received: 2020-09-28

Published online: 2020-10-31

DOI: 10.24075/brsmu.2020.068

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VIEWS 2568

Kudryavtsev GYu, Kudryavtseva LV, Mikhaleva LM, Kudryavtsevа YaYu, Solovyeva NA, Osipov VA, Babichenko II

Prostate cancer is the most common type of cancer among men, which is mainly due to extensive use of screening tests and high total number of prostate biopsies. Verification of tumors with poorer prognosis is the primary goal of prostate cancer management. The study was aimed to determine the clinical and morphological associations and the prognostic value of the Nanog protein expression in prostate cancer of distinct Grade Groups. We used the prostate tissue specimens obtained during surgery, and the biopsy specimens, the total of 89 cases. Histological and immunohistochemical assessment was performed using antibodies to Ki-67 and Nanog. Correlations between the expression of markers and the Grade Groups were revealed using the Spearman's rank correlation coefficient, and the correlation with clinical and morphological characteristics was determined using the chi-squared test (χ2). There was a positive correlation between the expression of Ki-67 and Nanog, and the Grade Group numerical order (rs = 0.619, p < 0.001 and rs = 0.786, p < 0.001 respectively). We managed to find the relationship between the high Nanog expression and the extraprostatic extension (p = 0.041). High expression of Nanog protein in the prostate cancer cells was associated with a higher-grade adenocarcinoma and indicated a poor prognosis.

Received: 2020-10-06

Published online: 2020-10-31

DOI: 10.24075/brsmu.2020.067

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VIEWS 2479

Klochkov AS, Zimin AA, Khizhnikova AE, Suponeva NA, Piradov MA

The key factor promoting post-stroke gait disturbances is motor impairment of the ankle joint (AJ) which results in pathological synergies. Robotic devices used for gait training are equipped with hip and knee joint actuators. However, there is no consensus in the literature on their effect on AJ movements. The aim of this study was to investigate the effect of robot-assisted gait training on AJ movements in patients with post-stroke paresis. The study recruited 22 hemispheric stroke survivors. They motor function was assessed using clinical scales and motion capture analysis. All patients received 11 robot-assisted gait training session. After rehabilitation, the total score on the Fugl-Meyer Assessment scale increased from 146.5 to 152 points (p < 0.05); for the lower limb, the score increased from 18 to 20.5 points (p < 0.05). The muscle tone of ankle extensors decreased from 2.5 to 2.0 points on the modified Ashworth scale (p < 0.05). The duration of the stance phase increased from 28.0 to 33.5% relative to the total gait cycle (GC). The main difference in the GC structure before and after rehabilitation is the presence of 3 GC parts instead of 5, suggesting consolidation of patients’ goniograms at 1-61% of GC. Comparison of joint angles before and after rehabilitation revealed that only the interquartile ranges (IR) were different (р < 0.05). The authors conclude that robot-assisted training with knee and hip joint actuators indirectly affects the kinematic parameters of AJ by promoting a shift towards the average gait kinematics.

Received: 2020-09-28

Published online: 2020-10-30

DOI: 10.24075/brsmu.2020.066

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VIEWS 2478

Gaydina TA, Dvornikova EG

Early detection of melanocytic nevus progression to malignant melanoma is a pressing concern. Traditionally, patients with multiple melanocytic nevi (MMN) are monitored for extended periods of time and excisional biopsies are performed on individual suspicious melanocytic nevi (MN). This approach is costly and tremendously time-consuming for both doctors and patients. The aim of this study was to evaluate the efficacy of a smartphone-compatible optical instrument in the assessment of MN for malignancy. Seven patients aged 43 to 65 years with MMN on the trunk and upper/lower extremities were followed-up for 4 years. Dermoscopy images of MN were taken and analyzed using a Handyscope smartphone-compatible optical system operated at 20x magnification and a Handyscope3 application. A total of 74 MN were surgically removed during the follow-up period. None of the patients had melanoma. The results of dermoscopy image analysis generated by the convolutional neural network coincided with histopathology findings in all cases. The optical Handyscope system demonstrated its efficacy in assessing MN for malignancy. AI can be used for primary screening of MMN dermoscopy images. However, histopathological verification of the diagnosis is still needed.

Received: 2020-09-11

Published online: 2020-10-28

DOI: 10.24075/brsmu.2020.065

Comments 0

VIEWS 2675