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Early Alteration of Retinal Neurons in <i>Aipl1</i> <sup>?/?</sup> Animals
摘要： PURPOSE. Mutations in the photoreceptor cell-specific gene encoding aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) lead to Leber congenital amaurosis (LCA4), retinitis pigmentosa, and cone–rod dystrophy. Gene therapy appears to be promising in the treatment for AIPL1-mediated vision loss in humans. Prior to initiating these treatments, however, it is crucial to understand how the retinal neurons remodel themselves in response to photoreceptor cell degeneration. In this study, using an animal model for AIPL1-LCA, Aipl1(cid:2)/(cid:2) mice, we investigate the changes in postreceptoral retinal neurons during the course of photoreceptor cell loss. METHODS. Morphology of the Aipl1(cid:2)/(cid:2) retina from postnatal day 8 to 150 was compared to that of age-matched, wild-type C57Bl6/J retina (WT) by immunocytochemistry using cell-specific markers. RESULTS. Expression of postsynaptic proteins in bipolar cells is reduced prior to photoreceptor cell degeneration at postnatal day 8. Bipolar and horizontal cells retract their dendrites. Cell bodies and axons of bipolar and horizontal cells are disorganized during the course of degeneration. M¨uller cell processes become hypertrophic and form a dense fibrotic layer outside the inner nuclear layer. CONCLUSIONS. An early defect in photoreceptor cells in the AIPL1-LCA mouse model affects the expression of postsynaptic markers, suggesting abnormal development of bipolar synapses. Once degeneration of photoreceptor cells is initiated, remodeling of retinal neurons in the Aipl1(cid:2)/(cid:2) animal is rapid.
关键词： childhood blindness,photoreceptor degeneration,retina,LCA,remodeling
更新于2025-09-23 15:22:29
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Stimulation of collagen and elastin production in-vivo using 1,540??nm Er:Glass laser: assessment of safety and efficacy
摘要： Introduction: Induction of collagen and elastin remodeling in the human skin can be achieved by non-ablative fractional laser (NAFXL) and ablative fractional laser (AFXL). Our objective was to compare the safety, efficacy, tolerability, and ability to induce collagen and elastin remodeling of NAFXL versus AFXL in a series of treatments over time. Materials and Methods: In this prospective, proof of principle, single-case study, the safety, tolerability and efficacy of the laser systems were assessed via histopathology and clinical evaluations including photographs. Optical biopsies by means of multiphoton tomography (MPT) were used to evaluate the induction of collagen and elastin remodeling. Results: Treatments by both NAFXL and AFXL were well tolerated. The NAFXL system was found to be less painful and resulted in a shorter down- and healing times. MPT findings showed the superior capability of the AFXL procedure to induce collagen; on the other hand, elastin induction was more pronounced after NAFXL treatments. Conclusions: While NAFXL is as effective and safe as the traditional AFXL, it is better tolerated and has a shorter downtime. Serial optical biopsies over time over time can be a useful tool to assess the induction of collagen and elastin remodeling in the human skin.
关键词： remodeling,optical biopsy,10600 nm,ablative,collagen,multi-photon tomography,non-ablative,fractional,elastin,140 nm,Laser
更新于2025-09-23 15:21:01
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The effect of low-level laser radiation and doxycycline on the levels of osteoprotegerin and receptor activator of nuclear factor kappa-B ligand
摘要： The present in vitro study was conducted to investigate the effect of low-level laser (LLL) radiation and doxycycline on the levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) derived from MG-63 osteosarcoma cell line. MG-63 cells were divided into four groups. In the first group, 2 mg/mL of doxycycline was injected into the cell culture medium. Diode laser (810 nm, 100 mw, 75 s) was radiated to the culture medium of the second group. The third group received both doxycycline and laser radiation. In the fourth group (control), the culture medium was replaced daily, similar to the above three groups. Mentioned interventions were performed once a day for 4 consecutive days. Then, on the sixth day, the levels of OPG and RANKL mediators were measured using real-time polymerase chain reaction by isolating the cells from the samples. OPG expression had the highest to lowest levels in the laser + doxycycline, doxycycline, laser, and control groups, respectively. The level of OPG was significantly different between all the study groups (p < 0.05) except in the doxycycline + laser and doxycycline groups (p = 0.061). The highest to lowest levels of RANKL was observed in the doxycycline, laser + doxycycline, control, and laser groups, respectively. The RANKL expression was not significantly different between all the study groups (p > 0.05). The results of this study revealed that LLL and doxycycline reduced the RANKL/OPG ratio derived from the MG-63 osteosarcoma cell line, which may result in the diminished activity of osteoclasts and osteoclastogenesis.
关键词： OPG,Remodeling,RANKL,Laser,Doxycycline,Bone
更新于2025-09-23 15:21:01
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Visible-light-initiated Sonogashira coupling reactions over CuO/TiO <sub/>2</sub> nanocomposites
摘要： Magnesium lithospermate B (MLB) shows multiple biological activities including anti-oxidation and anti-proliferation in various diseases. However, the function of MLB in pulmonary arterial hypertension (PAH) is still unknown. This study aims to investigate the effect of MLB on hypoxia-induced phenotypic transformation of pulmonary arterial smooth muscle cells (PASMCs) and the underlying mechanisms. SD rats (or PASMCs) were exposed to 10% O2 for 3 weeks ( or 3% O2 for 48h) along with MLB or NADPH oxidase （NOX） inhibitor intervention. The effects of MLB on hemodynamics, pulmonary vascular remodeling and phenotypic transformation of PASMCs were observed first. Then, its effects on the protein levels of NOX (NOX2 and NOX4), ERK and p-ERK were examined. The results showed that MLB prevented the elevation in right ventricular systolic pressure and the increase in ratio of wall thickness to vessel external diameter of pulmonary arteries in PAH rats, and attenuated phenotypic transformation of PASMCs (decrease in α-smooth muscle actin while increase in osteopontin), accompanied by downregulation of NOX (NOX2 and NOX4) protein levels, decrease of ROS and H2O2 production, and suppression of the phosphorylation of ERK. NOX inhibitor (VAS2870) achieved similar results to that of MLB did in the hypoxia-treated PASMCs. Based on the observations, we conclude that MLB is able to prevent phenotypic transformation of pulmonary arteries in hypoxic PAH rats through suppression of NOX/ROS/ERK pathway, and MLB might have the potentials in PAH therapy.
关键词： pulmonary vascular remodeling,pulmonary arterial hypertension,Magnesium lithospermate B,NADPH oxidase,phenotypic transformation
更新于2025-09-19 17:15:36
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A highly sensitive SERS probe for bisphenol A detection based on functionalized Au@Ag nanoparticles
摘要： Cardiac remodeling is the response of the heart to a range of pathological stimuli. Cardiac remodeling is initially adaptive; however, if sustained, it ultimately causes adverse clinical outcomes. Cardiomyocyte loss or hypertrophy, inflammation and fibrosis are hallmarks of cardiac remodeling. Proteoglycans, which are composed of glycosaminoglycans and a core protein, are a non-structural component of the extracellular matrix. The lack of proteoglycans results in cardiovascular defects during development. Moreover, emerging evidence has indicated that proteoglycans act as significant modifiers in ischemia and pressure overload-related cardiac remodeling. Proteoglycans may also provide novel therapeutic strategies for further improvement in the prognosis of cardiovascular diseases.
关键词： Cardiac remodeling,Pressure overload,Proteoglycan,Myocardial ischemia,Heart failure
更新于2025-09-19 17:15:36
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SRRF-stream imaging of optogenetically controlled furrow formation shows localized and coordinated endocytosis and exocytosis mediating membrane remodeling
摘要： Cleavage furrow formation during cytokinesis involves extensive membrane remodeling. In the absence of methods to exert dynamic control over these processes, it has been a challenge to examine the basis of this remodeling. Here we used a subcellular optogenetic approach to induce this at will and found that furrow formation is mediated by actomyosin contractility, retrograde plasma membrane flow, localized decrease in membrane tension and endocytosis. FRAP, 4-D imaging and inhibition or upregulation of endocytosis or exocytosis show that ARF6 and Exo70 dependent localized exocytosis supports a potential model for intercellular bridge elongation. TIRF and Super Resolution Radial Fluctuation (SRRF) stream microscopy show localized VAMP2-mediated exocytosis and incorporation of membrane lipids from vesicles into the plasma membrane at the front edge of the nascent daughter cell. Thus, spatially separated but coordinated plasma membrane depletion and addition are likely contributors to membrane remodeling during cytokinetic processes.
关键词： SRRF-stream,optogenetics,Cleavage furrow,membrane remodeling,endocytosis,exocytosis
更新于2025-09-19 17:13:59
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Ablative fractional laser resurfacing for treatment of sclerosis and contractures in chronic graft-versus-host disease: A pilot study
摘要： To the Editor: Cutaneous sclerosis is a disabling complication of chronic graft-versus-host disease (cGVHD) that leads to joint contractures and reduced range of motion (ROM). Current therapies are limited by adverse effects and poor efficacy, and no systemic treatment successfully reverses cGVHD-induced sclerotic skin changes.1 There is an urgent need for therapies to address the debilitating effects of cutaneous sclerosis in cGVHD. The ablative fractional CO2 laser remodels collagen and reduces fibrosis. It has been used for treatment of scars and contractures secondary to linear morphea, burns, and traumatic injury, conditions resembling the sclerosis of cGVHD.2,3 We evaluated the safety, tolerability, and efficacy of the ablative fractional CO2 laser for cGVHD-related sclerosis and joint contractures. Six patients with cGVHD-related sclerosis were enrolled prospectively and completed the study. Eligible patients had clinically severe, refractory sclerosis from longstanding cGVHD, with demonstrable ROM limitation and contractures across a joint amenable to laser therapy. After administration of topical anesthesia, patients had 3 monthly treatments of an approximately 10 3 6-cm area of skin at the target joint using the 10 600-nm fractional Ultrapulse CO2 laser (Ultrapulse Encore; Lumenis, Inc, Santa Clara, CA) in Deep FX mode (energy settings, 20-25 mJ; density, 5%-15%). Photographs, ROM measurements, and high-resolution ultrasonography were recorded at baseline, 1 week after each laser session, and 3 months after the final session. Punch biopsy and patient and provider assessments, including validated health and disability questionnaires, were performed at baseline and 3 months after the final session. The study was approved by the University of Pennsylvania institutional review board, and all patients provided written informed consent. Before enrollment, patients had received a mean of 5.5 systemic therapies for cGVHD-related sclerosis. Laser treatments were well tolerated, without infectious or other serious complications. ROM measurements, particularly the twisting motions of supination and pronation, improved in all patients (Table I). Immunohistochemical analysis of skin biopsy specimens showed decreased thickened collagen bundles, decreased intensity of collagen staining, and greater abundance of type III collagen in treated areas (Fig 1).3 Dermal echogenicity measured via high-resolution ultrasonography increased after the laser treatment, suggestive of collagen remodeling. Less haphazard organization of collagen is postulated to produce increased echogenicity.4 Patient photographs and disability assessments similarly showed evidence of improvement. The results of this pilot study highlight the safety, tolerability, and potential efficacy of the fractional ablative CO2 laser for treatment of cGVHD-related sclerosis and joint contracture, resulting in small but measurable histologic, radiologic, and functional improvements. Small sample size, small treatment area, and imperfect objective response measures are limitations. Longer follow-up, larger treatment areas, use of other laser settings, and laser-assisted delivery of topical medications should be evaluated in future studies.5 In summary, the fractional ablative CO2 laser was safe and well tolerated in a small group of medically complex patients with treatment-refractory cGVHD. Treatment of a target area of sclerotic skin appeared to induce collagen remodeling, with resulting modest improvement in ROM and joint function. These findings suggest that the fractional ablative CO2 laser may be an effective novel therapy for disabling sclerotic joint contractures in some patients with cGVHD.
关键词： sclerosis,ablative fractional laser resurfacing,contractures,chronic graft-versus-host disease,collagen remodeling
更新于2025-09-16 10:30:52
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FAILED LASER RETINOPEXY IN A PATIENT UNDERGOING PAZOPANIB THERAPY
摘要： To report a case of failed endolaser retinopexy in patient taking pazopanib and possible association with impaired retinal remodeling. Methods: Case report. Results: A 68-year-old man with a history of radiation-induced high-grade metastatic mediastinal leiomyosarcoma, on pazopanib 600 mg daily, presented with a superior retinal tear 2 months after initiating pazopanib. The patient was treated with pars plana vitrectomy and endolaser retinopexy without any immediate complications. One month postoperatively, the patient was found to have a new superior macula-sparing rhegmatogenous retinal detachment extending through the laser barricade nasally. A large proportion of the laser lesions in this area had notably remained chalk-white. The patient underwent pars plana vitrectomy with scleral buckling, and repeat endolaser retinopexy. Pazopanib therapy was stopped 1 week later in consultation with the oncology team and was reinitiated after the retina seemed stable under silicone oil for several weeks. The scars from the patient’s repeat endolaser retinopexy remained pale white at his clinic visit 2 months after the procedure, and at that time, his initial laser scars had only just begun to darken with pigment. Four and a half months after the initial vitrectomy and endolaser retinopexy, and three and a half months after his repeat vitrectomy and endolaser retinopexy, all the patient’s laser scars have developed increased pigment, and his retina remains completely flat under silicone oil tamponade. Conclusion: Pazopanib may have had an adverse effect on retinal wound healing after vitrectomy with endolaser retinopexy, leading to persistence of pale laser lesions many weeks after laser application. It is possible that this may have impaired the typical development of chorioretinal laser scar formation and led to subsequent retinal detachment.
关键词： pazopanib,retinal remodeling,scar formation,retinal detachment,retinopexy,retinal laser photocoagulation,wound healing
更新于2025-09-12 10:27:22
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Engineering State‐of‐the‐Art Plasmonic Nanomaterials for SERS‐Based Clinical Liquid Biopsy Applications
摘要： Metabolic reprogramming, hallmarked by enhanced glycolysis and reduced mitochondrial activity, is a key event in the early phase of somatic cell reprogramming. Although extensive work has been conducted to identify the mechanisms of mitochondrial remodeling in reprogramming, many questions remain. In this regard, different laboratories have proposed a role in this process for either canonical (ATG5-dependent) autophagy-mediated mitochondrial degradation (mitophagy), noncanonical (ULK1-dependent, ATG5-independent) mitophagy, mitochondrial fission or reduced biogenesis due to mTORC1 suppression. Clarifying these discrepancies is important for providing a comprehensive picture of metabolic changes in reprogramming. Yet, the comparison among these studies is difficult because they use different reprogramming conditions and mitophagy detection/quantification methods. Here, we have systematically explored mitochondrial remodeling in reprogramming using different culture media and reprogramming factor cocktails, together with appropriate quantification methods and thorough statistical analysis. Our experiments show lack of evidence for mitophagy in mitochondrial remodeling in reprogramming, and further confirm that the suppression of the mTORC1-PGC1 pathway drives this process. Our work helps to clarify the complex interplay between metabolic changes and nutrient sensing pathways in reprogramming, which may also shed light on other contexts such as development, aging and cancer.
关键词： mitochondrial remodeling,reprogramming,mitophagy,PGC1,mTORC1
更新于2025-09-11 14:15:04
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Evaluation of Energy and Daylight Performance of Old Office Buildings in South Korea with Curtain Walls Remodeled Using Polymer Dispersed Liquid Crystal (PDLC) Films
摘要： Globally, energy standards for new buildings are being reinforced to improve energy efficiency, and remodeling policies are being promoted for old buildings. The South Korean Government is promoting green remodeling projects, and focusing on research and product development to improve the performance of old windows and curtain walls. In line with this, the present study proposes two remodeling methods using polymer dispersed liquid crystal (PDLC) films, which can adjust solar radiation for old office buildings. In addition, energy efficiency improvement and daylight performance according to remodeling were analyzed. Attaching PDLC films to the glass of old curtain walls was analyzed; this can reduce heating and cooling energy, reduce the annual discomfort glare occurrence rate, and increase the annual indoor appropriate illuminance ratio. Furthermore, producing a window by laminating a PDLC film between two sheets of glass and putting it over the existing curtain wall was also analyzed; this can reduce annual building energy consumption and the annual discomfort glare occurrence rate, and improve the annual indoor appropriate illuminance ratio. Therefore, PDLC film is expected to be applicable as a next-generation green remodeling material because using it in remodeling can improve energy efficiency of old office buildings and indoor daylight performance.
关键词： EnergyPlus,polymer dispersed liquid crystal,green remodeling,building energy efficiency
更新于2025-09-11 14:15:04