Second-Generation JK-206 Targets the Oncogenic Signal Mediator RHOA in Gastric Cancer.

Ras homologous A (RHOA), a signal mediator and a GTPase, is known to be associated with the progression of gastric cancer (GC), which is the fourth most common cause of death in the world. Previously, we designed pharmacologically optimized inhibitors against RHOA, including JK-136 and JK-139. Based on this previous work, we performed lead optimization and designed novel RHOA inhibitors for greater anti-GC potency. Two of these compounds, JK-206 and JK-312, could successfully inhibit the viability and migration of GC cell lines. Furthermore, using transcriptomic analysis of GC cells treated with JK-206, we revealed that the inhibition of RHOA might be associated with the inhibition of the mitogenic pathway. Therefore, JK-206 treatment for RHOA inhibition may be a new therapeutic strategy for regulating GC proliferation and migration.

Associations of Abnormal Sleep Duration with Occupational and Leisure-time Physical Activity in the Working Population: A Nation-wide Population-based Study.

BACKGROUND: The present study investigated the association between two domains of physical activity (occupational physical activity [OPA] and leisure-time physical activity [LTPA]) and sleep duration. METHODS: We investigated 3,421 paid workers from the Korea National Health and Nutrition Examination Survey, 2014-2015. Sleep duration was categorized into three categories (short for less than 5 h, optimal for 5-9 h, and long for more than 9 h). OPA and LTPA were defined in terms of answers to relevant questions. Odds ratios were calculated for sleep duration according to each physical activity domain using multinomial logistic regression models. RESULTS: There were 464 subjects (13.6%) who showed short sleep duration, and 169 subjects (4.9%) who showed long sleep duration. Prevalence of OPA and LTPA was higher in male workers than in female workers (for OPA: 3.67% and 1.76%, respectively, p = 0.0108; for LTPA: 16.14% and 6.07%, respectively, p < 0.0001). The odds ratio of OPA for long sleep duration in female workers was 3.35 (95% confidence interval, 1.37-8.21). Otherwise, LTPA was not associated with sleep duration in female paid workers, nor both physical activity domains in male paid workers. CONCLUSION: Female paid workers with work-related physical activity were at risk of oversleeping. These findings also suggested that physical activity has distinct associations with sleep duration according to the physical activity domains and sex.