Role of a Mixture of Polyphenol Compounds Released after Blueberry Fermentation in Chemoprevention of Mammary Carcinoma: In Vivo Involvement of miR-145.

Epigenetic mechanisms such as microRNA (miRNA) deregulation seem to exert a central role in breast cancer initiation and progression. Therefore, targeting epigenetics deregulation may be an effective strategy for preventing and halting carcinogenesis. Studies have revealed the significant role of naturally occurring polyphenolic compounds derived from fermented blueberry fruits in cancer chemoprevention by modulation of cancer stem cell development through the epigenetic mechanism and regulation of cellular signaling pathways. In this study, we first investigated the phytochemical changes during the blueberry fermentation process. Fermentation favored the release of oligomers and bioactive compounds such as protocatechuic acid (PCA), gallic acid, and catechol. Next, we investigated the chemopreventive potentials of a polyphenolic mixture containing PCA, gallic acid, and catechin found in fermented blueberry juice in a breast cancer model by measuring miRNA expression and the signaling pathways involved in breast cancer stemness and invasion. To this end, 4T1 and MDA-MB-231 cell lines were treated with different doses of the polyphenolic mixture for 24 h. Additionally, female Balb/c mice were fed with this mixture for five weeks; two weeks before and three weeks after receiving 4T1 cells. Mammosphere formation was assayed in both cell lines and the single-cell suspension obtained from the tumor. Lung metastases were counted by isolating 6-thioguanine-resistant cells present in the lungs. In addition, we conducted RT-qPCR and Western blot analysis to validate the expression of targeted miRNAs and proteins, respectively. We found a significant reduction in mammosphere formation in both cell lines treated with the mixture and in tumoral primary cells isolated from mice treated with the polyphenolic compound. The number of colony-forming units of 4T1 cells in the lungs was significantly lower in the treatment group compared to the control group. miR-145 expression significantly increased in the tumor samples of mice treated with the polyphenolic mixture compared to the control group. Furthermore, a significant increase in FOXO1 levels was noted in both cell lines treated with the mixture. Overall, our results show that phenolic compounds found in fermented blueberry delay the formation of tumor-initiating cells in vitro and in vivo and reduce the spread of metastatic cells. The protective mechanisms seem to be related, at least partly, to the epigenetic modulation of mir-145 and its signaling pathways.

COVID-19 pandemic and violence: rising risks and decreasing urgent care-seeking for sexual assault and domestic violence survivors.

BACKGROUND: There is little information on care-seeking patterns for sexual assault and domestic violence during the COVID-19 pandemic. The objective of this study was to examine the changes in emergency department (ED) admissions for sexual assault and domestic violence since the COVID-19 pandemic was declared. METHODS: Observational ED admissions data from The Ottawa Hospital were analyzed from March 4 to May 5 (62 days) in 2020 (COVID-19 period) and compared to the same period in 2018 (pre-COVID-19). Total and mean weekly admissions were calculated for all-cause ED admissions and for sexual and domestic violence cases. A Poisson regression (without offset term) was used to calculate the weekly case count ratio and 95% confidence intervals (CI) between the two time periods. Case characteristics were compared using chi-square tests, and percent differences were calculated. RESULTS: Compared to pre-COVID-19, total ED admissions dropped by 1111.22 cases per week (32.9% reduction), and the Sexual Assault and Domestic Violence Program cases dropped 4.66 cases per week. The weekly case count ratio for sexual assault cases was 0.47 (95% CI 0.79-0.27), equivalent of 53.49% reduction in cases, and 0.52 (95% CI 0.93-0.29), equivalent to a 48.45% reduction in physical assault cases. The characteristics of presenting cases were similar by age (median 25 years), sex (88.57% female), assault type (57.14% sexual assault, 48.57% physical assault), and location (31.43% patient's home, 40.00% assailant's home). There was a significant increase in psychological abuse (11.69% vs 28.57%) and assaults occurring outdoors (5.19% vs 22.86%). CONCLUSION: This study found a decrease in ED admissions for sexual assault and domestic violence during COVID-19, despite societal conditions that elevate risk of violence. Trends in care-seeking and assault patterns will require ongoing monitoring to inform the provision of optimal support for individuals experiencing violence, particularly as countries begin to re-open or lock-down again.