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      New Therapeutic Horizon of Graves’ Hyperthyroidism: Treatment Regimens Based on Immunology and Ingredients From Traditional Chinese Medicine

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          Abstract

          Graves’ disease is an autoimmune disease characterized by goiter and hyperthyroidism, and 25% patients develop GO. Traditional treatment options, such as antithyroid drugs, radioiodine or thyroidectomy, have remained largely unchanged over the past 70 years. For many patients, there is a high rate of recurrence after antithyroid drugs and lifelong hypothyroidism after ablation and thyroidectomy. The symptoms and quality of life of some patients have not been effectively improved. The clinical demand for new therapeutic regimens, coupled with a deeper understanding of the pathophysiology and immunobiology of Graves’ disease, has led to the emergence of several new therapeutic ideas, including biologics, small molecule peptides, immunomodulators and teprotumumab, a specific antibody targeting IGF-1R. Besides, the elements of TCM have attracted more and more interests in modern medicine, because some effective components have been successfully used in the treatment of autoimmune diseases. Based on the pathophysiology and efficacy of clinical management and treatment in Graves’ hyperthyroidism, here we review the new strategies under investigation and summarize the effective components of traditional Chinese medicine used for Graves’ hyperthyroidism, and explore their mechanisms. These therapies have opened a new window for the treatment of Graves’ disease, but the exact mechanism and the research direction still need to be further explored.

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          Most cited references113

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          Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain.

          Transcription factor Nrf2 is essential for the antioxidant responsive element (ARE)-mediated induction of phase II detoxifying and oxidative stress enzyme genes. Detailed analysis of differential Nrf2 activity displayed in transfected cell lines ultimately led to the identification of a new protein, which we named Keap1, that suppresses Nrf2 transcriptional activity by specific binding to its evolutionarily conserved amino-terminal regulatory domain. The closest homolog of Keap1 is a Drosophila actin-binding protein called Kelch, implying that Keap1 might be a Nrf2 cytoplasmic effector. We then showed that electrophilic agents antagonize Keap1 inhibition of Nrf2 activity in vivo, allowing Nrf2 to traverse from the cytoplasm to the nucleus and potentiate the ARE response. We postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel Nrf2 nuclear shuttling mechanism. The activation of Nrf2 leads in turn to the induction of phase II enzyme and antioxidative stress genes in response to electrophiles and reactive oxygen species.
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            Graves' ophthalmopathy.

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              Graves' Disease.

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                05 April 2022
                2022
                : 13
                : 862831
                Affiliations
                [1] 1 Institute of Integrated Traditional Chinese and Western Medicine , Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China
                [2] 2 Grade 2017 of Integrated Traditional Chinese and Western Clinical Medicine , Second Clinical School , Tongji Hospital , Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China
                [3] 3 Department of Integrated Traditional Chinese and Western Medicine , Tongji Medical College , Tongji Hospital , Huazhong University of Science and Technology , Wuhan, China
                Author notes

                Edited by: Shuai Ji, Xuzhou Medical University, China

                Reviewed by: Silvia Martina Ferrari, University of Pisa, Italy

                Daniela Gallo, University of Insubria, Italy

                *Correspondence: Fuer Lu, felutjh88@ 123456163.com ; Jing Gong, jgongtcm@ 123456126.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                862831
                10.3389/fphar.2022.862831
                9020194
                35462920
                1ea76f2c-52a6-45d3-b8bc-73362e58a00c
                Copyright © 2022 He, Dong, Gong, Guo, Xia, Gong and Lu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 January 2022
                : 09 March 2022
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82174327
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                graves’ ophthalmopathy,graves’ disease (gd),traditional chinese medicine,immunology,treatment regimens

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