Vol 66, No 1 (2024)

The cause of many serious illnesses, including diabetes, obesity, osteoporosis and neurodegenerative diseases is chronic inflammation that develops in adipose tissue, bones or the brain. This inflammation occurs due to a shift in the polarization of macrophages/microglia towards the pro-inflammatory phenotype M1. It has now been proven that the polarization of macrophages is determined by the intracellular level of autophagy in the macrophage. By modulating autophagy, it is possible to cause switching of macrophage activities towards M1 or M2. Summarizing the material accumulated in the literature, we believe that the activation of autophagy reprograms the macrophage towards M2, replacing its protein content, receptor apparatus and including a different type of metabolism. The term reprogramming is most suitable for this process, since it is followed by a change in the functional activity of the macrophage, namely, switching from cytotoxic pro-inflammatory activity to anti-inflammatory (regenerative). Modulation of autophagy can be an approach to the treatment of oncological diseases, neurodegenerative disorders, osteoporosis, diabetes and other serious diseases.

Redox-sensitive NRF2 transcription factor is a target gene of microRNA miR-155. miR-155 mimic was transfected in dacarbazine-resistant melanoma cells. NRF2 expression levels were down-regulated in miR-155-overexpressed cells independently of oxidative stress induced by hydrogen peroxide. NRF2 suppression was associated with a decrease of melanoma cells viability. As a result, miR-155-mediated NRF2 overexpression that regulate intensity of a cell antioxidant processes can be associated with cancer cell survival leading to drug resistance. NRF2 repression by miR-155 highlighted a potential for NRF2 down-regulation as an approach in anticancer therapy.

Prostate cancer (PCa) is one of the most common oncological diseases, which goes through two stages in its development. The first stage, localized prostate cancer, can proceed indefinitely in a dormant form that does not require active medical intervention, or suddenly turn into an aggressive metastatic form with lethal outcome. The pathogenesis of the transition of the dormant form of PCa to the metastatic form remains not fully understood. The signaling pathways of the tumor suppressor pRb and the proto-oncogene β-catenin are probably the most involved in the pathogenesis of PCa but the role of their interaction in the pathogenesis of prostate cancer has not been studied. The publication on the pathogenesis of tumors in other tissues suggests that pRb may lose some properties of a tumor suppressor at the initial stage of PCa development due to its interaction with β-catenin that enables tumor cells to gain competitive advantages for reproduction. In this work, we have shown that the RB and β-catenin (CTNNB1) genes are well expressed in tumor and normal prostate tissue. Unlike β-catenin, pRb is not detected by immunoblotting in tumor and normal prostate tissue, but is easily determined in this way in extracts of control T98G cells. Co-immunoprecipitation with antibodies to pRb from extracts of tumor and normal prostate tissue makes it possible to detect this protein and β-catenin by subsequent immunoblotting, which indicates the physical interaction of these proteins in prostate tissue. On the other hand, immunoprecipitation of β-catenin with antibodies to its C-terminal fragment does not detect this protein in prostate extracts by subsequent immunoblotting using the same antibody. In contrast to prostate tissue, β-catenin is readily detected by immunoprecipitation combined with immunoblotting in T98G control cell extracts. The obtained data suggest that pRb and β-catenin physically interact with each other in cells of different tissue specificity. In T98G cells, this interaction probably occurs through the C-terminal fragment of β-catenin, but in prostate cells it occurs in a different way, since the C-fragment of β-catenin is shielded from such interaction, possibly due to its physical association with pRb.

The work is devoted to the study of neurodegenerative changes in the ultrastructural organization in CA1 of the hippocampus in adult rats subjected to prenatal hyperhomocysteinemia (pHHC). Electron microscopy revealed signs of pathological changes in the CA1 neural networks of the dorsal hippocampus in adult pHHC rats, unlike in control ones: cell degeneration, destruction of the myelin sheath of axons, and destruction of axial cylinders of basal and apical dendrites directed from the pyramidal neurons to the Schaffer collaterals and the temporo-ammonic tractus. In control animals, a dense network of varicose extensions in the distal branches of the dendrites in the stratum oriens and stratum radiatum layers was detected using the Golgi method, providing an increased area for synaptic contacts. In pHHC rats, significant destructive changes are found in these dendritic varicosities: destruction of mitochondrial cristae and appearance of huge cisterns. In adult rats, pHHC completely negated the preference for the smell of valerian, which is a physiologically significant stimulus in the norm, indicating the negative effect of pHHC on the work of the olfactory analyzer, whose activity is closely connected with the hippocampus. These findings indicate the deleterious effect of homocysteine on the formation of the dorsal hippocampus as a morphological substrate for the integration of the incoming impulses.