Int J Med Sci
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Background and aims: Macrophages play a critical role in the development of liver diseases. As an NAD+-dependent histone deacetylase, SIRT1 inhibits liver inflammation and fibrosis, but the mechanisms are not fully understood. Our aim was to investigate the molecular mechanism of SIRT1 in macrophages in liver inflammation and fibrosis. ⋯ Nevertheless, knockdown of NF-κB or NLRP3 and activation of SIRT1 inhibited inflammation of macrophages; inhibition or knockdown of SIRT1 enhanced macrophage inflammation. Furthermore, activation of SIRT1 could inhibit LPS-treated macrophages from activating hepatic stellate cells (HSCs). Conclusions: Activating SIRT1 inhibits the inflammation in macrophages by down-regulating NLRP3 pathway through deacetylating NF-κB p65, which in turn inhibits the activation of HSCs to alleviate hepatic inflammation and fibrosis.
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Rabies continues to be a huge threat to public health. The rabies virus envelope glycoprotein (RABV G) is a major rabies virus antigen and contains neutralizing epitopes, which are primary candidates for subunit vaccines and diagnostic antigens. However, the production and purification of rRABV G while retaining its antigenic and immunogenic remains to be a challenge. ⋯ Notably, we observed a neutralizing antibody response in immunized pigs rather than in mice. This discrepancy could potentially be attributed to factors such as the instability of the rRABV G protein, variations in host responses, and variances in the adjuvant used. Taking all these findings into account, the rRABV G protein generated in this study exhibits promise as a potential vaccine candidate for the prevention of rabies.
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Background: As a component of nucleosomes, histone H3 plays an important role in chromosome structure and gene expression. Current studies have mostly focused on the role of histones in epigenetics, but in addition to this, the role of histones themselves in tumor development and microenvironment have been less explored. Methods: Western blot and immunofluorescence were carried out to detect the content and localization of histone H3 in hepatocellular carcinoma. ⋯ We further demonstrated that histone H3 could also promote proliferation and metastasis of hepatocellular carcinoma through TLR9 activation of NLRP3 inflammasome. In addition, overexpression of histone H3 was also confirmed to promote hepatocellular carcinoma proliferation and metastasis in mouse models of hepatocellular carcinoma growth assay and lung metastasis. Conclusions: In hypoxic hepatocellular carcinoma cells, histone H3 can translocate to the cytoplasm and activate caspase-1 via TLR9, thereby producing pro-inflammatory cytokines that promote tumor proliferation and metastasis.
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Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. ⋯ Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.
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The SARS-CoV-2 Omicron is currently the predominant circulating variant in the COVID-19 pandemic. The dominating Omicron sublineages respond to host immune pressure and develop advantageous mutations or genetic recombination, which result in variants that are more contagious or better at escaping immune responses in response to previous infection or vaccination. Meanwhile, multiple genetic recombination events have been reported in coinfection cases, the majority of which have resulted from the recombination between co-circulating Omicron BA.1 (or BA.1.1) and Delta variant or BA.2. Here, we review the knowledge and characterization of recombination for SARS-CoV-2 at the population level, provide an update on the occurrence of newly circulating Omicron sublineages, and discuss the effectiveness of novel vaccines/therapeutic drugs against the Omicron variant.