Fangchinoline exerts antitumour activity by suppressing the EGFR­PI3K/AKT signalling pathway in colon adenocarcinoma.

Fangchinoline (FAN), an alkaloid extracted from Stephania tetrandra, has a variety of biological and pharmacological activities, but evidence of its effects on colon adenocarcinoma (COAD) is limited. Therefore, the present study aimed to elucidate the molecular mechanisms by which FAN affects COAD. The cytotoxicity, viability and proliferation of DLD­1 and LoVo cells were assessed in the presence of FAN using MTT and colony formation assays. The effects of FAN on apoptosis and the cell cycle in COAD cells were analysed by flow cytometry, and the migration and invasion of these cells were assessed by wound healing and Transwell experiments. Furthermore, a network pharmacological analysis was conducted to investigate the target of FAN and the results were confirmed by western blotting. In addition, a xenograft model was established in nude mice, and ultrasound imaging was used to assess the preclinical therapeutic effects of FAN in vivo. To the best of our knowledge, the results of this study provided the first evidence that FAN inhibited cellular proliferation, stemness, migration, invasion, angiogenesis and epithelial­mesenchymal transition (EMT), and induced apoptosis and G1­phase cell cycle arrest. Network pharmacological analysis further confirmed that FAN prevented EMT through the epidermal growth factor receptor (EGFR)­phosphoinositide 3­kinase (PI3K)/AKT signalling pathway. Finally, FAN significantly repressed tumour growth and promoted apoptosis in xenografts. Thus, targeting EGFR with FAN may offer a novel therapeutic approach for COAD.

Low Population Selenium Status Is Associated With Increased Prevalence of Thyroid Disease.

CONTEXT: Epidemiological studies have supported the premise that an adequate selenium intake is essential for thyroid gland function. OBJECTIVE: The objective was to investigate whether the prevalence of thyroid disease differed in two areas that were similar, except for very different soil/crop selenium concentrations. DESIGN: Cross-sectional observational study. SETTING: The setting was two counties of Shaanxi Province, China, here defined as adequate- and low-selenium. PARTICIPANTS: A total of 6152 participants were selected by stratified cluster-sampling. MAIN OUTCOME MEASURES: Participants completed demographic and dietary questionnaires and underwent physical and thyroid ultrasound examinations. Serum samples were analyzed for thyroid function parameters and selenium concentration. Serum selenium was compared between different demographic, dietary, and lifestyle categories in the two counties. The relationship between selenium status, dietary factors, and pathological thyroid conditions was explored by logistic regression. RESULTS: Complete data sets were available from 3038 adequate-selenium participants and 3114 low-selenium participants in whom median (interquartile range) selenium concentrations differed almost 2-fold (103.6 [79.7, 135.9] vs 57.4 [39.4, 82.1] µg/L; P = .001). The prevalence of pathological thyroid conditions (hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and enlarged thyroid) was significantly lower in the adequate-selenium county than in the low-selenium county (18.0 vs 30.5%; P < .001). Higher serum selenium was associated with lower odds ratio (95% confidence interval) of autoimmune thyroiditis (0.47; 0.35, 0.65), subclinical hypothyroidism (0.68; 0.58, 0.93), hypothyroidism (0.75; 0.63, 0.90), and enlarged thyroid (0.75; 0.59, 0.97). CONCLUSIONS: Low selenium status is associated with increased risk of thyroid disease. Increased selenium intake may reduce the risk in areas of low selenium intake that exist not only in China but also in many other parts of the world.