摘要: Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, and has become one of the most common diseases worldwide. In OA cartilage, various forms of cell death have been identified, including apoptosis, necroptosis and autophagic cell death. Ever-growing observations indicate that ferroptosis, a newly-discovered iron-dependent form of regulated cell death, is detrimental to OA occurrence and progression. In this review, we first analyse the pathogenetic mechanisms of OA by which iron overload, inflammatory response and mechanical stress contribute to ferroptosis. We then discuss how ferroptosis exacerbates OA progression, focusing on its impact on chondrocyte viability, synoviocyte populations and extracellular matrix integrity. Finally, we highlight several potential therapeutic strategies targeting ferroptosis that could be explored for the treatment of OA.

摘要: The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investigation revealed increased neural differentiation and decreased proliferation under heat stimulation, indicating that periodic heat exposure might lead to abnormal brain development by altering key developmental processes. Hence, our model of periodically heating brain organoids provides a platform for modelling the effects of maternal fever on foetal brain development and could be extended to applications in neurodevelopmental disorders intervention.

摘要: During the embryonic developmental stage in vertebrates, internal organs are arranged along the left-right axis. Disruptions in this process can result in congenital diseases or laterality disorders. The molecular mechanisms of left-right asymmetry in vertebrate development remain largely unclear. Due to its straightforward structure, zebrafish has become a favoured model for studying early laterality events. Here, we demonstrate that growth and development factor 11 (Gdf11) is essential for left-right development via TGF-beta signalling. Morphological analysis showed that gdf11 morphants and mutants displayed clear heart and liver laterality disorders in a Nodal signal-dependent manner. Additionally, we found that Kupffer's vesicle formation and ciliogenesis were impaired following gdf11 deletion. We also observed that Gdf11 may form a heterodimer with Spaw, which promotes Smad2/3 phosphorylation and activates TGF-beta signalling. Subsequently, Gdf11 promotes left-right laterality by stimulating Foxj1a and its target gene expression. In summary, we reveal a critical role of Gdf11 in left-right patterning, providing fundamental insights into the developmental process of left-right asymmetry.