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Thyroid Dysfunctions: Molecular Mechanisms Underlying Clinical Consequences

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 1892

Special Issue Editor


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Guest Editor
SOC Endocrinology, ASU FC—Oncology Area Department, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy
Interests: thyroid cancer; thyroid eye disease; thyroid; hormones; adrenal; adrenal disease; medullary thyroid cancer; multiple endocrine neoplasia; aldosterone; licorice
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Special Issue Information

Dear Colleagues,

Thyroid hormones play a fundamental role in the homeostasis of all organs and tissues. Therefore, thyroid dysfunction, both as an excess and defect of thyroid hormones, has a considerable impact on human health, particularly on the heart, bone tissue, skin, central and peripheral nervous systems, kidney, and adipose tissue; however, the diagnosis of thyroid dysfunction is not always easy and misdiagnoses can often occur due to interference with laboratory assay methods. Moreover, not all of the molecular mechanisms by which the excess or defect of thyroid hormones cause alterations to target organs are well known.

In this Special Issue, original studies on all aspects of the molecular mechanisms by which thyroid disorders lead to clinical implications are welcome, such as thyroid-induced osteoporosis, thyroid eye disease, thyroid cardiac alterations, thyroid cancer, or thyroid genetic disorder. It will also cover reports providing new insights into possible laboratory interference in thyroid hormone assays leading to clinical consequences.

Dr. Jacopo Manso
Guest Editor

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Keywords

  • thyroid
  • thyroid dysfunctions
  • thyroid hormones
  • thyroid disorders
  • molecular mechanisms

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Published Papers (2 papers)

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Research

12 pages, 1874 KiB  
Article
Anti-Proliferative and Anti-Migratory Activity of Licorice Extract and Glycyrrhetinic Acid on Papillary Thyroid Cancer Cell Cultures
by Jacopo Manso, Simona Censi, Maria Chiara Pedron, Loris Bertazza, Alberto Mondin, Edoardo Ruggeri, Susi Barollo, Chiara Sabbadin, Isabella Merante Boschin, Decio Armanini and Caterina Mian
Int. J. Mol. Sci. 2024, 25(19), 10800; https://doi.org/10.3390/ijms251910800 - 8 Oct 2024
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Abstract
Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the [...] Read more.
Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the potential anti-proliferative effects of licorice and GA on PTC cell cultures. Licorice extract (LE) was produced from the root and tested on BCPAP and K1 cell lines, as well as GA and aldosterone. We used the MTT test to investigate the anti-proliferative activity, the wound healing test for the migratory activity, and finally, we analyzed cell cycle distribution, apoptosis, and oxidative stress after LE, GA, or aldosterone incubation. Both LE and GA reduced cell viability at 48 h and cell migration at 24 h in both PTC cultures. Aldosterone reduced cell migration only in K1 cells. LE and GA induced cell cycle arrest in the G0/G1 phase in the BCPAP cell line, while LE and aldosterone induced it in the K1 culture. GA but not LE increased the apoptosis rate in both cell lines, whereas LE but not GA increased oxidative stress in both cultures. This study presents the first evidence of the in vitro anti-proliferative and anti-migratory activity of LE and GA on PTC. Full article
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17 pages, 7033 KiB  
Article
RNA Sequencing Reveals a Strong Predominance of THRA Splicing Isoform 2 in the Developing and Adult Human Brain
by Eugenio Graceffo, Robert Opitz, Matthias Megges, Heiko Krude and Markus Schuelke
Int. J. Mol. Sci. 2024, 25(18), 9883; https://doi.org/10.3390/ijms25189883 - 13 Sep 2024
Viewed by 861
Abstract
Thyroid hormone receptor alpha (THRα) is a nuclear hormone receptor that binds triiodothyronine (T3) and acts as an important transcription factor in development, metabolism, and reproduction. In mammals, THRα has two major splicing isoforms, THRα1 and THRα2. The better-characterized isoform, THRα1, is a [...] Read more.
Thyroid hormone receptor alpha (THRα) is a nuclear hormone receptor that binds triiodothyronine (T3) and acts as an important transcription factor in development, metabolism, and reproduction. In mammals, THRα has two major splicing isoforms, THRα1 and THRα2. The better-characterized isoform, THRα1, is a transcriptional stimulator of genes involved in cell metabolism and growth. The less-well-characterized isoform, THRα2, lacks the ligand-binding domain (LBD) and is thought to act as an inhibitor of THRα1 activity. The ratio of THRα1 to THRα2 splicing isoforms is therefore critical for transcriptional regulation in different tissues and during development. However, the expression patterns of both isoforms have not been studied in healthy human tissues or in the developing brain. Given the lack of commercially available isoform-specific antibodies, we addressed this question by analyzing four bulk RNA-sequencing datasets and two scRNA-sequencing datasets to determine the RNA expression levels of human THRA1 and THRA2 transcripts in healthy adult tissues and in the developing brain. We demonstrate how 10X Chromium scRNA-seq datasets can be used to perform splicing-sensitive analyses of isoforms that differ at the 3′-end. In all datasets, we found a strong predominance of THRA2 transcripts at all examined stages of human brain development and in the central nervous system of healthy human adults. Full article
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