RESUMO
Doxorubicin (DOX) is an extensively used chemotherapeutic drug to treat leukemia. However, there remains a pivotal clinical problem of resistance to DOX in patients with leukemia. Erythroid 2related factor 2 (Nrf2) is a master regulator of antioxidation response which serves a critical role in maintaining cellular oxidative homeostasis. However, whether Nrf2 is involved in DOX resistance is not totally clear. It is welldocumented that triptolide, a widely used drug to treat autoimmune disorders, possesses anticancer activities, yet whether triptolide affects leukemia cell sensitivity to DOX remains to be elucidated. The present study aimed to determine the role of triptolidemediated downregulation of Nrf2 in regulating leukemia cell ferroptosis and resistance to DOX. For this purpose, lowdose DOX was used to establish DOXresistant K562 cells and HL60 cells. Nrf2 mRNA and protein expression were examined by quantitative PCR and western blotting assays. The effects of triptolide on leukemia cell viability, reactive oxygen species (ROS) levels, or lipid oxidation were determined by CCK8 assay, DCFHDA assay, or BODIPY 581/591 C11 assay, respectively. The results show that Nrf2 expression was significantly upregulated in DOXresistant leukemia cells and clinical leukemia samples. Silencing of Nrf2 significantly sensitized leukemia cells to DOX. Furthermore, it was demonstrated that triptolide inhibited Nrf2 expression and induced leukemia cell ferroptosis, as evidenced by increased ROS levels and lipid oxidation as well as decreased glutathione peroxidase 4 expression. Ectopic expression of Nrf2 significantly rescued triptolideinduced leukemia cell ferroptosis. Notably, the present study showed that triptolide resensitized DOXresistant leukemia cells to DOX. In conclusion, the present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolideinduced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.
Assuntos
Ferroptose , Leucemia , Humanos , Doxorrubicina/farmacologia , Lipídeos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de OxigênioRESUMO
AIM: The purpose of this study was to explore the effect of implementing WeChat-assisted health education for parents of infants after enterostomy. METHODS: This study retrospectively analysed the clinical data of 106 infants after enterostomy whose parents received WeChat-assisted health education in our hospital from June 2017 to June 2019. The clinical data of 92 infants after enterostomy whose parents received traditional health education in our hospital from May 2015 to May 2017 were selected as the control group. RESULTS: The care ability of the WeChat health education group was significantly better than that of the traditional health education group (P < 0.05). The care burden of the WeChat health education group was significantly lower than that of the traditional health education group (P < 0.05). The results of the WHOQOL-BREF showed that the quality of life for WeChat health education group was significantly higher than that for the traditional health education group (P < 0.05). The incidence of complications, including mucosal oedema, allergic dermatitis, faecal dermatitis and avulsion injury, in the WeChat health education group was significantly lower than that in the traditional health education group. CONCLUSION: The implementation of WeChat-assisted health education for parents of infants after enterostomy can effectively improve parents' care ability, reduce parents' care burden, improve parents' quality of life and reduce the incidence of complications in patients.