LIVER DISEASES AND PATHOLOGIES

Аннотация

As a result of the work carried out, data were obtained on the role of population risk factors, as well as some interleukins (receptor for interleukin-1 type II and interleukin-6) in the process of bone tissue remodeling and the development of osteoporosis in early rheumatoid arthritis. For the first time, the influence of the parameters of the course of early rheumatoid arthritis, including the activity and serotype of rheumatoid factor (RF) and the presence of antibodies to cyclic citrullinated peptide (ACCP), on the change in the state of bone mineral density and the change in bone metabolism markers in patients with early rheumatoid arthritis depending on gender and the presence of menopause has been shown. Based on the data of regression analysis, the most significant factors influencing the change in bone mineral density in patients with early rheumatoid arthritis have been identified. For the first time, it has been shown that along with population risk factors, factors associated with the underlying disease (parameters of the course of early rheumatoid arthritis) have a significant effect. Key words: cell, senescence, SASP, DDR, inflammaging, liver, elderly. Introduction. It implies the harmful influence of senescent cells on younger cells through reactive forms of oxygen (ROS). They cause DNA damage and introduce non-senescent cells into permanent cell cycle arrest. In this way, the proliferative capacity of cells is reduced. The existence of “the bystander effect” was proven by determining senescence markers in younger cells, and it is interesting that in epithelial cells and cancer cells, this effect more often stimulates proliferation, which is the opposite of what was previously describe. It has been proven that SASP products of human diploid fibroblasts can lead to the proliferation and transformation of premalignant epithelial cells into malignant ones. The uniqueness, complexity and importance of SASP are also in the fact that it abounds in a multitude of effects, some of which are contradictory. For example, another paracrine effect of SASP is the stimulation of anti-tumor immunity. SASP paracrine products trigger the so-called “senescence surveillance” composed of components of the innate and adaptive immune response, which has a role in the removal of senescent cells, the suppression of tumor formation and their regression. SASP components actually enable tissue infiltration by natural killer (NK) cells that then eliminate senescent and tumor cells. In addition, individual SASP components play a role in changes in tissue morphology. For example, IL-1β, in addition to having a pro-inflammatory role, participates in the modulation of the tissue microenvironment. In a study conducted by Krizhanovsky et al. on mice liver models, chronic toxic liver damage is accompanied by the activity of hepatic stellate cells in terms of proliferation and formation of profibrotic secretome. This leads to the accumulation of hepatic stellate cells in which senescence is induced, and their secretome changes into a secretome similar to SASP. It is characterized by the presence of matrix-degrading enzymes, which limits the degree of liver fibrosis. Senescent hepatic stellate cells on the end are removed by the “senescence surveillance” mechanism. 39 ILM-FAN VA INNOVATSIYA ILMIY-AMALIY KONFERENSIYASI in-academy.uz/index.php/si After all, we can conclude that cellular senescence is very complex as it involves many different pathways, many molecules of different origins, enzymes and transcription factors. Therefore, it is necessary to take into account several different markers, as well as their combinations, in an attempt to detect senescence. As we have seen, SASP involves the production of numerous pro-inflammatory cytokines that play different roles in multiple processes that are vital for the cell. Their main role is in promoting the occurrence of chronic inflammation in tissues. According to numerous studies, chronic inflammation is an irreplaceable factor in aging process and the onset of age-related diseases such as dementia, atherosclerosis, osteoporosis, cancers, metabolic syndrome and vascular diseases. It leads to the activation of numerous proinflammatory signaling pathways. In light of the connection between cellular aging and inflammation, the term “inflammaging” was introduced. This term was created after Fagiolo et al. showed in that peripheral blood mononuclear cells of elderly people produce a higher amount of pro-inflammatory cytokines compared to cells of younger people. After that, this phenomenon was the subject of numerous studies that came to the conclusion that “inflammaging” is associated with the aforementioned increased production of pro-inflammatory cytokines in the elderly, genetic components and frequent subclinical viral infections seen in the elderly (Epstein Barr virus and cytomegalovirus infection). Inflammation as part of “inflammaging” is the so-called “sterile inflammation”,