The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury

Acute liver injury (ALI) is a globally important public health issue that, when severe, rapidly progresses to acute liver failure, seriously compromising the life safety of patients. The pathogenesis of ALI is defined by massive cell death in the liver, which triggers a cascade of immune responses. Studies have shown that the aberrant activation of the nod-like receptor protein 3 (NLRP3) inflammasome plays an important role in various types of ALI and that the activation of the NLRP3 inflammasome causes various types of programmed cell death (PCD), and these cell death effectors can in turn regulate NLRP3 inflammasome activation. This indicates that NLRP3 inflammasome activation is inextricably linked to PCD. In this review, we summarize the role of NLRP3 inflammasome activation and PCD in various types of ALI (APAP, liver ischemia reperfusion, CCl4, alcohol, Con A, and LPS/D-GalN induced ALI) and analyze the underlying mechanisms to provide references for future relevant studies

The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury

Acute liver injury (ALI) is a globally important public health issue that, when severe, rapidly progresses to acute liver failure, seriously compromising the life safety of patients. The pathogenesis of ALI is defined by massive cell death in the liver, which triggers a cascade of immune responses. Studies have shown that the aberrant activation of the nod-like receptor protein 3 (NLRP3) inflammasome plays an important role in various types of ALI and that the activation of the NLRP3 inflammasome causes various types of programmed cell death (PCD), and these cell death effectors can in turn regulate NLRP3 inflammasome activation. This indicates that NLRP3 inflammasome activation is inextricably linked to PCD. In this review, we summarize the role of NLRP3 inflammasome activation and PCD in various types of ALI (APAP, liver ischemia reperfusion, CCl4, alcohol, Con A, and LPS/D-GalN induced ALI) and analyze the underlying mechanisms to provide references for future relevant studies

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Citation: Dong M, Di G, Zhang X, Zhou Q, Shi W. Subconjunctival bevacizumab injection impairs corneal innervations and epithelial wound healing in mice. Invest Ophthalmol Vis Sci. 2017;58:146958: -147758: . DOI: 10.1167 PURPOSE. To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice. METHODS. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-b3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF. RESULTS. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection. CONCLUSIONS. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea