A long chain-induced depletion effect for abnormal grafting in the preparation of bimodal bidisperse polymer-grafted nanoparticles.

One of the challenging problems in the research field of polymer nanocomposites is how to prepare nanocomposites with high grafting density and strong ability of dispersion at the same time. For nanocomposites composed of bimodal bidisperse polymer chains and nanoparticles, the above requirements can be met by rationally adjusting the ratio of long and short polymer chains. In this study, the process of grafting bimodal bidisperse polymer chains onto the surface of nanoparticles in a grafting-to manner was investigated via computer simulation and theoretical methods. Three grafting strategies were designed: first short then long (SL) system, both short and long (Both) system and first long then short (LS) system. An abnormal phenomenon for the Both system was found by analyzing the grafting density of long and short polymer chains on the surface of nanoparticles. We speculate that the reason for this anomalous phenomenon is the "depletion effect" brought about by the long chains in the Both system. We employ the Polymer Reference Interaction Site Model (PRISM) theory to investigate this anomaly in-depth. By comparing the radial distribution function (RDF) predicted by the PRISM theory with the RDF results obtained by the molecular dynamics (MD) simulation, we found that with the increase of the number of long chains in the system, the grafting density of short polymer chains on the nanoparticle surface showed an obvious upward trend. The "depletion effect" brought by long chains was the main reason for higher short chains' grafting density of the Both system compared to the SL system. Our findings provide effective guidance for the design of nanoparticle-grafted bimodal bidisperse polymer chains and provide a theoretical basis for experimentation and production of polymer nanocomposites with better performance.

Serum polyamine metabolic profile in autoimmune thyroid disease patients.

OBJECTIVE: Polyamines are indispensable polycations and play important physiological roles in living cells. Some polyamine metabolites have been associated with autoimmune disorders. The aims of this study were to profile polyamine metabolites in autoimmune thyroid disease (AITD) and predict whether polyamine metabolites are associated with thyroid hormone, thyroid autoantibodies or disease progression. DESIGN, PATIENTS AND MEASUREMENTS: A total of 136 participants were recruited, including Graves' disease (GD) (n = 36), Hashimoto's thyroiditis (HT) (n = 33) and thyroid autoantibody-positive (pTAb) (n = 29) patients and 38 age- and sex-matched healthy controls (HCs). Fourteen polyamine metabolites, including polyamine precursors, polyamines and polyamine catabolite, were measured by UFLC-MS/MS RESULTS: Both GD and HT patients had higher L-arginine, L-ornithine, lysine and agmatine levels and lower putrescine, 1,3-diaminopropane, spermine, N-acetylputrescine levels than HCs. Some polyamine metabolite levels were different only in GD or HT patients compared to HCs: GD patients had significantly higher spermidine, N-acetylspermidine and γ-aminobutyric acid and lower cadaverine, whereas HT patients had significantly decreased N-acetylspermine. Only spermine and N-acetylspermine were significantly lower in pTAb than HCs. The spermine:spermidine ratio was significantly reduced in all AITD patients. In addition, spermine was negatively correlated with thyroid-specific antibodies grade. N-acetylspermidine might be a risk factor for pTAb progression to overt hypothyroidism. CONCLUSIONS: Compared with the HCs, most metabolites of GD and HT showed similar patterns, suggesting the possibility of a common pathophysiological basis or metabolic pathway. Moreover, pTAb progression to overt hypothyroidism may be related to high N-acetylspermidine. Thyroid autoimmunity was associated with low spermine.

A Density Functional Theory (DFT) Study of the Acyl Migration Occurring during Lipase-Catalyzed Transesterifications.

Acyl migration (AM) is the main side reaction in the large-scale, regio-specific lipase catalyzed production of structural triglycerides (STs). A detailed understanding of the mechanism of AM was obtained during the process of lipase-catalyzed schemes (LCSs), which play a vital role in improving the quality and total yield of STs. However, currently, the mechanism of AM remains controversial. Herein, the two mechanisms (non-catalyzed (NCM) and lipase-catalyzed (LCM)) of AM have been analyzed in detail by the density functional theory (DFT) at the molecular level. Based on the computational results, we concluded that the energy barrier of the rate-limiting step in the LCM was 18.8 kcal/mol, which is more in agreement with the available experimental value (17.8 kcal/mol), indicating that LCM could significantly accelerate the rate of AM, because it has an energy barrier ~2 times lower than that of the NCM. Interestingly, we also found that the catalytic triad (Asp-His-Ser) of the lipase and water could effectively drop the reaction barrier, which served as the general acid or base, or shuttle of the proton.

Synthesis of cocoa butter substitutes from Cinnamomum camphora seed oil and fully hydrogenated palm oil by enzymatic interesterification.

Cinnamomum camphora trees have a vast range of distribution in southern China and the seed oil has unique fatty acid (FA) properties and various bio-activities. In this work, Cinnamomum camphora seed oil (CCSO) was utilized to synthesize value-added cocoa butter substitute (CBS) by enzymatic interesterification. The synthesis was conducted in a solvent-free system by blending CCSO with fully hydrogenated palm oil under the catalysis of Lipozyme RM IM. The reacted products were assessed with physicochemical properties, i.e. FA composition, slip melting point (SMP), triacylglycerol (TAG), crystal polymorphism, microstructure, melting and crystallization properties and solid fat content (SFC). It showed that MCFAs (capric acid plus lauric acid) was the main fatty acid in products, accounting for over 45%. Comparing to physical blends, some novel TAG species such as LaLaLa and LaMLa/LaLaM were observed after enzymatic interesterification whereas SSS TAGs were reduced. IP presented a ball-like, well-distributed and nearly round crystal microstructure and a smaller crystal size. Moreover, it should be mentioned that SFC of IP ranging from 31.85 to 38.47% at 25 °C with most ß' crystal forms, was beneficial to improve the spreadability in term of confectionery products and baked goods. The SMP of the interesterified products was 35.75-36.15 °C which closed to the commercial CBS. Hence, the products synthesized can be used to as CBS, and the results in this study also showed CCSO have value-added applications.

miRNA-125b-5p Suppresses Hypothyroidism Development by Targeting Signal Transducer and Activator of Transcription 3.

BACKGROUND A deficiency of maternal thyroid hormones (THs) during pregnancy has severe impacts on fetal brain development. Neural stem cells (NSCs) are major targets of THs and provided a powerful model to explore the underlying mechanism of THs during brain development. Although miRNA-125 might be associated with the NSCs differentiation, the relationship between miR-125 and hypothyroidism (HypoT) development remains unclear. MATERIAL AND METHODS In our study, we screened a differentially expressed gene miR-125b-5p from brain between euthyroid (EuT) and HypoT rats. In vitro, we employed anion exchange resin to remove THs to stimulate HypoT. QRT-PCR and Western blot were used to examine the expression of signal transducer and activator of transcription 3 (Stat3). The relationship between miR-125b-5p and Stat3 was detected via a dual-luciferase assay. RESULTS QRT-PCR results showed that the level of miR-125b-5p in HypoT rat brains was significantly suppressed, suggesting some relationship between miR-125b-5p and HypoT. In C17.2, miR-125b-5p promoted cell differentiation into neurons by regulating the expression of tubulin beta chain 3 (TUBB3) and glial fibrillary acid protein (GFAP). QRT-PCR and Western blot results revealed that miR-125b-5p mimic modulated the contents of total Stat3 and p-Stat3. A dual-luciferase assay showed that miR-125b-5p negatively regulated the expression of Stat3 by binding with the first site in 3' UTR of Stat3. CONCLUSIONS These results revealed Stat3 is a new target of miR-125b-5p and revealed the mechanism of miR-125b-5p suppressing HypoT development. These findings provide a new target for HypoT therapy.

Gestation-specific changes in maternal thyroglobulin during pregnancy and lactation in an iodine-sufficient region in China: a longitudinal study.

OBJECTIVES: To describe the changes in thyroglobulin (Tg) based upon gestational and postpartum concentrations in healthy pregnant women from an iodine-sufficient region in China, and to evaluate the use of Tg as a biomarker for iodine-sufficient pregnant women. DESIGN: A longitudinal study of Tg change in normal pregnant women from an iodine-sufficient region. PATIENTS AND MEASUREMENTS: Blood and urine samples were obtained from 133 pregnant women. Urinary iodine concentration (UIC) was measured using an ammonium persulfate method. Serum iodine concentration was required by inductively coupled plasma mass spectrometry (ICP-MS). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), antithyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and Tg were measured using an electrochemiluminescence immunoassay. RESULTS: Thyroglobulin concentrations were higher in early pregnancy (pregnancy at 8 weeks vs nonpregnancy: 11·42 ng/ml vs 8·8 ng/ml, P < 0·01) and maintained a stable level, and then increased greatly at the 36th week. After delivery, Tg decreased to nonpregnant levels. During pregnancy, maternal Tg was not correlated with thyroid function, UIC or urine iodine-creatinine ratio (UI/Cr). Cord blood Tg was much higher compared to maternal Tg levels at the 36w (57·34 vs 14·86 ng/ml, P < 0·001) and correlated positively with cord FT4 (r = 0·256, P < 0·05), cord TT4 (r = 0·263, P < 0·05) and maternal UI/Cr at 36w (r = -0·214, P < 0·05). CONCLUSIONS: Our work demonstrates that Tg is elevated during pregnancy, and the effect of pregnancy should be taken into consideration when Tg is used as a biomarker for the iodine status. Cord blood Tg is much higher than maternal Tg levels at the 36w and is correlated with maternal iodine status.

No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration.

Concern has been expressed recently that Se may increase the risk of type 2 diabetes, but this has not been tested in a randomised-controlled trial (RCT) in pregnant women. We took advantage of having stored plasma samples from the Se in Pregnancy Intervention (SPRINT) RCT of Se supplementation in pregnancy to test the effect of Se supplementation on a marker of insulin resistance in UK pregnant women. Because our blood samples were not fasted, we measured plasma adiponectin concentration, a recognised marker of insulin resistance that gives valid measurements in non-fasted samples, as diurnal variability is minor and there is no noticeable effect of food intake. In SPRINT, 230 primiparous UK women were randomised to treatment with Se (60 µg/d) or placebo from 12 weeks of gestation until delivery. We hypothesised that supplementation with Se at a nutritional level would not exacerbate the fall in adiponectin concentration that occurs in normal pregnancy, indicating the lack of an adverse effect on insulin resistance. Indeed, there was no significant difference between the two groups in the change in adiponectin from 12 to 35 weeks (P=0·938), nor when the analysis was restricted to the bottom or top quartiles of baseline whole-blood Se (P=0·515 and 0·858, respectively). Cross-sectionally, adiponectin concentration was not associated with any parameter of Se status, either at 12 or 35 weeks. It is reassuring that a nutritional dose of Se had no adverse effect on the concentration of adiponectin, a biomarker of insulin resistance, in pregnant women of modest Se status.

Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency.

PURPOSE: Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response. We aimed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody (TPO-Ab) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population. METHODS: Samples and data were from a secondary analysis of Selenium in PRegnancy INTervention (SPRINT), a double-blind, randomized, placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation. Women were randomized to receive 60 µg/day selenium or placebo until delivery. Serum thyroid peroxidase antibodies (TPO-Ab), thyrotropin (TSH) and free thyroxine (FT4) were measured at 12, 20 and 35 weeks and thyroglobulin antibodies (Tg-Ab) at 12 weeks. RESULTS: 93.5% of participants completed the study. Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy. In women who were either TPO-Ab or Tg-Ab negative at baseline (Thy-Ab(-ve)), TSH increased and FT4 decreased significantly throughout gestation (P < 0.001), with no difference between treatment groups. In women who were Thy-Ab(+ve) at baseline, TSH tended to decrease and was lower than placebo at 35 weeks (P = 0.050). FT4 fell more on Se than placebo supplementation and was significantly lower at 35 weeks (P = 0.029). CONCLUSIONS: Low-dose selenium supplementation in pregnant women with mild-to-moderate deficiency had no effect on TPO-Ab concentration, but tended to change thyroid function in Thy-Ab(+ve) women.

Association of single nucleotide polymorphism rs3792876 in SLC22A4 gene with autoimmune thyroid disease in a Chinese Han population.

BACKGROUND: The autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are caused by interactions between susceptibility genes and environmental triggers. Single nucleotide polymorphisms (SNPs) of Solute carrier family 22, member 4 (SLC22A4) have been shown to be associated with several autoimmune diseases, including Crohn's disease (CD) and rheumatoid arthritis (RA). The aim of this study is to investigate whether SNP rs3792876 in the SLC22A4 gene is associated with GD, HT and AITD in a Chinese Han population. METHODS: In this study, we collected specimens from 553 Chinese Han individuals of 92 AITD pedigrees in 10 cities in Liaoning province, China (80 GD pedigrees, 478 members; 12 HT pedigrees, 75 members). SNP rs3792876 was genotyped using the TaqMan allelic discrimination assay. Hardy-Weinberg Equilibrium tests were performed among founders of the pedigrees using Haploview software. Family-based association tests performed using FBAT software. RESULTS: No deviation from Hardy-Weinberg equilibrium was observed (p > 0.05). There were not significant association between the SLC22A4 gene polymorphism (rs3792876) and GD, HT and AITD was found. CONCLUSIONS: These results suggest a lack of association between the SLC22A4 gene polymorphism rs3792876 and susceptibility to GD, HT and AITD in a Chinese Han population.

Selenium status in U.K. pregnant women and its relationship with hypertensive conditions of pregnancy.

Dietary intake/status of the trace mineral Se may affect the risk of developing hypertensive conditions of pregnancy, i.e. pre-eclampsia and pregnancy-induced hypertension (PE/PIH). In the present study, we evaluated Se status in U.K. pregnant women to establish whether pre-pregnant Se status or Se supplementation affected the risk of developing PE/PIH. The samples originated from the SPRINT (Selenium in PRegnancy INTervention) study that randomised 230 U.K. primiparous women to treatment with Se (60 µg/d) or placebo from 12 weeks of gestation. Whole-blood Se concentration was measured at 12 and 35 weeks, toenail Se concentration at 16 weeks, plasma selenoprotein P (SEPP1) concentration at 35 weeks and plasma glutathione peroxidase (GPx3) activity at 12, 20 and 35 weeks. Demographic data were collected at baseline. Participants completed a FFQ. U.K. pregnant women had whole-blood Se concentration lower than the mid-range of other populations, toenail Se concentration considerably lower than U.S. women, GPx3 activity considerably lower than U.S. and Australian pregnant women, and low baseline SEPP1 concentration (median 3.00, range 0.90-5.80 mg/l). Maternal age, education and social class were positively associated with Se status. After adjustment, whole-blood Se concentration was higher in women consuming Brazil nuts (P= 0.040) and in those consuming more than two seafood portions per week (P= 0.054). A stepwise logistic regression model revealed that among the Se-related risk factors, only toenail Se (OR 0.38, 95% CI 0.17, 0.87, P= 0.021) significantly affected the OR for PE/PIH. On excluding non-compliers with Se treatment, Se supplementation also significantly reduced the OR for PE/PIH (OR 0.30, 95% CI 0.09, 1.00, P= 0.049). In conclusion, U.K. women have low Se status that increases their risk of developing PE/PIH. Therefore, U.K. women of childbearing age need to improve their Se status.

Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial.

Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 µg/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.

Selenium in the treatment of mild-to-moderate Graves' orbitopathy: a 5-year prospective controlled cohort study.

PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

Effect of maternal excessive iodine intake on neurodevelopment and cognitive function in rat offspring.

BACKGROUND: Iodine deficiency and iodine excess are both associated with adverse health consequences. Iodine deficiency during pregnancy leads to insufficient maternal thyroid hormone, subsequently causing irreversible adverse effects on the neurological and cognitive functions of the offspring. The results of our previous epidemiological study suggested that mild iodine excess might increase the prevalence of subclinical hypothyroidism. In the present study, female Wistar rats maintained on low-iodine grain were randomly assigned to three groups based on iodated water concentration: low iodine (LI, 1.2 µg/d), normal iodine (NI, 5-6 µg/d), and 3-fold high iodine (3HI, 15-16 µg/d). The present study investigated whether higher-than-normal iodine intake (3HI) by rats from before pregnancy until breastfeeding affects the postnatal (PN) neurodevelopment (PN7 and PN45) of their offspring during particularly sensitive periods in brain development. RESULTS: After 12 weeks of treatment (before pregnancy), iodine concentrations in urine and thyroid tissue and circulating thyroxine of adult females correlated with iodine intake. Brain-derived neurotrophic factor (BDNF) expression in the hippocampi of pups on PN7 and PN45 was decreased in 3HI group compared to the NI controls (P < 0.05, all) On PN7 and PN45, the BDNF levels of the 3HI pups were 83.5% and 88.8%, respectively, that of the NI pups. In addition, the 3HI group had a higher neuroendocrine-specific protein A (NSP-A) level than the NI controls on PN7 (P < 0.05). NSP-A levels of the 3HI pups were 117.0% that of the NI pups. No significant difference was observed in the expressions of c-Fos or c-Jun in the hippocampal CA1 region of the 3HI group compared to the controls (P > 0.05). Results from the Morris water maze test revealed that pups of the 3HI group had mild learning and spatial memory deficits. CONCLUSIONS: The neurodevelopmental and cognitive deficits of the 3HI pups were mild and temporary, likely related to the changes in hippocampal protein expressions of BDNF and NSP-A.

MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens.

BACKGROUND: Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation. METHODS: Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored. RESULTS: In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway. CONCLUSION: Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.

Concentration-dependent Differences in Urinary Iodine Measurements Between Inductively Coupled Plasma Mass Spectrometry and the Sandell-Kolthoff Method.

A large amount of historical data regarding urinary iodine concentration (UIC) were measured with the Sandell-Kolthoff (S-K) method for iodine nutrition surveillance. The congruence in urinary iodine measurements between inductively coupled plasma mass spectrometry (ICP-MS) and the S-K method has been debated. A total of 2064 adult urine samples were included in the present study. The UIC measurement results obtained simultaneously by standardized ICP-MS and the S-K method were analyzed. The UIC obtained with ICP-MS was significantly higher than that obtained with the S-K method (158 µg/L vs. 148 µg/L, p < 0.001). The Bland-Altman difference plot showed a small but significant mean difference of 6.12 µg/L between the two methods. The stratified analysis showed that the correlation coefficient was higher in the UIC < 300 µg/L group than the UIC ≥ 300 µg/L group (0.93 vs. 0.88, p = 0.0001). The mean difference between the S-K and ICP-MS methods was positively correlated with the UIC. The ICP-MS and S-K methods were comparable when the UIC was less than 300 µg/L; however, UIC values between 300 and 600 µg/L should be compared with caution after considering the research objective. We do not suggest comparing UICs obtained from the ICP-MS and S-K methods in iodine monitoring studies if the UIC is greater than 600 µg/L.

miRNA expression in a human papillary thyroid carcinoma cell line varies with invasiveness.

The purpose of these studies was to explore the expression pattern of miRNAs associated with invasion and metastasis of human papillary thyroid carcinoma (PTC). A transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human PTC with cervical lymph node metastasis, IHH-4. Three sublines with progressive invasiveness, designated IHH-4M-1, IHH-4M-2 and IHH-4M-3, were obtained through this in vitro selection process. The sublines manifested an increase in colony-forming ability on soft agar and metastatic potency in nude mice. Then metastasis-related miRNAs differentially expressed between them were analyzed utilizing the miRNA microarray technique. We found that 11 metastasis-related miRNAs were differentially expressed between the invasive subpopulations and their control subpopulations; these miRNAs may account for their significant difference in the invasion capabilities and favor lymphatic metastasis of PTC.

Dynamic Changes in Antithyroperoxidase and Antithyroglobulin Antibodies Suggest an Increased Risk for Abnormal Thyrotropin Levels.

Background: Antithyroperoxidase (TPOAb) and antithyroglobulin (TgAb) antibodies are associated with abnormal thyrotropin (TSH) levels. However, the effect of dynamic changes in TPOAb and TgAb on incident abnormal TSH is unknown. Methods: A total of 2,387 euthyroid participants aged 18 years or older from three rural areas in northern China were enrolled in this cohort study. Questionnaire interviews and laboratory measurements were performed at baseline in 1999 and at follow-up in 2004. Multinomial logistic regression was used to examine the relationship between changes in thyroid antibodies and incident abnormal TSH levels. Results: In this 5 year follow-up study, TPOAb tier gain was significantly associated with an increased risk of subnormal TSH levels (adjusted RR, 1.535; 95% CI: 1.357-1.736) and supranormal TSH levels (adjusted RR, 1.378; 95% CI: 1.196-1.587), and TgAb tier gain was significantly associated with an increased risk of supranormal (adjusted RR, 1.090; 95% CI: 1.007-1.179) TSH levels. Both thyroid antibody-positive seroconversion and persistent positivity were significantly associated with an increased risk of incident abnormal TSH levels. Thyroid antibody positive seroconversion was associated with a higher risk of incident subnormal TSH than incident supranormal TSH, whereas persistent positive thyroid antibody was associated with a higher risk of incident supranormal TSH than incident subnormal TSH. Conclusions: Dynamic thyroid antibody changes may be related to incident abnormal TSH levels. Those with persistent positive thyroid antibody were more likely to have supranormal TSH than subnormal TSH, and those with positive seroconversion were more likely to have subnormal TSH than supranormal TSH. Further studies are needed to confirm this conclusion and to explore this association mediated by TSH receptor antibodies.

Effect of iodine intake on thyroid diseases in China.

BACKGROUND: Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 microg per liter), more than adequate (median, 243 microg per liter), and excessive (median, 651 microg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease. METHODS: Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up. RESULTS: Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function. CONCLUSIONS: More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis.

[The changes of thyrotropin level in euthyroid population: a 5-year follow-up study in communities with different iodine intakes].

OBJECTIVE: To determine the factors that influence the development of abnormal thyrotropin (TSH) level in an euthyroid population. METHODS: We conducted a follow-up study in 3 communities with different iodine status. Of the 3403 euthyroid subjects at baseline screened in 1999, 80.1% (n = 2727) was visited and sampled in 2004 for measuring TSH, thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). RESULTS: Iodine status in the 3 communities were stable. Decreased TSH level (< 0.3 mU/L) developed in 2.5% (n = 68) of sampled subjects, while raised TSH level (> 4.8 mU/L) in 2.4% (n = 64). A logistic analysis showed that risk factors for developing decreased TSH level included positive conversion of TPOAb (OR = 5.5), positive TPOAb both in 1999 and in 2004 (OR = 4.0), positive TgAb in 2004 (OR = 3.7) and TSH < 1.0 mU/L in 1999 (OR = 2.6). Risk factors involved in developing raised TSH level included iodine status of Zhangwu community (OR = 4.1), iodine status of Huanghua community (OR = 3.9), positive TgAb in 2004 (OR = 3.7), positive TPOAb both in 1999 and 2004 (OR = 3.6), positive conversion of TPOAb (OR = 2.7) and TSH > 1.9 mU/L in 1999 (OR = 2.6). CONCLUSIONS: Exposure to long-term iodine excess imposes danger of developing hypothyroidism. The risk will be even higher when exposing to iodine adequacy after correction of iodine deficiency. An interval between 1.0 and 1.9 mU/L of TSH level was optimal with the least probability of developing abnormal TSH level.

Association of Overt and Subclinical Hyperthyroidism During Weeks 4-8 with Adverse Pregnancy Outcomes.

Background: Although increasing data suggest that hyperthyroidism is associated with adverse pregnancy outcomes, there are only a few reports with different conclusions on whether the mild transient reduction in thyrotropin (TSH) with or without free thyroxine (FT4) elevation during the early stage of pregnancy also causes adverse pregnancy outcomes. Subjects and Methods: We analyzed data from 3,783 women in this study from August 2011 to December 2013. Participants completed a questionnaire survey. Samples of blood were obtained in the 4th-8th week of pregnancy and their TSH, FT4, thyroid peroxidase antibody, and thyroglobulin antibody were measured. We divided the participants into overt hyperthyroidism group (OHG), subclinical hyperthyroidism group (SHG), and control group based on their blood results and followed up on their pregnancy outcomes. Results: (1) The serum level of FT4 in the SHG was much higher than the control group (p < 0.05). No difference was found in the TSH between the OHG and SHG. The positive rate of autoimmune thyroid antibodies in the OHG (25.6%) was significantly higher than that in the SHG (14.2%) and control group (13.9%) (p < 0.05), whereas there was no difference between the SHG and control group. (2) The SHG had a lower incidence of miscarriage (1.7% vs. 7.2%; OR = 0.218, p = 0.016) than the control group, and the OHG had a higher incidence of placenta previa (3.3% vs. 0.8%; OR = 4.366, p = 0.039) than the control group. (3). We used a binary logistic regression to take other factors into consideration and found that subclinical hyperthyroidism was associated with a lower risk of abortion (OR = 0.206; 95% CI = 0.050-0.840; p = 0.028) but higher risk of preeclampsia (OR = 5.143; 95% CI = 1.463-18.076; p = 0.011) and placental abruption (OR = 4.676; 95% CI = 1.017-21.509; p = 0.048), and overt hyperthyroidism may increase the incidence of placenta previa (OR = 4.193; 95% CI = 1.222-14.382; p = 0.023). Conclusions: Subclinical hyperthyroidism during weeks 4-8 of pregnancy may be associated with the decreased incidence of abortion but might be a risk factor for preeclampsia and placental abruption. Meanwhile, pregnancy with overt hyperthyroidism may be an independent risk factor for placenta previa.