Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2/HO-1/GPX4 Activation

Background and Aims:Liver ischemia-reperfusion(IR)injury is a common pathological process in liver surgery.Ferroptosis,which is closely related to lipid peroxidation,has recently been confirmed to be involved in the pathogenesis of IR injury.However,the development of drugs that regulate ferroptosis has been slow,and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved.Fucoidan(Fu)is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity.Methods:In this study,we established models of IR injury using erastin as an activator of ferroptosis,with the ferroptosis inhibitor ferrostatin-1(Fer-1)as the control.We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels,mitochondrial morphology,and key pathways in theta were involved.Results:Ferroptosis was closely related to IR-induced hepatocyte injury.The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation,while those effects were reversed after treatment with erastin.Iron accumulation,mitochondrial membrane rupture,and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2(Nrf2)into the nucleus and reduced downstream heme oxygenase-1(HO-1)and glutathione peroxidase 4(GPX4)protein levels.However,fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin.Conclusions:Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

Data mining of microarray for differentially expressed genesin liver metastasis from gastric cancer

Tumor metastasis is the leading cause of death for gastric cancer.Metastasis is the main reason for the failure of clinical treatment for gastric cancer.In order to find metastasis-related genes and abnormal signal transduction pathway of high-invasive gastric cancer,samples of gastric cancer with liver metastasis were collected for microarray detection;up-regulated or down-regulated genes in all three cases were simultaneously screened out.Subsequently,from the preliminary screened genes,molecular pathways possibly impacting liver metastasis from gastric cancer were investigated by the Gene Cluster with Literature Profiles(GenCLip)analysis software.Many biological effects including apoptosis have been validated.Functional analysis of differentially expressed genes revealed that a variety of biological pathways,such as blood circulation and gas exchange,vasodilation and vasoconstriction regulation,and immune defense,could be significantly activated.Besides,gene sequences,specific keywords or gene regulatory networks were further searched by GenCLiP.We conclude that data mining allows to quickly identify a series of special signal transduction pathways involving abnormally expressed genes.