Staphylococcus pseudintermedius (S. pseudintermedius) is a common pathogen that causes canine corneal ulcers. However, the pathogenesis remained unclear. In this study, it has been demonstrated that S. pseudintermedius invaded canine corneal epithelial cells (CCECs) intracellularly, mediating oxidative damage and pyroptosis by promoting the accumulation of intracellular reactive oxygen species (ROS) and activating the NLRP3 inflammasome. The canine corneal stroma was infected with S. pseudintermedius to establish the canine corneal ulcer model in vivo. The intracellular infectious model in CCECs was established in vitro to explore the mechanism of the ROS - NLRP3 signalling pathway during the S. pseudintermedius infection by adding NAC or MCC950. Results showed that the expression of NLRP3 and gasdermin D (GSDMD) proteins increased significantly in the infected corneas (p < 0.01). The intracellular infection of S. pseudintermedius was confirmed by transmission electron microscopy and immunofluorescent 3D imaging. Flow cytometry analysis revealed that ROS and pyroptosis rates increased in the experimental group in contrast to the control group (p < 0.01). Furthermore, NAC or MCC950 inhibited activation of the ROS - NLRP3 signalling pathway and pyroptosis rate significantly, by suppressing pro-IL-1β, cleaved-IL-1β, pro-caspase-1, cleaved-caspase-1, NLRP3, GSDMD, GSDMD-N, and HMGB1 proteins. Thus, the research confirmed that oxidative damage and pyroptosis were involved in the process of CCECs infected with S. pseudintermedius intracellularly by the ROS - NLRP3 signalling pathway. The results enrich the understanding of the mechanisms of canine corneal ulcers and facilitate the development of new medicines and prevention measures.

Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL₄)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-β/Smad signaling pathway.

Schistosomiasis, caused by Schistosoma japonicum, continues to pose a major public health threat in East Asia, with an estimated 71 million people at risk of infection. Domestic animals, especially buffaloes and goats, serve as important reservoir hosts, facilitating the transmission of the parasite to humans. While praziquantel (PZQ) is the first-line treatment for schistosomiasis due to its broad-spectrum efficacy against adult schistosomes, its prophylactic potential is less explored. This study aimed to evaluate the efficacy of PZQ in preventing S. japonicum infection in buffaloes and goats via assessing worm burden, worm size, hematological changes, and immune modulation. In the present study, buffaloes and goats were pretreated with PZQ at various doses (7–25 mg/kg body weight), followed by infection with S. japonicum cercariae. The results showed significant reductions in total worm burden and female worm burden, with one oral administration at 13 mg/kg for buffaloes and one injection at 25 mg/kg for goats offering the most robust protection. Worm length was also significantly reduced in both buffaloes and goats, indicating that PZQ not only prevented infection in this study but also inhibited worm growth. Furthermore, PZQ pretreatment modulated immune responses, as evidenced by increased levels of nitric oxide (NO) and interleukin-2 (IL-2) in buffaloes and Lym% in goats. These findings suggest that PZQ has significant prophylactic potential in livestock, offering a practical solution for reducing schistosome transmission from animals to humans in endemic regions. Additionally, this study indicates that PZQ pretreatment does not contribute to resistance development, as newly established infections are effectively cleared during the initial treatment window.

Liver fibrosis, a critical precursor to hepatocellular carcinoma (HCC), results from chronic liver injury and significantly contributes to HCC progression. Schistosomiasis, a neglected tropical disease, is known to cause liver fibrosis; however, this process can be modulated by schistosome-derived miRNAs. Previous studies from our laboratory have demonstrated that Schistosoma japonicum extracellular vesicles (EVs) deliver sja-let-7 to hepatic stellate cells, leading to the inhibition of Col1α2 expression and alleviation of liver fibrosis. Given the well-documented antifibrotic and antiproliferative properties of the let-7 miRNA family, this study aims to preliminarily investigate the effects of the sja-let-7/Col1α2 axis on BALB/c mice and HCC cell line SNU387, providing a basis for the potential application of parasite-derived molecules in HCC therapy. In the present study, schistosome-induced fibrosis datasets were analyzed to identify the role of Col1α2 in extracellular matrix organization. Pan-cancer analysis revealed that Col1α2 is upregulated in various cancers, including HCC, with significant associations with immune cell infiltration and clinical parameters, highlighting its diagnostic importance. Functional assays demonstrated that transfection with sja-let-7 mimics significantly reduced Col1α2 expression, inhibited HCC cell proliferation, migration, and colony formation. These findings suggest that sja-let-7, by targeting Col1α2, has the potential to serve as a therapeutic agent in HCC treatment. This study indicates the pivotal role of Col1α2 in liver fibrosis and HCC, and the promising therapeutic application of helminth-derived miRNAs.

Schistosomiasis remains an important zoonotic parasitic disease, and hepatic fibrosis is a major cause of chronic pathology following Schistosoma japonicum