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Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献3.
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Weiping Ren Bin Wu Xin Peng Jing Hua Hsiao-Nan Hao Paul H Wooley 《Journal of orthopaedic research》2006,24(8):1575-1586
Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response. 相似文献
5.
β-胡萝卜素立体异构体对环磷酰胺处理小鼠免疫功能的比较研究 总被引:3,自引:0,他引:3
就β-胡萝卜素立体异构体对环磷酰胺处理小鼠的免疫功能影响进行了比较研究。结果显示β-胡萝卜素立体异构体对外磷酰胺造成的免疫功能低下具有不同程度的改善作用,提高胸腺和脾脏指数,增强脾脏细胞对刀豆素A(ConA)的反应性和NK活性,血清溶菌酶含量也有所增加。综合各项指标,9-顺式和全反式混合物的作用最明显,提示一定浓度的9-顺式对于提高β-胡萝卜素对机体的总体作用是有一定意义的。 相似文献
6.
晶体玻璃体视网膜联合手术治疗复杂性视网膜脱离 总被引:6,自引:2,他引:4
目的探讨玻璃体视网膜手术(vitreretinalsurgery,VR术)联合晶体切除/超声粉碎的效果。方法对81例(81只眼)应用晶体玻璃体视网膜联合手术(lenticular-vitreoretinalsurgery,LVR术)治疗的复杂性视网膜脱离进行回顾性分析。结果解剖性成功者64只眼(79.01%),功能性成功者45只眼(55.56%);手术成功率显著降低的原因是前部增殖性玻璃体视网膜病变(proliferativevitreo-retinopathy,PVR)(成功率42.86%,P<0.01)和术中/术后眼内出血(成功率58.82%,P<0.025)。结论LVR术是治疗复杂性视网膜脱离的主要方法;显著影响手术预后的因素是前部PVR和术中/术后眼内出血。 相似文献
7.
为探讨钙调素在慢性缺氧性肺动脉高压发病中的作用,将40只Wistar大鼠随机分为四组,I组为正常对照组,不接受任何处理。Ⅱ、Ⅲ、Ⅳ组为实验组,分别间断缺氧1、2、3周,而后采用火焰原子吸收分光光度法及磷酸二酯酶法测定四组大鼠肺组织Ca^2+含量及CaM活性。 相似文献
8.
Hitoshi Ogino Nongchana Klangsuk Wu Jin Christopher T. Bowles Magdi H. Yacoub 《Artificial organs》1995,19(6):525-534
Abstract: The dependence of transient pressure characteristics of a ventricular assist device (VAD) on the compliance of its housing and cannulas was investigated in a mock circulation. The peak rate of change of pressure ( dP/dt max ) values was greater in the cannulas than other compartments and was associated with valve closure-induced pressure oscillations. When cannula compliance was increased from 0.0057 to 0.0129 cm3 /mm Hg, these values decreased by ˜20%, and outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%. This trend was also apparent in the inflow. A VAD housing compliance increase from 0.0162 to 0.0483 cm3 /mm Hg caused a dP/dt max decrease of 30% in both the blood chamber and the outflow cannula. The effect of this change on the inflow was weaker implying that housing absorbs the energy associated with outflow deceleration more effectively than the inflow. These findings suggest that increasing VAD housing and cannulas compliance can improve hydrodynamic performance. 相似文献
9.
医源性胆管狭窄X线表现 总被引:1,自引:0,他引:1
本文报道了13例医源性胆管狭窄,分析其影像表现。特点为:环形狭窄;线样狭窄,包括规则的和不规则的线样狭窄;闭塞性狭窄;胆管闭塞和胆管中断分离。ERCT和PCT对狭窄的形态,位置及长度显示优于CT和US。 相似文献
10.