How Gameful Experience Affects Public Knowledge, Attitudes, and Practices Regarding COVID-19 Among the Taiwanese Public: Cross-sectional Study.

BACKGROUND: In 2019, with the COVID-19 pandemic sweeping across the globe, public health systems worldwide faced severe challenges. Amid the pandemic, one simulation game, Plague Inc., has received substantial attention. This game has indirectly drawn greater public attention to public health issues by simulating pathogen transmission and disease symptoms. OBJECTIVE: Against this backdrop, this research investigates whether the gameful experience of Plague Inc. has indirectly affected public knowledge, attitudes, and practices (KAP) regarding COVID-19. METHODS: An online survey was conducted through social networking services in Taiwan from May 6-28, 2020. RESULTS: A total of 486 subjects participated in this study, of which 276 (56.8%) had played Plague Inc. This study had several findings. First, participants who had played Plague Inc. demonstrated higher levels of knowledge (P=.03, median 7, IQR 7-8) and attitudes (P=.007, median 8, IQR 7-8) than participants who had not played Plague Inc. (knowledge: median 7, IQR 6-8; attitude: median 7, IQR 6-8). Second, there was a significant correlation between creative thinking (ρ=.127, P=.04) and dominance (ρ=.122, P=.04) in attitude. Finally, there was a significant correlation between creative thinking (ρ=.126, P<.001) and dominance (ρ=.119, P=.049) in practice. CONCLUSIONS: Serious games highlighting the theme of pathogen transmission may enhance public knowledge and attitudes regarding COVID-19. Furthermore, the creative thinking and dominance involved in gameful experiences may act as critical factors in public attitudes and practices regarding COVID-19. These findings should be further verified through experimental research in the future.

Estrogen receptor antagonist fulvestrant inhibits proliferation and promotes apoptosis of prolactinoma cells by regulating the IRE1/XBP1 signaling pathway.

The aim of the present study was to evaluate the effects of an estrogen receptor antagonist, fulvestrant, on proliferation and apoptosis of prolactinoma cells, and to reveal potential regulatory mechanisms. Prolactinoma GH3 cells were treated with 10­6 mol/l fulvestrant for 2, 4, 8, 12 and 24 h. GH3 cell growth was observed under a microscope and cell viability was detected by MTT assay. Morphological changes of the nuclei in GH3 cells were observed by Hoechst 33258 staining and apoptotic rates were detected by flow cytometry. Preprolactin (PPL) and prolactin (PRL) secretion levels from GH3 cells were measured using ELISA. In addition, the protein expression levels of inositol­requiring enzyme 1 (IRE1), X­box binding protein (XBP)­1 and glucose­regulated protein, 78 kDa (GRP78) in GH3 cells were detected by western blot analysis. Cell density and cell viability of GH3 cells were significantly reduced in a time­dependent manner following treatment with fulvestrant (P<0.05). GH3 cells treated with fulvestrant also acquired an apoptotic morphology and the apoptotic rate of GH3 cells was significantly increased by fulvestrant in a time­dependent manner (P<0.05). PPL and PRL secretion levels were significantly reduced by fulvestrant treatment in a time­dependent manner (P<0.05). The protein expression levels of IRE1, XBP1 and GRP78 were also significantly reduced in a time­dependent manner following treatment with fulvestrant (P<0.05). Therefore, fulvestrant may inhibit proliferation and promote apoptosis of GH3 cells by downregulating the IRE1/XBP1 signaling pathway.

Ellagic acid induces cell cycle arrest and apoptosis through TGF-ß/Smad3 signaling pathway in human breast cancer MCF-7 cells.

Breast cancer represents the second leading cause of cancer-related deaths among women worldwide and preventive therapy could reverse or delay the devastating impact of this disease. Ellagic acid (EA), a dietary flavonoid polyphenol which is present in abundance in pomegranate, muscadine grapes, walnuts and strawberries, has been shown to inhibit cancer cells proliferation and induce apoptosis. Here, we investigated the growth inhibitory effects of EA on MCF-7 breast cancer cells. In the present study, we first found that EA inhibits the proliferation of MCF-7 breast cancer cells mainly mediated by arresting cell cycle in the G0/G1 phase. Moreover, gene expression profiling of MCF-7 breast cancer cell line treated with EA for 6, 12 and 24 h was performed using cDNA microarray. A total of 4,738 genes were found with a >2.0-fold change after 24 h of EA treatment. Among these genes, 2,547 were downregulated and 2,191 were upregulated. Furthermore, the changes of 16 genes, which belong to TGF-ß/Smads signaling pathway, were confirmed by real-time RT-PCR and/or western blot analysis. TGF-ß/Smads signaling pathway was found as the potential molecular mechanism of EA to regulate breast cancer cell cycle arrest in vitro. Therefore, the regulation of TGF-ß/Smads pathway in breast cancer cells could be a novel therapeutic approach for the treatment of patients with breast cancer. Further studies with in vitro models, as well as an analysis of additional human samples, are still needed to confirm the molecular mechanisms of EA in inhibition or prevention of breast cancer growth.

Ellagic acid exerts anti-proliferation effects via modulation of Tgf-ß/Smad3 signaling in MCF-7 breast cancer cells.

Ellagic acid has been shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF- 7 human breast cancer cells via regulation of the TGF-ß/Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-ß/Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-ß/Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells.

Anti-proliferative effect of an extract of the root of Polygonum multiflorum Thunb. on MCF-7 human breast cancer cells and the possible mechanisms.

The root of Polygonum multiflorum Thunb. (PM) is utilized to treat many diseases associated with aging. Research also indicates that PM inhibits the proliferation of certain types of cancer cells. The aim of the present study was to evaluate the inhibitory effect of PM extract (PME) on the proliferation of MCF-7 cells and to investigate the underlying mechanisms. Inhibition of the proliferation of MCF-7 cells was determined by the MTT assay. Cell cycle distribution and apoptotic rates were evaluated by flow cytometry, and cell cycle and apoptosis-related protein expression was assessed by Western blotting. Apoptotic characteristics of MCF-7 cells were detected by transmission electron microscopy. The present study showed that PME at doses of 100, 150, 200 and 250 µg/ml significantly inhibited proliferation of MCF-7 cells in a time- and dose-dependent manner. Flow cytometry showed that the cell apoptotic rates were 9.1 ± 1.67 and 17.7 ± 2.93% after treatment with 100 and 200 µg/ml PME for 48 h, respectively. The proportions of cells in the G2/M phase were 37.9 ± 1.47 and 42.0 ± 1.71% after treatment with 100 and 200 µg/ml PME for 24 h, respectively. Western blot analysis showed that PME down-regulated the protein expression of Cdc25B and Cdc25C phosphatases accompanied by an increase in phospho-Cdk1, and PME promoted cytochrome c release from mitochondria into the cytosol to activate caspase-9. The present study demonstrated that PME inhibited MCF-7 cell proliferation by inducing cell cycle arrest in the G2/M phase and promoting cell apoptosis. The effects of PME on MCF-7 cells were associated with the modulation of the expression levels of proteins involved in the cell cycle and apoptosis. These data suggest that PME has promise as a treatment against breast cancer by inhibiting the proliferation of cancer cells.