This study aimed at exploring the role of EgRad54 and the effect of harmine (HM) or HM derivatives (HMDs) on DNA damage in Echinococcus granulosus. DNA damage in E. granulosus protoscoleces (PSCs) was assessed by using a comet assay, after treatment with HM or HMDs. Efficiency of electroporation-based transfection of PSCs and subsequent EgRad54 knockdown was evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR) and fluorescence intensity. Viability of PSCs was determined via eosin exclusion test, and expression of related genes was analyzed via RT-qPCR. HM and HMDs significantly (p < 0.05) increased DNA damage in E. granulosus, and upregulated EgRad54 expression. Compared with HM and HMD-only treatment groups, EgRad54 knockdown combined with HM and HMD treatment further reduced E. granulosus viability. This combined approach resulted in significant (p < 0.05) downregulation of Rad54 and Topo2a expression, and upregulation of ATM expression, whereas H2A and P53 expression was significantly higher compared with control groups. These data show that EgRad54 knockdown, combined with HM or HMD treatment, enhances DNA damage in E. granulosus via upregulation of ATM and H2A, and downregulation of Rad54 and Topo2a, thereby inhibiting E. granulosus growth, and suggest that EgRad54 is a potential therapeutic target for cystic echinococcosis treatment.

中文翻译：

---

杀虫剂结合Rad54击倒通过增强DNA损伤抑制粒棘球E的生存能力。

这项研究旨在探讨EgRad54的作用以及harmine（HM）或HM衍生物（HMDs）对细粒棘球DNA虫DNA损伤的影响。在用HM或HMDs处理后，通过彗星试验评估颗粒状大肠杆菌（PSC）中的DNA损伤。通过使用实时定量聚合酶链反应（RT-qPCR）和荧光强度评估基于电穿孔的PSC转染效率和随后的EgRad54敲低。通过曙红排除试验确定PSC的生存力，并通过RT-qPCR分析相关基因的表达。HM和HMDs显着（p  <0.05）增加了颗粒肠球菌的DNA损伤并上调EgRad54表达。与仅HM和HMD治疗组相比，EgRad54敲低结合HM和HMD治疗进一步降低了颗粒大肠杆菌的生存能力。这种组合方法导致Rad54和Topo2a表达显着（p  <0.05）下调，以及ATM表达上调，而H2A和P53表达明显高于对照组。这些数据表明，EgRad54基因敲低结合HM或HMD处理，可通过上调ATM和H2A来增强颗粒大肠杆菌的DNA损伤。，以及Rad54和Topo2a的下调，从而抑制了大肠杆菌的生长，并表明EgRad54是囊性棘球co虫病治疗的潜在治疗靶标。