Aging is one of the most serious factors for central nervous dysfunctions, which lead to cognitive impairment. New highly effective drugs are required to slow the development of cognitive dysfunction. This research studied the effect of dimethyl fumarate (DMF), methylene blue (MB), and resveratrol (RSV) on the cognitive functions of 15-month-old mice and their relationship to the maintenance of mitochondrial quality control in the brain and the bacterial composition of the gut microbiome. We have shown that studied compounds enhance mitochondrial biogenesis, mitophagy, and antioxidant defense in the hippocampus of 15-month-old mice via Nrf2/ARE pathway activation, which reduces the degree of oxidative damage to mtDNA. It is manifested in the improvement of short-term and long-term memory. We have also shown that memory improvement correlates with levels of Roseburia, Oscillibacter, ChristensenellaceaeR-7, Negativibacillus, and Faecalibaculum genera of bacteria. At the same time, long-term treatment by MB induced a decrease in gut microbiome diversity, but the other markers of dysbiosis were not observed. Thus, Nrf2/ARE activators have an impact on mitochondrial quality control and are associated with a positive change in the composition of the gut microbiome, which together lead to an improvement in memory in aged mice.

Renal cell carcinoma (Rcc) is the most common form of kidney cancer, accounting for about 90 % of cancers in the kidney. clear cell renal cell carcinoma (ccRcc) is the most common histological type of Rcc. clear cell renal cell carcinoma is characterized by specific genomic and transcriptomic aberrations in the tumor. We performed a targeted sequencing of key oncogenes and a genome-wide expression study in 58 patients with Rcc belonging to a population of the western part of the Russian Federation. the integrative analysis of genomics and transcriptome data revealed that the NFkβ nuclear complex, ERBB2 receptor, and tP53 transcription factor were the key regulators of observed changes in the expression. We also carried out the analysis of the mutational landscape in key genes associated with cancer. We found the difference in the molecular mechanisms of Rcc between different populations, since the detected expression regulators were not previously described as expression mediators in Rcc. since the ERBB2 receptor is a highly attractive target for therapeutic interventions of breast cancer, we will eventually be able to develop new treatment modalities for Rcc.