Ambient atmospheric PM worsens mouse lung injury induced by influenza A virus through lysosomal dysfunction.

BACKGROUND: Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. RESULTS: Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. CONCLUSIONS: Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.

Orally administered BZL-sRNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice.

The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.

Lepidium meyenii Walp Exhibits Anti-Inflammatory Activity against ConA-Induced Acute Hepatitis.

Strong inflammation is a prominent pathogenesis of acute hepatitis, which can induce hepatocyte death and lead to liver failure. Lepidium meyenii Walp (Maca) is a traditional herbal medicine mostly used in improving sperm motility and serum hormone levels, etc. However, there are no reports that showed Maca was designed for treating hepatitis so far. Therefore, the protective effects and pharmacological mechanisms of Maca are unknown in hepatitis. In this study, we found that the protective effects of Maca extract ameliorate ConA-induced acute hepatitis (CIH) and underlying mechanisms. We determined that pretreatment with Maca extract significantly suppressed the production of aminotransferases and inflammatory cytokines, including IFN-γ, TNF-α, IL-1ß, IL-2, IL-6, IL-12, and IL-17a, and moderated acute liver injury in CIH. Maca recruited more myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of natural killer T cells (NKT cells) and macrophages in the liver. Furthermore, our data indicated the molecular mechanism of the inhibitory inflammatory effects of Maca, which should suppress the activation of NF-κB, IFN-γ/STAT1, and IL-6/STAT3 signalings. Collectively, this present research explores Maca as an effective hepatoprotective medicine to inhibit inflammation and liver injury caused by acute hepatitis.