Naru-3 inhibits inflammation, synovial hyperplasia, and neovascularization in collagen-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Naru-3 is a prescribed formulation based on the theory of Mongolian medicine for the treatment of rheumatoid arthritis (RA). Naru-3 consists of three medicinal agents: Aconitum kusnezoffii Reichb (caowu), Terminalia chebula Retz (hezi), and Piper longum L (biba). These medicinal agents are widely distributed in the Mongolian area of China and have been used to treat rheumatism for centuries. BACKGROUND: Mongolian medicine Naru-3 is commonly prescribed to treat RA, but its mechanism of action is unknown. METHODS: A rat collagen-induced arthritis (CIA) model was established to investigate the mechanism of Naru-3. Rats were treated with Naru-3, Etanercept (ETN), and sodium carboxymethylcellulose (CMC) for four weeks. After treatment was terminated, paw thickness, ankle diameter, and arthritis index (AI) were scored. Synovial hyperplasia was evaluated using hematoxylin and eosin (H&E) staining and two-dimensional ultrasonography. Synovitis and neovascularization were assayed using power Doppler imaging (PDI) and contrast-enhanced ultrasonography (CEUS). Levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1, and CD31 in the serum or synovium were detected using ELISA and immunohistochemistry analyses. RESULTS: Naru-3 and ETN alleviated the symptoms of CIA as evidenced by diminished paw thickness, ankle diameter, and AI scores. Mechanistically, Naru-3 inhibited synovial hyperplasia, synovitis, and neovascularization by diminishing systemic and local inflammation, as indicated by the relative expression of CD31, VEGF and IL-1 in the serumor synovium. After four weeks of treatment, no significant neovascularization was observed in the Naru-3 group, but neovascularization and synovitis occurred in the ETN group, as demonstrated by H&E staining, PDI, and CEUS examination. CONCLUSION: Naru-3 inhibited inflammation, synovial hyperplasia, and neovascularization and alleviates RA in our CIA rat model. No symptom recurrence was observed four weeks after drug treatment.

Gene therapy for cystic fibrosis: Challenges and prospects.

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.