Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis. Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis. Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay. Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas. Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

MicroRNAs are evolutionarily conserved small non-coding RNA molecules 18–25 nucleotides long found in plants, animals, and some viruses that are involved in the transcriptional and post-transcriptional regulation of gene expression by RNA interference. Due to the unique biochemical and biophysical properties of the microRNA-associated catalytic protein complex RISC (RNA-inducible gene knockdown complex), these molecules carry out epigenetic regulation of the expression of a surprisingly large number of regulatory targets, including in humans. This article reviews the fundamentals and recent discoveries in the field of molecular mechanisms of microRNA functioning, the role of microRNA in the pathogenesis and course of socially significant diseases and diseases that occupy key positions in the structure of population mortality, namely, cardiovascular diseases, malignant neoplasms, human immunodeficiency virus (HIV). Also, this article presents some of the latest achievements in bioengineering and pharmacology in the development of new drugs based on RNA interference.

The aim of the study was to investigate the mechanisms of action of multipotent mesenchymal stromal cells (MMSCs) in a model of tetrachloromethane-induced liver fibrosis in mice. The experiments were performed on 50 mice. MSCs isolated from mouse placenta choriona were used in the study. MSCs were transplanted at a dose of 1 million cells into the tail vein. α-SMA, MMP-9, MMP 13, and TIMP-1 positive regions were analyzed by immunohistochemical method to evaluate the mechanisms of MMSCs action. Sirius red dye was used for connective tissue staining. HGF and TGF-β were determined by immunoassay in liver homogenate. We obtained that transplantation of MMSCs leads to a decrease in the area of α-SMA, TIMP-1 positive regions, an increase in the number of cells expressing MMP-9 and MMP 13. An increase in the level of hepatocyte growth factor and a decrease in transforming growth factor beta in liver homogenate after hMSCs transplantation in liver fibrosis was found. The results of the study demonstrated the efficacy of placental MMSCs in liver fibrosis. The antifibrotic mechanisms of action of hMSCs can include the ability to increase the expression of HGF, decrease the level of TGF-β, increase the production of matrix metalloproteinases-9 and -13, as well as the ability to inhibit the expression of tissue inhibitor of matrix metalloproteinases type 1.

Aim. To study the changes of splenic morphometric parameters in aged laboratory animals exposed to ionizing radiation in the dose of 4Gr after multipotent mesenchymal and hematopoietic stem cells transplantation. Methods. The experiments were conducted on 72 white male laboratory mice at the third year of life with the body weight of 50 g. Multipotent mesenchymal stem cells and hematopoietic stem cells were obtained from 8 laboratory female mice with the body weight of 30 g aged 3-4 months, the gestation term was 14 days. The first group (36 animals exposed to radiation) was subdivided to 2 subgroups of 18 animals each. The suspension of multipotent mesenchymal stem cells (6 000 000 cells/kg) and hematopoietic stem cells (330 000 cells/kg) was introduced as single intravenous injection to the experimental subgroup (18 animals) 1 hour after the animals were exposed to radiation. The animals of control subgroup (18 animals) were injected 0.2 ml of normal saline. The second group included two subgroups 18 mice each that underwent the same procedure without being exposed to radiation. 9 animals from each group were withdrawn from the study at 1st and 7th day each. The lymphoid follicle gross area, area of the T-cell and B-cell zones, general numbers of cells in the red pulp of spleen, including erythrocyte and lymphocyte count, were measured in splenic histologic specimens using the morphometric «BioVision 2008» software. Results. It was shown that on the 7th day after exposure to ionizing radiation followed by stem cells transplantation, the area of thymus-independent zone of lymphoid follicle restored back to normal ranges. The effect of multipotent mesenchymal stem cells and hematopoietic stem cells transplantation also resulted in the increase of the number of cells in the red pulp of spleen. There were no significant changes observed in numbers of erythroid cells and white blood cells in the spleen red pulp compared to control subgroup. At the same time, the leukocyte number in the red pulp of spleen restored to normal values. Conclusion. The restoration of the basic morphometric parameters in spleen of aged laboratory animals exposed to ionizing radiation may be explained be increased homing of splenic colony-forming units with subsequent activation of extramedullary hematopoiesis in spleen, and apoptosis-reducing effect of multipotent mesenchymal stem cells.

Цель исследования – изучение влияния микроРНК mir162a на жизнеспособность опухолевых клеток линии остеосаркомы SAOS-2. Методика. Исследования выполнены на клеточной линии SAOS-2. Была произведена трансфекция микроРНК mir162a в дозе 90 пмоль. Через 24, 48 и 72 ч после трансфекции методом флуоресцентной микроскопии производился подсчет жизнеспособных клеток, клеток в состоянии некроза и апоптоза, а также оценивался уровень аутофагии. Результаты. Трансфекция клеток SAOS-2 микроРНК mir162a через 24, 48, 72 ч приводила к снижению доли жизнеспособных клеток, увеличению доли клеток с признаками апоптоза и некроза по сравнению с контрольными образцами. Через 24 ч с момента трансфекции процент жизнеспособных клеток в опытных образцах был ниже чем в контрольных на 29,3%, через 48 ч – на 33,9%, через 72 ч – на 47,4%. Трансфекция SAOS-2 микроРНК mir162a приводила к четырехкратному снижению активности аутофагии. Заключение. Полученные результаты свидетельствуют о наличии у микроРНК mir162a терапевтического потенциала в качестве средства патогенетической терапии злокачественных опухолевых заболеваний.