Sedanolide Activates KEAP1-NRF2 Pathway and Ameliorates Hydrogen Peroxide-Induced Apoptotic Cell Death.

Sedanolide is a bioactive compound with anti-inflammatory and antitumor activities. Although it has been recently suggested that sedanolide activates the nuclear factor E2-related factor 2 (NRF2) pathway, there is little research on its effects on cellular resistance to oxidative stress. The objective of the present study was to investigate the function of sedanolide in suppressing hydrogen peroxide (H2O2)-induced oxidative damage and the underlying molecular mechanisms in human hepatoblastoma cell line HepG2 cells. We found that sedanolide activated the antioxidant response element (ARE)-dependent transcription mediated by the nuclear translocation of NRF2. Pathway enrichment analysis of RNA sequencing data revealed that sedanolide upregulated the transcription of antioxidant enzymes involved in the NRF2 pathway and glutathione metabolism. Then, we further investigated whether sedanolide exerts cytoprotective effects against H2O2-induced cell death. We showed that sedanolide significantly attenuated cytosolic and mitochondrial reactive oxygen species (ROS) generation induced by exposure to H2O2. Furthermore, we demonstrated that pretreatment with sedanolide conferred a significant cytoprotective effect against H2O2-induced cell death probably due to preventing the decrease in the mitochondrial membrane potential and the increase in caspase-3/7 activity. Our study demonstrated that sedanolide enhanced cellular resistance to oxidative damage via the activation of the Kelch-like ECH-associated protein 1 (KEAP1)-NRF2 pathway.

Influence on human sleep patterns of lowering and delaying the minimum core body temperature by slow changes in the thermal environment.

STUDY OBJECTIVES: We hypothesized that appropriate changes in thermal environment would enhance the quality of sleep. DESIGN/SETTING: Controlled laboratory study. PARTICIPANTS: Healthy young men (n = 7, mean age 26 years). INTERVENTIONS: Nocturnal sleep structures in semi-nude subjects were compared between a condition where an ambient temperature (Ta) of 29.5 degree C was maintained throughout the night (constant Ta), and a second condition (dynamic Ta) where Ta changed slowly within the thermoneutral range (from 27.5 C to 29.5 degree C). MEASUREMENTS AND RESULTS: Statistically significant (P < 0.05) results included a lower and a later occurrence of minimum core body temperature (Tc), and a longer duration of slow-wave (stages 3+4) sleep in dynamic versus constant T. However, total sleep time, sleep efficiency, the total durations of light (stages 1+2) and rapid eye movement sleep, and the latencies to sleep onset, slow-wave sleep, and rapid eye movement sleep did not differ between conditions. CONCLUSIONS: Lowering the minimum and delaying the nadir of nocturnal Tc increases slow-wave sleep (probably by an increase of dry heat loss); use of this tactic might improve the overall quality of sleep.