RESUMEN
The development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic â¢OH from H2O2 via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.
Asunto(s)
Nanopartículas , Osteoartritis , Ratones , Animales , Sulfato de Cobre , Condrogénesis , Peróxido de Hidrógeno , Cartílago/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismoRESUMEN
The anaplastic lymphoma kinase (ALK) gene rearrangement is a driving mutation that underlies about 5-6% of non-small cell lung cancer (NSCLC) cases. Lung cancers that are ALK gene rearrangement-positive can be effectively treated with ALK inhibitors. However, the response of patients with rarer ALK gene rearrangements to ALK inhibitors remains unknown. Herein, we described a case of lung adenocarcinoma carrying ALK-HLA-DRB1 fusion in a 48-year-old nonsmoking woman. A similar case of ALK-HLA-DRB1 rearrangement in NSCLC has not been described previously neither in NSCLC nor in other disease. The patient achieved a progression-free survival of 18 months after sequential therapy consisting of crizotinib and then ceritinib during the follow-up. These findings provide basis for the application of ALK inhibitors in patients carrying the rare ALK-HLA-DRB1 fusion.