Systemic chemotherapy for oral squamous cell carcinoma (OSCC) is associated with multidrug resistance and systemic adverse effects. Cobalt‐ferrocene metal–organic framework (Co‐Fc) is a nanoparticle synthetized by ferrocene and cobalt with a stronger Fenton reaction that can locally generate hydroxyl radical and effectively kill tumors. However, tumor cells can remove exogenous substances through autophagy activity to maintain the internal environment homeostasis. Herein, Co‐Fc loaded with the classical autophagy inhibitor hydroxychloroquine (HCQ) to construct Co‐Fc@HCQ nanoparticles is synthetized. The ferrocene in Co‐Fc catalyzes the production of endogenous reactive oxygen species (ROS) through the Fenton reaction. The presence of HCQ inhibits the fusion of autophagy vesicles with lysosomes and reduces the scavenging of ROS. In addition, to enhance the tumor targeting effect of Co‐Fc@HCQ nanoparticles, oral cancer cell membranes (CM) are extracted from CAL‐27 cell line to construct CM@Co‐Fc@HCQ nanoparticles with good homologous targeting and immune escape effects. The results prove the good tumor targeting, biosafety as well as the therapeutic effect of CM@Co‐Fc@HCQ. In conclusion, via specific tumor targeting and local autophagy‐conducted ROS boosting, CM@Co‐Fc@HCQ nanoparticles, a smart local delivery chemo‐dynamic substance, provide a promising approach for effectively treating OSCC.
Background This study was aimed to evaluate the application of WeChat-based flipped classroom in root canal filling teaching in a preclinical endodontic course. Methods A two‐group comparative study was designed. The pre-class test, on-site quiz, and root canal filling on extracted premolars were performed by students from a lecture-based classroom group (LG, n = 30) and a WeChat-based flipped classroom group (WFG, n = 30). Results of the Pre-class test and on-site quiz were analyzed by independent samples t-test. Post-filling radiographs were taken and evaluated by a specialist in oral radiology who was blinded to grouping. Results of root canal fillings were analyzed by the Pearson chi-square test. Student responses in questionnaires were analyzed by Fisher’s exact test. Results The students in WFG could get significantly higher scores in the on-site test and make better performances in root canal filling than those in LG. In terms of questionnaires, students from WFG were perceived to be more motivated to learn, better to understand the knowledge, better to improve communication and clinical skills, easier to perform root canal filling but spending more time. Conclusion The WeChat-based flipped classroom teaching can have a better effect than lecture-based teaching on root canal filling learning for students with limited endodontic experiences.
Purpose: Despite considerable efforts to improve treatment modalities for cholangiocarcinoma, a common form of malignant tumor, its long-term survival rate remains poor. Hydroxychloroquine (HCQ) is a 4-aminoquinoline derivative antimalarial drug that has antimalarial and autophagy inhibition effects and exhibits comprehensive therapeutic effects on various cancers. In this study, we aimed to explore the anticancer potential and the underlying molecular mechanism of HCQ in cholangiocarcinoma treatment in vitro and in vivo.Methods: Autophagy-related genes (ARGs) were obtained from the Human Autophagy Database and Molecular Signatures Database, and the expression profiles of ARGs were downloaded from the database of The Cancer Genome Atlas. Different expression gene sets were performed using R software. The Gene Ontology and KEGG enrichment analyses were performed to reveal significantly enriched signaling pathways and to identify differentially expressed genes in cholangiocarcinoma tissues. HuCCT-1 and CCLP-1 cells were exposed to different concentrations of HCQ. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell apoptosis and cycle arrest were detected by the Live/Dead cell assay and flow cytometry (FCM). The inhibition of autophagy was observed using fluorescence microscopy. The reactive oxygen species levels were assessed by fluorescence microscopy and flow cytometry. The protein levels were determined by western blot. A cholangiocarcinoma cell line xenograft model was used to evaluate the antitumor activity of HCQ in vivo.Results: Compared with normal tissues, there were 141 ARGs with an aberrant expression in cholangiocarcinoma tissues which were mainly enriched in autophagy-related processes. Inhibition of autophagy by HCQ effectively suppressed cholangiocarcinoma in vitro and in vivo. HCQ inhibited cell proliferation and induced apoptosis and cycle arrest in vitro by increasing ROS accumulation, which was involved in autophagy inhibition. The ROS scavenger reduced l-glutathione distinctly weakened HCQ-induced cell apoptosis and viability inhibition in cholangiocarcinoma cells. In addition, HCQ inhibited growth of cholangiocarcinoma cell line xenograft tumors.Conclusion: HCQ could inhibit cell proliferation and induce apoptosis in cholangiocarcinoma by triggering ROS accumulation via autophagy inhibition, which makes HCQ a potential antitumor drug candidate for cholangiocarcinoma treatment.
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