LncRNA MALAT1-miR-339-5p-NIS axis is involved in the increased level of thyroid stimulating hormone (TSH) induced by combined exposure of high iodine and hyperlipidemia.

Hypothyroidism and subclinical hypothyroidism were both characterized by elevated levels of thyroid stimulating hormone (TSH). Previous studies had found that high iodine or hyperlipidemia alone was associated with increased TSH level. However, their combined effects on TSH have not been elucidated. In this study, combination of high iodine and hyperlipidemia was established through the combined exposure of high-water iodine and high fat diet in Wistar rats. The results showed that combined exposure of high iodine and high fat can induce higher TSH level. The mRNA and protein levels of sodium iodide transporters (NIS) and type 1 deiodinase (D1) in thyroid tissues, which were crucial genes in the synthesis of thyroid hormones, decreased remarkably in combined exposure group. Mechanistically, down-regulated long non-coding RNA (lncRNA) metastasis associated in lung denocarcinoma transcript 1 (MALAT1) may regulate the expression of NIS by increasing miR-339-5p, and regulating D1 by increasing miR-224-5p. Then, the above findings were explored in subjects exposed to high water iodine and hyperlipidemia. The results indicated that in population combined with high iodine and hyperlipidemia, TSH level increased to higher level and lncRNA MALAT1-miR-339-5p-NIS axis was obviously activated. Collectively, this study found that combined exposure of high iodine and hyperlipidemia induced a higher level of TSH, and lncRNA MALAT1-miR-339-5p-NIS axis may play important role.

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.

The Role of Thyroid Hormone Synthesis Gene-Related miRNAs Profiling in Structural and Functional Changes of The Thyroid Gland Induced by Excess Iodine.

At recent years, the impairment caused by iodine excess are paid more attention. However, there is still largely unknown about the exact mechanism induced by excessive iodine. MiRNAs have been found to act as biomarkers for a variety of diseases, whereas fewer studies focused on miRNAs related to a cluster of genes regulating thyroid hormone synthesis, such as NIS, Pendrin, TPO, MCT8, TSHR, TSHα, and TSHß-related miRNAs in structural and functional changes of the thyroid gland induced by subchronic and chronic high iodine exposure. In the present study, one hundred and twenty 4-week-old female Wistar rats were randomly divided into control group (I50µg/L KIO3); HI 1 (I6000µg/L KIO3); HI 2 (I10000µg/L KIO3); and HI 3 (I50000µg/L KIO3), the exposure period was 3 months and 6 months, respectively. The iodine contents in the urine and blood, thyroid function, and pathological changes were determined. In addition, levels of thyroid hormone synthesis genes and the associated miRNAs profiling were detected. The results showed that subclinical hypothyroidism occurred in the high iodine groups with subchronic high iodine exposure, while 6-month exposure led to hypothyroidism in the I10000µg/L and I50000µg/L groups. Subchronic and chronic high iodine exposure caused mRNA and protein levels of NIS, TPO, and TSHR decreased significantly, and Pendrin expression increased significantly. In addition, MCT8 mRNA and protein levels are only remarkably decreased under the subchronic exposure. PCR results showed that levels of miR-200b-3p, miR-185-5p, miR-24-3p, miR-200a-3p, and miR-25-3p increased significantly exposed to high iodine for 3 months, while miR-675-5p, miR-883-5p, and miR-300-3p levels increased significantly under the exposure to high iodine for 6 months. In addition, miR-1839-3p level was markedly decreased exposed to high iodine for 3 and 6 months. Taken together, the miRNA profiling of genes regulating thyroid hormone synthesis remarkably altered from subclinical hypothyroidism to hypothyroidism induced by excess iodine exposure, and some miRNAs may play an important role in subclinical hypothyroidism or hypothyroidism through regulating NIS, Pendrin, TPO, MCT8, and TSHR providing promising targets to alleviate the impairment on the structure and function of thyroid gland.

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.

Efficacy and Safety of Citric Acid and Heparin Anticoagulation in Patients with Septic Acute Kidney Injury Undergoing Continuous Renal Replacement Therapy: A Meta-Analysis.

Objective: This meta-analysis compares the clinical efficacy and safety of citrate anticoagulation with heparin anticoagulation in continuous renal replacement therapy for acute kidney injury in sepsis. Methods: The experimental group underwent local anticoagulation with citrate, whereas the control group received systemic anticoagulation with heparin. Relevant data from randomized controlled trials (RCTs) meeting the inclusion criteria were independently extracted through computer searches of the China Journal Full Text Database (CNKI), Wanfang, and Vipul databases. Additionally, references to included literature were searched to expand the dataset. Extracted RCTs that met inclusion criteria underwent independent quality evaluation and cross-checking using the Cochrane systematic review method. Subsequently, a meta-analysis was conducted using Stata 12.0 software. Results: The analysis included seven studies involving a total of 652 patients. After treatment, renal function improvement was significantly more significant in the citrate group, while creatinine and urea nitrogen levels showed a more significant decrease in the heparin group, with statistically significant differences (WMD = -51.30, 95% CI = -68.54 ~ -34.06, P = .000 and WMD = 3.68, 95% CI = -4.52 ~ -2.85, P = .000). The filter lifespan in the citrate group was significantly longer than in the heparin group, with a statistically significant difference (WMD = 6.93, 95% CI = 6.30 ~ 7.55, P = .000). Adverse bleeding reactions were significantly less common in the citrate group compared to the heparin group, with a statistically significant difference (RR = 0.14, 95% CI = 0.06 ~ 0.32, P = .000). Conclusions: The results of this meta-analysis indicate that citrate anticoagulation is more effective than heparin anticoagulation in continuous renal replacement therapy for patients with acute kidney injury in sepsis. Citrate anticoagulation contributes to improved renal function and extended filter usage and reduces the incidence of adverse bleeding reactions.

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.

Flame-retardant PNIPAAm/sodium alginate/polyvinyl alcohol hydrogels used for fire-fighting application: Preparation and characteristic evaluations.

A novel fire-preventing triple-network (TN) hydrogel was prepared and laminated on cotton fabric to improve fire-resistant performance of cellulose fabric. The TN hydrogel composed of Poly (N-isopropylacrylamide) (PNIPAAm)/sodium alginate (SA)/ Poly (vinyl alcohol) (PVA) exhibited excellent swelling ratio, swelling-deswelling behavior and antibacterial property. Results indicated that introduction of SA could improve water retention capabilities of TN hydrogels. Thermogravimetric experiments showed that the thermal stability of hydrogels was best at a SA: PVA ratio of 2:1. Furthermore, the obtained hydrogel-cotton fabric laminates displayed efficient flame retardancy. Compared to original fabric, hydrogel-fabric laminates were nearly undamaged when exposed to fire for 12 s. This result is attributed to energy absorption as water is heated and evaporates in the hydrogel. The present work provides a new concept to prepare fire-resistant polymer fabric, which may be used in fire-protective clothing to protect the skin from burn injuries.

Pigment epithelium-derived factor (PEDF) ameliorates arsenic-induced vascular endothelial dysfunction in rats and toxicity in endothelial EA.hy926 cells.

Although the harmful effects of arsenic exposure on the cardiovascular system have received great attention, there is still no effective treatment. Vascular endothelial dysfunction (VED) is the initial step of cardiovascular diseases, where pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function. Here, we explored the protective role of PEDF in VED induced by arsenic, and its underlying molecular mechanism, designing an in vivo rat model of arsenic exposure recovery and in vitro endothelial EA. hy926 cell-based assays. The edema of aortic endothelial cells in rats significantly improved during recovery from arsenite exposure compared with rats exposed to 10 and 50 mg/L arsenite continuously. In addition, serum levels of nitric oxide (NO), von Willebrand factor, and nitric oxide synthase (inducible and total activities) in rats, which were greatly affected by arsenite exposure, returned to levels similar to those in the control group after recovery with distilled water. The recovery from arsenite exposure was associated with increased levels of PEDF; decreased protein levels of Fas, FasL, P53, and phospho-p38; and inhibited apoptosis in aortic endothelial cells in vivo. Recombinant human PEDF treatment (100 nM) prevented the toxic effects of arsenite (50 µM) on endothelial cells in vitro by increasing NO content, decreasing reactive oxygen species (ROS) levels, and inhibiting apoptosis, as well as increasing cell viability and decreasing levels of P53 and phospho-p38. Our findings suggest that PEDF protects endothelial cells from arsenic-induced VED by increasing NO release and inhibiting apoptosis, where P53 and p38MAPK are its main targets.