Development and application of animal models to study thyroid-associated ophthalmopathy

Shen, Feiyang; Liu, Jin; Fang, Lianfei; Fang, Yun; Zhou, Huifang

doi:10.1016/j.exer.2023.109436

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…In this study, we measured α-SMA expression to assess myofibroblast differentiation by orbital fibroblasts, and measured fibronectin and collagen 1α expression to assess ECM formation, which were found to be mediated by IRE1. Since an established animal model of GO is currently not available, 38 indirect evaluations like these are frequently used and validated to assess fibrosis in GO. 22 39 40 Nevertheless, the contribution of IRE to in vitro study of GO indicates the need for further research.…”

Section: Discussionmentioning

confidence: 99%

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

Lee,

Kim,

Yoon

et al. 2024

Yonsei Med J

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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. GO fibroblasts were transfected with IRE1 small-interfering RNA and treated with bafilomycin A1 (Baf-A1) to evaluate the inhibitory effects of ER stress and autophagy, and protein-expression levels were analyzed through western blotting after stimulation with transforming growth factor (TGF)-β. Results TGF-β stimulation upregulated IRE1 in GO orbital fibroblasts, whereas silencing IRE1 suppressed fibrosis and autophagy responses. Similarly, Baf-A1, an inhibitor of late-phase autophagy, decreased the expression of pro-fibrotic proteins. Conclusion IRE1 mediates autophagy and the pro-fibrotic mechanism of GO, which provides a more comprehensive interpretation of GO pathogenesis and suggests potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

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

Lee,

Kim,

Yoon

et al. 2024

Yonsei Med J

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“…Area under the receiver operating characteristic curve (AUC): The receiver operating characteristic (ROC) curve plots SEN against (1 -SPE) for different threshold values. AUC measures the entire two-dimensional area underneath the ROC curve from (0,0) to (1,1). Thus, AUC evaluates the predictive performance independent of the threshold.…”

Section: $8andmentioning

confidence: 99%

“…T HYROID-associated orbitopathy (TAO) is an autoimmune disorder characterized by changes in several structures near the eyes [1]. Specifically, TAO is characterized by orbital inflammation, adipose tissue expansion, and an upregulated synthesis of hydrophilic glycosaminoglycans [2].…”

Section: Introductionmentioning

confidence: 99%

Multihead Neural Network for Multiple Segmented Images-Based Diagnosis of Thyroid-Associated Orbitopathy Activity

Lee,

Lee

2024

IEEE Access

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Adverse event reporting of the IGF-1R monoclonal antibody teprotumumab: a real-world study based on the US food and drug administration adverse event reporting system

Zhao,

Tao

2024

Front. Pharmacol.

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BackgroundTeprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries.MethodsAll AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.ResultsA total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0–92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women.ConclusionThis study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.

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Development and application of animal models to study thyroid-associated ophthalmopathy

Cited by 3 publications

References 53 publications

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

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

Multihead Neural Network for Multiple Segmented Images-Based Diagnosis of Thyroid-Associated Orbitopathy Activity

Adverse event reporting of the IGF-1R monoclonal antibody teprotumumab: a real-world study based on the US food and drug administration adverse event reporting system

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