Melanoma is one of the most malignant and aggressive cancers with high cancer-related deaths. However, it is unclear whether Ku80 regulates tumor growth in human melanoma. In this study, we screened a siRNA library targeting 6024 human genes and identified Ku80 as a potential therapeutic target in melanoma cells. Knockdown of Ku80 significantly suppressed melanoma cell proliferation and induced apoptosis, as well as enhanced the antitumor effect of melatonin in melanoma in vitro and in vivo. Overexpression of Ku80, however, promoted melanoma growth and increased the insensitivity of melanoma cells to melatonin. Mechanistically, we found that Ku80 bound to the PDK1 promoter and activated the transcription of PDK1. Moreover, we showed that the binding of Ku80 at the PDK-1 promoter was HIF1-α dependent, and melatonin degraded HIF1-α in melanoma cells. Furthermore, clinical data revealed that the expression of Ku80 and PDK-1 proteins were positively correlated and elevated in the tumor tissues of melanoma patients, and high expression of Ku80 predicted a poor prognosis in melanoma. Collectively, our study demonstrated that Ku80 promoted melanoma growth and regulated antitumor activity of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway, suggesting that Ku80 may be a potential molecular target for melanoma treatment.
Evidence of SARS-CoV-2 infection in gallbladder and aggravating cholecystitis to septic shock: a case report Xiaopeng Hong, Jianzhong He, Peiping Li, Jiafan Chen, Baojia Zou, Zhanyu Li, Yingbin Jia, Ye Liu, Lukun Yang, Jian Li
Coronavirus disease 2019 (COVID-19) outbreaks have occurred in many countries around the world. The numbers of confirmed cases and deaths continue to increase. It is increasingly likely that COVID-19 patients will require emergency surgeries in the operating room (OR). As COVID-19 can easily be transmitted to healthcare workers and other patients during surgery, it is important to establish a set of infection prevent and control management strategy to prevent COVID-19 from spreading in the OR. Based on our experience in COVID-19 prevention and control in the OR, we introduce this COVID-19 prevention and control management strategy for preventing COVID-19 from spreading in the OR. This management strategy includes a number of COVID-19 prevention and control procedures including (I) conduct COVID-19 knowledge training at the early stage of outbreak, (II) formulate the surgery arrangement procedures and suspend the elective surgery if the patient confirmed to COVID-19, (III) divide an isolated OR area for COVID-19 surgery, (IV) preoperative preparation procedures, (V) procedures for wearing and removing personal protective equipment, (VI) anesthesia management, intraoperative management, (VII) post-operative disposable waste management and disinfection. This management strategy has worked very effectively since the outbreak of COVID-19 in Wuhan at the end of 2019. We have performed emergency surgeries on several COVID-19 confirmed patient and dozens of COVID-19 suspected patients under this COVID-19 prevention and control management strategy, and have achieved an excellent result of zero COVID-19 infection in the OR.