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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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 3628

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 3552

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 3539

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

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VIEWS 3764

Voroshilina ES, Zornikov DL, Ivanov AV, Pochernikov DG, Panacheva EA

To this day semen microbiota is still poorly understood, and clinical significance of detecting specific microorganism groups has not been clearly determined. The aim of this work was to conduct cluster analysis of semen microbiota detected using real-time PCR. 634 semen samples of reproductive age men were analyzed. Microbial DNA in the quantity of no less than 103 GE/ml was detected in 460 samples (72.5%). From 1 to 14 microorganism groups were detected in 350 samples (55.2%) in the quantities that exceeded the threshold values (the detection rate of specific groups: 3.3–21.0%). In these 350 samples 4 stable microbiota clusters were determined. Each of the clusters was characterized by the prevalence of a specific microorganism group: obligate anaerobes (cluster 1; n = 172; detection rate — 49.1%), Lactobacillus spp. (cluster 2; n = 78; detection rate — 22.3%), gram-positive facultative anaerobes (cluster 3; n = 62; detection rate — 17.7%), Enterobacteriaceae / Enterococcoccus (cluster 4; n = 62; detection rate — 10.9%). Cluster 1 was less stable and was characterized by the larger species diversity compared to other clusters.

Received: 2020-09-21

Published online: 2020-10-28

DOI: 10.24075/brsmu.2020.064

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VIEWS 3961

Takhchidi KhP, Takhchidi NKh, Kasmynina TA, Tebina EP, Mokrunova MV

Eales’ disease is an idiopathic occlusive inflammatory vasculopathy resulting in peripheral retinal ischemia, neovascularization, recurrent hemophthalmos, and proliferative tissue formation. It is often complicated by tractional retinal detachment, secondary glaucoma, and central retinal vein occlusion. The management of patients with Eales’ disease includes mainly glucocorticosteroid therapy, the use of angiogenesis inhibitors, vitreoretinal surgery and laser photocoagulation. The clinical case reported demonstrates the potential of retinal laser photocoagulation for treatment of the Eales’ disease in the ischemic and proliferative stages. The results of retinal laser photocoagulation used as monotherapy demonstrate the clinical and functional indices improvement: enhanced visual acuity, stabilized central retinal sensitivity value, restored clarity to the ocular media, regression of neovascularization and macular edema in the patient’s eye being in the proliferative (3b) stage, and the process stabilization in the eye being in the ischemic (2a) stage of the disease.

Received: 2020-09-20

Published online: 2020-10-23

DOI: 10.24075/brsmu.2020.063

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VIEWS 3345

Tairova RT, Gaydina TA, Dvornikov AS, Tazartukova AD, Lyang OV

Patients with severe SARS-CoV-2 infection (COVID-19) and multiple comorbidities should be monitored for possible adverse reactions to prescribed drugs, including drug eruptions (DE) at any stage of treatment. Below, we describe a clinical case of a 92-year-old female patient with severe PCR-confirmed COVID-19. The patient was treated with amoxicillin/clavulanic acid, moxifloxacin, acetylcysteine, and sodium enoxaparin. On day 9 into treatment, the patient developed moderately itching macular rashes showing a tendency to coalesce, but overall showed no signs of deterioration. On day 15, the rashes regressed, following a short course of dexamethasone and chloropyramine. This kind of skin reaction might have been provoked by β-lactams and fluoroquinolones included in the treatment regimen, a secondary bacterial infection, compromised immunity due to advanced age, and high viral load associated with dermatological symptoms. Delayed onset of skin symptoms might be regarded as a marker of COVID-19 severity.

Received: 2020-09-23

Published online: 2020-10-21

DOI: 10.24075/brsmu.2020.062

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VIEWS 4213

In the journal Bulletin of the Russian State Medical University (July – August 2020/04, p. 60–66), mistakes were made in the article:DOI: 10.24075/brsmu.2020.049 Maltseva DV, Shkurnikov MYu, Nersisyan SA, Nikulin SV, Kurnosov AA, Raigorodskaya MP, et al. Hypoxia enhances transcytosis in intestinal enterocytes. Bulletin of RSMU. 2020; (4): 60–6. DOI: 10.24075/brsmu.2020.049The editors ask for the following changes:Printed by:p. 60, "Funding"the study received public financial support from the Ministry of Science and Higher Education of the Russian Federation (prоject ID RFMEFI60519X0184).It should be:the study was supported by the Ministry of Science and Higher Education of the Russian Federation (Project ID RFMEFI61719X0056).

Received: 2020-10-16

Published online: 2020-10-17

DOI: 10.24075/brsmu.2020.061

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VIEWS 2951