No abstract

Liver X receptors (LXRs) are nuclear receptors that play a central role in cholesterol metabolism. When activated, LXRs induce a series of genes that are involved in cholesterol efflux, absorption, transport and excretion. In recent studies, LXRs have also been shown to play an important role in inflammatory signaling. LXR agonists show promise as potential therapeutics, given their anti-atherogenic and anti-inflammatory properties. The function of LXRs in cholesterol efflux and inflammatory signaling make them attractive as therapies for cardiovascular and inflammatory diseases.

Our results suggest a critical role for cathepsin B as activators of proinflammatory caspases-11 and the regulatory effect in LPS-induced caspases-11-dependent necrosis.

To investigate the effect and mechanism of macrophage membrane-coated nanoparticles (M-NPs) on hepatic ischemia-reperfusion injury (I/RI) caused by orthotopic liver transplantation. In addition, the advantages of TLR4 + /M-NPs compared to M-NPs are discussed. Materials and Methods: We prepared biomimetic M-NPs and identified their characteristics. M-NPs were injected into an SD rat model of orthotopic liver transplantation, and the anti-inflammatory and anti-I/RI activities of M-NPs were studied in vivo and in vitro. In addition, we overexpressed macrophage membrane Toll-like receptor 4 (TLR4) in vitro and prepared TLR4+/M-NPs. Then, we assessed the characteristics and advantages of TLR4 +/M-NPs. Results: The M-NPs neutralized endotoxin, inhibited the overactivation of Kupffer cells (KCs) and suppressed the secretion of inflammatory factors by inhibiting the endotoxinmediated TLR4/MyD88/IRAK1/NF-κB signaling pathway. In an orthotopic liver transplantation model in SD rats, M-NPs showed significant therapeutic efficacy by neutralizing endotoxin and suppressing the secretion of inflammatory factors. Moreover, overexpression of TLR4 on the macrophage membrane by using a TLR4 +-plasmid in vitro effectively reduced the amount of M-NPs needed to neutralize an equivalent dose of endotoxin, reducing the potential risks of NP overuse. Conclusion: This study indicates that M-NPs can effectively alleviate I/RI induced by liver transplantation.

Sirtuin 1 (SIRT1) is an NAD(+)-dependent deacetylase, and a critical regulator in various metabolic processes, such as non-alcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether activating SIRT1 could modulate the CD36 and nuclear factor (NF)-κB pathways to protect against liver injury induced by a high-fat diet (HFD) in mice. A mouse NAFLD model was established by administration of a HFD for 8 weeks. During the last 4 weeks, SRT1720, a specific SIRT1 activator, was added daily to the HFD feed. The hepatic morphological structure was observed using hematoxylin and eosin staining, and the ultrastructures in the liver tissue were observed using transmission electron microscopy. Protein expression of SIRT1, CD36 and P65 in liver tissues was detected by immunohistochemistry. Kupffer cells (KCs) from the livers of the mouse models were isolated to determine the mRNA and protein expression of SIRT1, CD36 and P65. SIRT1 activation attenuated the HFD-induced liver injury and significantly reduced the body weight and the levels of alanine transaminase, aspartate aminotransferase, triglyceride, tumor necrosis factor-α and interleukin-6. We observed an increased expression of SIRT1 in the liver tissues from the HFD+SRT1720 group compared with the HFD group. Simultaneously, the expression of CD36 and P65 in the liver tissues was downregulated in the HFD+SRT1720 group. The mRNA and protein expression of SIRT1 was elevated in the HFD+SRT1720 group, whereas the mRNA and protein expression of CD36 and P65 in KCs was significantly decreased in the HFD+SRT1720 group. The present study demonstrated that SIRT1 activation attenuated HFD-induced liver steatosis and inflammation by inhibiting CD36 expression and the NF-κB signaling pathway.

No abstract

No abstract

No abstract