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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Fursov VV, Zinchenko DI, Namestnikova DD, Kuznetsov DA

The search for effective pharmacophores to treat ischemic stroke is precipitated by the prevalence and high mortality of the condition. Optimization of preclinical scenarios for promising neuroprotectants by mathematical modeling using up-to-date computational platforms is a well-defined and urgent task. This study aimed to develop a drug-oriented model represented by an ordinary differential equation system to study pharmacokinetics of 25Mg2+-releasing porphyrin-fullerene nanocationite PMC16 in silico using MATLAB and adjust computating model's adequatness using in vivo rat model. The developed five-compartment model predicts the distribution of nanoparticles in organs and tissues (e.g. the brain, the heart and the liver) for the purpose of experimental parameters optimization. The in silico produced pharmacokinetic curves show good agreement with the data obtained using in vivo rat model of ischemic stroke. The in silico and in vivo results indicate that PMC16 nanoparticles effectively cross the blood-brain barrier.

Received: 2022-07-05

Published online: 2022-07-22

DOI: 10.24075/brsmu.2022.037

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VIEWS 1697

Savelieva GM, Breusenko VG, Kareva EN, Golukhov GN, Gutorova DS, Ovchinnikova AV, Ivanovskaya TN, Shcherbatyuk KV

The limited efficacy of hormone therapy for endometrial proliferative process (EPP) in postmenopausal patients and its side effects on the immune system functionalities have not been studied in detail. Here we assess the feasibility of hormone therapy for EPP in postmenopausal patients through evaluation of estradiol and progesterone receptor gene expression in endometrial tissue and peripheral blood mononuclear cells (PBMC). The study enrolled 92 postmenopausal patients with EPP, including 37 pts with glandular-fibrous polyps, 7 pts with non-atypical endometrial hyperplasia (EH), 8 pts with atypical endometrial hyperplasia (AEH), 31 pts with moderately differentiated adenocarcinoma and 9 pts with highly differentiated adenocarcinoma. The PBMC isolates and endometrial samples were tested for ER⍺, ERβ, mER, PRA, PRB, mPR and PGRmC1 expression by reverse real time polymerase chain reaction (RT–PCR). Differential changes in PBMC receptor profiles upon in vitro exposure to progesterone or mifepristone were determined for patients with endometrial polyps and healthy women. The results indicate elevated expression of ERα, ERβ, PRA, PRB, mPR and PGRmC1 by endometrial tissues in EH and elevated expression of mER, ER⍺ and PRA by PBMC in AEH, apparently reflecting suppressed functionalities of monocytes, macrophages, Т-cells and natural killer cells. Unaltered expression of the studied genes by PBMC in endometrial adenocarcinoma may reflect the incrementing tumor autonomy. In vitro, mifepristone inhibited ER⍺, ERβ, mPR, PGRmC1, PRA and PRB expression in PBMC isolated from patients with endometrial polyps. We suppose that such effects can mitigate the negative influence of sex steroid hormones on immunocompetent cells.

Received: 2022-05-18

Published online: 2022-06-28

DOI: 10.24075/brsmu.2022.036

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VIEWS 1645

Chalenko YM, Abdulkadieva MM, Safarova PV, Kalinin EV, Slonova DA, Yermolaeva SA

The virulence of gram-positive bacterium Listeria monocytogenes depends on its capacity to infect non-professional phagocytes and proliferate inside them. Listerias monocytogenes captured by mononuclear phagocytic cells during the infectious process are resistant to lysosomal digestion and can proliferate inside macrophages. Internalin B (InlB), one of the key pathogenicity factors of L. monocytogenes, interacts with mammalian receptors c-Met and gC1q-R. For epithelial cells, such interactions with surface receptors promote activation of these receptors and cytoskeletal remodeling, which leads to massive bacterial invasion into nonprofessional phagocytes. For macrophages, by contrast, nothing is known about the role of InlB in their interactions with L. monocytogenes apart from the fact that both receptors are abundantly expressed by macrophages and participate in the development of immune reactions. This study aimed at determination of the potential role of InlB in the interactions between L. monocytogenes and macrophages. We found that 1) InlB expression promoted a significant 3.5-fold increase in the rates of L. monocytogenes capture by macrophages; 2) the 24 h fold increase in bacterial number inside macrophages constituted 182.5 ± 16.7, 96 ± 12 and 13.3 ± 3 for EGDe∆inlB, EGDe and EGDe∆inlB::pInlB strains, respectively; 3) the EGDe∆inlB::pInlB strain, complemented with a plasmid copy of inlB, produced InlB at 3.3fold higher rates than the type strain EGDe. We conclude that InlB negatively affects the survival of listeria inside macrophages. The results enable advanced understanding of the host-pathogen interactions for L. monocytogenes.

Received: 2022-05-11

Published online: 2022-06-24

DOI: 10.24075/brsmu.2022.034

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VIEWS 1810

Krukov IA, Ershov AV, Cherpakov RA, Grebenchikov OA

The majority of stroke patients have cognitive symptoms and about 50% of them live with neurological deficits that critically limit social adaptation capacities even in the absence of significant motor impairments. The aim of this study was to select the optimal length of 0.5 MAC xenon exposure in order to alleviate the neurological and cognitive impairments in experimental stroke. The focal ischemia-reperfusion injury was modeled in rats (n = 70) ising Longa method. The intervention was immediately followed by inhalation of 0.5 MAC xenon for 30, 60 or 120 min. The neurological deficit was assessed using a 'Limb placement' seven-test battery and the cognitive functionalities were assessed by the Morris water maze test. A 30 min 0.5 MAC xenon exposure provided a 40% increase in the limb placement scores and a 17.6% decrease in the Morris water maze test latency compared with the control group (р = 0.055 and р = 0.08, respectively). With a longer 60 min exposure, the trends became significant, the scores improving 2-fold and by 44.4% compared with the control group (р = 0.01 and р = 0.04, respectively), whereas 120 min exposures afforded 2-fold improvements in both tests (р = 0.01). We conclude that, although 30 min post-stroke inhalations provide negligible benefits in terms of neurological status and learning capacity, prolonged exposure times of 60–120 min afford significant improvement in neurological and cognitive indicators and largely alleviate the deteriorating ischemic damage.

Received: 2022-05-21

Published online: 2022-06-24

DOI: 10.24075/brsmu.2022.035

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VIEWS 1784

Vorobyev PO, Kochetkov DV, Vasilenko KV, Lipatova AV

Transient gene expression is one of the most common methods in molecular biology, equally relevant for basic research projects and biotechnological industries. Despite the existence of commercial transfection systems, which afford high transfection efficiency and high expression levels of reporter genes, expanding such systems to industrial scales is often problematic due to high costs of the reagents. The well-described methods of cationic and calcium-phosphate transfection are accessible and ensure reproducible results at much lower costs. This study is aimed at comparative validation of calcium phosphate and cationic (polyethylenimine-based) transfection protocols along with the commercially available TurboFect reagent for mono- and cotransfections on a panel of commonly used cell lines including HEK293T, Huh7, BHK-21, CHO and MRC5. The efficiency of transfection with plasmid constructs encoding different fluorescent proteins was measured by flow cytometry. Of all the tested methods, calcium phosphate transfection afforded the highest efficiency of plasmid DNA delivery in all the cell lines except BHK21, for which the PEI method turned out to be more efficient than calcium phosphate transfection, and CHO, for which both methods showed comparable efficiency.

Received: 2022-04-22

Published online: 2022-06-23

DOI: 10.24075/brsmu.2022.031

Comments 0

VIEWS 1896

Ganin IP, Kaplan AYa

The P300-based brain–computer interfaces (P300 BCI) allow the user to select commands by focusing on them. The technology involves electroencephalographic (EEG) representation of the event-related potentials (ERP) that arise in response to repetitive external stimulation. Conventional procedures for ERP extraction and analysis imply that identical stimuli produce identical responses. However, the floating onset of EEG reactions is a known neurophysiological phenomenon. A failure to account for this source of variability may considerably skew the output and undermine the overall accuracy of the interface. This study aimed to analyze the effects of ERP variability in EEG reactions in order to minimize their influence on P300 BCI command classification accuracy. Healthy subjects aged 21–22 years (n = 12) were presented with a modified P300 BCI matrix moving with specified parameters within the working area. The results strongly support the inherent significance of ERP variability in P300 BCI environments. The correction of peak latencies in single EEG reactions provided a 1.5–2 fold increase in ERP amplitude with a concomitant enhancement of classification accuracy (from 71–78% to 92–95%, p < 0.0005). These effects were particularly pronounced in attention-demanding tasks with the highest matrix velocities. The findings underscore the importance of accounting for ERP variability in advanced BCI systems.

Received: 2022-05-04

Published online: 2022-06-21

DOI: 10.24075/brsmu.2022.033

Comments 0

VIEWS 2125

Voroshilina ES, Khayutin LV, Kudryavtseva EV, Kovalev VV, Plotko EE

Detecting high risk of preterm birth (PB) early makes its prevention possible. The aim of the work was to develop a mathematical predictive model for assessing the risk of preterm birth based on a quantitative analysis of the vaginal microbiota in the first trimester of pregnancy. The study included 199 pregnant women, i.e. 41 pregnancies that ended in preterm birth, and 158 — in term birth. Vaginal microbiota was analyzed in all patients in the 1st trimester of pregnancy by quantitative real-time PCR (qPCR). The method of dicriminant analysis was used to develop a predictive model. A method for predicting PB was developed with the calculation of the PRIMA prognostic index (Premature Birth. Index Of Microbiological Analysis). If the value of PRIMA > 0 – the risk of premature birth is low, if PRIMA < 0 – the risk is high. The sensitivity and specificity of the method are respectively 70.7% and 79.75%, the effectiveness is 77.89%. Evaluation of vaginal microbiota in the 1st trimester makes it possible to identify a high-risk group of PB and perform timely preventive measures.

Received: 2022-04-28

Published online: 2022-06-19

DOI: 10.24075/brsmu.2022.032

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VIEWS 4996

Zavyalova MV, Loos DM, Pismenny DS, Durova AA, Pankova OV, Rodionov EO, Tuzikov SA, Tashireva LA, Perelmuter VM

Lung cancer occupies the leading position in the global structure of oncological diseases. Despite significant advances in its treatment, the survival remains low. Morphological changes to the bronchial epithelium outside the tumor may provide important cues on progression of the disease in patients with lung cancer. This study aimed to identify associations between morphological and clinical features of non-small cell lung cancer and morphological changes to the epithelium in small bronchi outside the tumor. The study encompassed tumor specimens collected from 90 patients, 75 (83%) men and 15 (17%) women, diagnosed with non-small cell lung cancer. The average age of the patients was 67.8 ± 7.4 years. The results indicate higher frequency of lymphogenous metastasis in patients with combined basal cell hyperplasia and squamous metaplasia (BCH+SM+ group) compared to patients with isolated basal cell hyperplasia (BCH+SM– group, p = 0.05). The BCH+SM– group presented with higher rates of hematogenous metastasis compared to BCH+SM+ and BCH–SM– groups (p = 0.004 and p = 0.0019, respectively), as well as increased representation of low-differentiated structures in the primary tumors. The results suggest a commonality of parenchymal-stromal interactions in non-small cell lung cancers and their surroundings and a significant impact of these interactions on differentiation status and progression of the tumors.

Received: 2022-05-04

Published online: 2022-06-15

DOI: 10.24075/brsmu.2022.030

Comments 0

VIEWS 1766