Acute lung injury (ALI), characterized by a severe inflammatory process, is a complex syndrome that can lead to multisystem organ failure. Fatty acid amide hydrolase (FAAH) and
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-acylethanolamine acid amidase (NAAA) are two potential therapeutic targets for inflammation-related diseases. Herein, we identified carmofur, a 5-fluorouracil-releasing drug and clinically used as a chemotherapeutic agent, as a dual FAAH and NAAA inhibitor. In Raw264.7 macrophages, carmofur effectively reduced the mRNA expression of pro-inflammatory factors, including IL-1β, IL-6, iNOS, and TNF-α, and down-regulated signaling proteins of the nuclear transcription factor κB (NF-κB) pathway. Furthermore, carmofur significantly ameliorated the inflammatory responses and promoted resolution of pulmonary injury in lipopolysaccharide (LPS)-induced ALI mice. The pharmacological effects of carmofur were partially blocked by peroxisome proliferator-activated receptor-α (PPARα) antagonist MK886 and cannabinoid receptor 2 (CB2) antagonist SR144528, indicating that carmofur attenuated LPS-induced ALI in a PPARα- and CB2-dependent mechanism. Our study suggested that carmofur might be a novel therapeutic agent for ALI, and drug repurposing may provide us effective therapeutic strategies for ALI.
The purpose of this study was to evaluate the role of the canonical Wnt signaling in the development of the myopia.
METHODS.Plasma from adult patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation (FD) induced mouse model of myopia were used. Niclosamide, a canonical Wnt pathway inhibitor, was orally administrated in animal models. Plasma levels of DKK-1 were determined by using enzyme-linked immunosorbent assay. Refraction, vitreous chamber depth (VCD), axial length (AL), and other parameters, were measured at the end of the FD treatment. Canonical Wnt signaling changes were evaluated by Western blot analysis and immunostaining analysis.
RESULTS.Plasma level of Wnt inhibitor DKK-1 was markedly decreased in patients with myopia. Meanwhile, the canonical Wnt pathway was progressively activated during myopia development in mice. Moreover, inhibition of canonical Wnt signaling by niclosamide in mouse models markedly reduced lens thickness (LT), VCD, and AL elongation, resulting in myopia inhibition.
CONCLUSIONS. Dysregulation of canonicalWnt signaling is a characteristic of myopia and targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia.
PurposeTo evaluate the surgical outcome of levator resection with suspensory ligament of the superior fornix (SLSF) suspension in severe congenital ptosis with poor levator function (LF).Patients and methodsThe medical records of 25 patients who underwent levator resection with SLSF suspension between March 2011 and January 2013 were retrospectively reviewed. All of the patients had severe congenital ptosis (>4 mm) and poor LF (<4 mm). The follow-up time ranged from 12 to 18 months (median, 15 months). Data regarding eyelid position, cosmetic outcomes, and postoperative complications were evaluated.ResultsThe average preoperative margin reflex distance-1 (MRD1) measured -0.30±0.11 mm. The average postoperative MRD1 measured 3.1±1.25 mm at the last follow-up visit. There was a statistically significant difference between preoperative and postoperative MRD1 values (P<0.001). Excellent cosmetic results occurred in 14 patients, good cosmetic results occurred in eight patients and poor cosmetic results did not occur. Three patients (12%) underwent reoperation for residual ptosis. No serious postoperative complications occurred.ConclusionLevator resection with SLSF suspension is very effective in the treatment of severe congenital ptosis with poor LF. This surgery technique results in high functional and cosmetic successes in the long term.
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