Bioinformatics analysis of SARS-CoV-2 infectionassociated immune injury and therapeutic prediction for COVID-19

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.

Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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.

Up-regulation of Tim-3 Expression Contributes to Development of Burn-induced T Cell Immune Suppression in Mice

T cell immunoglobulin and mucin domain 3 （Tim-3） is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3＋ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4＋ and CD8＋ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3＋ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

The Pathogenesis of Acute on Chronic Hepatitis B liver Failure

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.

Effects of combined radiation and thermal burn injury on the survival of skin allograft and immune function in rats

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.