[Registry-based comparison of multiple sclerosis epidemiology trend data in 1999 and 2019: the case of Yaroslavl]. / Dinamika osnovnykh epidemiologicheskikh pokazatelei rasseyannogo skleroza po rezul'tatam sravneniya registrov patsientov 1999 i 2019 gg. v Yaroslavle.

OBJECTIVE: To compare the epidemiological indicators of multiple sclerosis (MS) in Yaroslavl when comparing the 1999 and 2019 registers to study the pathomorphism of the disease in this territory. MATERIAL AND METHODS: During the work, the data of the 1999 and 2019 registers were used, including the age of the debut, the date of diagnosis, the form of the disease, clinical characteristics, the treatment received and its duration. In 1999, 257 patients living in the city of Yaroslavl (155 women and 102 men) were included in the MS registry with a reliable diagnosis of MS according to Poser's criteria with confirmation according to neuroimaging data. In 2019, 479 people living in the territory of Yaroslavl (342 women and 137 men) were included in the register with a diagnosis of MS based on the criteria of MacDonald 2005, 2010, 2017. As of 01.01.19, 970 patients (530 women and 440 men) were included in the patient register of the Yaroslavl region. RESULTS AND CONCLUSION: Clinical and epidemiological review of Yaroslavl MS Registry data in 1999 and 2019 showed significant changes in disease pattern. The prevalence rate increased from 42.6 to 78.5 cases per 100,000 people. The morbidity rate rose from 1.58 to 3.28 cases per 100,000 people. The reasons for the increase are improvement in the diagnostic quality, new diagnostic criteria and the true growth of prevalence and morbidity. The use of disease modifying drugs (DMDs) has extended «the time to EDSS 3,0¼ by 4 years, «the time to EDSS 6,0¼ by 5-8 years.

Correlation between Expression of KLF5 and ZEB1 Transcription Factor Genes in Pancreatic Cancer.

The mRNA content of the transcription factors KLF5 and ZEB1 was studied in pancreatic tumor tissues and in fetal and normal pancreas. Transcription of these factors was not high and similar in normal and fetal pancreatic tissues but greatly increased in the pancreatic ductal adenocarcinoma tissues. A significant positive correlation between the KLF5 and ZEB1 transcription levels in the pancreatic tumor tissues was observed.

Dependence of expression of regulatory master genes of embryonic development in pancreatic cancer cells on the intracellular concentration of the master regulator PDX1.

Exogenous expression of the gene encoding the pancreatic master regulator PDX1 in cell lines with different degrees of differentiation of pancreatic cancer cells is accompanied by changes in the expression of known master genes involved in cancer progression. In BxPC3PDX+ cells, as compared to BxPC3PDX-, we detected an increased expression of the following genes: NKX6.1 (2 times), NR5A2 (2.5 times), KLF5 (1.8 times), ZEB1 (3 times), and ONECUT1 (1.3 times), as well as a decreased expression of MUC1 and SLUG genes (3 and 2 times, respectively). In PANC1PDX+ cells, as compared to the control PANC1PDX- cells, we detected a decreased expression of ISL1 (2 times) and an increased expressed of KRT8 (2 times) and MUC1 (by 30%). In the high-grade cell lines (including the BxPC3 line studied), the total content of sites containing the marks of active enhancers was higher than that in the low-grade cell lines (PANC1).

PDX1: A Unique Pancreatic Master Regulator Constantly Changes Its Functions during Embryonic Development and Progression of Pancreatic Cancer.

Multifunctional activity of the PDX1 gene product is reviewed. The PDX1 protein is unique in that being expressed exclusively in the pancreas it exhibits various functional activities in this organ both during embryonic development and during induction and progression of pancreatic cancer. Hence, PDX1 belongs to the family of master regulators with multiple and often antagonistic functions.

[An effect of disease-modifying drugs on the development of children born to mothers with multiple sclerosis]. / Vliianie na razvitie rebenka terapii preparatami, izmeniaiushchimi techenie rasseiannogo skleroza, u materei s rasseiannym sklerozom.

AIM: To evaluate an effect of mother's treatment with disease-modifying drugs (DMD) on the mental and physical development of the child in the first year of life. MATERIAL AND METHODS: Thirty pregnancies resulted in birth of live babies in patients with multiple sclerosis (MS) were studied. The diagnosis of MS was made to the mother before conception of the child. Seven mothers did not receive DMD at the moment of conception (controls), 13 mother were treated with interferon-beta (IFN) and 10 with glatiramer acetate. A structure interview, examination of the child with the assessment of common anthropometric indices, the WHO scale for achievement of six milestones, medical history and statistical analysis were used. RESULTS AND CONCLUSION: The data on the negative effect of MS on the growth and development of the fetus and the positive impact of treatment of the mother with DMD in the early stages of pregnancy on anthropometric indices and development of the child in the first year of life were confirmed. It has been concluded that DMD positively influence the disease course of the female patient and potentially improve the prognosis for her future offspring.

[ADULT STEM CELLS AND CELLS OF MALIGNANT ORIGIN. PART I].

Recent data on adult stem cells are reviewed. According to the present dominant paradigm, it is most probable that cancer predisposition arises or cancer is initiated in these cells.

[ADULT STEM CELLS AND CELLS OF MALIGNANT ORIGIN. PART II].

Recent data on adult stem cells are reviewed. According to the present dominant paradigm, it is most probable that cancer predisposition arises or cancer is initiated in these cells.

Cancer Stem Cells: Plasticity Works against Therapy.

Great successes in identification and deciphering of mechanisms of the adult stem cells regulation have given rise to the idea that stem cells can also function in tumors as central elements of their development, starting from the initial stage and continuing until metastasis. Such cells were called cancer stem cells (CSCs). Over the course of intense discussion, the CSCs hypothesis gradually began to be perceived as an obvious fact. Recently, the existence of CSCs has been indeed confirmed in a number of works. However, when are CSCs universal prerequisites of tumors and to what extent their role is essential for tumor evolution remains an issue far from resolved. Likewise, the problem of potential use of CSCs as therapeutic targets remains unsolved. The present review attempts to analyze the issue of cancer stem cells and the potential of targeting them in tumor therapy.

[Pioneer Transcription Factors in Normal Development and in Carcinogenesis].

Pioneer transcription factors constitute a heterogeneous group of regulatory proteins of animals, which, unlike other transcription factors, are able to recognize and bind target DNA sequences within closed chromatin. This binding can change the local chromatin structure and facilitate binding of other proteins, thus establishing competence for gene expression. The ability to bind silent genes in the closed environment makes the pioneer factors very useful in the processes leading to cardinal alteration of cell phenotype, such as differentiation in embryonic development or cell reprogramming. These proteins can remain bound to target sequences during mitotic division, and due to this probably take part in the maintenance of cellular memory. Apparently, pioneer transcription factors are active participants in carcinogenesis and maintenance of tumor cell phenotype, although their role in these processes needs additional research. It is reasonable to suppose that a further study will help to shed more light on the genetic processes in embryonic development, increase the efficiency of cell reprogramming and also develop new approaches to diagnostics and therapy of cancer diseases.

[Master Transcription Regulators Specifying Cell-Lineage Fates in Development As Possible Therapeutic Targets in Oncology].

The transformation of normal precursors into cancer cells is an intricately regulated, multistep process. The master regulatory genes that play a crucial role in the process of organism development may also play a key role in carcinogenesis. From such a point of view, cancer is not simply a genetic disease that is due to a progressive accumulation of mutation--it is also a disorder of the developmental system of the tissue in which cancer emerges. Master regulators and their genes disturb stem cell differentiation upon mutation and thus may serve as targets for cancer therapy, in addition to the classic oncogenes and suppressors of tumor formation. This review is an attempt to give a modern concept of master genes and their functions in adult stem cells of the organism and in carcinogenesis, with pancreatic cancer as an example.

[Comparative analysis of activity of different promoters for NIS gene expression in melanoma cells].

Development of targeted drug delivery system is key problem of cancer gene therapy. To ensure specific delivery of these therapeutic compounds to the tumor it is preferable for therapeutic gene expression to occur predominantly in cancer cells. Therefore, when testing drug in vivo, it is necessary to study distribution of therapeutic gene expression products in different tissues of the organism. Sodium iodide symporter (NIS) is attractive reporter because its tissue level is easily quantitatively detected by noninvasive imaging methods. Different promoters are used to direct expression of therapeutic genes in tumor cells: strong nonspecific, moderate tissue-specific and tumor-specific. Tumor-specific promoters function in wide range of tumor cells, however they are relatively weak. Relationship between promoter and sodium iodide symporter activity is unclear to date. In this report we examined activity of different promoters in two melanoma cell lines, functional activity of NIS driven by these promoters, also we compared promoter strength and NIS activity. We demonstrated that in spite of strong differences in promoter activity functional activity of NIS directed by these promoters varies weakly. Relatively weak melanoma-specific promoter directs high NIS activity in melanoma cell, however weaker cancer-specific promoters drive high NIS activity only in certain melanoma cell line.

[The evaluation of eosinophilogram of peripheral blood in children with eosinophilia].

The need in study and interpretation of eosinophilograms in children with allergic diseases is conditioned by higher rate of eosinophilia, large specter of morphologic and functional signs of eosinophils, dependence of indicators from character of clinical course of disease, presence of complications and schemes of treatment. The level of laboratory techniques applied in routine clinical practice to evaluate morphological and functional characteristics of eosinophils is not developed enough. The implementation of such modern high-tech techniques as computer morphometry, highly sensitive and highly specific modifications ELISA, which are applied to detect associated with eosinophilia cytokines, chemokines and growth factors make it possible to approach to this issue at the new qualitative level.

[Quantitative comparison of expression for genes linked in bicistronic vectors via ires or 2A-peptide of porcine teschovirus-1 sequence].

Simultaneous expression of multiple target genes is often required in biotechnology. Multicistronic vectors coding for several proteins are being actively developed for this purpose. In commercially available vectors different variants ofencephalomyocarditis virus internal ribosome entry site (IRES EMCV) are used most often. However, many researchers consider that utilization ofself-cleaving 2A peptides sequences within multi- and bicistronic vectors is more promising. In this work, we compared the efficiency of gene expression in cells transfected with bicistronic vectors based on IRES EMCV and 2A peptide sequence derived form porcine teschovirus-1 (P2A). Efficiency ofgene expression was determined in three mammalian cell lines by measurement of co-expression levels of genes coding for RFP and EGFP proteins linked by IRES or P2A sequence. Higher level oftransgene expression was exhibited by cells transfected with the vector containing the 2A peptide sequence.

[The analysis and forecast of the demographic situation tendencies in the Republic of Udmurtiya].

The unfavorable demographic situation tendencies in the Republic of Udmurtiya are characterized by the decrease of population size and incidentally the regressive type of age structure is supported. The evolution of demographic processes (natality, mortality, life expectancy) affected the age gender structure of population of the republic. The reproduction of population and generations replacement decelerated in the region with low population density

Promoters with cancer cell-specific activity for melanoma gene therapy.

Melanoma is one of the most aggressive tumors. It develops from pigment-forming cells (melanocytes) and results in a high number of lethal outcomes. The use of genetic constructs with the ability to specifically kill melanoma cells, but not normal cells, might increase the lifespan of patients, as well as improve their quality of life. One of the methods to achieve a selective impact for therapeutic genes on cancer cells is to utilize a transcriptional control mechanism using promoters that are specifically activated only in cancerous cells. In this review, promoters of the genes that are preferentially expressed in melanoma cells are described. These promoters, and other highly melanoma-specific regulatory elements, reduce the unspecific expression of therapeutic genes in normal tissues. Moreover, cancer-specific promoters and their elements are advantageous for the development of universal anticancer drugs. Examples of the use of double promoters that have a high potential as instruments in cancer gene therapy are also given in this review.

[Core promoters as an example of the evolution of views on molecular mechanisms of vital activity under the impact of whole-genome information].

DNA sequences of a large number of animal genomes, combined with the information on new classes of regulatory elements traditionally viewed as intergenic, led to the revision of the concept of the genome as a linear sequence of genes with their promoters spaced by distinct intergenic regions. Instead, there emerged a conception of 'transcriptional landscape' characterized by the practical absence of boundaries between what was commonly considered genes. The concept of the core promoter, the main transcriptional cis-acting element, was also dramatically changed. The knowledge of the mechanisms of functioning of this central element of the cellular transcription system underlies the understanding of metazoan transcription in general. The review attempts to summarize the data on core promoters obtained in the last 7-10 years and to trace the evolution of the conception of them. This evolution led finally to the understanding that core promoters are active participants of the transcription regulation process rather than just passive scaffold for assembling preinitiation transcription complexes.