Investigating COVID-19 Vaccine Communication and Misinformation on TikTok: Cross-sectional Study.

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.

Activated CAMKKß-AMPK signaling promotes autophagy in a spheroid model of ovarian tumour metastasis.

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 CAMKKß 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 CAMKKß-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.

Inhibiting ULK1 kinase decreases autophagy and cell viability in high-grade serous ovarian cancer spheroids.

Metastasis in high-grade serous ovarian cancer (HGSOC) occurs through an unconventional route that involves exfoliation of cancer cells from primary tumors and peritoneal dissemination via multicellular clusters or spheroids. Previously, we demonstrated autophagy induction in HGSOC spheroids grown in vitro and in spheroids collected from ovarian cancer patient ascites; thus, we speculate that autophagy may contribute to spheroid cell survival and overall disease progression. Hence, in this study we sought to evaluate whether ULK1 (unc-51-like kinase-1), a serine-threonine kinase critical for stress-induced autophagy, is important for autophagy regulation in HGSOC spheroids. We demonstrate that HGSOC spheroids have increased ULK1 protein expression that parallels autophagy activation. ULK1 knockdown increased p62 accumulation and decreased LC3-II/I ratio in HGSOC spheroids. In addition, knocking down ATG13, a protein that regulates ULK1 activity via complex formation, phenocopied our ULK1 knockdown results. HGSOC spheroids were blocked in autophagic flux due to ULK1 and ATG13 knockdown as determined by an mCherry-eGFP-LC3B fluorescence reporter. These observations were recapitulated when HGSOC spheroids were treated with an ULK1 kinase inhibitor, MRT68921. Autophagy regulation in normal human fallopian tube epithelial FT190 cells, however, may bypass ULK1, since MRT68921 reduced viability in HGSOC spheroids but not in FT190 cells. Interestingly, ULK1 mRNA expression is negatively correlated with patient survival among stage III and stage IV serous ovarian cancer patients. As we observed using established HGSOC cell lines, cultured spheroids using our new, patient-derived HGSOC cells were also sensitive to ULK1 inhibition and demonstrated reduced cell viability to MRT68921 treatment. These results demonstrate the importance of ULK1 for autophagy induction in HGSOC spheroids and therefore justifies further evaluation of MRT68921, and other novel ULK1 inhibitors, as potential therapeutics against metastatic HGSOC.