Vol 16, No 4 (2021)

"Flexibility” is a physical quality of a person, which is characterized by the ability to perform movements with a large amplitude. Flexibility is important for success in such activities as sports (artistic and rhythmic gymnastics, figure skating, etc.), as well in classical choreography, for example, ballet. Extracellular matrix producing cells and structural proteins of connective tissues take an active part in the formation of mobility of the elements of the musculoskeletal system. Connective tissues are a complex structural and functional system, the components of which are encoded by many genes. Mutations in them lead to various hereditary diseases that increase or decrease "flexibility”. The role of genes in the formation of conditions encoded in the ICD-11 LD28.Z remains unclear - "Syndromes involving connective tissue as the main feature, unspecified”, and their prognostic significance for people experiencing intense physical exertion. The purpose of this review is to generalize modern ideas about the role of genes, extracellular matrix and cells producing it in the formation of such a physical quality as flexibility.

The review considers the main stages of isolating, processing and clinical use of human mesenchymal stromal cells (MSCs). They included: donor selection, selection of the source of MSCs, methods of isolation of cellular suspension from tissue, culturing in vitro for cell biomass propagation, priming of the resulting cell product, timing and ways of its clinical application, selection of the recipient of MSCs. The analysis of the stages of MSCs preparation and conditions for their use was carried out from the position of the influence on the final therapeutic effect of cell therapy in patients (or experimental animals - in preclinical studies). The optimal parameters of work with MSCs at each stage, the possibility to improve their quality / biological activity in order to increase their therapeutic efficacy were determined. The analysis and ways of avoiding the influence of adverse factors associated with the manufacturing and use of MSCs on the effectiveness of cell therapy in patients were given.

The prognosis of glioblastoma (GLB) is poor: the 5-year survival rate is less than 10%. Almost all patients relapse after surgery according to the standard of treatment: resection, radiation therapy, and temozolomide. T reatment options today for relapse are limited, and no amount of therapy prolongs patients' lives. The development of resistance to therapy is associated with the microenvironment and tumor stem cells. Objective: to study the expression of stem cell markers, transcription factors and PD-L1 in malignant gliomas. A retrospective study included 17 patients with high-grade gliomas who underwent surgery. All patients underwent traditional histological examination, immunohistochemical analysis with antibodies to IDH1R132H, BRAF V600E, Ki-67, GFAP, NANOG, Nestin, CD133, SALL4, OCT4, SOX2, CD38, PD-L1, FOXM1, morphometric analysis with calculation of the average ratio cells with antigen expression to the number of all tumor cells. Expression of NANOG was observed in 47% of cases, Nestin - in 88%, CD133 - in 71%, SOX2 - in 100%, CD38 and FOXM1 - in 65%. None of the tumors expressed SALL4, only one OCT4. PD-L1 expression was detected only in 2 cases. Correlation analysis established the presence of significant associations between the expression of Nestin and CD133; FOXM1 and NANOG; Nestin and CD38; Ki-67 and SOX2. The presence of expression of stem cell markers and transcription factors NANOG, Nestin, CD133, CD38, SOX2, FOXM1 in malignant gliomas, in our opinion, dictates further targeted study of these markers on a larger sample and opens up new potential targets for targeted therapy.

In the present study, we used multicolor flow cytometry assay to measure the numbers of various myeloid suppressor cell subpopulations (Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD14+HLA-DRlow/-) in peripheral blood of 51 participants, including 33 patients with viral- and 1 8 patients with «nonviral» (alcoholic or biliary/autoimmune) liver cirrhosis. Patients in both groups had increased proportions of Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD 14+HLA-DRlow/-cells which levels did not depend on the type and replication of the virus in viral liver cirrhosis. In viral liver cirrhosis, the relative numbers of Lin-HLA-DR-CD33+cells directly correlated with the albumin levels (Rs=0.45; p=0.029). In «nonviral» group an inverse relationship was found between these indicators (Rs = -0.56; p=0.02), in addition the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells directly correlated with disease severity scores (Child-Pugh and MELD) direct correlation of the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells with the disease severity scores (Child-Pugh and MELD). Comparison of the initial content of myeloid suppressors with the response to complex therapy (that included autologous bone marrow-derived cell transplantation), showed that in viral liver cirrhosis, the proportion of Lin-HLA-DR-CD33+cells was characterized by a prognostic significance and, at values <1.9%, allowed to predict a decrease in the Child-Pugh score at 12 month follow-up with a sensitivity of 83.3% and a specificity of 71.4%. The data obtained indicate the relationship between myeloid-derived suppressor cells and albumin levels, disease severity and response to therapy, suggesting myeloid suppressors as a new therapeutic target in the liver cirrhosis.