Enhanced Experimental Corneal Neovascularization along with Aberrant Angiogenic Factor Expression in the Absence of IL-1 Receptor Antagonist

PURPOSE. To address the roles of the endogenously produced IL-1ra in the course of corneal neovascularization (CNV). METHODS. CNV was induced by alkali injury and compared in wild-type (WT), IL-1 receptor antagonist (ra) knockout (KO) mice and anti-IL-1ra antibody-treated WT mice 2 weeks after injury. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by RT-PCR and immunohistochemical analysis, respectively. RESULTS. The mRNA expression of IL-1ra, IL-1␣, and IL-1␤ was augmented, together with infiltration of F4/80 ϩ macrophages and Gr-1 ϩ neutrophils, in corneas after alkali injury. Intracorneally infiltrating macrophages, but not neutrophils, expressed IL-1ra. Compared with WT mice, either IL-1ra KO mice or anti-IL-1ra antibody-treated WT mice exhibited enhanced CNV 2 weeks after injury, as evidenced by enlarged CD31 ϩ areas. Concomitantly, the infiltration of F4/80 ϩ macrophages was more significantly enhanced in IL-1ra KO mice than in WT mice. Intraocular mRNA expression enhancement of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) was greater in IL-1ra KO mice than in WT mice after injury. Moreover, IL-1␣ and IL-1␤ enhanced VEGF and iNOS expression by murine peritoneal macrophages. CONCLUSIONS. IL-1ra KO exhibited enhanced alkali-induced CNV through enhanced intracorneal macrophage infiltration and increased expression of VEGF and iNOS. (Invest Ophthalmol Vis Sci. 2009;50:4761-4768

Additional file 1 of Global, regional, and national burdens of intraocular foreign bodies in children and adolescents from 1990 to 2019: a trend analysis

Supplementary Material

Extraction, Purification, Characterization, and Antiangiogenic Activity of Acidic Polysaccharide from Buddleja officinalis

Firstly, optimal parameters of crude polysaccharide from Buddleja officinalis were obtained as follows: ratio of water to raw material of 26 : 1, ultrasonic power of 240 W, ultrasonic time of 45 min, and ultrasonic temperature of 62°C. Secondly, acidic polysaccharide (APBOM) from Buddleja officinalis was successfully acquired with the yield of 9.57% by using DEAE-52 cellulose and Sephadex G-100 gel column chromatography. Then, we found that total polysaccharide content of APBOM was 94.37% with a sulfuric acid group of 1.68%, uronic acid content of 17.41%, and average molecular weight of 165.4 kDa. Finally, APBOM was confirmed to have significant antiangiogenic effects

Effect of <i>Trichinella spiralis</i>-Derived Antigens on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice

Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. No approved effective therapeutic medicine is available to date for NAFLD. Helminth therapy is believed to be a novel direction and therapeutic strategy for NAFLD. Our previous study showed that Trichinella spiralis-derived antigens (TsAg) had the potential for partially alleviating obesity via regulating gut microbiota. However, the effect of TsAg on NAFLD remains unclear. In this study, high-fat diet (HFD)-induced model mice were treated with TsAg and microbiota transplantation experiments, and alterations in the pathogenesis of nonalcoholic liver disease were assessed. The results showed that TsAg markedly reduced hepatic steatosis, improved insulin resistance, and regulated the abnormal expression of hepatic lipid-related genes. Of note, TsAg ameliorated hepatic inflammation by decreasing pro-inflammatory TNF-α and IL-1β, suppressing hepatic macrophage infiltration, as well as promoting M2 macrophage polarization. Moreover, TsAg reversed gut dysbiosis, as especially indicated by an increase in beneficial bacteria (e.g., Akkermansiaceae and Rikenellaceae). Furthermore, our study found that TsAg reduced LPS hepatic translocation and hepatic TLR4/NF-κB signaling, which further contributed to inhibiting hepatic inflammation. In addition, TsAg inhibited hepatic oxidative stress involving Nrf2/NQO-1 signaling. Microbiota transplantation showed that TsAg-altered microbiota is sufficient to confer protection against NAFLD in HFD-induced mice. Overall, these findings suggest that TsAg involving gut–liver axis and Nrf2/NQO-1 signaling is a novel promising candidate for NAFLD treatment. TsAg restores intestinal microbiota and intestinal barrier to inhibit bacteria and LPS translocation into the liver, contributing to reduce inflammation, oxidative stress, and hepatic steatosis in the liver of NAFLD mice. The effects were attributed to, at least in part, the inactivation of NF-κB pathway and the activation of Nrf-2/NQO-1 pathway. This study provides new insights for understanding immune modulation by T. spiralis-derived products as well as the potential application of TsAg as a modality for NAFLD