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Background: In the current study, we used the information-hierarchical system approach to examine human metabolism. Metabolism hierarchical structure, beginning from enzyme level, is controlled by the established information principle and divine section numbers. This structure represents a key mechanism of the hierarchical biological clock (HBC) of human body. Time cycles of HBC hierarchical levels are nested into each other according to strict dynamics schemes. The cycles form the HBC scales of 1, 6, 42 seconds, 24 hours (circadian rhythm), and 11 days and jointly make up the precision HBC similar to the conventional countdown (1 s, 1 m, 1 hr, 1 day, and 1 month). Method: Diagnostic/prognostic studies of cancer require a detailed analysis of metabolic HBC disorders. We utilized the information-hierarchical system approach and the information principle in order to analyze HBC run under different dietary patterns. Results: We characterized hierarchical metabolic systems with 24-hour and 11- day operation times. The 24-hour circadian rhythm comprised citrate, pentose, and fatty acid (anabolic or catabolic) biochemical cycles individually. The 11-day cyclicity referred to these cycles combined into a ternary system of the higher-rank hierarchical level. Disorder of systems operation should lead to a radical change in HBC run with subsequent transformation of normal cells into cancer cells. Conclusion: Mutations of metabolic enzyme genes can damage HBC run, thereby leading to cancer and other chronobiological disorders. Organized rhythmicity of external factors (everyday food intake, 11-day periodical dietary pattern, and so forth) made it possible to heal cancer cells per se. Applying a particular kind of diet, the human lifespan could significantly increase. The proposed direction of cancer prevention and treatment can be called a cancer metabolism chronotherapy. [ABSTRACT FROM AUTHOR]

Background: Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a key role in promoting chemoresistance in various cancers. PD-L1 is one of the downstream targets of the Nrf2 signaling pathway. This molecule has some beneficial impacts on tumors growth by inhibition of the immune system. This study aimed to investigate the potential role of the Nrf2-PD-L1 axis in the promotion of oxaliplatin resistance in colon cancer cells. Methods: We examined Nrf2, PD- L1, and CD80 expression in the tumor and margin tissue samples from CRC patients. After that role of the Nrf2-PD-L1 axis in promotion of Oxaliplatin resistance was investigated. Results: Our data revealed that Nrf2 and PD-L1 mRNA expressions were markedly higher in tumor tissues compared to margin tissues. The PD-L1 mRNA expression level was also increased in the resistant cells. However, Nrf2 expression was decreased in SW480/Res cells and increased in LS174T/Res cells. The inhibition of Nrf2 through siRNA treatment in SW480/Res and LS174T/Res cells has decreased the IC50 values of oxaliplatin. Inhibition of the Nrf2 has significantly increased the oxaliplatin-induced apoptosis, and reduced the migration in SW480/Res cells. Conclusion: It is suggested that effective inhibition of Nrf2-PD-L1 signaling pathways can be considered as a novel approach to improve oxaliplatin efficacy in colon cancer patients. [ABSTRACT FROM AUTHOR]