There is a theory that the unavoidable graft damage caused by ischemia-reperfusion injury(IRI)during liver transplantation(LT)can lead to severe IRI-related inflammation and trigger an early activation of the innate i...There is a theory that the unavoidable graft damage caused by ischemia-reperfusion injury(IRI)during liver transplantation(LT)can lead to severe IRI-related inflammation and trigger an early activation of the innate immune response mediated by T-cells,which potentially worsening the acute cellular rejection(ACR)cascade.As a result,machine perfusion(MP)has been placed great expectations for the potential to diminish post-LT ACR and other related immune responses by alleviating IRI through removing harmful substances and restoring cellular metabolism homeostasis(1,2).However,there has been much debate about MP’s benefits on ACR as relative data is limited.展开更多
Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protecti...Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.展开更多
文摘There is a theory that the unavoidable graft damage caused by ischemia-reperfusion injury(IRI)during liver transplantation(LT)can lead to severe IRI-related inflammation and trigger an early activation of the innate immune response mediated by T-cells,which potentially worsening the acute cellular rejection(ACR)cascade.As a result,machine perfusion(MP)has been placed great expectations for the potential to diminish post-LT ACR and other related immune responses by alleviating IRI through removing harmful substances and restoring cellular metabolism homeostasis(1,2).However,there has been much debate about MP’s benefits on ACR as relative data is limited.
基金supported by Public Projects of Zhejiang Province(No.LGF21H030006)Major Science and Technology Projects of Hainan Province(No.ZDKJ2019009)+2 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LZ21H180001)a Research Project of Jinan Microecological Biomedicine Shandong Laboratory(Nos.JNL-2022002A,JNL-2022007B,and JNL-2022023C)the National Natural Science Foundation of China(No.82000618).
文摘Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.