Scutellarin inhibits caspase-11 activation and pyroptosis in macrophages via regulating PKA signaling

@#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.

Investigation on incidence and risk factors of pressure ulcer in surgical patients / 中国基层医药

Objective To discuss the incidence and risk factors of pressure ulcer in surgical patients of our hospital.Methods Totally 10 737 surgical patients were recruited.The patients were assessed by the Braden Scale. The incidence of pressure ulcer in patients with the Braden score lower than 18 was recorded.Besides,the data of patients with pressure ulcers on admission were also collected.All risk factors in patients with pressure ulcer were ana-lyzed.Results The incidence rate of pressure ulcer in surgical patients was 0.54%.The incidence of pressure ulcer was highest in department of Neurosurgery(1.46%),followed by the department of Orthopedics(0.61%),which was significantly higher than other departments,the difference was statistically significant(P <0.05).Single factor analy-sis indicated that age,smoking,nutrition,diabetes,paralysis,and large,urinary incontinence,consciousness,operation situation,serum albumin,use of analgesics,presence of caregivers contributed to pressure ulcer,the difference was sta-tistically significant(P <0.05).Multivariable logistic regression analysis showed that age,diabetes,paralysis,con-sciousness,albumin levels,use of analgesic,presence of caregivers were independent risk factors of pressure ulcers in patients.Conclusion There are many factors affecting the incidence of pressure ulcer,while age,diabetes,paralysis, consciousness,albumin levels,use of analgesic,presence of caregivers are independent risk factors of pressure ulcers.