The increased incidence of inflammatory bowel disease (IBD) has seriously affected the life quality of patients. IBD develops due to excessive intestinal epithelial cell (IEC) apoptosis, disrupting the gut barrier, colonizing harmful bacteria, and initiating persistent inflammation. The current therapeutic approaches that reduce inflammation are limited. Although IBD can be treated significantly by directly preventing IEC apoptosis, achieving this therapeutic approach remains challenging. Accordingly, we are the first to develop an oral pifithrin-α (PFTα, a highly specific p53 inhibitor) embedded nanomedicine (OPEN) to effectively treat IBD by inhibiting excessive IEC apoptosis. As a major hub for various stressors, p53 is a central determinant of cell fate, and its inhibition can effectively reduce excessive IEC apoptosis. The tailored OPEN can precisely inhibit the off-target and inactivation resulting from PFTα entry into the bloodstream. Subsequently, it persistently targets IBD lesions with high specificity to inhibit the pathological events caused by excessive IEC apoptosis. Eventually, OPEN exerts a significant curative effect compared with the clinical first-line drugs 5-aminosalicylic acid (5-ASA) and dexamethasone (DEX). Consequently, the OPEN therapeutic strategy provides new insights into comprehensive IBD therapy. This article is protected by copyright. All rights reserved
Tissue-like cultured meats of some livestock have successfully been established by different approaches. However, the production of a structure similar to fish fillets is still challenging. Here, we develop tissue-like cultured fish fillets by assembly of large yellow croaker muscle fibers and adipocytes with 3D-printed gel. Inhibition of Tgf-β and Notch signals significantly promoted myogenic differentiation of piscine satellite cells (PSCs). The mixture of fish gelatin and sodium alginate combined with a p53 inhibitor and a Yap activator supported PSC viability and proliferation. Based on the texture of fish muscle tissue, a 3D scaffold was constructed by gelatin-based gel mixed with PSCs. After proliferation and differentiation, the muscle scaffold was filled with cultured piscine adipocytes. Finally, tissue-like fish fillets with 20 × 12 × 4 mm were formed, consisting of 5.67 × 10 7 muscles and 4.02 × 10 7 adipocytes. The biomanufacture of tissue-like cultured fish fillet here could be a promising technology to customize meat production with high fidelity.
危险品化学品经营许可证（带存储）