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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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

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VIEWS 1445

Sokolinskaya EL, Putlyaeva LV, Gorshkova AA, Lukyanov KA

Despite the extensive research spurred by the catastrophic effects of COVID-19 pandemic, precise molecular mechanisms of some stages in SARS-CoV-2 life cycle remain elusive. One of such stages is the detachment of viral particles during budding. Using confocal fluorescence microscopy, we observed formation of specific structures by endoplasmic reticulum in human cells expressing SARS-CoV-2 M-protein, implicating oligomerization of M-protein across parallel membranes. In our opinion, such intermembrane oligomerization may provide a driving force for pinching off the viral particles during SARS-CoV-2 budding.

Received: 2022-05-13

Published online: 2022-06-04

DOI: 10.24075/brsmu.2022.029

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VIEWS 1481

MicroRNAs are short non-coding molecules which regulate translation in a gene-specific manner. MicroRNA isoforms that differ by few extra or missing nucleotides at the 5'-terminus (5'-isomiR) show strikingly different target specificity. This study aimed to identify functional roles of 5′-isomiR in colorectal cancers. Transcriptomic targets of microRNA isoforms were predicted using bioinformatics tools miRDB and TargetScan. The sets of putative targets identified for 5′-isomiR were integrated with mRNA and microRNA sequencing data for primary colorectal tumors retrieved from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database. The network of interactions among miRNA, their targets and transcription factors was built using the miRGTF-net algorithm. The results indicate that microRNA isoforms highly expressed in colorectal cancer and differing by a single nucleotide position at the 5'-terminus have ≤ 30% common targets. The regulatory network of interactions enables identification of the most engaged microRNA isoforms. Anti-correlated expression levels of canonical microRNA hsa-miR-148a-3p and its putative targets including CSF1, ETS1, FLT1, ITGA5, MEIS1, MITF and RUNX2 proliferation regulators suggest an anti-tumor role for this molecule. The canonical microRNA hsa-miR-203a-3p|0 and its 5′-isoform bind different sets of anti-correlated putative targets, although both of them interact with genes involved in the epithelial-mesenchymal transition: SNAI2 and TNC.

Received: 2022-04-29

Published online: 2022-05-30

DOI: 10.24075/brsmu.2022.028

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VIEWS 1570

Yunusova EM, Mukhamadeev TR, Bakirov BA

Chronic myeloproliferative disorders (CMPD) include hemoblastoses with abnormal proliferation of myeloid lineages and concomitant alterations in the peripheral blood indicators. The aim of this study was to assess the frequency and structure of ophthalmic complications as a quality of life factor in patients with CMPD. A group of patients with hemoblastoses of this type (n = 41) were surveyed using National Eye Institute Visual Function Questionnaire-25 along with a comprehensive examination by noninvasive ophthalmological techniques. The patients typically reported impaired visual acuity, visual discomfort and foreign body sensation in the eyes. Though many of the patients assessed their general health and vision as satisfactory, the vast majority (68.3%) expressed serious concerns about their visual abilities. The ophthalmological examination revealed various defects including refractive errors (61%), corkscrew dilation and tortuosity of conjunctival and retinal vessels (77.9%), recurrent subconjunctival hemorrhages (39%) and dilated optic nerve sheaths (36.6%). The survey data indicate that visual impairments significantly affect quality of life in patients with CMPD. Overall, the results underscore the importance of interdisciplinary approach in the management of patients with CMPD to enable early diagnosis and feasible correction of the ophthalmic component.

Received: 2022-05-02

Published online: 2022-05-29

DOI: 10.24075/brsmu.2022.027

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VIEWS 1476

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: 2022-04-03

Published online: 2022-05-20

DOI: 10.24075/brsmu.2022.026

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VIEWS 1438

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 2083

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 1477

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 1764