NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses:implications of NETosis inhibition for acne skin inflammation treatment

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections.Thus,inflammasomes participate in many conditions,such as acne.Recently,it was shown that NETosis,a type of neutrophil cell death,is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes.However,the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied.In this study,we determined whether NETosis is induced in P.acnes-induced skin inflammation and whether activation of the nucleotide-binding domain,leucine-rich family,and pyrin domain-containing-3(NLRP3)inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation.We found that NETosis was induced in P.acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P.acnes-induced skin inflammation.In addition,our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin.These results indicate that inflammasomes and NETosis can interact with each other to induce P.acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.

GnRH impairs diabetic wound healing through enhanced NETosis

It has been reported that neutrophil extracellular traps(NETs)impair wound healing in diabetes and that inhibiting NET generation(NETosis)improves wound healing in diabetic mice.Gonadotropin-releasing hormone(GnRH)agonists are associated with a greater risk of diabetes.However,the role of GnRH in diabetic wound healing is unclear.We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing.A mouse model of diabetes was established using five injections with streptozotocin.Mice with blood glucose levels>250 mg/dL were then used in the experiments.GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice.In contrast,GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing.The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients.In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate(PMA)-induced NETosis in mouse and human neutrophils.Furthermore,GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis,which were increased by GnRH treatment.These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds.Thus,inhibition of GnRH might be a novel treatment of diabetic foot ulcers.

尼可地尔在经皮冠状动脉介入治疗不稳定心绞痛时对心肌的保护作用

心肌损伤通常在经皮冠状动脉介入治疗(PCI)过程中出现,并且损伤可以通过对心肌酶的测试使之容易被监控。众所周知,尼可地尔是三磷酸腺苷ATP-敏感的K+通道的开启器,通过减小作用电位从而具有抗心律失常效应和保护心脏作用。比如,通过松弛血管平滑肌以减少微冠状动脉血流阻力。研究尼可地尔的心肌保护作用,IONA研究(尼可地尔对心绞痛的作用)即大规模对稳定型心绞痛进行的研究表明,尼可地尔口服给药能够减少冠心病致死率和非致命型心肌梗塞或胸痛意外住院治疗。目前已经对数个不稳定心绞痛(UAP)或急性心肌梗塞病人进行了尼可地尔心脏保护效应的研究评估,但还没有进行大规模研究。此研究的目的在于通过对经尼可地尔注射并PCI治疗12~48h后的不稳定心绞痛患者的心肌酶进行评估来预期考察尼可地尔的心脏保护作用。

尼可地尔在经皮冠状动脉介入治疗不稳定心绞痛时对心肌的保护作用

2结果 在200例患者中,36例由于其胸痛不是缺血性心脏病引起的而被排除,9例由于胸痛难以控制在给药12h内需要进行紧急冠状动脉造影术,另外155例在给药12-48h间进行选择性冠状动脉造影术。在155例中,39例没有明显表现出冠状动脉狭窄,13例由于PCI没有表明因此进行了冠状动脉旁路移植术或内科治疗,结果,103例患者接受了PCI,由于没有血液回流或旁支路闭塞,6例按计划或因需要抢救服用IIb／IIIa抑制剂，1例由于完全性心脏传导阻滞需抢救而使用临时起搏器．

尼可地尔在经皮冠状动脉介入治疗不稳定心绞痛时对心肌的保护作用

（接2017年12月下） 3讨论 PCI治疗中的冠状动脉疾病患者均出现了心肌肌钙蛋白浓度升高的现象,这是由于PCI过程中心肌细胞被破坏所致。然而,心肌肌钙蛋白浓度并没有很好地被用于监测成功PCI之后对心肌细胞的破坏作用。心肌肌钙蛋白是控制心肌收缩的一种蛋白,且在正常的血液中不会被检测到,因为它是心脏特性指标,

尼可地尔在经皮冠状动脉介入治疗不稳定心绞痛时对心肌的保护作用

1.2冠状动脉造影术和PCI冠状动脉造影术主要利用5或6号法国冠状动脉插管器（Judkins或Amplatz）作用于桡动脉或者股动脉。损伤按照美国大学心脏学/美国心脏学会（ACC/AHA）标准进行分类,冠状动脉血流量用心肌梗塞中血栓的溶解来评估。