[Cancer-Associated Fibroblasts: Heterogeneity and Bimodality in Oncogenesis].

Cancer-associated fibroblasts (CAFs) often form a major component of the tumor microenvironment (TMA), providing conditions for cancer cells to thrive. CAFs may contribute to tumor growth, invasion, metastasis, and resistance to therapy. However, clinical trials of treatment strategies targeting CAFs have largely failed. Moreover, there is evidence that CAFs are capable of inhibiting tumor development. The review considers the current data on the functional heterogeneity of CAFs and their bimodality in tumor development and progression. Understanding the tumor-promoting and tumor-inhibiting activities of CAFs can help to develop new diagnostic and therapeutic approaches.

[Cerebral venous thrombosis associated with COVID-19]. / Tserebral'nye venoznye trombozy, assotsiirovannye s COVID-19.

The literature reports that cerebral venous thrombosis (CVT) develops in 1-1.5% of patients with COVID-19. Recently, a new syndrome named vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described. VITT is a rare side-effect of COVID-19 vaccination that also causes CVT. The article presents an overview of the above problem and a clinical case of a patient with CVT that developed within a month after the first component of the Sputnik V vaccination and COVID-19.

Neuroinflammation and Neuropathology.

This review addresses the current understanding of the role of autoimmune neuroinflammation in the pathogenesis of vascular, neurodegenerative, and other diseases of the nervous system. The mechanisms of responses of resident CNS cells (glial cells, astrocytes) and peripheral immune system cells are presented. The therapeutic potentials of phosphodiesterase inhibitors, which have antiaggregant properties and can suppress autoimmune inflammation, are discussed. The phosphodiesterase inhibitor dipyridamole is regarded as a potential drug for this purpose.

[Cerebral venous thrombosis]. / Tserebral'nye venoznye trombozy.

Cerebral venous thrombosis (CVT) is one of the rare causes of stroke. It can manifest itself in different symptoms, making its timely diagnostics greatly complicated. Early recognition of symptoms and correct treatment tactics improve the prognosis in these patients. The article is a review of modern data about pathogenesis, clinical picture, principles of diagnosis and treatment of cerebral venous and sinus thrombosis.

[Neuroinflammation and neuropathology]. / Neirovospalenie i nevropatologiya.

The review highlights the current understanding of the role of autoimmune neuroinflammation in the pathogenesis of vascular, neurodegenerative and other diseases of the nervous system. The mechanisms of the response of the resident cells of the central nervous system (microglia, astrocytes) and peripheral cells of the immune system are considered. Possible therapeutic potential of phosphodiesterase inhibitors, which have antiplatelet properties and the ability to suppress autoimmune inflammation, are outlined. The authors consider dipyridamole, an inhibitor of phosphodiesterase, as a promising drug.

Organism-Level Tumor Models in Zebrafish Danio rerio.

Development and implementation of adequate organism-level models is one of the key elements in biomedical research that focuses on experimental oncology. Over the last decade, studies using Zebrafish (Danio rerio) have gained in popularity in this area of research. This review describes the various approaches that have been used in developing highly effective models for oncological (clinical term, better cancer or tumor) studies based on D. rerio. Priority is given to transplantation models of cancer and their application to optically transparent D. rerio lines, including clonal ones, and utilization tumors of various origins bearing fluorescent labels. The combination of tumor transplantation at organism-level models in transparent clonal D. rerio lines with fluorescent microscopy, FACS-fractionation of tumor cell subsets, and transcription analysis can result in one of the most promising research approaches in providing new information on tumor formation and growth.

Effect of Nerve Growth Factor on Neural Differentiation of Mouse Embryonic Stem Cells.

The cholinergic, GABAergic, and catecholaminergic neurons derived from mouse embryonic stem cells in a culture medium supplemented with recombinant NGF were phenotyped and scored. NGF stimulated generation of neurons, but not neuronal progenitors from embryonic stem cells and affected the proportion of specific types of neurons in cultures of differentiating embryonic stem cells. These findings open vista to employ NGF for generation of specific neuron types from embryonic stem cells for fundamental and toxicological studies.

[COMPARATIVE EVALUATION OF THE TRANSGENE EXPRESSION EFFICIENCY PROVIDED BY THE MODEL GENETIC CONSTRUCTS OF DIFFERENT STRUCTURE.]

Comparative evaluation of the transgene expression efficiency provided by the model genetic constructs of different structure is an important stage in the development of new expression methods and optimization of the existing expression vectors. However, presently there is no versatile approach to this problem. The goal of this work was to suggest an experimental system for comparative evaluation of the expression efficiency provided by nonviral genetic vectors of various size and topology in human cell cultures. Such system is based on the gene of the green fluorescence protein used as a reporter as well as flow cytofluorometry for evaluation of the expression level and quantitative PCR for adequate selection of the transfection conditions. This system was tested in two model constructs: linear molecule of DNA and plasmid.

[Oligomeric organization of recombinant human neurotrophins expressed in Escherichia coli cells].

Genes of human neurotrophins NGF, BDNF, NT-3 were cloned, and the corresponding proteins and their fragments were expressed in Escherichia coli BL-21 (DE3lambda) cells. Their intracellular localization was determined. The conditions for isolation and purification of the target recombinant proteins and for folding of BDNF and NT-3 precursors were selected. The recombinant proprecursors of human neurotrophines have been shown to possess complex oligomeric structure.

[The regulation of Bacillus intermedius glutamyl endopeptidase biosynthesis in the recombinant Bacillus subtilis strain during sporulation]. / Reguliatsiia biosinteza vnekletochnoi glutamiléndopeptidazy Bacillus intermedius v rekombinantnom shtamme Bacillus subtilis na stadii sporoobrazovaniia.

The growth of the recombinant Bacillus subtilis strain AJ73 carrying the Bacillus intermedius 3-19 glutamyl endopeptidase gene on a multicopy plasmid and the effect of some nutrients on the efficiency of extracellular glutamyl endopeptidase production in the stationary growth phase were studied. In this phase, the concentration of glutamyl endopeptidase in the culture liquid peaked at the 48th and 78th h of cultivation and depended on the composition of the cultivation medium. Unlike the synthesis of glutamyl endopeptidase in the trophophase (i.e., during vegetative growth), which was suppressed by glucose, the synthesis of this enzyme during sporulation was resistant to glucose present in the cultivation medium. A multifactorial experimental design allowed optimal proportions between the concentrations of major nutrients (peptone and inorganic phosphate) to be determined. Inorganic phosphate and ammonium ions augmented the production of glutamyl endopeptidase by 30-150%, and complex organic substrates, such as casein and gelatin, enhanced the production of glutamyl endopeptidase by 50-100%. During sporulation, the production of glutamyl endopeptidase was stimulated by some bivalent cations (Ca2+, Mg2+, and Co2+) and inhibited by others (Zn2+, Fe2+, and Cu2+). The inference is drawn that the regulatory mechanisms of glutamyl endopeptidase synthesis during vegetative growth and sporulation are different.

[The pro-dependent folding of microbial proteolytic enzymes]. / Prozavisimyi folding mikrobnykh proteoliticheskikh fermentov.

Modern published data on the folding of microbial proteolytic enzymes mediated through their pro-parts, or on a so-called pro-dependent folding, are surveyed. Various aspects related with the functioning of pro-sequences are under discussion. The possibility to build up, on the basis of one and the same amino-acid sequence, the special protein conformers involving different pro-peptides is in the focus of attention.