Downregulation of chemoresistance by claudin-14 silencing in human colorectal cancer cells.

An exceptional expression of claudins (CLDNs), tight junction (TJ) proteins, is observed in various solid cancer tissues. However, the pathophysiological roles of CLDNs have not been clarified in detail. CLDN14 is highly expressed in human colorectal cancer (CRC) tissues and cultured cancer epithelial cells. We found CLDN14 silencing decreased cell viability without affecting spheroid size in the three-dimensional (3D) spheroid model of DLD-1 cells derived from human CRC. Mitochondria activity and oxidative stress level were reduced by CLDN14 silencing. Furthermore, CLDN14 silencing decreased the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target antioxidative genes. CLDN14 was colocalized with ZO-1, a scaffolding protein in the TJ. CLDN14 silencing induced the disruption of TJ barrier such as the reduction of transepithelial electrical resistance and elevation of fluxes of small molecules including glucose in two-dimensional (2D) cultured model,. The depletion of glucose induced the elevation of ROS generation, mitochondria activity, and Nrf2 expression. These results suggest that CLDN14 increases Nrf2 expression in spheroids mediated via the formation of paracellular barrier to glucose. The cytotoxicities of doxorubicin, an anthracycline anticancer drug, and oxaliplatin, a platinum-based agent, were augmented by an Nrf2 activator in 2D cultured cells. The anticancer drug-induced toxicity was enhanced by CLDN14 silencing in 3D spheroids. We suggest that CLDN14 may potentiate chemoresistance mediated by the suppression of paracellular glucose permeability and activation of the Nrf2 signaling pathway in CRC cells.

The Relationship between Insomnia and Lifestyle-Related Diseases among Japanese Male Truck Drivers.

Previously, insomnia and adverse lifestyle were prevalent among truck drivers, but the association between the two remains unknown in this particular occupational cohort. This study aimed to examine the relationship between insomnia and lifestyle-related diseases among truck drivers. We investigated 875 male truck drivers of the Japan Truck Association, Akita branch, as of July 2020. The definition of insomnia was based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Data from a self-administered questionnaire were merged with health records and health insurance claims data of 2020. In total, 40.1% had either one of the lifestyle-related diseases including hypertension (29.7%), diabetes mellitus (11.7%), and dyslipidemia (24.8%), whereas according to ICSD-3, 13.2% had insomnia. Multivariate logistic regression models demonstrated that individuals with insomnia had approximately 2-fold increased risk of having at least one lifestyle-related disease (p < 0.001), hypertension (p = 0.0027), diabetes mellitus (p = 0.0654) and dyslipidemia (p < 0.001). Occupational characteristics including daily driving hours, driving distance, and travel days were not associated with any lifestyle-related diseases except for an association between short-haul and at least one disease. In conclusion, insomnia is significantly associated with increased risks of lifestyle-related diseases among male truck drivers in Japan.

Diabetes and anxiety were associated with insomnia among Japanese male truck drivers.

OBJECTIVE/BACKGROUND: Insomnia among truck drivers may contribute to traffic accidents. We previously reported that truck drivers had adverse lifestyle habits, including smoking and drinking alcohol, in addition to enforced sedentarism making them more vulnerable to lifestyle-related diseases. This study aimed to investigate the association between insomnia and diabetes, as well as the effect of anxiety related to driving tasks on this association. PATIENTS/METHODS: A total of 755 male truck drivers under 65 years of age who belonged to Akita prefecture Truck Association in Japan were investigated. Insomnia and State-Trait Anxiety Inventory (STAI) score were assessed using a self-administered questionnaire in 2020. Insomnia was defined in accordance with International classification of sleep disorders-third edition. Diabetes was defined as a fasting blood glucose level of ≥126 mg/dL and/or use of anti-diabetic drugs using data obtained from health checkups in 2018. RESULTS: The proportions of truck drivers with insomnia and diabetes were 13.9% and 9.7%, respectively, which were higher than those in the general working population in Japan. After adjusting for age, smoking, drinking, daily hours of driving and sleep, and hypertension, the STAI score (odds ratio [OR] for the highest quartile vs. the lowest: 3.88, 95% confidence interval [CI]: 1.84-8.18) and diabetes (OR: 2.49, 95% CI: 1.11-5.60) were found to be associated with insomnia. A statistical interaction with STAI scores was not observed between diabetes and insomnia. CONCLUSIONS: The present study demonstrated that diabetes and anxiety are independently and significantly associated with insomnia in male Japanese truck drivers.