The p53 Protein Family in the Response of Tumor Cells to Ionizing Radiation: Problem Development

Survival mechanisms are activated in tumor cells in response to therapeutic ionizing radiation. This reduces a treatments effectiveness. The p53, p63, and p73 proteins belonging to the family of proteins that regulate the numerous pathways of intracellular signal transduction play a key role in the development of radioresistance. This review analyzes the p53-dependent and p53-independent mechanisms involved in overcoming the resistance of tumor cells to radiation exposure.

Detection of antinuclear antibodies targeting intracellular signal transduction, metabolism, apoptotic processes and cell death in critical COVID-19 patients

Background The heterogeneity of COVID-19 lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) has been shown to be the leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Results Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Initial screening for antinuclear antibodies (ANA) IgG revealed that 1.6% (2/126) and 4% (5/126) of ICU COVID-19 cases developed strong and moderate ANA levels, respectively. However, all the non-ICU cases (n = 273) were ANA negative. The high ANA level was confirmed by immunofluorescence (IFA) and large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). Indeed, the majority of the samples showed "speckled" ANA pattern by microscopy, and we demonstrate that samples of ICU patients with strong and moderate ANA levels contain autoantibody specificities that predominantly targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death; further denoting reactivity to nuclear and cytoplasmic antigens. Conclusion Our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of Covid-19.

TRIM65 in White Matter Lesions, Innate Immunity and Tumor

Most of the tripartite motif (TRIM) family proteins have E3 ubiquitin ligase activities and also have a variety of functions in cellular processes such as intracellular signal transduction, apoptosis, innate immunity and carcinogenesis. TRIM65 is a member of the TRIM family. More and more evidences have shown a unique and importance of TRIM65 protein in the occurrence and development of some diseases. In this review, the importance on TRIM65 in white matter lesions, innate immunity and the effect of tumors was mainly reviewed.

Targeted Regulation of Intracellular Signal Transduction in Regeneration-Competent Cells: A new Direction for Therapy in Regenerative Medicine

A scientific and theoretical justification for developing the original direction for targeted therapy in regenerative medicine - "Strategy of pharmacological regulation of intracellular signal transduction in regeneration-competent cells" is presented. It is proposed to use intracellular signaling molecules, which play an important role in regulating the proliferative and differentiation status of progenitors and microenvironment cells, as targets of drugs with regenerative activity. The selectivity of stimulation of the regeneration of individual tissues is determined by the peculiarities of intracellular signaling in different progenitor cells and/or tissue-specific expression of certain types and isoform signaling molecules. The results of their basic research on the role of some signaling molecules (potential targets) in regulating the cell cycle of the progenitors of different types and the functioning of the tissue microenvironment cells are given. Experimental models of some pathological conditions (CNS, skin, and hematopoietic tissue) show the effectiveness of implementing the proposed concept of pharmacotherapy. The results are fundamental to the creation of novel targeted drugs for the treatment of degenerative diseases.