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Bulletin of RSMU

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Nowadays, great attention is paid to the study of circulating tumor cells (CTCs) due to their key role in distant metastasis. At the same time there is little data on the properties of circulating cells showing simultaneous expression of the leukocyte and epithelial markers and their possible role in tumor progression and chemotherapy resistance. The study was aimed to assess subpopulations of cells with hybrid epithelial/leukocyte phenotype and estimate the features of stemness, epithelial–mesenchymal transition (EMT), and integrin interface, which determine the cells’ possible metastatic properties in breast cancer (BC). The survey data from 128 patients with invasive breast carcinoma of no special type were included. Multicolor flow cytometry was used to assess the population structure and metastatic potential of the cells circulating in blood and primary tumor cells with hybrid phenotype. The primary tumor cell suspension was prepared by mechanical disaggregation. The high degree of heterogeneity was noted in the population of cells with hybrid phenotype, including the combination of the stemness and EMT features, and diverse integrin interface. Cells with hybrid phenotype are involved in the mechanisms underlying lymph node and distant metastasis. In lymph node metastasis, metastatic potential of these cells is associated with the stemness features (р = 0.0422) and co-expression of β3-, β4-, and αVβ5-integrins (р = 0.0338). In distant metastasis, metastatic potential of hybrid cells is associated with the stemness features (р = 0.015) and is not associated with the EMT features and integrin expression.
Studying the mechanism underlying tooth eruption is an important and promising area due to the increased incidence of the diseases associated with tooth eruption abnormalities or difficulties that can result in purulent and septic complications. The study was aimed to explore variability and structural features of the hard tissue mineral component and organic matrix in mandibular third molars being at different stages of tooth eruption. Microscopic examination and biochemical testing of the enamel, dentin, and dentin–enamel junction of the study participants’ (n = 67; females aged 14–36) mandibular third molars were performed by scanning electron microscopy and Fourier transform infrared (FT-IR) spectroscopy. The association of the tooth eruption stage with the hard tissue structural features, such as the degree of mineralization and the size of dentinal tubules, orientation and size of the enamel prisms, was revealed. There were significant differences in the mandibular third molar hard tissue water content, which was demonstrated by metabolic processes and maturation rate (p < 0.05). According to the IR spectroscopy data, intensity of the collagen absorption bands in the enamel increases with age, while in dentin it decreases (1202, 1249, and 1342 cm–1). Furthermore the combination of the reduced intensity of the 1202 cm–1 band with the increase in the 1342 cm–1 dentin–enamel junction band confirms the important role it plays as a link between the enamel and dentin due to its metabolic, shock-absorbing, protective, and nutritional functions. The findings demonstrate significant changes in the wrapping and orientation of the collagen fibrils and fibers in the hard tissue, which affect primary spatial orientation and mandibular dental topography.
There are persistent infections that contribute to the emergence and development of multiple sclerosis (MS) exacerbations; they are triggered by the Epstein–Barr, herpes type 6, herpes simplex types 1 and 2, varicella-zoster viruses. Cytokines are crucial to arresting the spread of a herpes infection in a body. If their production is out of balance, MS can progress faster. This study aimed at determining the level of cytokines in the blood serum of MS patients, assessing their clinical significance and how they affect reactivation of herpes infection. We examined 36 patients (12 male and 24 female) with confirmed MS (McDonald criteria) in remission. In 18 of them, we diagnosed reactivation of peripheral herpes virus. Serum levels of 15 cytokines (IL1ß, IL4, IL6, TNF-a, INF-γ, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, sCD40L) were determined with the help of xMAP multiplexing. Compared to the control group, MS patients had increased levels of IL10, IL33 (p < 0.001), with high IL33 identified most often (20 patients; 52.8%). During exacerbations, the average level of IL10 grew up (p < 0.01), as did that of IL31, the high levels of which were detected significantly more often (42.8 and 6.9%, respectively; p = 0.04). In addition, a prevailing scenario was the increased levels of IL33 and other cytokines (IL17A, IL17F, IL21, IL31) (57.1 and 6.9% of cases, respectively; p = 0.008). Reactivation of herpes translated into higher levels of IL1ß, IL23 and IL33 compared to cases without reactivation (p < 0.05 and p < 0.01, respectively). High levels of IL33 were significantly more frequently recorded in this group of patients (77.7 and 33.3%; p = 0.008). We discuss involvement of IL10, IL31, IL33 and other cytokines in the pathogenesis of herpes-associated MS.

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Eastern Caucasus is home to more than 30 peoples speaking Caucasian, Iranian and Turkic languages. Fusion of multiple migration flows together with the complex population structure of the Eastern Caucasus make it more difficult to analyze its gene pool: this is the most poorly studied one among all regions of the Caucasus. The study is aimed to identify the main patterns of the autosomal gene pool variation in this region. A total of 356 genomes of 29 ethnic groups were studied using the large panels of SNP markers: 243 genomes of 22 peoples of the Eastern Caucasus and 113 genomes of 7 peoples living in adjacent regions. The bioinformatics analysis involved the use of the ADMIXTURE ancestral component method and the gene pool variability principal component analysis (РСА). The hypothesis of three genetic strata, the interaction of which forms the structure of gene pool of the Eastern Caucasus, was put forward. The “Dagestan” stratum carries information about the gene pool of the ancient autochthonous population of the Eastern Caucasus. The “Iranian” stratum represents the legacy of ancient and middle-aged migrations surges of the Iranian-speaking population: it constitutes three quarters of the gene pool of modern Azerbaijan and about one third of the Dagestan peoples' gene pool. The “Steppe” stratum represents a negligible influence of the Eurasian steppe. Interaction of three genetic strata is only indirectly related to the peoples' linguistic affiliation, however, the association with linguistics is more obvious in the Caucasian-speaking peoples. Four genetically distinct groups of indigenous population of the Eastern Caucasus have been identified, the combination of which should be included in the characteristics of its autosomal gene pool: 1) Dargins, Laks; 2) Avars, Lezghins, Tabasarans, Aghuls, Rutul people, Tsakhur people; 3) Kumyks, Tat people and Azerbaijanis living in Dagestan; 4) Azerbaijanis and Talysh living in Azerbaijan. The directions of further research have been defined.
Among oncolytic viruses, modified vaccinia virus Ankara (MVA), a highly attenuated vaccinia virus (VV) is a well-studied variant with promising results in preclinical and clinical trials. The Lister VV strain from the Moscow Institute of Viral Preparations (LIVP) has been studied to a lesser extent than MVA and has a different oncolytic property from MVA. The aim of this work was to compare the oncolytic efficacy of LIVP and MVA strains against solid tumors. We developed recombinant variants LIVP-RFP and MVA-RFP; to enhance onco-selectivity thymidine kinase (TK) gene was inactivated by insertion of red fluorescent protein (RFP) gene to the TK locus. The replication kinetics and oncolytic activity of the obtained recombinant strains were evaluated in vitro and in vivo on tumor cell lines and mouse syngeneic tumor models of metastatic mouse 4T1 mammary adenocarcinoma, CT26 colon adenocarcinoma, and B16 melanoma. Both MVA-RFP and LIVP-RFP showed high replication efficiency in tumor cells and pronounced oncolytic activity against B16 melanoma and 4T1 breast adenocarcinoma allografts. In relation to 4T1, which is a model of triple negative human breast cancer, LIVP-RFP showed more than 50% increased cytotoxicity in in vitro tests compared to MVA-RFP, as well as a significant slowdown in the progression of 4T1 allografts and an increase in animal survival in experiments in vivo. Thus, the LIVP strain may be more promising than MVA as a platform for the development of recombinant oncolytic viruses for the breast cancer treatment.
Dear researcher!
At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.
Richard FEYNMAN Cargo cult science
American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.
Ivan PAVLOV On the Russian mind
In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.