This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2...This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.展开更多
CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebr...CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury.To validate this hypothesis in the present study,we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro,respectively.We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells.When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately,mouse neurological dysfunction was greatly improved;the cerebral infarct volume was reduced;the survival rate of HT22 cells was increased;HT22 cell injury was alleviated;the expression of ferroptosis-related glutathione peroxidase 4,cystine-glutamate antiporter,and glutathione was increased;the levels of malondialdehyde,iron ions,and the expression of transferrin receptor 1 were decreased;and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased.Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway.Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury,thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.展开更多
Objective:To study the effect of paeoniflorin on TLR4 inflammatory pathway and Nrf2 oxidative stress pathway in rat model with spinal cord injury.Methods:Male SD rats were selected and divided into sham group, spinal ...Objective:To study the effect of paeoniflorin on TLR4 inflammatory pathway and Nrf2 oxidative stress pathway in rat model with spinal cord injury.Methods:Male SD rats were selected and divided into sham group, spinal cord injury group and paeoniflorin group, spinal cord injury rat models were established and then given 30 mg/kg paeoniflorin for 14 d of intervention in a row, and then serum and spinal cord specimens were collected to determine the expression of cell apoptosis genes, TLR4 pathway genes and Nrf-2 pathway genes. Results:Spinal cord caspase-3, caspase-8, caspase-9, TLR4, MyD88, NF-kB, AP-1, Nrf-2 and ARE mRNA expression as well as serum IL-6, TNF-α and IL-12 contents of spinal cord injury group were significantly higher than those of sham group while spinal cord HO-1, SOD and GSH-PX contents were significantly lower than those of sham group;spinal cord caspase-3, caspase-8, caspase-9, TLR4, MyD88, NF-kB and AP-1 mRNA expression as well as serum IL-6, TNF-α and IL-12 contents of paeoniflorin group were significantly lower than those of spinal cord injury group while spinal cord Nrf-2 and ARE mRNA expression as well as HO-1, SOD and GSH-PX contents were significantly higher than those of spinal cord injury group.Conclusion:Paeoniflorin can inhibit the TLR4 inflammatory pathway and enhance the Nrf2 anti-oxidative stress pathway to reduce the spinal cord injury and inhibit cell apoptosis in rats.展开更多
文摘This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC.
基金supported by the National Natural Science Foundation of China,No.81402930Natural Science Foundation of Universities in Anhui Province,No.KJ2021A0688+2 种基金National College Students Innovation and Entrepreneurship Program,No.202110367071Key projects of science and technology projects of Bengbu Medical College,No.2020byzd017512 Talents Training Program of Bengbu Medical College,No.BY51201104(all to SYD).
文摘CDGSH iron sulfur domain 2 can inhibit ferroptosis,which has been associated with cerebral ischemia/reperfusion,in individuals with head and neck cancer.Therefore,CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury.To validate this hypothesis in the present study,we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro,respectively.We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells.When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately,mouse neurological dysfunction was greatly improved;the cerebral infarct volume was reduced;the survival rate of HT22 cells was increased;HT22 cell injury was alleviated;the expression of ferroptosis-related glutathione peroxidase 4,cystine-glutamate antiporter,and glutathione was increased;the levels of malondialdehyde,iron ions,and the expression of transferrin receptor 1 were decreased;and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased.Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway.Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury,thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.
文摘Objective:To study the effect of paeoniflorin on TLR4 inflammatory pathway and Nrf2 oxidative stress pathway in rat model with spinal cord injury.Methods:Male SD rats were selected and divided into sham group, spinal cord injury group and paeoniflorin group, spinal cord injury rat models were established and then given 30 mg/kg paeoniflorin for 14 d of intervention in a row, and then serum and spinal cord specimens were collected to determine the expression of cell apoptosis genes, TLR4 pathway genes and Nrf-2 pathway genes. Results:Spinal cord caspase-3, caspase-8, caspase-9, TLR4, MyD88, NF-kB, AP-1, Nrf-2 and ARE mRNA expression as well as serum IL-6, TNF-α and IL-12 contents of spinal cord injury group were significantly higher than those of sham group while spinal cord HO-1, SOD and GSH-PX contents were significantly lower than those of sham group;spinal cord caspase-3, caspase-8, caspase-9, TLR4, MyD88, NF-kB and AP-1 mRNA expression as well as serum IL-6, TNF-α and IL-12 contents of paeoniflorin group were significantly lower than those of spinal cord injury group while spinal cord Nrf-2 and ARE mRNA expression as well as HO-1, SOD and GSH-PX contents were significantly higher than those of spinal cord injury group.Conclusion:Paeoniflorin can inhibit the TLR4 inflammatory pathway and enhance the Nrf2 anti-oxidative stress pathway to reduce the spinal cord injury and inhibit cell apoptosis in rats.