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Pyroptosis is a form of pro-inflammatory cell death that can be mediated by gasdermin D (GSDMD) activation induced by inflammatory caspases such as caspase-1. Emerging evidence suggests that targeting GSDMD activation or pyroptosis may facilitate the reduction of vascular inflammation and atherosclerotic lesion development. The current study investigated the therapeutic effects of inhibition of GSDMD activation by the novel GSDMD inhibitor N-Benzyloxycarbonyl-Leu-Leu-Ser-Asp(OMe)-fluoromethylketone (Z-LLSD-FMK), the specific caspase-1 inhibitor N-Benzyloxycarbonyl-Tyr-Val-Ala-Asp(OMe)-fluoromethylketone (Z-YVAD-FMK), and a combination of both on atherosclerosis in ApoE−/− mice fed a western diet at 5 weeks of age, and further determined the efficacy of these polypeptide inhibitors in bone marrow-derived macrophages (BMDMs). In vivo studies there was plaque formation, GSDMD activation, and caspase-1 activation in aortas, which increased gradually from 6 to 18 weeks of age, and increased markedly at 14 and 18 weeks of age. ApoE−/− mice were administered Z-LLSD-FMK (200 µg/day), Z-YVAD-FMK (200 µg/day), a combination of both, or vehicle control intraperitoneally from 14 to 18 weeks of age. Treatment significantly reduced lesion formation, macrophage infiltration in lesions, protein levels of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, and pyroptosis-related proteins such as activated caspase-1, activated GSDMD, cleaved interleukin(IL)-1β, and high mobility group box 1 in aortas. No overt differences in plasma lipid contents were detected. In vitro treatment with these polypeptide inhibitors dramatically decreased the percentage of propidium iodide-positive BMDMs, the release of lactate dehydrogenase and IL-1β, and protein levels of pyroptosis-related proteins both in supernatants and cell lysates elevated by lipopolysaccharide + nigericin. Notably however, there were no significant differences in the above-mentioned results between the Z-LLSD-FMK group and the Z-YVAD-FMK group, and the combination of both did not yield enhanced effects. These findings indicate that suppression of GSDMD activation by Z-LLSD-FMK or Z-YVAD-FMK reduces vascular inflammation and lesion development in ApoE−/− mice.

Brookite TiO2, the latest TiO2 photocatalyst, promises to be an interesting candidate for photocatalytic applications because of its unique physical and chemical properties. In this study, pure-phase brookite TiO2 with a quasi-spherical nanostructure was successfully synthesized via a solvothermal method using tetrabutyl titanate (Ti(OC4H9)4, TBOT) as the Ti source in the presence of oxalic acid. NaOH was used to regulate the pH of solution. The structure and morphology of the samples were then analyzed using multiple methods, such as X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) measurements and ultraviolet-visible diffuse spectroscopy (UV-Vis). Photocatalytic activities of the as-synthesized brookite TiO2 were evaluated by degrading aqueous methylene blue solution under UV light irradiation. The effect of thermal treatment temperature on photocatalytic activity of the samples was also investigated. The produced brookite TiO2 nanopowders calcined at 500 °C for 2 h showed the highest photocatalytic activity, and the corresponding degradation rate of methylene blue (10 mg/L) reached 96.7% after 90 min of illumination. In addition, the formation mechanism of pure-phase brookite TiO2 was investigated. It was found that the formation of pure-phase brookite TiO2 in this study was ascribed to the combined action of oxalic acid and sodium hydroxide. [ABSTRACT FROM AUTHOR]