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Activation of the NLRP3 inflammasome promotes pathological cardiac remodeling induced by pressure overload. However, the therapeutic effects of NLRP3 inhibition after cardiac remodeling remain unknown. The present study aimed to investigate whether the selective NLRP3 inhibitor, MCC950, could reverse transverse aortic constriction (TAC)-induced cardiac remodeling. Mice were divided into four groups based on the treatment given: sham, sham + MCC950, TAC, and TAC + MCC950. MCC950 (10 mg/kg, intraperitoneal injection, once per day) was administered from two weeks after TAC or sham surgery for four weeks. Echocardiography, histological analysis, RT-PCR, and Western blotting were performed to explore the function of MCC950 after TAC. We found that MCC950 reversed cardiac dysfunction after TAC. MCC950 attenuated cardiac hypertrophy by down-regulating calcineurin expression and inhibiting MAPK activation. Further, it also alleviated cardiac fibrosis post-TAC by inhibiting the TGF-β/Smad4 pathway, and reduced cardiac inflammation and macrophage infiltration post-TAC, including both M1 and M2 macrophages. Taken together, MCC950 can attenuate cardiac remodeling due to pressure overload by inhibiting hypertrophy, fibrosis, and inflammation. Our study provides a basis for the clinical application of NLRP3 inhibitors in the treatment of non-ischemic heart failure.

This study has investigated the impact of foaming and expansion of municipal solid waste incinerator (MSWI) bottom ash (BA) during alkali reaction. Furthermore, the activity enhancement of the BA has been investigated. Based on the microanalytic appearance and compressive strength of the samples, the results show that the reaction between the metallic aluminium in the BA and alkali in the activator, which produced large quantities of hydrogen, is the primary cause for both foaming and expansion. The residual organic matter and unburnt substances in the BA are the main factors that affect the activity. However, the alkali defoaming and calcination-melting pretreatments completely prevented the expansion and calcining further improved the BA activity. The alkali activated materials prepared with the BA calcined at 700 °C, granulated blast furnace slag, and slaked lime followed by alkali defoaming pretreatment produced the best mechanical properties.