Background: A hallmark of epithelial ovarian cancer (EOC) metastasis is the process of spheroid formation, whereby tumour cells aggregate into 3D structures while in suspension in the peritoneal cavity. EOC spheroids are subjected to bioenergetic stress, thereby activating AMP-activated protein kinase (AMPK) signaling to enter a metabolically quiescent state, which can facilitate cell survival under nutrient-limiting conditions. Independently, we have also demonstrated that EOC spheroids induce autophagy, a process that degrades and recycles intracellular components to restore energy and metabolites. Herein, we sought to examine whether AMPK controls autophagy induction as a cell survival mechanism in EOC spheroids. Results: We observed a coordinate increase in phosphorylated AMPK and the autophagy marker LC3-II during EOC spheroid formation. Reduced AMPK expression by siRNA-mediated knockdown of PRKAA1 and PRKAA2 blocked autophagic flux in EOC spheroids as visualized by fluorescence microscopy using the mCherry-eGFP-LC3B reporter. A complementary approach using pharmacologic agents Compound C and CAMKKβ inhibitor STO-609 to inhibit AMPK activity both yielded a potent blockade of autophagic flux as well. However, direct activation of AMPK in EOC cells using oligomycin and metformin was insufficient to induce autophagy. STO-609 treatment of EOC spheroids resulted in reduced viability in 7 out of 9 cell lines, but with no observed effect in non-malignant FT190 cell spheroids. Conclusions: Our results support the premise that CAMKKβ-mediated AMPK activity is required, at least in part, to regulate autophagy induction in EOC spheroids and support cell viability in this in vitro model of EOC metastasis.
Background The COVID-19 pandemic has highlighted the need for reliable information, especially around vaccines. Vaccine hesitancy is a growing concern and a great threat to broader public health. The prevalence of social media within our daily lives emphasizes the importance of accurately analyzing how health information is being disseminated to the public. TikTok is of particular interest, as it is an emerging social media platform that young adults may be increasingly using to access health information. Objective The objective of this study was to examine and describe the content within the top 100 TikToks trending with the hashtag #covidvaccine. Methods The top 250 most viewed TikToks with the hashtag #covidvaccine were batch downloaded on July 1, 2021, with their respective metadata. Each TikTok was subsequently viewed and encoded by 2 independent reviewers. Coding continued until 100 TikToks could be included based on language and content. Descriptive features were recorded including health care professional (HCP) status of creator, verification of HCP status, genre, and misinformation addressed. Primary inclusion criteria were any TikToks in English with discussion of a COVID-19 vaccine. Results Of 102 videos included, the median number of plays was 1,700,000, with median shares of 9224 and 62,200 followers. Upon analysis, 14.7% (15/102) of TikToks included HCPs, of which 80% (12/102) could be verified via social media or regulatory body search; 100% (15/15) of HCP-created TikToks supported vaccine use, and overall, 81.3% (83/102) of all TikToks (created by either a layperson or an HCP) supported vaccine use. Conclusions As the pandemic continues, vaccine hesitancy poses a threat to lifting restrictions, and discovering reasons for this hesitancy is important to public health measures. This study summarizes the discourse around vaccine use on TikTok. Importantly, it opens a frank discussion about the necessity to incorporate new social media platforms into medical education, so we might ensure our trainees are ready to engage with patients on novel platforms.
BACKGROUND The COVID-19 pandemic has highlighted the need for reliable information, especially, around vaccines. Vaccine hesitancy is a growing concern and a great threat to broader public health. The prevalence of social media within our daily lives emphasizes the importance of accurately analyzing how health information is being disseminated to the public. TikTok is of particular interest as it is an emerging social media platform that young adults may be increasingly using to access health information. OBJECTIVE To examine and describe the content within the top 100 TikToks trending with the hashtag #covidvaccine. METHODS The top 250 most viewed TikToks with the hashtag of #covidvaccine were batch downloaded on 01/07/2021 with their respective metadata. Each TikTok was subsequently viewed and encoded by two independent reviewers. Coding continued until 100 TikToks could be included based on language and content. Descriptive features were recorded including health care professional (HCP) status of creator, verification of health care provider status, genre and myths addressed. Primary inclusion criteria were any TikToks in English with discussion of a covid vaccine. RESULTS Of the 102 videos included, the median number of plays was 1700000, with median shares of 9224 and followers 62200. Upon analysis, 14.7% of TikToks included HCPs (n=15) of which 80.0% (n=12) could be verified via social media or a google search. 100% of HCP TikToks supported vaccine use, and overall 81% of all TikToks (created by either a layperson or HCP) supported vaccine use. CONCLUSIONS As the pandemic continues, vaccine hesitancy poses a threat to lifting restrictions and discovering reasons for this hesitancy is important to public health measures. This study summarizes the discourse around the vaccine use on TikTok. Importantly it opens up a frank discussion about the necessity to incorporate new social media platforms into medical education so we might ensure our trainees are ready to engage with patients where they receive information. CLINICALTRIAL N/A (not a clinical trial)
Background A hallmark of epithelial ovarian cancer (EOC) metastasis is the process of spheroid formation, whereby tumour cells aggregate into 3D structures while in suspension in the peritoneal cavity. EOC spheroids are subjected to bioenergetic stress, thereby activating AMP-activated protein kinase (AMPK) signaling to enter a metabolically quiescent state, which can facilitate cell survival under nutrient-limiting conditions. Independently, we have also demonstrated that EOC spheroids induce autophagy, a process that degrades and recycles intracellular components to restore energy and metabolites. Herein, we sought to examine whether AMPK controls autophagy induction as a cell survival mechanism in EOC spheroids. Results We observed a co-ordinate increase in phosphorylated AMPK and the autophagy marker LC3-II during EOC spheroid formation. Reduced AMPK expression by siRNA-mediated knockdown of PRKAA1 and PRKAA2 blocked autophagic flux in EOC spheroids as visualized by fluorescence microscopy using the mCherry-eGFP-LC3B reporter. A complementary approach using pharmacologic agents Compound C and CAMKKβ inhibitor STO-609 to inhibit AMPK activity both yielded a potent blockade of autophagic flux as well. However, direct activation of AMPK in EOC cells using oligomycin and metformin was insufficient to induce autophagy. STO-609 treatment of EOC spheroids resulted in reduced viability in 7 out of 9 cell lines, but with no observed effect in non-malignant FT190 cell spheroids. Conclusions Our results support the premise that CAMKKβ-mediated AMPK activity is required, at least in part, to regulate autophagy induction in EOC spheroids and support cell viability in this in vitro model of EOC metastasis.
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