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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.
Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans. 总被引:1,自引:0,他引:1 下载免费PDF全文
Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects. 相似文献
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Facial muscle spasms, which are rare in adults, present a particularly difficult entity for the optometrist to recognise. The condition may not even manifest itself at an eye examination and the optometrist may have to rely on subjective symptoms to assist in the recognition of the condition. It is important to diagnose the condition correctly as specific and effective treatment is available. 相似文献
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D. Birch M. Payne Y. Chia S. McPherson 《Annals of the Royal College of Surgeons of England》1995,77(3):185-187
The Forrest Report led to the introduction of the breast screening programme with the aim of reducing mortality from breast cancer. In 1989 a breast screening programme was introduced to the South Bucks District and now two cycles have been completed. The findings are of a high yield of good prognosis tumours 71% and 72%, respectively. These encouraging figures are reflected in a high response rate and with a fall in the incidence of non-screen-detected tumours. 相似文献
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Lina P Theodorakopoulou P Lionel Sadowsky Alex Jacobson William Lacefield 《American journal of orthodontics and dentofacial orthopedics》2004,125(3):329-336
The objectives of this study were to evaluate and compare the shear bond strengths and bond failure locations of 2 currently available orthodontic ceramic brackets. Forty polycrystalline ceramic brackets (Clarity, 3M Unitek, Monrovia, Calif) and 40 monocrystalline ceramic brackets (Inspire, Ormco, Orange, Calif) were bonded to 80 extracted premolars with the same bonding system. All bonded specimens were placed in distilled water for 42 hours at 37 degrees C followed by thermal cycling for 700 complete cycles. Forty ceramic brackets, 20 of each type, were tested on a universal testing machine to determine the shear force levels required to debond them. Forty ceramic brackets were removed with the debonding pliers recommended by the manufacturers. All teeth were examined under an optical microscope, and the adhesive remnant index was used to assess the bond failure locations. The mean shear bond strength of the Clarity brackets was 21.67 +/- 5.19 MPa, and the mean shear bond strength of the Inspire brackets was 20.32 +/- 8 MPa. The mean shear bond strengths of both brackets were higher than those considered clinically optimal. Most of the brackets (85% of Clarity and 75% of Inspire) tested on the machine failed at the bracket-adhesive interface. One premolar bonded with an Inspire bracket had enamel fracture upon debonding. Most of the brackets (90% of Clarity and 95% of Inspire) debonded with pliers failed at the bracket-adhesive interface. No enamel damage was evident in any specimen when the brackets were removed with the appropriate pliers. The results indicate that the safest way to remove ceramic brackets with respect to reducing the chance of enamel damage is to use the debonding technique specifically designed for each. 相似文献
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Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts. 总被引:1,自引:0,他引:1
Catherine M Cowan Xinquan Jiang Tiffany Hsu Chia Soo Beiji Zhang Joyce Z Wang Shun'ichi Kuroda Benjamin Wu Zhiyuan Zhang Xinli Zhang Kang Ting 《Journal of bone and mineral research》2007,22(6):918-930
Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery. 相似文献
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