Chrysophanol administration alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast proliferation and Wnt/β-catenin signaling

Purpose: To determine the functional effect of chrysophanol (CH) on bleomycin (BLM)-induced pulmonary fibrosis (PF) and reveal its mechanism of action.Methods: A mouse model of PF was established by intratracheal instillation of BLM (5 mg/kg), prior to CH administration. Masson’s trichrome staining was used to analyze interstitial fibrosis and collagen deposition. Hydroxyproline (HYP) content was measured, and lung fibroblast viability determined by MTT assay. Bronchoalveolar lavage fluid (BALF) was collected, and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ) were evaluated using enzyme-linked immunosorbent assays (ELISA). Expression of cell signaling, adhesion, and apoptotic proteins were determined by western blotting.Results: Administration of CH reduced collagen deposition and HYP content, downregulated α-smooth muscle actin, upregulated E-cadherin, and decreased the levels of TNF-α, IL-1β, IL-6, and IFN-γ in BLM-treated mice. The viability of lung fibroblasts was also reduced, and Bcl-2-associated X protein and cleaved caspase-3 were upregulated after CH treatment in BLM-treated mice. In addition, CH treatment in BLM-treated mice significantly increased levels of cytoplasmic β-catenin but decreased its expression in the nucleus.Conclusion: Administration of CH alleviated BLM-induced PF by inhibiting lung fibroblast proliferation and nuclear translocation of β-catenin. Thus, this study provides a potential therapeutic strategy for PF. Keywords: Chrysophanol, Bleomycin, Pulmonary fibrosis, Hydroxyproline, E-cadheri

The Lyman-α\alpha Emission in a C1.4 Solar Flare Observed by the Extreme Ultraviolet Imager aboard Solar Orbiter

The hydrogen Lyman-$\alpha$ (H {\sc i} Ly$\alpha$) emission during solar flares has rarely been studied in spatially resolved images and its physical origin has not been fully understood. In this paper, we present novel Ly$\alpha$ images for a C1.4 solar flare (SOL2021-08-20T22:00) from the Extreme Ultraviolet Imager aboard Solar Orbiter, together with multi-waveband and multi-perspective observations from the Solar Terrestrial Relations Observatory Ahead and the Solar Dynamics Observatory spacecraft. It is found that the Ly$\alpha$ emission has a good temporal correlation with the thermal emissions at 1--8 \AA\ and 5--7 keV, indicating that the flaring Ly$\alpha$ is mainly produced by a thermal process in this small event. However, nonthermal electrons play a minor role in generating Ly$\alpha$ at flare ribbons during the rise phase of the flare, as revealed by the hard X-ray imaging and spectral fitting. Besides originating from flare ribbons, the Ly$\alpha$ emission can come from flare loops, likely caused by plasma heating and also cooling that happen in different flare phases. It is also found that the Ly$\alpha$ emission shows fairly similar features with the He {\sc ii} 304 \AA\ emission in light curve and spatio-temporal variation along with small differences. These observational results improve our understanding of the Ly$\alpha$ emission in solar flares and also provide some insights for investigating the Ly$\alpha$ emission in stellar flares.Comment: 19 pages, 7 figures, and 2 tables. ApJ accepted. Comments are welcom