Therapeutic effects of coptisine derivative EHLJ7 on colorectal cancer by inhibiting PI3K/AKT pathway.

Colorectal cancer (CRC) is the third most common cancer in the world with high mortality rate. EHLJ7 is a quaternary coptisine derivative synthesized by our institute. In this study, the role and mechanism of EHLJ7 on CRC are further elucidated. Using target fishing, colon cancer-associated target screening and molecular docking analysis, PI3K/AKT pathway was selected for the target of EHLJ7 at CRC. Results of Flow cytometry, wound healing assay and transwell migration assay confirmed that EHLJ7 could inhibit migration and apoptosis of colon cancer cells by specifically inhibiting PI3K/AKT pathway in vitro. Xenograft tumor models and a newly established azoxymethane (AOM)/dextran sulfate sodium (DSS)/Peptostreptococcus anaerobiu (P.anaerobius)-induced CRC mouse model are applied to access the anti-cancer action and mechanism of EHLJ7 using western-blot, immunohistochemistry and analysis of exosomes. The key findings in this study are listed as follows: (1) EHLJ7 exerts superior anti-tumor effect with good safety on Xenograft tumor model and CRC model; (2) EHLJ7 exerted its anti-CRC effect by specifically inhibiting PI3K/AKT pathway and apoptosis in vivo and in vitro. In summary, we demonstrated that EHLJ7 exerts therapeutic effect against CRC by PI3K/AKT pathway, which made it possible as a potentially effective compound for the treatment of CRC.

The impact of external resources on the development of an indigenous school in rural areas: Taking a junior high school in Taiwan as an example.

The UN SDGs presented a vision for sustainability and the reduction of inequality within a country. The Taiwanese government uses many external resources to develop rural education. This study was conducted in a small public junior high school in a remote indigenous community in central Taiwan. Due to the economic downturn, the population in the indigenous community is outflowing, and the number of students is decreasing. With external resources, such as the Project of Female Science and Technology Talent Development from the Ministry of Science and Technology in Taiwan and other plans, this study introduces a full-time researcher as a teacher to promote science education in the research school. Implementing the projects improves students' academic performance and encourages students to participate in science competitions and achieve success. This study explores first the impact of the school's implementation of the Ministry of Science and Technology program on the development of the school; second, the results of the development of the school-based curriculum; and finally, it quantifies the statistics of the students' changes in the National High School Entrance Examination results. The impact of external resources on school development is determined by analyzing the performance of the participating students. This study finds that the Ministry of Science and Technology program plays an essential role in the development of the school, providing a key platform for teachers' growth, enriching school funding, developing featured courses, and encouraging students' performance. External resources have significantly improved students' results on the National Examination and facilitated students' motivation to learn science.

CS-semi5 Inhibits NF-κB Activation to Block Synovial Inflammation, Cartilage Loss and Bone Erosion Associated With Collagen-Induced Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that affects 1% of the population. CS-semi5 is a semisynthetic chondroitin sulfate. In this study, CS-semi5 was shown to have positive effects on a model of collagen-induced arthritis (CIA). CS-semi5 treatment had obvious effects on weight loss and paw swelling in CIA mice. Post-treatment analysis revealed that CS-semi5 alleviated three main pathologies (i.e., synovial inflammation, cartilage erosion and bone loss) in a dose-dependent manner. Further study showed that CS-semi5 could effectively reduce TNF-α and IL-1ß production in activated macrophages via the NF-κB pathway. CS-semi5 also blocked RANKL-trigged osteoclast differentiation from macrophages. Therefore, CS-semi5 may effectively ameliorate synovial inflammation, cartilage erosion and bone loss in RA through NF-κB deactivation.