Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.
Today, considerable progress in the renal cell carcinoma (RCC) treatment has been made due to development of targeted and immunotherapeutic approaches to the RCC treatment, especially in metastasising carcinoma. In the early stages of RCC, it is possible to use partial or total surgical nephrectomy, but in metastases development, the range of efficient treatment methods is dramatically limited. Appearance of targeted drugs like PD-1 and CTLA-4 receptors and their ligands' inhibitors in clinical practice has significantly increased the total survival rate of patients with renal cell carcinoma. Emergence of adoptive cell therapy has opened new possibilities and prospects in RCC treatment. Previously activated in vitro cells are used there, which provides antineoplastic activity. For example, it could be antigen-specific cytotoxic T-lymphocytes (CTL), lymphokine-activated natural killers (LAK-NK-cells) and tumour-infiltrating lymphocytes (TILs). In this review, the authors specified the main molecular markers, associated with RCC; and signalling pathways (VEGFR-and EGFR-signalling pathway), which directly take part in carcinogenesis. The paper also looks at clinically applicable targeted immune drugs and the principle of their effect on tumorous cells. Besides, modern clinical studies of cell drugs have been considered. At the moment, there are a number of variants of targeted and immune drugs for the metastatic RCC treatment. Patients have no opportunity to use all the available agents because of their cost and toxicity level. For the most efficient treatment of patients with diagnosed metastatic RCC, it is necessarily to carry out risk stratification and prognostic factors for the response to treatment.
Introduction: To investigate the influence of secretomes from native and dexamethasone-treated adipose-derived multipotent mesenchymal stromal cells (MMSC) on the proliferation of mononuclear cells (MNCs) and on their expression of phospho-NF-κB p65 in vitro. Materials and Methods: MMSCs were isolated from the fat of 5 healthy donors. The cells were grown in culture up to passage four, then treated with dexamethasone for 3 hours, washed off the preparations, and incubated in a serum-free medium for 48 hours. Some of the cells were not treated with dexamethasone. Supernatants from cell cultures were concentrated by ultrafiltration, standardized by the content of galectin-1, sterilized, and added to MNCs from peripheral blood of 8 healthy donors. MNCs were isolated in a Ficoll density gradient according to a standard protocol. The expression of phospho-NF-κB p65 and Ki-67 in MNCs under the influence of MMSC secretomes in isotypic and negative controls was determined on a flow cytometer. Results and Discussion: The expression of phospho-NF-kκB p65 and Ki-67 is decreased by the MMSC secretome. At the same time, a statistically significant decrease in phospho-NF-κB p65 by 36.2% (p < 0.05) is observed when using a secretome from native cells. Ki-67 expression is reduced by 42.3% (p < 0.05) under the influence of a secretome from dexamethasone-treated MMSCs. Conclusion: The MMSC secretome, as well as MMSCs themselves, has an anti-inflammatory effect due to the effect on the expression of the active form of NF-κB and the proliferative activity of mononuclear cells. At the same time, pretreatment of cells with dexamethasone reduces the effect on phospho-NF-κB expression and increases the inhibitory effect on MNC proliferation.
A model test-system was developed for validation in vitro of antihypoxic and endothelio-differentiating activity of newly created glycogen synthase kinase-3 inhibitors in comparison with the reference drug β4-thymosin.
The aim of this study was to evaluate the effect of treatment with valproic acid, erythropoietin, and dexamethasone on the anti-inflammatory and immunosuppressive activity of the secretome of adipose-derived multipotent mesenchymal stromal cells (MMSCs) in an in vitro experiment.Materials and methods. MMSCs were isolated from the fat of 6 healthy donors. The cells were grown in the culture up to passage 4. Then they were treated with valproic acid, erythropoietin or dexamethasone for 3 hours, washed from preparations, and incubated in a serum-free medium for 48 hours. Some of the cells were not treated with preparations. Supernatants from the cell cultures were concentrated by ultrafiltration, and protein standardization was performed using a nanophotometer. Then the supernatants were sterilized and added to mononuclear cells from peripheral blood of 8 healthy donors. The mononuclear cells were isolated by Ficoll density gradient centrifugation according to the standard protocol. Concentrations of TNFα, IL-2, IL-4, IL-6, IL-10, and IFNγ cytokines in 24-hour cultures and IL-9, IL-10, IL-17A, and IL-21 cytokines in 48-hour cultures were determined using multiplex analysis.Results. The production of IL-2, IL-6, TNFα, and IL-10 was reduced by the secretome of MMSCs treated with valproic acid. The production of IL-2, IL-6, and TNFα decreased during incubation of the mononuclear cells with the secretome of MMSCs treated with erythropoietin. The secretome of dexamethasone-treated MMSCs suppressed the production of IFNγ, IL-1β, IL-1ra, IL-2, IL-6, IL-9, IL-10, and IL-17A. No statistically significant differences were revealed in the production of IL-4, IL-5, IL-9, and IL-21.Conclusion. Among the studied inducers, dexamethasone enhanced the anti-inflammatory and immunosuppressive activity of MMSCs the most, which was manifested through the effect of their supernatants on peripheral blood mononuclear cells.
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