Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance
in vitro
. Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.
stringent measures for controlling the novel coronavirus epidemic have been gradually enforced and strengthened in mainland China. The detection and diagnosis have been improved, as well. However, the daily reported cases remaining at a high level make the epidemic trend prediction difficult. Methods: Since the traditional SEIR model does not evaluate the effectiveness of control strategies, a novel model in line with the current epidemic's process and control measures was proposed, utilizing multisource datasets including the cumulative number of reported, deceased, quarantined and suspected cases.Results: Results show that the trend of the epidemic mainly depends on quarantined and suspected cases. The predicted cumulative numbers of quarantined and suspected cases nearly reached static states, and their inflection points have already been achieved, with the epidemic's peak coming soon. The estimated effective reproduction numbers using model-free and model-based methods are decreasing, as well as new infections, while newly reported cases are increasing. Most infected cases have been quarantined or put in the suspected class, which has been ignored in existing models. Conclusions: The uncertainty analyses reveal that the epidemic is still uncertain, and it is important to continue enhancing the quarantine and isolation strategy and improving the detection rate in mainland China.
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