Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury...Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.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
We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease(cGVHD)by analyzing the autoantibody profiles of 65 patients(34 cGVHD and 31 non-cGVHD)surviving longer than three months a...We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease(cGVHD)by analyzing the autoantibody profiles of 65 patients(34 cGVHD and 31 non-cGVHD)surviving longer than three months after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Autoantibodies to at least one antigen were detected in 45 patients(70.8%),with multiple autoantibodies detected in 30 patients(46.2%).Antinuclear antibodies(ANAs)were the most frequently detected autoantibodies,with a significantly higher prevalence in non-cGVHD patients and c GVHD patients than that in healthy controls(HCs).ANA-nucleolar(ANA-N)was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and c GVHD groups.There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC.Liver cGVHD was significantly associated with anti-Ro52-positivity.However,cGVHD activity and severity were not associated with the presence of autoantibodies.Similarly,there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies.Our results suggest that autoantibodies have limited value in predicting cGVHD.展开更多
基金support from the National Key Research and Development Program of China(2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(92159202)+2 种基金the National Natural Science Foundation of China(82272396 and 81930016)the Key Research&Development Plan of Zhejiang Province(2019C03050)the Construction Fund of Key Medical Disciplines of Hangzhou(OO20200093)。
文摘Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.
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.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY15H080002)
文摘We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease(cGVHD)by analyzing the autoantibody profiles of 65 patients(34 cGVHD and 31 non-cGVHD)surviving longer than three months after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Autoantibodies to at least one antigen were detected in 45 patients(70.8%),with multiple autoantibodies detected in 30 patients(46.2%).Antinuclear antibodies(ANAs)were the most frequently detected autoantibodies,with a significantly higher prevalence in non-cGVHD patients and c GVHD patients than that in healthy controls(HCs).ANA-nucleolar(ANA-N)was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and c GVHD groups.There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC.Liver cGVHD was significantly associated with anti-Ro52-positivity.However,cGVHD activity and severity were not associated with the presence of autoantibodies.Similarly,there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies.Our results suggest that autoantibodies have limited value in predicting cGVHD.
