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1.
Cell Signal ; 120: 111220, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38740234

RESUMEN

Synovitis and cartilage destruction are crucial characteristics of osteoarthritis (OA). Inflammatory cytokines, such as IL-1ß, are secreted by synovial macrophages, leading to cartilage destruction. Pyroptosis is a lytic form of programmed cell death, which could be triggered by the NLRP3 inflammasome of macrophages. Pyroptosis promotes the secretion of IL-1ß and is supposed as a potential biomarker for OA. However, the function of Pyroptosis and NLRP3 inflammasome and its regulatory mechanism for activation is unclear in OA. In this study, we found that Degrasyn could alleviate the GSDMD-mediated pyroptosis of macrophages and the release of IL-1ß, caspase-1, and LDH. Furthermore, it selectively impedes the form of ASC oligomer and speckle to effectively suppress the NLRP3 inflammasome during its assembly phase. Notably, Degrasyn exhibited potential chondroprotective effects in a co-culture system. Additionally, these results also indicate that Degrasyn mitigates synovitis and cartilage damage in a murine model of destabilization of the medial meniscus (DMM)-induced OA. In summary, Degrasyn emerges as a promising pharmaceutical agent for synovitis, paving the way for innovative therapeutic approaches to OA. Our findings underscore the potential of Degrasyn as a viable candidate for OA therapeutics, demonstrating its ability to regulate pyroptosis and NLRP3 inflammasome activation.


Asunto(s)
Condrocitos , Péptidos y Proteínas de Señalización Intracelular , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Osteoartritis , Proteínas de Unión a Fosfato , Piroptosis , Transducción de Señal , Piroptosis/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/tratamiento farmacológico , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/patología , Ratones , Transducción de Señal/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Proteínas de Unión a Fosfato/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Inflamasomas/metabolismo , Ratones Endogámicos C57BL , Masculino , Humanos , Células RAW 264.7 , Interleucina-1beta/metabolismo , Gasderminas
2.
Macromol Rapid Commun ; 43(22): e2200119, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35467054

RESUMEN

Two polymerized naphthalimide derivatives, named as N-TBHOB and N-DBH, are prepared by quaternization. They exhibit excellent performance as electron-transport layers (ETLs) in inverted organic solar cells (i-OSCs). The results indicate N-TBHOB with a reticulated structure owns a superior performance on electron extraction, electron transport, thickness tolerance, and less carrier recombination compared with N-DBH with linear structure. The i-OSCs based on N-TBHOB with PTB7-Th:PC71 BM as the active layer achieve power conversion efficiencies (PCEs) of 10.72% and 10.03% under the thickness of 11 and 48 nm respectively, which indicates N-TBHOB possesses better thickness tolerance than most of organic ETLs in i-OSCs. N-TBHOB also shows more competent performance than N-DBH and ZnO in nonfullerene i-OSCs for comprehensively improved Jsc , Voc , and fill factor (FF) values. Its i-OSC with PM6:Y6 blend presents a high PCE of 16.78%. The study provides an efficient strategy to prepare ETLs by combining conjugated and nonconjugated units with a reticulated structure in the backbone for high-performance i-OSCs.

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