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Since the 1990s, when it was demonstrated by Hammel and others that liver fibrosis is reversible, researchers and physicians actively search for new antifibrotic therapies. In recent years, knowledge of liver fibrosis pathophysiology has greatly advanced and new cellular and molecular mechanisms were described. The cells that determine extracellular matrix components distribution are myofibroblasts, but their origin is diverse. They can be activated hepatic stellate cells (HSCs), portal fibroblasts (PF), or circulating mesenchymal stem cells of the bone marrow. Among large number of substrates to inhibit activation, to inhibit proliferation of myofibroblasts, and to induce their apoptosis we, chose curcumin and gliotoxin. Primarily, in the current work, we optimized the explantation culture method for isolation of hepatic myofibroblasts and received two different cultures—myofibroblasts of HSC and PF origin. Exposition of 50 μM curcumin and 0.1 μM gliotoxin was the most optimal; we observed suppression of hepatic myofibroblast activation and inhibition of their proliferation. These results extend the current knowledge of the cells within the liver fibrogenic populations and prove inhibitory influence of biologically active substances (curcumin and gliotoxin) on portal myofibroblasts.

Diverse transcription factors influencing cell differentiation are often chosen as markers of β cell progenitors. One of these transcription factors is MafA, which according to data in literature activates the expression of insulin gene in β cells. Other data support the hypothesis that MafA is required solely for the regulation of insulin secretion by β cells of adult islets and is not involved in the development of islet cells. In this paper, we study the role of MafA through both examination of human pancreas ontogeny and comparison of these data with dynamic changes in the population of insulin-positive and glucagon-positive cells. The aim of this research was the immunohistochemical analysis of MafA, insulin, and glucagon expression during human pancreas ontogeny. The research was conducted on whole embryos and isolated human fetal organs, obtained as a result of either miscarriage or legal medical abortion with voluntary consent of patients, and also on autopsy material from infant and adult human pancreas. As a result of this study, it was found that, during the ontogeny of human pancreas, the first MafA-positive cells appear in the islets at 12.5 weeks of gestation, that is, later than both insulin-positive cells (11.5 weeks of gestation) and glucagon-positive cells (8.5 weeks of gestation). No MafA-positive cells were found in the epithelium of pancreatic ducts. The number of MafA-positive cells in the islets increases during pancreatic organogenesis. The results of our research do not allow us to regard MafA as a marker of undifferentiated progenitors of islet cells. Based on this, we believe that the results obtained in this study are a supplementary contribution to the hypothesis that relates MafA to the markers of adult β cells.

Alcoholic liver disease is a huge medical and social problem that leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Unfortunately, the last stages of the disease do not have efficient treatment, except liver transplantation, and require development of new therapeutical approaches. Transplantation of stem cells might be the most promising approach. In our research, we studied transplantation of autologous hematopoietic stem cells (HSC) into the celiac trunk of patients with alcoholic liver cirrhosis. In this article, we pay particular attention to proliferation and apoptosis—two fundamental processes, which determine the fate of regeneration. Liver biopsy specimens before treatment, 3 and 12 months after transplantation of HSC, were stained immunohistochemically with antibodies against PCNA and Bcl-2. The results showed that treatment was safe and effective, hepatocytes increased proliferation, and inflammatory cells decreased antiapoptotic activity, signifying improvement in liver regeneration. However, effect of treatment after 12 months decreases and requires repeated HSC transplantation.

Effect of poly(succinimide) (PSI) and poly(aspartic acid) (PASP) on free radical reactions and cell viability was assessed. Molecular weight (MW) of PASPs was determined by static light scattering technique and found as 3.9 and 8.3 kDa. Among PSIs and PASPs, only poly(aspartic acid) with higher MW was found to inhibit formation of hydroxyl-radical in Fenton’s reaction, although each polymers studied were not able to eliminate diphenylpicrylhydrazyl radical. PASPs were almost non-toxic for 3 T3 fibroblasts and PC-3 cells (IC50 ≫ 3 mg/mL), whereas PSIs diminished cell viability with different IC50 values depending on cell type and polymer MW. Our preliminary data indicate the MW dependence of bioactivity of l-aspartic acid-derived polymers designed as drug carriers and biocompatible materials.

C-kit—a stem cell receptor, or CD117, is one of the markers of human pancreatic endocrinocyte progenitor cells. Its important role in the proliferation and differentiation of pancreatic endocrine cells during human prenatal development has already been proven. However, the presence and role of c-kit-positive cells in adult pancreatic islets remains unclear. The purpose of our study was to establish the presence of c-kit-positive cells in the adult pancreatic islets and to assess whether they retain the ability to proliferate during a lifetime. We studied pancreatic autopsies of adults aged 50 to 70 years, which were obtained in pathology departments of Kazan hospitals. Samples of the pancreas were embedded in paraffin using standard techniques. Paraffin sections of the pancreas were stained immunohistochemically with commercial antibodies against c-kit, insulin, glucagon, and Ki-67. Few c-kit-positive cells simultaneously secreting insulin or glucagon were detected in all samples studied. These data suggest that such cells are in a state of differentiation into endocrinocytes, but no proliferation of c-kit-positive cells was observed.

Peripheral arterial diseases are characterized by a progressing tissue ischemia which results in the invalidization of patients. The aim of our research was to study the morphological effects of autologous peripheral blood stem cells intramuscular injection into patients with peripheral arterial disease. Peripheral blood stem cells were transplanted intramuscularly into a 48-year-old male patient with peripheral arterial disease stage IIb by Fontaine. The biopsies of his gastrocnemius muscle were taken before the stem cells were transplanted and 3 months after transplantation. These biopsies were stained with H&E and also with antibodies against CD34, myogenin, caspase 3, and bcl-2. Immunohistochemical study results showed an increase of capillary density of 32.7 % (P = 0.005). In muscular biopsies obtained before therapy, we identified single myogenin+ myosatellite cells, while 3 months after transplantation we detected the presence of cells with myogenin-positive nuclei and multinucleated myotubes. We also observed the formation of young myogenin+ muscle fibers with central nuclei. There was no significant difference in the expression of caspase-3 before transplantation and 3 months after transplantation. An increased number of bcl-2+ myosatellite cells, myotubes, and muscle fibers were detected after transplantation. The patient’s ankle-brachial index increased by 13.56 % (0.59 before and 0.67 3 months post transplantation). The patient’s pain-free walking distance by 89.97 % (from 59.56 to 113.77 m). Control arteriograms showed the formation of new collaterals. Transplanted autologous peripheral blood stem cells stimulated the formation of new capillaries, the activation of myosatellite cells and bcl-2 expression in muscle fibers.

The application of natural antimutagens and antioxidants, particularly those derived from higher plants has been seen as a promising approach to the protection of human health. In this work, we studied methanolic extracts from Sansevieria cylindrica, Sansevieria trifasciata, and Polianthes tuberosa plants focusing on their antioxidative and antimutagenic capacities based on the following parameters: inhibitory activity on lipid peroxidation, suppressing ability on direct-acting mutagen sodium azide-induced mutagenesis in Salmonella typhimurium cells. A clear dose-dependent decrease in lipid peroxidation was observed with all the extracts tested. Extracts from leaves of P. tuberosa and rhizomes of S. cylindrica and S. trifasciata (1 mg/mL) displayed the highest antioxidant effect. At the same time, extracts from rhizomes of S. cylindrica and S. trifasciata significantly reduced the sodium azide-induced mutations. The highest antimutagenic activity (76 %) in the S. typhimurium TA100 strain was obtained for the S. cylindrica rhizomes extract (1 mg/plate). We propose that the observed protective effects of plant extracts tested may correspond to a synergic participation of several secondary metabolites and mainly to polyphenolic compounds.