Background:Severe acute respiratory syndrome coronavirus 2 is a highly contagious viral infection,without any available targeted therapies.The high mortality rate of COVID-19 is speculated to be related to immune dama...Background:Severe acute respiratory syndrome coronavirus 2 is a highly contagious viral infection,without any available targeted therapies.The high mortality rate of COVID-19 is speculated to be related to immune damage.Methods:In this study,clinical bioinformatics analysis was conducted on transcriptome data of coronavirus infection.Results:Bioinformatics analysis revealed that the complex immune injury induced by coronavirus infection provoked dysfunction of numerous immune-related molecules and signaling pathways,including immune cells and toll-like receptor cascades.Production of numerous cytokines through the Th17 signaling pathway led to elevation in plasma levels of cytokines(including IL6,NF-kB,and TNF-a)followed by concurrent inflammatory storm,which mediates the autoimmune response.Several novel medications seemed to display therapeutic effects on immune damage associated with coronavirus infection.Conclusions:This study provided insights for further large-scale studies on the target therapy on reconciliation of immunological damage associated with COVID-19.展开更多
Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatop...Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.展开更多
Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of A...Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would benefit for the prognosis and raise the survival rate of patients.展开更多
Abstract Objectives To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival ...Abstract Objectives To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival and the changes of immune functions of the thymocytes and splenocytes in rats. Methods Wistar rats were irradiated with 3, 4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA Ⅲ degree burn was inflicted to the rats. Twenty four hours after the burn injury, allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before skin grafting, the bone marrow cells (4×10 8) from the same donor were also transplanted. All rats were carefully observed after injury. The rats with single radiation injury of 5 Gy gamma rays, with single burn injury and with combined radiation burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting for immunological assay and pathological study. Results All the allografts in the single burn group were rejected in 10 days. In the combined injury groups, the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were 20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy radiation, the 10 day survival rates of the allografts were 69%, 88% and 100% respectively, and the 30 day survival rates in the three groups were 36%, 42% and 100% separately. The grafted allogenic skin, with normal epithelial cells and good vascularity, healed well with the recipient's skin. Hairs grew well from the allografts 30 days after grafting. Three, 7 and 15 days after allografting, in the single burn group, the proliferative activities of the thymocytes were 90%, 185% and 130% of the preinjury level, and the antibody forming capacities of the splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the combined injury groups, the proliferative activities were 6%, 99% and 91% of the preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury level. Conclusions The survival rate of allograft in rats undergoing combined radiation and thermal burn injury rises with the increase in radiation dosage. The allograft covering single bun injury is severely rejected by immune reaction. The prolongation of the survival of allograft in combined injury group mainly results from radiation that suppresses immune functions.展开更多
基金supported by the 2017 National Geriatrics Clinical Medical Research Center Bidding Project(NCRCG-PLAGH-2017011)the Translational Medicine Project of Chinese PLA General Hospital(2017TM-020)+2 种基金Pudong New Area Health and Health Committee Subject Leader Program(PWRd2019-04)Pudong New Area TCM Peak Disease Subject(PDZY-2018-0603)the Innovation Project of Chinese PLA General Hospital(CX19028).
文摘Background:Severe acute respiratory syndrome coronavirus 2 is a highly contagious viral infection,without any available targeted therapies.The high mortality rate of COVID-19 is speculated to be related to immune damage.Methods:In this study,clinical bioinformatics analysis was conducted on transcriptome data of coronavirus infection.Results:Bioinformatics analysis revealed that the complex immune injury induced by coronavirus infection provoked dysfunction of numerous immune-related molecules and signaling pathways,including immune cells and toll-like receptor cascades.Production of numerous cytokines through the Th17 signaling pathway led to elevation in plasma levels of cytokines(including IL6,NF-kB,and TNF-a)followed by concurrent inflammatory storm,which mediates the autoimmune response.Several novel medications seemed to display therapeutic effects on immune damage associated with coronavirus infection.Conclusions:This study provided insights for further large-scale studies on the target therapy on reconciliation of immunological damage associated with COVID-19.
基金We appreciate the financial support from the National Natural Science Foundation of China(82070593,92057122,80223003,82002965 to Yongping Chen,Zhifeng Huang,Xiaokun Li,and Lintao Song)Key Project of Zhejiang Provincial Natural Science Foundation(LD21H030002,DQ24H310001 to Yongping Chen and Zhifeng Huang,China)Key Project from Science Technology Department of Wenzhou(ZY2021022 to Zhifeng Huang,China).
文摘Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.
文摘Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would benefit for the prognosis and raise the survival rate of patients.
文摘Abstract Objectives To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival and the changes of immune functions of the thymocytes and splenocytes in rats. Methods Wistar rats were irradiated with 3, 4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA Ⅲ degree burn was inflicted to the rats. Twenty four hours after the burn injury, allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before skin grafting, the bone marrow cells (4×10 8) from the same donor were also transplanted. All rats were carefully observed after injury. The rats with single radiation injury of 5 Gy gamma rays, with single burn injury and with combined radiation burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting for immunological assay and pathological study. Results All the allografts in the single burn group were rejected in 10 days. In the combined injury groups, the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were 20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy radiation, the 10 day survival rates of the allografts were 69%, 88% and 100% respectively, and the 30 day survival rates in the three groups were 36%, 42% and 100% separately. The grafted allogenic skin, with normal epithelial cells and good vascularity, healed well with the recipient's skin. Hairs grew well from the allografts 30 days after grafting. Three, 7 and 15 days after allografting, in the single burn group, the proliferative activities of the thymocytes were 90%, 185% and 130% of the preinjury level, and the antibody forming capacities of the splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the combined injury groups, the proliferative activities were 6%, 99% and 91% of the preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury level. Conclusions The survival rate of allograft in rats undergoing combined radiation and thermal burn injury rises with the increase in radiation dosage. The allograft covering single bun injury is severely rejected by immune reaction. The prolongation of the survival of allograft in combined injury group mainly results from radiation that suppresses immune functions.