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A Signal-On Fluorosensor Based on Quench-Release Principle for Sensitive Detection of Antibiotic Rapamycin
摘要： An antibiotic rapamycin is one of the most commonly used immunosuppressive drugs, and also implicated for its anti-cancer activity. Hence, the determination of its blood level after organ transplantation or tumor treatment is of great concern in medicine. Although there are several rapamycin detection methods, many of them have limited sensitivity, and/or need complicated procedures and long assay time. As a novel fluorescent biosensor for rapamycin, here we propose “Q’-body”, which works on the fluorescence quench-release principle inspired by the antibody-based quenchbody (Q-body) technology. We constructed rapamycin Q’-bodies by linking the two interacting domains FKBP12 and FRB, whose association is triggered by rapamycin. The fusion proteins were each incorporated position-specifically with one of fluorescence dyes ATTO520, tetramethylrhodamine, or ATTO590 using a cell-free translation system. As a result, rapid rapamycin dose-dependent fluorescence increase derived of Q’-bodies was observed, especially for those with ATTO520 with a lowest detection limit of 0.65 nM, which indicates its utility as a novel fluorescent biosensor for rapamycin.
关键词： rapamycin,fluorescent biosensor,fluorescence quenching,photoinduced electron transfer,antibiotics
更新于2025-09-23 15:22:29
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Laser-Assisted Delivery of Topical Rapamycin
摘要： Birt–Hogg–Dube syndrome (BHDS) is a genodermatosis that presents with multiple adnexal tumors (fibrofolli- culomas and trichodiscomas) and has increased suscep- tibility for renal tumors, pulmonary cysts, and spontaneous pneumothorax. No specific treatment exists for the cutaneous lesions of BHDS, and ablative laser therapies have only demonstrated modest results with relapse after 6 months. We present a patient with BHDS whose fibrofolliculomas were successfully treated with topical rapamycin and nonablative fractional laser.
关键词： Birt–Hogg–Dube syndrome,mTOR inhibition,fibrofolliculomas,nonablative fractional laser,topical rapamycin
更新于2025-09-12 10:27:22
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Treatment of port wine stain with Tixel‐induced rapamycin delivery following pulsed dye laser application
摘要： Background: Although pulsed dye laser (PDL) is considered the gold standard treatment for port wine stains (PWS), post PDL revascularization is one of the main causes of incomplete regression and recurrence. Recently, topical sirolimus have been shown to improve treatment outcome probably through minimizing post-laser revascularization. Objectives: We sought to evaluate the added value of the Tixel drug delivery system (DDS) to the PDL and topical rapamycin treatment for PWS. Materials and Methods: This case series includes 3 teenager patients with previously treated PWS with PDL. Upon enrollment, every stain was divided into A and B halves for treatment assignments to the following regimens: (A) PDL + DDS + Rapamycin; (B) PDL+ Rapamycin. Subjects were instructed to apply Rapamycin topically over the PWS twice daily for the entire treatment period. Assessment of the treatment and adverse reactions as well as photographs was performed at baseline and before every PDL treatment. Results: There were clinically significant differences in blanching responses favoring PWS receiving PDL + DDS + Rapamycin as compared to PDL + Rapamycin alone. Transient hyperpigmentation was noted in 1 patient. Two patients developed mild transient irritation and dermatitis following the treatment on both halves. Conclusion: The use of drug delivery system combined with topical rapamycin has no remarkable adverse effects, improves the results of PDL treatment for port wine stains, and can reduce the total number of required PDL sessions.
关键词： tixel,port wine stain,pulsed dye laser,Drug delivery,Rapamycin
更新于2025-09-11 14:15:04
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The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants
摘要： The development of photoreceptor degenerative disorders requires the identification of the optimal cell source and immunosuppressive regimen in a large animal model. Allotransplants are not acutely rejected in swine subretinal space, although it is not known if survival can be improved with immunosuppression. Here we investigated the survival and integration of expanded pig retinal progenitor cells (pRPCs) in normal recipients with and without transient anti-inflammatory suppression. pRPCs were derived from the neural retina of E60 GFP transgenic pigs, expanded for six passages, characterized, and transplanted into the subretinal space of 12 pigs. Six recipients received a single intravitreal injection of rapamycin and dexamethasone. pRPCs expressed the photoreceptor development genes Sox2, Pax6, Lhx2, Crx, Nrl, and Recoverin in vitro. Transplanted cells were identified in 9 out of 12 recipients 4 weeks after the injection. pRPCs integrated primarily into the photoreceptor inner segment layer and outer nuclear layer with single cells present in the inner nuclear layer. Donor cells remained recoverin-positive and acquired rhodopsin. We did not observe any signs of graft proliferation. The immunosuppression did not affect the survival or distribution of grafts. No macrophage infiltration or loss of retinal structure was observed in either group. Local immunosuppression with rapamycin and dexamethasone does not improve the outcome of pRPC allotransplantation into the subretinal space. Survival and integration of pRPC together with the lack of graft proliferation suggests that allogeneic RPC transplantation without transient immunosuppression is a favorable approach for photoreceptor cell replacement.
关键词： rapamycin,retina,retinal progenitor cells,cell therapy,photoreceptors
更新于2025-09-04 15:30:14