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1.

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   
2.
This study aimed to evaluate changes in sleep during the COVID‐19 outbreak, and used data‐driven approaches to identify distinct profiles of changes in sleep‐related behaviours. Demographic, behavioural and psychological factors associated with sleep changes were also investigated. An online population survey assessing sleep and mental health was distributed between 3 April and 24 June 2020. Retrospective questions were used to estimate temporal changes from before to during the outbreak. In 5,525 Canadian respondents (67.1% females, 16–95 years old: Mean ± SD = 55.6 ± 16.3 years), wake‐up times were significantly delayed relative to pre‐outbreak estimates (p < .001,  = 0.04). Occurrences of clinically meaningful sleep difficulties significantly increased from 36.0% before the outbreak to 50.5% during the outbreak (all p < .001, g ≥ 0.27). Three subgroups with distinct profiles of changes in sleep behaviours were identified: “Reduced Time in Bed”, “Delayed Sleep” and “Extended Time in Bed”. The “Reduced Time in Bed” and “Delayed Sleep” subgroups had more adverse sleep outcomes and psychological changes during the outbreak. The emergence of new sleep difficulties was independently associated with female sex, chronic illnesses, being employed, family responsibilities, earlier wake‐up times, higher stress levels, as well as heavier alcohol use and television exposure. The heterogeneity of sleep changes in response to the pandemic highlights the need for tailored interventions to address sleep problems.  相似文献   
3.
目的分析乙型肝炎(乙肝)病毒(Hepatitis B virus,HBV)高载量孕妇孕期HBV脱氧核糖核酸(HBV desoxyribonucleic acid,HBV-DNA)水平和HBVe抗原(HBV e antigen,HBeAg)阳性率以及孕期抗病毒治疗结合标准阻断措施对其所生婴儿母婴传播阻断失败率的影响。方法通过医院信息系统收集HBV-DNA高载量(≥2×10^6IU/mL)孕妇血清学检测结果、抗病毒药物使用等信息,描述HBV-DNA载量和HBeAg阳性率;对HBV-DNA高载量孕妇所生婴儿进行乙肝疫苗(Hepatitis B vaccine,HepB)和乙肝免疫球蛋白(Hepatitis B immunoglobulin,HBIG)联合免疫,在完成第3剂HepB后7月龄-2岁对乙肝表面抗原和HBV-DNA进行随访检测,分析母婴传播阻断失败率。结果共纳入1822名HBV-DNA高载量孕妇,接受、未接受抗病毒治疗分别占75.19%、24.81%。孕妇妊娠期、分娩前HBV-DNA≥1.0×10^8IU/mL比例分别为68.10%(933/1370)、0.15%(2/1370)(χ^2=2692.27,P<0.0001)。接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为96.53%(1001/1037)、96.16%(1251/1301)(χ^2=0.23,P=0.635),未接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为97.70%(298/305)、96.98%(417/430)(χ^2=0.36,P=0.550)。两组HepB和HBIG联合免疫后母婴传播阻断失败率分别为0.42%(3/714)、6.67%(14/210)(χ^2=31.69,P<0.0001)。结论孕妇HBV-DNA高载量以≥1.0×10^8IU/mL为主,孕期抗病毒治疗可显著降低孕妇HBV-DNA载量,结合HepB和HBIG联合免疫可显著降低其所生婴儿HBV母婴传播阻断失败率。  相似文献   
4.
5.
We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.  相似文献   
6.
7.
Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery.  相似文献   
8.
9.
Liang  Xiongyan  Gu  Yufang  Chen  Xueyang  Li  Tuofan  Gao  Yulong  Wang  Xiaomei  Fang  Chun  Fang  Shouguo  Yang  Yuying 《Virus genes》2019,55(5):726-733
Virus Genes - Avian leukosis virus (ALV) caused tremendous economic losses to poultry industry all over the world, especially in China. One natural recombinant ALV strain, designated as HB2015032,...  相似文献   
10.
目的颈动脉粥样硬化斑块的形成是脑血管病变的独立危险因素之一。对颈动脉内膜剥脱术(carotid endarterectomy,CEA)斑块进行充分的组织学判读和研究,将有助于全面把握CEA斑块的组织学表现,进而推进临床辅助诊断。方法本文我们将运用数字病理扫描仪对CEA斑块的切片经H&E染色后进行扫描,介绍数字病理扫描在CEA斑块组织学研究中的应用。结果经数字病理扫描所得的图片,有助于全面掌握和保存CEA斑块组织切片的全层面信息;在软件的帮助下有助于非常方便地测量斑块内各成分的大小;有助于精确评估斑块的狭窄程度。结论综上,数字病理成像应用于CEA斑块,结合MRI,有助于高效且准确地判读斑块组成和预测斑块稳定性,亦有助于人工智能的训练。  相似文献   
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