Role of Lysyl Oxidase-Like Protein 3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.

Purpose: The lysyl oxidase (LOX) family has been implicated in the pathogenesis of diseases caused by inflammation and fibrosis. Therefore, we aimed to examine the role of lysyl oxidase-like protein 3 (LOXL3) in Graves' orbitopathy (GO) pathogenesis and its potential as a treatment target.

Methods: Quantitative real-time polymerase chain reaction compared the transcript levels of the five LOX family subtypes in orbital tissue explants obtained from patients with GO (n = 18) and healthy controls (n = 15).

Inhibition of Cancer Cell Migration and Invasion In Vitro by Recombinant Tyrosine-Sulfated Haemathrin, A Thrombin Inhibitor.

Thrombin, a key enzyme in the regulation of hemostasis, has been implicated in cancer progression. This study explored the effect of recombinant tyrosine-sulfated haemathrin on cancer cell behavior and signaling pathways compared to wild-type (WT) haemathrin 2. The recombinant proteins, tyrosine-sulfated haemathrin 2 (haemathrin 2S), and WT haemathrin 2 were produced in and subsequently purified and applied to SKOV3 and MDA-MB-231 cells with and without thrombin stimulation.

Therapeutic role of physalin A in the pathogenesis of Graves' orbitopathy.

Background: Graves' orbitopathy (GO) is an autoimmune condition that causes serious ocular symptoms; its treatment strategies are limited. Physalin A is a phytosterol that has shown various therapeutic properties, including anti-inflammatory and anti-fibrotic effects. In this study, we investigated whether physalin A could inhibit inflammation, fibrosis, hyaluronan (hyaluronic acid) production, and adipogenesis, which are crucial to the pathogenesis of GO.

Therapeutic role of histone deacetylase inhibition in an model of Graves' orbitopathy.

Graves' orbitopathy (GO), a manifestation of Graves' disease, is characterized by orbital fibroblast‑induced inflammation, leading to fibrosis or adipogenesis. Histone deacetylase (HDAC) serves a central role in autoimmune diseases and fibrosis. The present study investigated HDAC inhibition in orbital fibroblasts from patients with GO to evaluate its potential as a therapeutic agent.

Pentraxin 3 mediates inflammation and adipogenesis in Graves' orbitopathy pathogenesis.

Pentraxin 3 (PTX3) is a prototypic humoral soluble pattern-recognition molecule known to function in immunity-related inflammation. Given the lack of information on the precise functions of PTX3 in the pathogenesis of Graves' orbitopathy (GO), this study investigated the role of PTX3 in the inflammation and adipogenesis mechanisms of GO. We first compared the PTX3 expression between orbital tissues from patients with GO and normal controls using real-time PCR, which estimated significantly higher PTX3 transcript levels in the GO tissues than in the normal tissues.

Hematological Second Primary Malignancy in Pediatric Retinoblastoma: A Case Report and Systematic Review.

Purpose: The impact of heredity and treatment modalities on the development of hematologic second primary malignancies (SPMs) is unclear. This study primarily reviewed the literature on patients with hematologic SPMs after retinoblastoma.

Methods: The PubMed and Web of Science databases were searched to identify all cases of hematologic SPMs after retinoblastoma through December 2023 (International prospective register of systematic reviews CRD42023488273).

Orbital decompression following treatment with teprotumumab for thyroid eye disease.

Objective: To quantify the observed decrease in orbital decompressions being performed at one tertiary care institution and to determine the rate and predictive factors of orbital decompression surgery following treatment with teprotumumab for thyroid eye disease.

Methods: Epic's SlicerDicer program was used to analyze recent trends in the overall number of thyroid eye disease (TED) patients evaluated in the oculoplastic surgery department, as well as usage trends of CPT codes 67445 (lateral orbitotomy with bone removal for decompression) and 67414 (orbitotomy with removal of bone for decompression). A retrospective chart review of active moderate-to-severe TED patients treated with teprotumumab was performed at a single tertiary care center.

Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.

Purpose: Orbital fibroblasts play key roles in the pathogenesis of Graves' orbitopathy (GO), and previous findings have shown that endoplasmic reticulum (ER) stress and autophagy also contribute to GO. In this study, we investigated the presently unclear roles of inositol-requiring enzyme 1 (IRE1) and related autophagy processes in the pro-fibrotic mechanism of GO.

Materials And Methods: Orbital adipose/connective tissues were obtained from eight GO patients and six normal individuals during surgery.

Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves' orbitopathy.

Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry.

A Review of Novel Medical Treatments for Thyroid Eye Disease.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. There has been no effective medication to prevent proptosis in thyroid eye disease until 2020 when the anti-insulin-like growth factor 1 receptor (anti-IGF-1R) antibody, Teprotumumab, was approved by the US Food and Drug Administration, sparking increased interest in immune-based drug development. This study aims to review the newly developed drug therapy as well as conventional treatment for TED.

Inhibitory effect of recombinant tyrosine‑sulfated madanin‑1, a thrombin inhibitor, on the behavior of MDA‑MB‑231 and SKOV3 cells .

Thrombin, which plays a crucial role in hemostasis, is also implicated in cancer progression. In the present study, the effects of the thrombin‑targeting recombinant tyrosine‑sulfated madanin‑1 on cancer cell behavior and signaling pathways compared with madanin‑1 wild‑type (WT) were investigated. Recombinant madanin‑1 2 sulfation (madanin‑1 2S) and madanin‑1 WT proteins were generated using .

The Effect of Rho Kinase Inhibitors on In Vitro Human Orbital Preadipocytes.

Purpose: To identify the effects of Rho Kinase (ROCK) inhibitor medications on human orbital adipogenesis, fibroblast proliferation, and fibrosis.

Methods: Orbital adipose tissue was obtained from patients with Graves' ophthalmopathy (GO) as well as controls (non-GO or normal) after informed consent was done. These tissue samples were cultured and adipogenesis was initiated.

Yes-Associated Protein Mediates the Transition from Inflammation to Fibrosis in Graves' Orbitopathy.

In Graves' orbitopathy (GO), localized orbital inflammation within the fixed orbit often leads to a fibrotic phenotype resulting in restrictive myopathy or refractory proptosis. However, the molecular pathways related to the transition from inflammation to fibrosis in GO are less understood. Yes-associated protein (YAP) and its homolog, transcriptional coactivator with PDZ-binding motif (TAZ; a Hippo pathway effector), are critical mechanosensors of mechanical stimuli and activate signaling cascades for cell proliferation, differentiation, and transformation.

Cre-loxP System-Based Mouse Model for Investigating Graves' Disease and Associated Orbitopathy.

Graves' disease (GD), one of the most common forms of autoimmune thyroid disorders, is characterized by hyperthyroidism caused by antibodies (Abs) against the extracellular A-subunit of the thyrotropin receptor (TSHR). Various approaches have been used to create mouse models of GD, including transfected fibroblasts and immunization with plasmids or adenoviruses expressing human TSHR A-subunit (hTSHR A-subunit). These models, however, require repeated immunization and produce inconsistent results.

The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.

Purpose: Graves' orbitopathy (GO) is an orbital manifestation of autoimmune Graves' disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves' orbital fibroblasts.

Preoperative Risk Factors for Proptosis Recurrence After Rehabilitative Orbital Decompression in Graves' Orbitopathy Patients.

Purpose: Rehabilitative orbital decompression treats disfiguring exophthalmos in patients with Graves' orbitopathy (GO). This study aimed to identify risk factors associated with the postoperative recurrence of proptosis after orbital decompression.

Design: Retrospective, case-control study.

Sarcopenia as a potential risk factor for senile blepharoptosis: Nationwide Surveys (KNHANES 2008-2011).

As the world's population is aging, sarcopenia is recognized as essential to assess people's lifelong condition and do appropriate early intervention. Senile blepharoptosis is also a problem in old age deteriorating visual function and causing a cosmetic decline. We investigated the association between sarcopenia and the prevalence of senile blepharoptosis, using a nationwide representative survey in Korea.

Therapeutic effect of ibrutinib, a selective Bruton's tyrosine kinase inhibitor, in orbital fibroblasts from patients with Graves' orbitopathy.

Purpose: Bruton's tyrosine kinase (BTK) is an essential protein in B-cell antigen receptor (BCR) signaling pathway and is known to be related to pathogenetic effect on B-cell related malignancies and various autoimmune diseases. In this study, we investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK inhibitor in the pathogenesis of Graves' orbitopathy (GO) in in vitro model.

Methods: Expression of BTK in orbital tissues from GO and normal control subjects were evaluated by real-time polymerase chain reaction (PCR).

Comparison of total energy intakes estimated by 24-hour diet recall with total energy expenditure measured by the doubly labeled water method in adults.

Background/objectives: The doubly labeled water (DLW) method is the gold standard for estimating total energy expenditure (TEE) and is also useful for verifying the validities of dietary evaluation tools. In this study, we compared the accuracy of total energy intakes (TEI) estimated by the 24-h diet recall method with TEE obtained using the doubly labeled water method.

Subjects/methods: This study involved 71 subjects aged 20-49 yrs.