Background: Graves’ disease (GD) is one of the most common autoimmune thyroid diseases (AITDs) in humans, and thyrotropin receptor antibody (TRAb) is a characterized autoantibody in GD. The use of radioactive iodine therapy (RAI) for GD treatment is increasing.Objectives: We studied the biological properties of TRAb and evaluated the effect of RAI therapy on TRAb in GD patients.Methods: In total, 225 patients (22 onset GD patients without¹³¹I therapy, 203 GD patients treated with¹³¹I therapy) and 20 healthy individuals as normal controls were included in this study. Clinical assessments were performed, and we examinedin vitrothe biological properties of TRAb in the 22 onset GD patients and 20 controls as well as 84 GD patients with¹³¹I therapy.Results: Serum TRAb and thyroid peroxidase antibody (TPOAb) levels increased in the initial year of RAI treatment, and both antibodies decreased gradually after one year. After 5 years from radioiodine treatment, TRAb and TPOAb levels decreased in 88% and 65% of GD patients, respectively. The proportion of patients positive for thyroid-stimulatory antibody (TSAb) was significantly higher in the 7–12-month group, and thyroid-blocking antibody (TBAb) levels were elevated after one year in half of the patients who received¹³¹I treatment.Conclusions: Treatment of GD patients with radioiodine increased TPOAb and TRAb (their main biological properties were TSAbs) within the first year after therapy, and the main biological properties of elevated TRAb were TBAbs after 1 year.

Purpose: Thyroid cancer (TC) is one of the most common endocrine malignancies, and its morbidity continues to rise. N⁶-methyladenosine (m⁶A) RNA methylation, an epigenetic modification, is an important regulator of gene expression in TC. Therefore, it’s worth finding the characteristics and predictive value of the m⁶A RNA methylation regulators in thyroid cancer (TC). Method: RNA-seq data of TC was downloaded from the Cancer Genome Atlas (TCGA) database to screen out the differential expressed regulators. The absolute contraction selection operator (Lasso) Cox regression was used to construct the risk model of m⁶A methylation regulators. The predictive value of the risk scoring model was evaluated by Kaplan Meier (K-M) analysis and receiver operating characteristic (ROC) curves. The underlying mechanism of m⁶A methylation regulators in TC was predicted by gene set enrichment analysis (GSEA). Further validation was performed by using immunohistochemistry (IHC) and q-PCR. The correlation between risk-related gene and immune infiltration was evaluated by Tumour Immune Estimation Resource (TIMER). Results: IGF2BP2, YTHDF1 and YTHDF3 were screened out as strong independent prognostic factors of TC. Then a risk score model was established to further screen the predictors. Finally, according to the results of overall survival (OS) and clinical characteristics of TC, YTHDF3 was screened out as a potential predictor. Meanwhile, IHC and qPCR confirmed that YTHDF3 was expressed differential in TC. The expression of YTHDF3 was positively associated with the infiltration level of CD4⁺ T cells and macrophages. It was strongly correlated with a variety of immune markers in TC. Conclusion: We confirmed that YTHDF3 can be used as a potential prognostic biomarker of TC. It not only plays a decisive role in the initiation and development of TC, but also provides a new perspective for understanding the modification of m⁶A RNA in TC.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation inhgfaand two missense mutations inmetby positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation inhgfaormet. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation ofE-cadherinexpression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation ofE-cadherinin thyrocytes via MAPK-snail pathway.

In recent years, considerable concerns have been raised regarding environmental pollution caused by water-soluble polymers (WSPs). Polyvinyl alcohol (PVA), used in the textile industry and in the manufacture of medical consumables, is one type of WSPs. After use, PVA is discharged and enters aquatic ecosystems, but most of it cannot be completely biodegraded in the environment. In this study, we investigated the effects of PVA on developmental toxicity and thyroid endocrine disruption using a zebrafish (Danio rerio) model. We treated zebrafish embryos with 10 g/L and 5 mg/L PVA for 96 h and found that the proportion of coagulated embryos significantly increased, resulting in a remarkable decrease in hatching rate and larval survival. The body length of zebrafish larvae in the exposed group was remarkably shorter than that of the control group (Control: 3.64 ± 0.03 mm vs. 10 g/L PVA: 3.46 ± 0.03 mm; p=0.001). Compared to the control group, the levels of T3 and T4 in embryos of the exposed group were significantly lower, while thyroid stimulating hormone (TSH) levels were significantly increased. Notable up-regulation of trh, tshβ, and tshr genes, as well as down-regulation of trα , tg, ttr, dio1, and dio2 genes, were observed in embryos of the exposed group. Collectively, these findings suggest that PVA negatively influences the development and function of the thyroid gland during zebrafish embryogenesis. These effects may be partly attributed to the disruption of hypothalamic-pituitary-thyroid (HPT) axis regulation. Therefore, raising awareness about the possible thyroid toxicity associated with PVA is crucial.

Thyroid dysgenesis (TD) is a major cause of primary congenital hypothyroidism; however, the molecular mechanism underlying this process is unclear. Current knowledge regarding the morphogenesis of the thyroid gland and vascular anomalies affecting thyroid development is limited. To monitor the early stages of thyroid gland development, we generated double transgenic zebrafish embryos Tg(tg:mCherry/flk1:EGFP). We described the volume of the thyroid from 2 days postfertilization (dpf) to 5 dpf using 3D reconstruction images. We treated zebrafish embryos with the fibroblast growth factor (FGF) inhibitor PD166866 to better understand the impact of vascular defects on thyroid development and the effects of drug administration at specific time periods on different stages of thyroid development. The 3D reconstruction data revealed that the thyroid glands underwent significant transformation at critical time points. PD166866 treatment from 48 to 72 hours postfertilization (hpf) and from 72 to 96 hpf did not cause obvious reductions in thyroid volume but did result in observable abnormalities in thyroid morphology. The treatment also affected thyroid volume from 36 to 48 hpf, thus indicating that there are time‐point‐specific effects of drug administration during thyroid development. Three‐dimensional image reconstruction provides a comprehensive picture of thyroid anatomy and can be used to complement anatomical fluorescence information. The effects of an FGF pathway inhibitor on thyroid development were determined to be time‐point‐dependent.