Anti-FADD monoclonal antibody, clone FQ998Z

Osteoarthritis (OA) is a prevalent debilitating disease which is predominantly characterized by cartilage degeneration. In the current study, destabilization of the medial meniscus (DMM) mouse model was used to investigate the effects of Antarctic krill peptides (AKP) on cartilage protection. As observed, AKP clearly ameliorate cartilage degeneration as evidenced by increased cartilage thickness and cartilage area and decreased histological Osteoarthritis Research Society International (OARSI) scores. Toluidine blue staining showed that AKO remarkably inhibited the loss of cartilage matrix in mice with OA. Hypoxia-inducible factor-2 alpha (HIF-2 alpha) has a key role in catabolic regulation and inflammation cascades which are the main causes of OA. AKP can down-regulate the expression of HIF-2 alpha and its downstream genes such as MMP-13, Adamts-S, IL-1 beta, iNOS, CXCL-1, and NOS2. Consistent with this, anabolic genes such as Acan and Col2 alpha 1 were restored after treatment with AKP. Chondrocyte apoptosis and the reduction in cartilage cell viability are also involved in the process of OA. The HIF-2 alpha-mediated death receptor apoptosis signaling pathway has been involved in the regulation of chondrocyte apoptosis. AKP can reduce the expressions of key pro-apoptosis genes in Fas-FasL and DR3-DR3L signaling pathways such as Fas, FasL, FADD, caspase8, caspase3, DR3, DR3L, RIP, and NF-kappa B. In addition, expressions of antiapoptosis genes such as c-AIP and c-FLIP were increased significantly. These findings indicate that AKP can be used as a new functional factor in the development of functional foods and chondroprotective drugs.

Background The objective of this study was to clarify the molecular pathways involved in hepatitis B virus (HBV)-induced hepatoblastoma. Method The expression of factors in different signaling pathways (H19, miR-675, miR-138, protein tyrosine kinase 2 [PTK2], fas-associated death domain [FADD], hypoxia-inducible factor 1-alpha [HIFIA], focal adhesion kinase [FAK], caspase-8, and caspase-3) was compared between HBV (+) and HBV (-) groups using quantitative real-time polymerase chain reaction and Western blot analysis. Subsequently, immunohistochemistry (IHC) and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays were used to verify the expression of above proteins in HBV (+) and HBV (-) groups. Computational analysis was conducted to predict the target genes of miR-675 and miR-138, whose regulatory relationships were then clarified using luciferase assays and cell transfection studies. Result The expression of H19, miR-675, PTK2, HIFIA, and FAK was increased in the HBV (+) group, while the expression of miR-138, FADD, caspase-8, and caspase-3 was decreased in the HBV (+) group. FADD and PTK2 were identified as target genes of miR-675 and miR-138, respectively. In addition, miR-675 was upregulated while miR-138 was downregulated by X protein (HBx). Conclusion In summary, the results of this study revealed the molecular pathways involved in HBV-induced hepatoblastoma. In the presence of HBV, HBX upregulated the expression of H19 through HIFIA. Consecutively, overexpressed H19 upregulated the expression of PTK2 via targeting miR-138 and downregulated the expression of FADD via targeting miR-675. Finally, increased expression of PTK2 and reduced expression of FADD both led to the inhibition of cell apoptosis, thus promoting the tumorigenesis of hepatoblastoma.