Background: Schistosomiasis is an immunopathogenic disease in which Th17 cells play vital roles. Hepatic granuloma formation and subsequent fibrosis are its main pathologic manifestations and the leading causes of hepatic cirrhosis, and effective therapeutic interventions are lacking. In this study, we explored the effects of fasudil, a selective RhoA–Rho-associated kinase (ROCK) inhibitor, on Th17 cells and the pathogenesis of schistosomiasis. Methods: Mice were infected with Schistosoma japonicum and treated with fasudil. The worm burden, hepatic granuloma formation, and fibrosis were evaluated. The roles of fasudil on Th17, Treg, and hepatic stellate cells were analyzed. Results: Fasudil therapy markedly reduced the granuloma size and collagen deposit in livers from mice infected with S. japonicum. However, fasudil therapy did not affect the worm burden in infected mice. The underlying cellular and molecular mechanisms were investigated. Fasudil suppressed the activation and induced the apoptosis of CD4⁺ T cells. Fasudil inhibited the differentiation and effector cytokine secretion of Th17 cells, whereas it upregulated Treg cells in vitro. It also restrained the in vivo interleukin (IL)-4 and IL-17 levels in infected mice. Fasudil directly induced the apoptosis of hepatic stellate cells and downregulated the expressions of hepatic fibrogenic genes, such as collagen type I (Col-I), Col-III, and transforming growth factor-1 (TGF-β1). These effects may contribute to its anti-pathogenic roles in schistosomiasis. Conclusions: Fasudil inhibits hepatic granuloma formation and fibrosis with downregulation of Th17 cells. Fasudil might serve as a novel therapeutic agent for hepatic fibrosis due to schistosome infections and perhaps other disorders.

Background: Mounting evidence suggested a complex correlation between host lipid metabolism and Toxoplasma gondii (T. gondii) infection. However, the inherent association between T. gondii infection and host lipid state remains elusive either in mice or in human hosts. Methods: Through a study in a sample of 1045 healthy participants from eastern China, we determined the association of T. gondii infection and host lipid levels using serological methods. We then examined the host lipid levels in C57BL/6 J mice at both acute and chronic T. gondii infection stages (for a period up to 36 weeks post infection). Results: In our case-control study, T. gondii seropositive individuals had higher low-density lipoproteins (LDL) (P = 0.0043) and total cholesterol (TC) (P = 0.0134) levels compared to seronegative individuals. Furthermore, individuals with LDL (OR = 3.25; 95% CI:1.60–6.61) and TC (OR = 2.10; 95% CI:1.22–3.63) levels above the upper limit of normal range had higher odds ratio to be T. gondii IgG positive. Consistently, in vivo data revealed that a significantly increased LDL level was first observed at early acute stage but plateaued to later time (chronic infection with T. gondii). Conclusions: In both healthy population and T. gondii-infected mice, seropositive individuals had higher LDL level. Individuals with positive T. gondii IgG had more odds of being with LDL and TC abnormality. Latent T. gondii infection is common worldwide, potential medical interventions to host lipid metabolism may be a breakthrough point to the prevention and control of this parasite infection.

Schistosomiasis is an immunopathogenic disease in which a T helper (Th) cell type 2-like response plays vital roles. Hepatic fibrosis is its main pathologic manifestations, which is the leading cause of hepatic cirrhosis. Co-infections of Schistosoma japonicum (Sj) with other pathogens are frequently encountered but are easily ignored in clinical studies, and effective therapeutic interventions are lacking. In this study, we explored the effect of Toxoplasma gondii (Tg) prior infection on Th1/Th2 response, community shifts in gut microbiome (GM), and the pathogenesis of schistosomiasis in murine hosts. Mice were prior infected with Tg before Sj infection. The effects of co-infection on Th1/Th2 response and hepatic fibrosis were analyzed. Furthermore, we investigated this issue by sequencing 16S rRNA from fecal specimens to define the GM profiles during co-infection. Tg prior infection markedly reduced the granuloma size and collagen deposit in livers against Sj infection. Prior infection promoted a shift toward Th1 immune response instead of Th2. Furthermore, Tg infection promoted the expansion of preponderant flora and Clostridiaceae was identified as a feature marker in the GM of the co-infection group. Redundancy analysis (RDA)/canonical correspondence analysis (CCA) results showed that liver fibrosis, Th1/Th2 cytokines were significantly correlated (P < 0.05) with the GM compositions. Tg infection inhibits hepatic fibrosis by downregulating Th2 immune response against Sj infection, and further promotes the GM shifts through “gut–liver axis” in the murine hosts. Our study may provide insights into potential anti-fibrosis strategies in co-infection individuals.

To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg)

Lysine acetylation is a dynamic and highly conserved post-translational modification that plays a critical role in regulating diverse cellular processes. Trichinella spiralis is a foodborne parasite with a considerable socio-economic impact. However, to date, little is known regarding the role of lysine acetylation in this parasitic nematode. In this study, we utilized a proteomic approach involving anti-acetyl lysine-based enrichment and highly sensitive mass spectrometry to identify the global acetylated proteome and investigate lysine acetylation in T. spiralis. In total, 3872 lysine modification sites were identified in 1592 proteins that are involved in a wide variety of biological processes. Consistent with the results of previous studies, a large number of the acetylated proteins appear to be involved in metabolic and biosynthetic processes. Interestingly, according to the functional enrichment analysis, 29 acetylated proteins were associated with phagocytosis, suggesting an important role of lysine acetylation in this process. Among the identified proteins, 15 putative acetylation motifs were detected. The presence of serine downstream of the lysine acetylation site was commonly observed in the regions surrounding the sites. Moreover, protein interaction network analysis revealed that various interactions are regulated by protein acetylation. These data represent the first report of the acetylome of T. spiralis and provide an important resource for further explorations of the role of lysine acetylation in this foodborne pathogen.

Ulcerative colitis inflammation is profoundly alleviated by colon-targeting delivery of low dose (0.4 mg kg⁻¹) rhamnolipid/fullerene nanocomposites via the synergism of oxidative stress mitigation and gut microbiome recovery.