Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage / 神经科学通报·英文版

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

Clinical randomzied study of postoperative radiochemotherapy compared with chemotherapy alone in the treatment of locally advanced gastric cancer / 中华放射肿瘤学杂志

ObjectiveTo investigate the efficacy and toxicity of postoperative radiochemotherapy compared with chemotherapy alone in the treatment of locally advanced gastric cancer.MethodsA total of 83 patients with resected adenocarcinoma of the stomach were randomly assigned to postoperative radiochemotherapy group (RCT) ( n =43 ) or chemotherapy alone group (CT) ( n =40 ).Patients in RCT group received radiotherapy concurrent with capecitabine chemotherapy then followed by 4 - 6 cycles of FOLFOX4 chemotherapy.The total dose of radiation was 45 Gy.The dose of capecitabine was 1600 mg/m2per day.In the CT group,patients received 6 - 8 cycles FOLFOX4 chemotherapy.Survival was analyzed using Kaplan-Meier method and Logrank test. Results The follow-up rate was 96％. The number of patients who had a minimum of 2-,3-year follow-up time were 37,12 in the RCT group and 31,10 in the CT group.The 1-,2-,3-year local control rates for RCT and CT groups were 100％,97％,94％ and 95％,87％,73％ (x2 =4.54,P =0.033),respectively.The 1-,2-,3-year survival rates were 98％,86％,81％ in the RCT group,with 93％,80％,64％ in the CT group ( x2 =3.96,P =0.047 ).The incidence of grade 3hematological toxicity in the RCT and CT group was 23％ vs 15％ ( x2 =0.93,P =0.630 ),and grade 3gastrointestinal toxicity was 16％ vs 10％ ( x2 =0.95,P =0.624 ). Conclusions Compared with chemotherapy alone,postoperative radiochemotherapy can improve survival of locally advanced gastric cancer patients with acceptable toxicities.