Fluorescein staining of chloroplast starch granules in living plants.

Chloroplast starch granules (cpSGs) store energy harvested through photosynthesis in plants, and cpSG dynamics have important roles in plant energy metabolism and stress responses. To date, cpSGs have been visualized using several methods, such as iodine staining; however, no method can be used to specifically visualize cpSGs in living cells from various plant species. Here, we report a simple method to visualize cpSGs in living plant cells in various species by staining with fluorescein, a commonly used fluorescent dye. We show that fluorescein is taken up into chloroplasts and interacts with cpSGs similarly to iodine. Fluorescein also interacts with refined starch in vitro. Using a fluorescein derivative for ultrabright cpSG imaging, we produced high-quality 3D reconstructions of cpSGs and evaluated their accumulation in multiple plant species. As fluorescein is well known and readily purchasable, our fluorescein-based staining method should contribute to all research regarding starch.

Circ_0004851 regulates the molecular mechanism of miR-296-3p/FGF11 in the influence of high iodine on PTC.

The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine's biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.

Iodine Metabolism in Urine and Breast Milk among Lactating Women with Adequate Iodine.

BACKGROUND: In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the kidneys and breasts. OBJECTIVES: This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE). METHODS: A 7-d iodine metabolism study was conducted on 41 lactating women with a mean age of 30 y in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined. RESULTS: Iodine metabolism studies were performed for 285 d. The median TII and TIE values were 255 and 263 µg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 µg/d, the BMIER decreased with the increase of the TII (ß: -0.90; 95% confidence interval: -1.08, -0.72). CONCLUSIONS: When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine concentrations is higher than their BMIE. This study was registered at clinicaltrials.gov as NCT04492657.

Study of iodine transport and thyroid hormone levels in the human placenta under different iodine nutritional status.

Iodine and thyroid hormones (TH) transport in the placenta are essential for fetal growth and development, but there is little research focus on the human placenta. The research aimed to investigate iodine and TH transport mechanisms in the human placenta. The placenta was collected from sixty healthy pregnant women. Urinary iodine concentration (UIC), serum iodine concentration (SIC), placenta iodine storage (PIS) and the concentration of serum and placenta TH were examined. Five pregnant women were selected as insufficient intake (II), adequate intake (AI) and above requirements intake (ARI) groups. Localisation/expression of placental sodium/iodide symporter (NIS) and Pendrin were also studied. Results showed that PIS positively correlated with the UIC (R = 0·58, P < 0·001) and SIC (R = 0·55, P < 0·001), and PIS was higher in the ARI group than that in the AI group (P = 0·017). NIS in the ARI group was higher than that in the AI group on the maternal side of the placenta (P < 0·05). NIS in the II group was higher than that in the AI group on the fetal side (P < 0·05). In the II group, NIS on the fetal side was higher than on the maternal side (P < 0·05). Pendrin was higher in the II group than in the AI group on the maternal side (P < 0·05). Free triiodothyronine (r = 0·44, P = 0·0067) and thyroid-stimulating hormone (r = 0·75, P < 0·001) between maternal and fetal side is positively correlated. This study suggests that maternal iodine intake changes the expression of NIS and Pendrin, thereby affecting PIS. Serum TH levels were not correlated with placental TH levels.

Mechanism of multi-organ compensation under different iodine intake in pregnant rats: results from a repeated-measures study of iodine metabolism.

PURPOSE: This study aimed to explore the differences in iodine metabolism and expression of NIS and Pendrin in pregnant rats under different iodine nutritional status. METHODS: Female Wistar rats were divided into four groups: low iodine (LI), normal iodine (NI), ten fold high iodine (10HI), and fifty fold high iodine (50HI). The intervention began after one week of adaptive feeding. Iodine metabolism experiments were performed beginning on the 15th day of pregnancy. 24-h iodine intake and excretion were calculated. The concentrations of iodine in urine, fecal, thyroid, and placenta were measured by ICP-MS. PCR and Western Blot were used to detect the mRNA levels and cell membrane protein of sodium/iodide symporter (NIS) and Pendrin in the small intestine, thyroid, kidney, and placenta. RESULTS: Fecal iodine excretion (FIE) and urinary iodine excretion (UIE) in the 50HI group were significantly higher than those in the NI group (P < 0.05). The NIS protein and mRNA in the kidney and small intestine have an upward trend in iodine deficiency and a downward trend in iodine excess. Thyroid and placental iodine storage in the 50HI group were significantly higher than those in the NI group (P < 0.05). NIS, Pendrin protein, and mRNA in the thyroid and placenta tend to increase when iodine is deficient and decrease when there is excess. CONCLUSION: Iodine excretion and iodine stores in the placenta and thyroid gland are positively correlated with iodine intake. NIS and Pendrin are also regulated by iodine intake.

Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake. MATERIAL METHODS: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting. RESULTS: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group. CONCLUSION: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.

One-Minute Iodine Isotope Labeling Technology Enables Noninvasive Tracking and Quantification of Extracellular Vesicles in Tumor Lesions and Intact Animals.

Real-time monitoring of the biological behavior of extracellular vesicles (EVs) in vivo is limited, which hinders its application in biomedicine and clinical translation. A noninvasive imaging strategy could provide us with useful information on EVs' distribution, accumulation and homing in vivo, and pharmacokinetics. In this study, the long half-life radionuclide iodine-124 (124I) was used to directly label umbilical cord mesenchymal stem cell-derived EVs. The resulting probe, namely, 124I-MSC-EVs, was manufactured and ready to use within 1 min. 124I-labeled MSC-EVs had high radiochemical purity (RCP, >99.4%) and stable in 5% human serum album (HSA) with RCP > 95% for 96 h. We demonstrated efficient intracellular internalization of 124I-MSC-EVs in two prostate cancer cell lines (22RV1 and DU145 cell). The uptake rates of 124I-MSC-EVs in human prostate cancer cell lines 22RV1 and DU145 cells were 10.35 ± 0.78 and 2.56 ± 0.21 (AD%) at 4 h. The promising cellular data has prompted us to investigate the biodistribution and in vivo tracking capability of this isotope-based labeling technique in tumor bearing animals. Using positron emission tomography (PET) technology, we showed that the signal from intravenously injected 124I-MSC-EVs mainly accumulated in the heart, liver, spleen, lung, and kidney in healthy kun ming (KM) mice, and the biodistribution study was similar to the imaging results. In the 22RV1 xenograft model, 124I-MSC-EVs accumulated significantly in the tumor after administration, and with the optimal image acquired at 48 h postinjection, the maximum of standard uptake value (SUVmax) of the tumor was 3-fold higher than that of DU145. Taken together, the probe has a high application prospect in immuno-PET imaging of EVs. Our technique provides a powerful and convenient tool for understanding the biological behavior and pharmacokinetic characteristics of EVs in vivo and facilitates the acquirement of comprehensive and objective data for future clinical studies of EVs.

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene-environment interactions in patients with autoimmune thyroiditis.

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3-1 cells.

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3-1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3-1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3-1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

Alleviative Effect of Iodine Pretreatment on the Stress of Saccharina japonica (Phaeophyceae, Laminariales) Caused by Cadmium and Its Molecular Basis Revealed by Comparative Transcriptomic Analysis.

Iodide is accumulated by the brown alga Saccharina japonica at a high concentration and has been proven to be an inorganic antioxidant that plays an important role in oxidative metabolism. Vanadium-dependent bromoperoxidases (vBPOs) and iodoperoxidases (vIPOs), which catalyze the oxidation of iodide, are essential for iodine accumulation and metabolism. Heavy metal pollutant cadmium (Cd) from anthropogenic activities can cause damage to algae mainly by producing oxidative stress. Here, the effects of iodine pretreatment on the stress of S. japonica caused by cadmium were analyzed. The growth experiment showed that iodine pretreatment could reduce the damage of low concentration cadmium on S. japonica young thalli. At the transcriptomic level, gene ontology (GO) enrichment analysis confirmed that cadmium stress could cause a peroxidation reaction in S. japonica. However, the most significant GO term was "photosystem I" in the series with iodine pretreatment. Weighted gene co-expression network analysis (WGCNA) indicated that iodine pretreatment alleviated cadmium stress responses of S. japonica by affecting the photosynthesis process. Analysis of the differentially expressed genes (DEGs) showed that five enzymes from the vBPO family and 13 enzymes from the vIPO family might play crucial roles in this process.

Selenium, Iodine and Iron-Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism.

The adequate availability and metabolism of three essential trace elements, iodine, selenium and iron, provide the basic requirements for the function and action of the thyroid hormone system in humans, vertebrate animals and their evolutionary precursors. Selenocysteine-containing proteins convey both cellular protection along with H2O2-dependent biosynthesis and the deiodinase-mediated (in-)activation of thyroid hormones, which is critical for their receptor-mediated mechanism of cellular action. Disbalances between the thyroidal content of these elements challenge the negative feedback regulation of the hypothalamus-pituitary-thyroid periphery axis, causing or facilitating common diseases related to disturbed thyroid hormone status such as autoimmune thyroid disease and metabolic disorders. Iodide is accumulated by the sodium-iodide-symporter NIS, and oxidized and incorporated into thyroglobulin by the hemoprotein thyroperoxidase, which requires local H2O2 as cofactor. The latter is generated by the dual oxidase system organized as 'thyroxisome' at the surface of the apical membrane facing the colloidal lumen of the thyroid follicles. Various selenoproteins expressed in thyrocytes defend the follicular structure and function against life-long exposure to H2O2 and reactive oxygen species derived therefrom. The pituitary hormone thyrotropin (TSH) stimulates all processes required for thyroid hormone synthesis and secretion and regulates thyrocyte growth, differentiation and function. Worldwide deficiencies of nutritional iodine, selenium and iron supply and the resulting endemic diseases are preventable with educational, societal and political measures.

Iodine-Biofortified Lettuce Can Promote Mitochondrial Dependent Pathway of Apoptosis in Human Gastrointestinal Cancer Cells.

Previously, our research provided evidence that exposure of gastric and colon cancer cells to extracts from iodine-biofortified lettuce leads to a reduction of cell viability and proliferation through cell cycle arrest and upregulation of pro-apoptotic genes. The aim of the present study was to determine the potential cellular mechanisms of induction of cell death in human gastrointestinal cancer cell lines after treatment with iodine-biofortified lettuce. We demonstrated that extracts from lettuce enriched with iodine induce apoptosis in gastric AGS and colon HT-29 cancer cells and the mechanism of programmed cell death may be triggered and executed through different signaling pathways, depending on the type of cells. Western blot analysis revealed that iodine-fortified lettuce leads to cell death through the release of cytochrome c to the cytosolic fraction and activation of the primary drivers of apoptosis: caspase-3, caspase-7, and caspase-9. Furthermore, we have reported that apoptotic effects of lettuce extracts may be mediated by poly (ADP-ribose) polymerase (PARP) and activation of pro-apoptotic Bcl-2 family proteins such as Bad, Bax, and BID. We also observed mitochondrial dysfunction with the dissipation of the mitochondrial membrane potential in cells exposed to lettuce extracts. Taken together, these results indicate that the organic form of iodine such as 5-ISA and 3,5-diISA is an important factor in the activation of intrinsic mitochondrial apoptotic pathway in AGS and HT-29 cancer cells in a p53-independent manner.

IMPACT OF MOTHER'S HYPOTHYROIDISM ON FETAL DEVELOPMENT AND OUTCOMES: A SYSTEMATIC REVIEW.

The thyroid, a gland with a butterfly-like shape in the base of the human neck, plays an important role in metabolism. Body heat, energy levels, weight, hair, fingernail, and regular menstruation cycles are controlled by three hormones produced by the thyroid. A system of feedback regulates the release of those hormones. Overproduction as well as underproduction of thyroid hormones can result from shifts in the stimulation and regulation of those hormones. These factors can have physiological or pathological origins. Pregnancy is a physiological factor. There is a plethora of physiological and psychological shifts that occur during pregnancy. A thyroid alteration in the mother is one example. Thyroid irregularities result from a failure to adjust to new circumstances. Thyroid hormone levels can drop, or manufacturing could be slowed during pregnancy due to variations in hormone concentration. Hypothyroidism describes this disorder. Hypothyroidism in women who are pregnant is either gestational or could be a disorder that is present before pregnancy. Gestational hypothyroidism cures itself throughout postpartum times, though it can stay as subclinical hyperthyroidism for some time after delivery. They pose a serious risk to development, stunt the growth of the unborn child and lead to defects in subsequent generations. Enhanced thyroid binding globulin levels, enhanced iodine clearance by the kidneys, modified effects of the human reproductive hormone and reduced dietary consumption of iodine lead to these alterations in the gland. Cretinism and mental disorders are among the serious health problems related to an iodine imbalance in maternal hypothyroidism. The growth of the brain, nervous system and Intelligence of an unborn child depends on thyroid hormones. As a result, normal early stages of development suffer due to changes in maternal hormone levels.

Effects of iodine excess on serum thyrotropin-releasing hormone levels and type 2 deiodinase in the hypothalamus of Wistar rats.

Iodine is an important element in thyroid hormone biosynthesis. Thyroid function is regulated by the hypothalamic-pituitary-thyroid axis. Excessive iodine leads to elevated thyroid-stimulating hormone (TSH) levels, but the mechanism is not yet clear. Type 2 deiodinase (Dio2) is a Se-containing protease that plays a vital role in thyroid function. The purpose of this study was to explore the role of hypothalamus Dio2 in regulating TSH increase caused by excessive iodine and to determine the effects of iodine excess on thyrotropin-releasing hormone (TRH) levels. Male Wistar rats were randomised into five groups and administered different iodine dosages (folds of physiological dose): normal iodine, 3-fold iodine, 6-fold iodine, 10-fold iodine and 50-fold iodine. Rats were euthanised at 4, 8, 12 or 24 weeks after iodine administration. Serum TRH, TSH, total thyroxine (TT4) and total triiodothyronine (TT3) were determined. Hypothalamus tissues were frozen and sectioned to evaluate the expression of Dio2, Dio2 activity and monocarboxylate transporter 8 (MCT8). Prolonged high iodine intake significantly increased TSH expression (P < 0·05) but did not affect TT3 and TT4 levels. Prolonged high iodine intake decreased serum TRH levels in the hypothalamus (P < 0·05). Dio2 expression and activity in the hypothalamus exhibited an increasing trend compared at each time point with increasing iodine intake (P < 0·05). Hypothalamic MCT8 expression was increased in rats with prolonged high iodine intake (P < 0·05). These results indicate that iodine excess affects the levels of Dio2, TRH and MCT8 in the hypothalamus.

Supplementation of Ascophyllum nodosum meal and monensin: Effects on diversity and relative abundance of ruminal bacterial taxa and the metabolism of iodine and arsenic in lactating dairy cows.

Previous research has shown that the brown seaweed Ascophyllum nodosum (ASCO) has antimicrobial and antioxidant properties and also increases milk I concentration. We aimed to investigate the effects of supplementing ASCO meal or monensin (MON) on ruminal fermentation, diversity and relative abundance of ruminal bacterial taxa, metabolism of I and As, and blood concentrations of thyroid hormones, antioxidant enzymes, and cortisol in lactating dairy cows. Five multiparous ruminally cannulated Jersey cows averaging (mean ± standard deviation) 102 ± 15 d in milk and 450 ± 33 kg of body weight at the beginning of the study were used in a Latin square design with 28-d periods (21 d for diet adaptation and 7 d for data and sample collection). Cows were fed ad libitum a basal diet containing (dry matter basis) 65% forage as haylage and corn silage and 35% concentrate and were randomly assigned to 1 of the following 5 dietary treatments: 0, 57, 113, or 170 g/d of ASCO meal, or 300 mg/d of MON. Supplements were placed directly into the rumen once daily after the morning feeding. Diets had no effect on ruminal pH and NH3-N concentration, which averaged 6.02 and 6.86 mg/dL, respectively. Total volatile fatty acid concentration decreased linearly in cows fed incremental amounts of ASCO meal. Supplementation with ASCO meal did not change the ruminal molar proportions of volatile fatty acids apart from butyrate, which responded quadratically with the lowest values observed at 56 and 113 g/d of ASCO supplementation. Compared with the control diet or diets containing ASCO meal, cows fed MON showed greater molar proportion of propionate. Diets did not affect the α diversity indices Shannon, Simpson, and Fisher for ruminal bacteria. However, feeding incremental levels of ASCO meal linearly decreased the relative abundance of Tenericutes in ruminal fluid. Monensin increased the relative abundance of the CAG:352 bacterial genus in ruminal fluid compared with the control diet. Linear increases in response to ASCO meal supplementation were observed for the concentrations and output of I in serum, milk, urine, and feces. Fecal excretion of As increased linearly in cows fed varying amounts of ASCO meal, but ASCO did not affect the concentration and secretion of As in milk. The plasma activities of the antioxidant enzymes and the serum concentrations of thyroid hormones did not change. In contrast, circulating cortisol decreased linearly in diets containing ASCO meal. The apparent total-tract digestibilities of dry matter, organic matter, and crude protein increased linearly with ASCO meal, but those of neutral and acid detergent fiber were not affected. In summary, feeding incremental amounts of ASCO meal decreased serum cortisol concentration, and increased I concentrations and output in serum, milk, feces, and urine.

Loss of Function of the RRMF Domain in OsROS1a Causes Sterility in Rice (Oryza sativa L.).

For crop seed production, the development of anthers and male fertility are the main agronomic traits and key biological processes for flowering plants. Active DNA demethylation regulates many plant developmental processes and is ensured by 5-meC DNA glycosylase enzymes. To find out the role of OsROS1a, OsROS1a gene editing mutants were generated using the CRISPR/Cas9 system. The osros1a mutants had shrink spikelets, smaller anthers and pollen grains, and were not stained by iodine staining showing a significant reduction in total soluble sugar and starch contents as compared to wildtype (WT), which caused complete male sterility. Similarly, the expression of genes involved in pollen and anther development was decreased in osros1a mutants as compared to WT. Furthermore, bisulfite sequencing showed that the CG and CHG methylation of the OsPKS2 gene promoter was significantly increased in the osros1a mutant, which caused a reduced expression of OsPKS2 in osros1a mutants. DNA methylation of the TDR gene promoter was similar between WT and osros1a mutants, indicating that the DNA methylation effect by OsROS1a was gene specific. The expression of OsROS1a in the mutants was not changed, but it produced a frame-shift mutation to truncate the Pem-CXXC and RRMF domains. Combined with previous studies, our findings suggested that the RRMF domain in OsROS1a is the functional domain and loss of RRMF for OsROS1a causes sterility in rice.

Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer.

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

A concern was raised 1 regarding the number of pregnant women in the analysis of reference range for the thyroid hormones in pregnancy 2, where we reported 185 cases and it was believed to be 145 cases.

Molecular Iodine Has Extrathyroidal Effects as an Antioxidant, Differentiator, and Immunomodulator.

Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. However, considerable evidence indicates that iodine could also be implicated in the physiopathology of other organs. We review the literature that shows that molecular iodine (I2) exerts multiple and complex actions on the organs that capture it, not including its effects as part of thyroid hormones. This chemical form of iodine is internalized by a facilitated diffusion system that is evolutionary conserved, and its effects appear to be mediated by a variety of mechanisms and pathways. As an oxidized component, it directly neutralizes free radicals, induces the expression of type II antioxidant enzymes, or inactivates proinflammatory pathways. In neoplastic cells, I2 generates iodolipids with nuclear actions that include the activation of apoptotic pathways and the inhibition of markers related to stem cell maintenance, chemoresistance, and survival. Recently, I2 has been postulated as an immune modulator that depending on the cellular context, can function as an inhibitor or activator of immune responses. We propose that the intake of molecular iodine is increased in adults to at least 1 mg/day in specific pathologies to obtain the potential extrathyroid benefits described in this review.

Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort.

BACKGROUND: Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes. METHODS: Maternal iodine status was estimated from spot urine samples collected at 26-28 weeks' gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score. RESULTS: There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 µg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 µg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies. CONCLUSION: Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT03552341. Registered on June 11, 2018.