Association Between Iodine Status and Prevalence of Hypothyroidism, Autoimmune Thyroiditis, and Thyroid Nodule: a Cross-Sectional Study in Shandong Province, China.

In this study, the aim was to investigate the correlation between varying levels of urinary iodine concentration (UIC) in adults and the occurrence of thyroid diseases, with the additional objective of determining the optimal iodine status level for adults. A cross-sectional study was conducted on adults from six areas with different drinking water iodine concentrations (WIC) without eating iodized salt in Heze and Jining counties, Shandong Province, China. A total of 1336 adults were included in this study, and drinking water samples, blood samples, urine samples, thyroid ultrasound, and a questionnaire were collected. UIC, free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were detected. There were no significant differences in the detection rates of hypothyroidism and thyroid autoimmunity (TAI) among the different median UIC groups (UIC < 100 µg/L, 100-199 µg/L, 200-299 µg/L, ≥ 300 µg/L). However, the detection rates of hypothyroidism were higher in the UIC < 100 µg/L group (16.67%) and the UIC ≥ 300 µg/L group (16.51%) compared to the other groups. The detection rate of TAI increased as UIC levels increased. The detection rate of thyroid nodule (TN) in the UIC < 100 µg/L group was significantly higher than that in the UIC 200-299 µg/L UIC group (χ2 = 10.814, P = 0.001). After adjusting confounding factors, it was found that low UIC (< 100 µg/L) was a risk factor for TN (OR 1.83, 95% CI [1.04-3.22]). Meanwhile, there no statistical difference between UIC 200 and 299 µg/L and UIC 100 and199 µg/L for OR of hypothyroidism, TAI, and TN. This study identified associations between different UIC levels and the prevalence of thyroid disorders, with low UIC (< 100 µg/L) posing a risk for TN, and the detection rate of TN and hypothyroidism was the lowest in UIC (200-299 µg/L) group. Therefore, the acceptable UIC range of 'adequate' iodine intake among adults can be widened from 100-199 µg/L to 100-299 µg/L.

Association between different water iodine exposures and thyroid cancer: A retrospective study of high water iodine areas in China from 2009 to 2020.

In recent years, the incidence of thyroid cancer has been on a significant rise worldwide, and a number of environmental factors have been suspected to be risk factors for thyroid cancer, especially the relationship between iodine intake and thyroid cancer has attracted attention. In this study, we want to assess the relationship between different water iodine exposures and thyroid cancer incidence before and after water alteration in areas with high water iodine in China. Thyroid cancer patients (2009-2020) were enrolled at two hospitals, both in Heze City, Shandong Province, an area with high water iodine levels. According to the criteria of the study, 5826 cases out of 8785 cases were selected for inclusion in the study. Before and after water alteration, the incidence of thyroid cancer was highest in areas with water iodine concentrations of 200-300 µg/L in high iodine areas. In areas where water iodine decreased to adequate iodine levels, there was a strong negative correlation between the decreased level of water iodine and the incidence of thyroid cancer. In addition, in cases with pathology reports, we found that the greater the decrease in water iodine values, the markedly smaller the maximum diameter of the thyroid cancer lesions. Taken together, these findings suggest that we should continue to monitor the incidence of thyroid cancer in areas with high water iodine and continue to optimize population iodine intake to reduce the incidence of thyroid cancer.

MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog.

Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 µmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 µmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 µmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer.

Serum thyroglobulin as a biomarker of iodine excess and thyroid disease occurrence in adults.

BACKGROUND: Thyroglobulin (Tg) is considered a sensitive indicator of iodine deficiency. However, the usefulness of Tg as a biomarker of excess iodine is uncertain. The present study aimed to determine the influence of different iodine intake on serum Tg levels, evaluate the influence of thyroid diseases on the distribution of Tg, and identify the factors that may affect Tg levels. METHODS: A cross-sectional survey with a total of 1208 adults was conducted in different water iodine areas in China. Urinary iodine concentration (UIC), water iodine concentration (WIC), serum Tg, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. The thyroid volumes and nodules were measured by B-scan ultrasound. RESULTS: Based on the WIC data, subjects were divided into three groups. Based on the median urinary iodine concentration (MUIC) data, the iodine levels were adequate, more than adequate, and excess for the WIC < 10 µg/L group, 10 µg/L ≤ WIC ≤ 100 µg/L g, and WIC > 100 µg/L groups, respectively. The median Tg was significantly higher in the excess iodine group than in the adequate iodine group and the more than adequate iodine group (14.6 µg/L vs.12.7 µg/L, P = 0.042; 14.6 µg/L vs.12.5 µg/L, P = 0.004). Multiple linear regression analysis showed that excess iodine intake, goitre, thyroid nodules, and hypothyroidism were significantly related to higher serum Tg levels. CONCLUSION: Serum Tg level can be a promising biomarker of excessive iodine intake, but other factors, especially the presence of thyroid disease, should be considered when using this parameter.

High Iodine Induces the Proliferation of Papillary and Anaplastic Thyroid Cancer Cells via AKT/Wee1/CDK1 Axis.

High iodine can alter the proliferative activity of thyroid cancer cells, but the underlying mechanism has not been fully elucidated. Here, the role of high iodine in the proliferation of thyroid cancer cells was studied. In this study, we demonstrated that high iodine induced the proliferation of BCPAP and 8305C cells via accelerating cell cycle progression. The transcriptome analysis showed that there were 295 differentially expressed genes (DEGs) in BCPAP and 8305C cells induced by high iodine, among which CDK1 expression associated with the proliferation of thyroid cancer cells induced by high iodine. Moreover, the western blot analysis revealed that cells exposed to high iodine enhanced the phosphorylation activation of AKT and the expression of phospho-Wee1 (Ser642), while decreasing the expression of phospho-CDK1 (Tyr15). Importantly, the inhibition of AKT phosphorylation revered the expression of CDK1 induced by high iodine and arrested the cell cycle in the G1 phase, decreasing the proliferation of thyroid cancer cells induced by high iodine. Taken together, these findings suggested that high iodine induced the proliferation of thyroid cancer cells through AKT-mediated Wee1/CDK1 axis, which provided new insights into the regulation of proliferation of thyroid cancer cells by iodine.

Cartilage oligomeric matrix protein affects the biological behavior of papillary thyroid carcinoma cells by activating the PI3K/AKT/Bcl-2 pathway.

Objective: To explore the effect of cartilage oligomeric matrix protein (COMP) on papillary thyroid carcinoma (PTC). Methods: COMP expression levels in PTC tissues and matched adjacent normal tissues were measured using tissue microarrays. Human PTC cells were cultured and transduced with lentiviral short hairpin RNA against COMP (COMP-shRNA), a negative control (NC) shRNA, or mock transfected (Control). We used the Cell Counting Kit-8, performed colony formation assays, wound healing assays, Transwell invasion assays, flow cytometry, and measured the expression of apoptosis-related proteins at the mRNA and protein levels to explore the effects of COMP on the biological behavior of PTC cells and to discover the specific signaling pathway involved in these processes. Results: COMP expression was significantly higher in PTC tissues than in adjacent normal tissues. At the cellular level, COMP promoted cell migration, increased the invasiveness of PTC cells, and inhibited apoptosis. However, differences in cell proliferation were only observed within 72 hours. At the same time, colony formation assays showed that silencing COMP inhibited the proliferation of PTC cells. We also found that COMP regulated the behavior of PTC cells by activating the PI3K/AKT/Bcl-2 pathway. Conclusions: COMP is upregulated in PTC, which enhances cancer cell invasion and inhibits apoptosis, contributing to the development and progression of PTC. Thus, COMP may serve as a new biomarker for PTC.

Nitric oxide is involved in the hypothyroidism with significant morphology changes in female Wistar rats induced by chronic exposure to high water iodine from potassium iodate.

Epidemiological studies indicated that chronic exposure to high water iodine is associated with primary hypothyroidism (PH) and subclinical hypothyroidism (SCH). However, the mechanism is not well understood. In this study, we explored whether chronic exposure to high water iodine from potassium iodate (KIO3) can induce hypothyroidism in addition to determining if nitric oxide (NO) is involved in the pathogenesis. 96 female Wistar rats were divided into six groups: control, I1000µg/L, I3000µg/L, I6000µg/L, N-nitro-L-arginine methylester (L-NAME) and L-NAME+I6000µg/L. After 3 months, urine iodine concentration, thyroid hormone, NO and nitric oxide synthase (NOS) serum levels were determined. Additionally, thyroid expression of inducible nitric oxide synthase (iNOS) was also investigated. Thyroid morphology was observed under light microscopy and transmission electron microscope. SCH as indicated by elevated serum thyrotropin (TSH) was induced among rats exposed to 3000 µg/L I-, while rats treated with 6000 µg/L I- presented PH characterized by elevated TSH and lowered total thyroxine in serum. Moreover, serum NO, NOS and iNOS expression in the thyroid were significantly increased in I3000µg/L and I6000µg/L groups. Changes in thyroid function and morphology in the L-NAME+I6000µg/L group were extenuated compared to I6000µg/L group. These findings suggested that chronic exposure to high water iodine from KIO3 likely induces hypothyroidism with significant morphology changes in female Wistar rats and NO appears to be involved in the pathogenesis.

Association between chronic exposure to different water iodine and thyroid cancer: A retrospective study from 1995 to 2014.

The controversy that iodine intake may increase the risk of thyroid cancer has heightened over the past twenty years. In this retrospective study, we mainly analyzed the association between water iodine and thyroid cancer and discussed the possible cause of the increase in thyroid cancer. This study was supported by three hospitals in areas with different water iodine concentration. 5574 patients with thyroid disease were recruited, of which 1429 patients had been diagnosed with thyroid cancer. These samples collectively were used to analyze the relationship of incidence and prevalence associated with water iodine. In addition, the ratio of maximum tumor diameter was analyzed. By analyzing the proportion of patients with thyroid cancer in thyroid diseases, we found a decrease in the proportion of thyroid cancer with increasing water iodine (P<0.0001). In addition, there was no significant correlation between the median water iodine and the prevalence of thyroid cancer, including papillary thyroid cancer (P>0.05). Meanwhile, the 5years' cumulative incidence of thyroid cancer increased with years (P<0.01). Comparing Cao county and Shan county, which are areas with high water iodine, to adequate iodine area such as in Mudan district, an increasing incidence is observed in 2010-2014 in Mudan district. Again, we observed a significant increase in the proportion of thyroid cancer with tumor size <1cm (P<0.01). Therefore, we concluded that cause(s) of increase in thyroid cancer may be ascribed to the sensitive diagnostic techniques and the improvement of living condition, but not water iodine.