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@#Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.
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Objective To observe the curative and poison side effect of the chemical and heat treatment in treating the middle and late period NSCLC. Methods There are forty-seven middle and late patients, all of them for three weeks by using the Hp plan. The heat treatment group(24) :on the first day,the patients use the heat treatment twice a week,four times a period;the comparision group(23) :give them the chemical treatment by using the same method,but dont give them the heat treatment. To observe the recent treatment effect and the poison side effect. Re-suits The heat treatment group is better than the comparision group. But it doesn't have the statistic sianificance(P>0.05 ), then we observe the pathology, the effect of the glandular cancer in heat treatment group (46.2%) is better than the comparision group(25.0% ) ( P<0.05 ). The poison side effect mostly depends on the first and second de-gree. The heat treatment group is better than the comparision group. But it has no statistic significance ( P>0.05 ).Conclusion The chemical and the heat treatment to treat the middle and late NSCLC,the patients completly support (bear). The recent treatment effect is better than the single chemical effect. Especially the effect of the glandular cancer is the best by using the heat treatment.