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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Demina OM, Rumyantsev AG, Potekaev NN

Acne is one of the most common dermatoses. A prominent genetic component for this disease has been reported and the manifestation in first-line relatives is considered an important risk factor. Here we present a clinical case illustrating the relevance of particular genetic polymorphisms mapped to NCF1, CD3E, ORAI1, IGHM and TAZ in patients with severe forms and burdened family history of the disease. Genetic examination identified the same allelic variants in five candidate target genes (NCF1, CD3E, ORAI1, IGHM and TAZ) in two closely related patients (father and son) with severe acne. The identified genetic configuration may interfere with the oxidase activity and promote defects in mitochondrial function along with reduced T cell proliferation and imbalanced immunoglobulin production. The findings may provide an important reference point for further clinical investigation and treatment of severe torpid dermatoses.

Received: 2022-05-04

Published online: 2022-05-20

DOI: 10.24075/brsmu.2022.026

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VIEWS 15

Lomova NA, Chagovets VV, Dolgopolova EL, Novoselova AV, Petrova UL, Shmakov RG, Frankevich VE

Systemic nature of the human body response to SARS-CoV-2 requires dedicated analysis at the molecular level. COVID-19 during pregnancy affects maternal health and may entail complications in the early neonatal period and possibly long-term consequences for the offspring. The aim of the study was to assess the impact of COVID-19 on amino acid profiles in maternal venous blood, amniotic fluid and umbilical cord blood in order to develop a diagnostic panel accounting for possible consequences. The main group included 29 pregnant patients with a confirmed diagnosis of COVID-19 and the control group included 17 somatically healthy pregnant women. Amino acid profiles of the biological fluids were measured by high-performance liquid chromatography combined to mass spectrometry (HPLC-MS) and assessed in logistic regression models. The analysis revealed altered content of certain amino acids, their biosynthetic precursors and metabolites in the biological fluids collected from patients with COVID-19 possibly reflecting the development of systemic inflammatory reaction and associated changes in gene expression profiles. These findings may guide further research into health outcomes for neonates born from mothers infected with SARS-CoV-2 during pregnancy. The study may help to develop advanced recommendations and differential care protocols for pregnant women and newborns diagnosed with COVID-19.

Received: 2022-04-14

Published online: 2022-05-17

DOI: 10.24075/brsmu.2022.025

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VIEWS 40

Zaychikova MV, Bespiatykh DA, Malakhova MV, Bodoev IN, Vedekhina TS, Veselovsky VA, Klimina KM, Varizhuk AM, Shitikov EA

The spread of Mycobacterium tuberculosis drug resistance accentuates the demand for anti-tuberculosis drugs with a fundamentally new mechanism of action without conferring cross-resistance. G-quadruplexes (G4, non-canonical DNA structures) are plausible new drug targets. Although G4-stabilizing ligands have been shown to inhibit mycobacterial growth, the exact mechanism of their action is uncertain. The aim of this study was to assess a possible correlation between putative G4 elements in a model mycobacterial strain M. smegmatis MC2155 and transcriptomic changes under the action of subinhibitory concentrations of G4 ligands BRACO-19 and TMPyP4. We also planned to compare the results with corresponding data previously obtained by us using higher, inhibitory concentrations of these ligands. For BRACO-19, we identified 589 (316↑; 273↓) and 865 (555↑; 310↓) differentially expressed genes at 5 µМ and 10 µМ, respectively. For TMPyP4, we observed the opposite trend, the number of differentially expressed genes decreased at higher concentration of the ligand: 754 (337↑; 417↓) and 702 (359↑; 343↓) for 2 µМ and 4 µМ, respectively. Statistical analysis revealed no correlation between ligand-induced transcriptomic changes and genomic localization of the putative quadruplex-forming sequences. At the same time, the data indicate certain functional specificity of the ligand-mediated transcriptomic effects, with TMPyP4 significantly affecting expression levels of transcription factors and arginine biosynthesis genes and BRACO-19 significantly affecting expression levels of iron metabolism and replication and reparation system genes.

Received: 2022-04-08

Published online: 2022-05-15

DOI: 10.24075/brsmu.2022.024

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VIEWS 62

Hamad A, Soboleva AV, Vorobyev PO, Mahmoud M, Vasilenko KV, Chumakov PM, Lipatova AV

Diffuse gliomas are incurable, prevalent, and aggressive central nervous system tumors. Therefore, the development of selective oncolytic viral strains for malignant neoplasms is highly relevant. This study aimed to create an oncolytic virus based on a vaccine strain of poliovirus type 3 with natural antitumor activity. To achieve this goal, we replaced the internal ribosome entry site (IRES) of poliovirus with the corresponding fragment of human rhinovirus 30. The resulting recombinant oncolytic strain RVP3 retained the serotype of poliovirus type 3, as confirmed by virus neutralization micro-test with specific antiserum. In addition, the oncolytic efficacy of RVP3 was assessed in vitro on a broad panel of cell cultures. According to the results, RVP3 has changed its tropism, losing the ability to replicate in conditionally normal cell lines of embryonic astrocytes and embryonic fibroblasts while retaining the ability to replicate in tumor cells.

Received: 2022-04-18

Published online: 2022-04-30

DOI: 10.24075/brsmu.2022.023

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VIEWS 102

Egiazaryan KA, Ershov DS, Badriev DA, Soshnikov DY

Posterior fracture-dislocations often remain undiagnosed at initial medical attendance. In dislocation, the head of the humerus extends beyond the glenoid to form a zone of impaction, which “fixes” it. The injury is almost unidentifiable in standard frontal X-ray images. Meanwhile, continued fixation of the humerus in the state of posterior dislocation leads to a rapid progression of the traumatic impaction over up to 50% of the articular surface area. The associated damage to the articular lip of the scapula, rupture of the rotator cuff muscles, symptoms of shoulder instability after relocation, and severe pain syndrome require advanced treatments for this type of injury. Here we report a clinical case of anatomical neck fracture of the humerus with displaced consolidation, combined to posterior dislocation. To avoid subacromial impingement, instead of correcting the position of the head, we abandoned the reposition and performed an osteotomy with distal displacement of the greater tubercle of the humerus.

Received: 2022-04-09

Published online: 2022-04-29

DOI: 10.24075/brsmu.2022.022

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VIEWS 72

Guselnikova VV, Razenkova VA, Sufieva DA, Korzhevskii DE

The subfornical organ is an important regulator of water-salt metabolism and energy balance of the body, involved in the control of the cardiovascular system and immune regulation. The organ comprises several cell populations, among which microglia and macrophages remain uncharacterized. This study aimed at structural, cytochemical, and functional characterization of microglia and macrophages of the subfornical organ in rats. Brain specimens were collected from mature male Wistar rats (n = 8). Microglia and macrophages were revealed by immunostaining with poly- and monoclonal antibodies against calcium-binding protein Iba1 and lysosomal protein CD68; the slides were examined by light and confocal laser microscopy. The study provides a comprehensive morphological characterization of microglial cells and macrophages of the subfornical organ. We demonstrate that the majority of Iba1-expressing cells in this area of the brain are microglial cells, not macrophages. Pre-activated state of the subfornical organ microglia may reflect structural and functional features of this organ and specific functions of local microglia. Subependymal microglial cells, the processes of which penetrate into the third ventricle of the brain, constitute a distinct subpopulation among the Iba1-expressing cells of the subfornical organ. Apart from microglial elements, the subfornical organ contains few tissue macrophages with characteristic strong expression of CD68 accompanied by undetectable or weak expression of Iba1.

Received: 2022-03-27

Published online: 2022-04-28

DOI: 10.24075/brsmu.2022.020

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VIEWS 99

Zakharova IA, Petrash EA, Nikishina VB, Razuvaeva TN, Shuteeva TV

Sensory impairments (visual and auditory) reduce quantity and quality of the information input. The associated memory loss can be classified as intrinsic decline in memory functionalities or mere physiological effect of sensory deprivation. This study aimed to specify this issue by analyzing memory consolidation and reconsolidation processes in older people with sensory deficits. The study enrolled 65–75 year-old individuals (n = 61) distributed into four groups: patients with unilateral sensorineural hearing loss (n = 17); patients with bilateral sensorineural hearing loss (n = 14); patients with visual impairment (n = 19); and patients with combined sensory deficits (n = 11). The methods included Luria’s auditory-verbal (“10 words”) and visual memory tests and Bartlett’s experimental procedure. A decrease in memory volume for auditory-verbal and visual-figurative short-term memories was observed in all groups. The results reveal significant adverse dynamics of qualitative and quantitative indicators for memory consolidation and reconsolidation processes, associated with decreased volume of short-term memories, both auditory-verbal and visual-figurative. Based on these findings, we conclude that consolidation and reconsolidation efficiency depends on proper accommodation of the newly incoming information to already memorized modules (previous experience) and requires dosing of the newly incoming information in order to preserve its integrity at the stage of consolidation.

Received: 2022-03-22

Published online: 2022-04-28

DOI: 10.24075/brsmu.2022.018

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VIEWS 93

Kubekina MV, Kalinina AA, Korshunova DS, Bruter AV, Silaeva YY

Mitochondrial dysfunctions, which underlie many systemic diseases in animals and humans, may arise from accumulation of mutations in the mitochondrial genome. PolG-alpha enzyme encoded by Polg gene is crucial for replication and repair of the mitochondrial genome. The aim of this study was to assess the possible role of Polg mutations in mitochondrial dysfunctions using in vitro and in vivo animal models. The experiments involved transgenic mice with inducible expression of Polg mutant variant; the methods included cell culture, real time PCR assay, fluorescence flow cytometry, and skeletal muscle functional tests. The results indicate that mouse embryonic fibroblasts (MEFs) expressing Polg pathogenic mutant variant have decreased mitochondrial membrane potential and increased expression of mitophagy markers compared with control cultures. Transgenic animals with systemic expression of the pathogenic variant develop mitochondrial dysfunction which significantly affects muscular performance. In addition, systemic expression of mutated Polg in transgenic animals significantly inhibits expression of TCR subunit α and CD3 coreceptor complex subunits δ and ε in total splenocyte populations and significantly affects cellularity of the thymus without altering its CD4/CD8 subpopulation ratio. Thus, inducible expression of mutated Polg in transgenic animals provides a relevant model for studying mitochondrial dysfunction and its treatment in vitro and in vivo.

Received: 2022-04-14

Published online: 2022-04-27

DOI: 10.24075/brsmu.2022.021

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VIEWS 90