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Giovanna Leoni Philipp-Alexander Neumann Nazila Kamaly Miguel Quiros Hikaru Nishio Hefin R. Jones Ronen Sumagin Roland S. Hilgarth Ashfaqul Alam Gabrielle Fredman Ioannis Argyris Emile Rijcken Dennis Kusters Chris Reutelingsperger Mauro Perretti Charles A. Parkos Omid C. Farokhzad Andrew S. Neish Asma Nusrat 《The Journal of clinical investigation》2015,125(3):1215-1227
Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD. 相似文献
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Jane Lubchenco Marcia K. McNutt Gabrielle Dreyfus Steven A. Murawski David M. Kennedy Paul T. Anastas Steven Chu Tom Hunter 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(50):20212-20221
This introduction to the Special Feature presents the context for science during the Deepwater Horizon oil spill response, summarizes how scientific knowledge was integrated across disciplines and statutory responsibilities, identifies areas where scientific information was accurate and where it was not, and considers lessons learned and recommendations for future research and response. Scientific information was integrated within and across federal and state agencies, with input from nongovernmental scientists, across a diverse portfolio of needs—stopping the flow of oil, estimating the amount of oil, capturing and recovering the oil, tracking and forecasting surface oil, protecting coastal and oceanic wildlife and habitat, managing fisheries, and protecting the safety of seafood. Disciplines involved included atmospheric, oceanographic, biogeochemical, ecological, health, biological, and chemical sciences, physics, geology, and mechanical and chemical engineering. Platforms ranged from satellites and planes to ships, buoys, gliders, and remotely operated vehicles to laboratories and computer simulations. The unprecedented response effort depended directly on intense and extensive scientific and engineering data, information, and advice. Many valuable lessons were learned that should be applied to future events. 相似文献
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Robert L Findling Christoph U Correll Robert D McQuade Na Jin Svetlana Ivanova William H Carson Gabrielle A Carlson 《Bipolar disorders》2013,15(2):138-149
Objective: To evaluate the long‐term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. Methods: A randomized, double‐blind, 30‐week, placebo‐controlled study of aripiprazole (10 or 30 mg/day) in youths (10–17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double‐blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Results: Of the 210 subjects who entered the 26‐week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol‐specified last observation carried forward analyses, but not in observed case or mixed‐model repeated measures at week 30. Overall time to all‐cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children’s Global Assessment of Functioning and Clinical Global Impressions‐Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Conclusions: Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms. 相似文献
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Diego Coelho Lorenzoni Ana Carolina Cuzzuol Fracalossi Viviane Carlin Daniel Araki Ribeiro Eduardo Franzotti Sant'Anna 《The Angle orthodontist》2013,83(1):104
Objectives:To evaluate and compare mutagenicity (micronucleus) and cytotoxicity (karyorrhexis, pyknosis, and karyolysis) in exfoliated buccal mucosa cells of children following cone beam computed tomography (CBCT) or conventional radiograph exposure necessary for orthodontic planning.Materials and Methods:A total of 49 healthy children were submitted to CBCT or a conventional orthodontic radiographic protocol; they were divided into two groups based on exam: CBCT (n = 24) and Radiographic Set (n = 25) groups. The micronucleus test in the exfoliated buccal mucosa cells was applied.Results:There was not a statistically significant difference (P > .05) found between the number of micronucleated buccal mucosa cells (MNC) before and after exposure to radiation in either group, showing that neither group experienced a mutagenic effect. However, radiation did cause other nuclear alterations closely related to cytotoxicity, including karyorrhexis, pyknosis, and karyolysis, in both groups (P < .05). The CBCT group presented a greater increase in cell death than was noted in the Radiographic Set group (P < .044).Conclusion:According to the micronucleus test, mutagenicity was not induced by the CBCT or the conventional radiographs, but cytotoxicity was verified after these exams, especially after CBCT. That might have happened once the CBCT group received a greater radiation dose than the Radiographic Set group as a result of the protocols used in orthodontic planning for this study. 相似文献
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Aimee Claire Kok MD Gabrielle J. M. Tuijthof PhD Steven den Dunnen MSc Jasper van Tiel MD Michiel Siebelt MD Vincent Everts PhD C. Niek van Dijk PhD MD Gino M. M. J. Kerkhoffs PhD MD 《Clinical orthopaedics and related research》2013,471(11):3653-3662