No abstract

Cigarette smoking is known to aggravate Graves' orbitopathy (GO) severity by enhancing adipogenesis. We investigated the effect of quercetin, an antioxidant, on adipocyte differentiation induced by cigarette smoke extract (CSE) in primary cultured orbital fibroblasts (OFs) from GO patients. Freshly prepared CSE was added to the cells and H 2 O 2 was used as a positive control. Intracellular reactive oxygen species (ROS) generation and adipogenesis were measured. The expressions of proteins peroxisome proliferator-activated receptor (PPAR) g, CCAAT-enhancer-binding proteins (C/EBP) a and b, and heme oxygenase-1 (HO-1), an antioxidant enzyme, were examined during adipogenic differentiation. In result, CSE and H 2 O 2 dose-dependently stimulated intracellular ROS production in normal and Graves' OFs. The effect of 2% CSE was similar to that of 10 mM H 2 O 2 ; both concentrations were noncytotoxic and were used throughout the experiment. Quercetin pretreatment reduced the ROS generation stimulated by either CSE or H 2 O 2 in preadipocyte OFs. CSE and H 2 O 2 stimulated adipocyte differentiation in cultured OFs. The addition of quercetin (50 or 100 mM) suppressed adipogenesis. Quercetin also suppressed ROS generation in differentiating OFs during adipogenesis stimulated by CSE and H 2 O 2 . Additionally, the expressions of PPARg, C/EBPa, and C/EBPb proteins were reduced in the quercetin-treated OFs. Quercetin also reduced the CSE-and H 2 O 2 -induced upregulation of ROS and HO-1 protein in differentiated OFs and preadipocyte OFs. As shown in this study, quercetin inhibited adipogenesis by reducing ROS in vitro, supporting the use of quercetin in the treatment of GO. IntroductionOxidative stress is implicated in the pathogenesis of Graves' orbitopathy (GO), and cigarette smoking is known to be a major environmental factor that affects GO. Cigarette smoking has been shown to influence the incidence, severity, and responses to treatment of GO, and appears to do so in a dose-dependent and temporal manner. Reportedly, smokers with Graves' disease are approximately five times more likely to develop GO than Journal of Endocrinology Research J S YOON, H J LEE and othersTreatment of GO by quercetin, an antioxidant 216:2 145-156

An ocular prosthesis is a custom-made polymeric insert that can be placed in an anophthalmic socket for cosmetic rehabilitation of patients who have lost their eyes. The process of creating such a custom-made ocular prosthesis is time-consuming and labor-intensive because it involves artistic work that is carried out manually. This paper proposes a novel semi-automated method for fabricating customized ocular prostheses using three-dimensional (3D) printing and sublimation transfer printing. In the proposed method, an impression mold of the patient’s anophthalmic socket is first optically scanned using a 3D scanner to produce a 3D model. The ocular prosthesis is then produced via a digital light processing 3D printer using biocompatible photopolymer resin. Subsequently, an image of the iris and blood vessels of the eye is prepared by modifying a photographed image of the contralateral normal eye, and printed onto the 3D-printed ocular prosthesis using a dye sublimation transfer technique. Cytotoxicity assessments of the base material and fabricated ocular prosthesis indicate that there is no adverse effect on cellular viability and proliferation. The proposed method reduces the time and skill required to fabricate a customized ocular prosthesis, and is expected to provide patients with easier access to quality custom-made ocular prostheses.

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-κB (NF-κB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-κB activation. Also, we determined whether selective inhibition of NF-κB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-κB or expression of a recombinant adenovirus vector encoding an IκB-α mutant (Ad-IκBαM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-κB activation was determined by immunohistochemical staining, NF-κB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-κB activity. Treatment with inhibitors of NF-κB such as MG132, PDTC or expression of Ad-IκB-αM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.