Lan Yujian, Peng Qingping, Fu Bowen, Liu Huan
School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China.
Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510630, China; Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510145, China; Department of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510630, China.
Toxicology. 2025 Feb;511:154029. doi: 10.1016/j.tox.2024.154029. Epub 2024 Dec 8.
The growing prevalence of environmental pollutants has raised concerns about their potential role in thyroid dysfunction and related disorders. Previous research suggests that various chemicals, including plasticizers like acetyl tributyl citrate (ATBC), may adversely affect thyroid health, yet the precise mechanisms remain poorly understood. The objective of this study was to elucidate the complex effects of acetyl tributyl citrate (ATBC) on the thyroid gland and to clarify the potential molecular mechanisms by which environmental pollutants influence the disease process. Through an exhaustive exploration of databases such as ChEMBL, STITCH, and GEO, we identified a comprehensive list of 19 potential targets closely associated with ATBC and the thyroid gland. After rigorous screening using the STRING platform and Cytoscape software, we narrowed this list to 15 candidate targets, ultimately identifying five core targets: CBX5, HADHB, TRIM33, TP53, and CUL4A, utilizing three well-established machine learning methods. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses conducted in the DAVID database revealed that the primary pathways through which ATBC affects the thyroid gland involve key signaling cascades, including the FoxO signaling pathway and metabolic pathways such as fatty acid metabolism. Furthermore, molecular docking simulations using Molecular Operating Environment software confirmed strong binding interactions between ATBC and these core targets, enhancing our understanding of their interactions. Overall, our findings provide a theoretical framework for comprehending the intricate molecular mechanisms underlying ATBC's effects on thyroid damage and pave the way for the development of preventive and therapeutic strategies against thyroid disorders caused by exposure to ATBC-containing plastics or overexposure to ATBC.
环境污染物的日益普遍引发了人们对其在甲状腺功能障碍及相关疾病中潜在作用的担忧。先前的研究表明，包括柠檬酸乙酰三丁酯（ATBC）等增塑剂在内的各种化学物质可能会对甲状腺健康产生不利影响，但其确切机制仍知之甚少。本研究的目的是阐明柠檬酸乙酰三丁酯（ATBC）对甲状腺的复杂影响，并阐明环境污染物影响疾病进程的潜在分子机制。通过对ChEMBL、STITCH和GEO等数据库的详尽探索，我们确定了与ATBC和甲状腺密切相关的19个潜在靶点的综合列表。在使用STRING平台和Cytoscape软件进行严格筛选后，我们将该列表缩小至15个候选靶点，最终利用三种成熟的机器学习方法确定了五个核心靶点：CBX5、HADHB、TRIM33、TP53和CUL4A。在DAVID数据库中进行的深入基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，ATBC影响甲状腺的主要途径涉及关键信号级联反应，包括FoxO信号通路以及脂肪酸代谢等代谢途径。此外，使用分子操作环境软件进行的分子对接模拟证实了ATBC与这些核心靶点之间存在强烈的结合相互作用，加深了我们对它们相互作用的理解。总体而言，我们的研究结果为理解ATBC对甲状腺损伤的复杂分子机制提供了理论框架，并为开发针对因接触含ATBC塑料或过度接触ATBC而导致的甲状腺疾病的预防和治疗策略铺平了道路。
