Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses.

OBJECTIVES: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. METHODS: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). RESULTS: The median UIC was 168 µg/L (111-263 µg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 µg/L group in the first trimester (ß: 2.41, 95% CI: 1.09-3.72, p <0.001), as well as in the 250 ≤ UIC < 500 µg/L group (ß: 1.65, 95% CI: 0.61-2.70, p < 0.001) and UIC ≥500 µg/L group (ß: 3.35, 95% CI: 1.96-4.74, p < 0.001) in the third trimester. CONCLUSIONS: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 µg/L group in the first and third trimesters.

Urinary iodine excretion (UIE) estimated by iodine/creatinine ratio from spot urine in Chinese school-age children.

OBJECTIVE: To assess the validity of urinary iodine excretion (UIE) estimated by urinary iodine/creatinine ratio (UI/Cr) from spot urines in Chinese school-age children. DESIGN: A cross-sectional survey was performed in which twice-repeated collections of 24-h urine, and spot urine samples were obtained within 1 month. MEASUREMENTS: Urinary iodine concentration (UIC), urinary creatinine concentration (UCr), urine volume (Uvol) of spot and 24-h urine samples were measured. Measured 24-h UIE was calculated from 24-h UIC multiplied by 24-h Uvol, while the estimated 24-h UIE was calculated from spot UI/Cr multiplied by 24-h urinary creatinine excretion (24-h UCrE). RESULTS: No significant difference was observed in 24-h Uvol between two repeated collections (P = 0·70), while spot UIC, 24-h UIC, spot UI/Cr and measured 24-h UIE were significantly different (P < 0·05). The estimated 24-h UIE was 247 (136-431) µg/day in the first collection, lower than the measured 24-h UIE of 329 (183-536) µg/day (P < 0·001), while no significant difference was observed (P = 0·30) in the second sampling as the estimated 24-h UIE was 355 (168-624) µg/day and the measured 24-h UIE 350 (181-615) µg/day. The spot UIC (r = 0·57, P < 0·001), spot UI/Cr (r = 0·63, P < 0·001) and the estimated 24-h UIE (r = 0·83, P < 0·001) were strongly correlated with the measured 24-h UIE in the first collection. Likewise, in the second sampling, spot UIC (r = 0·60, P < 0·001), spot UI/Cr (r = 0·72, P < 0·001) and the estimated 24-h UIE (r = 0·89, P < 0·001) were also correlated with measured 24-h UIE. The Bland-Altman results indicated 95% of subjects were expected to locate within the limits of agreement (LOA), but showed an underestimation of the urinary iodine excretion by the estimated 24-h UIE. In addition, moderate-to-good agreement was found for the estimated and measured 24-h UIE, with kappa values of 0·55 and 0·66. CONCLUSIONS: Estimated 24-h UIE by UI/Cr ratio from spot urine could represent a valid and reliable alternative for measured 24-h UIE in estimating iodine excretion in children.

Urinary iodine in early pregnancy is associated with subclinical hypothyroidism in Tianjin, China: an observational study.

BACKGROUND: Subclinical hypothyroidism (SH) is associated with adverse obstetric outcomes and neurodevelopment disorders. Both iodine deficiency and excess are associated with SH; however, few data regarding iodine nutrition status of pregnant women with SH are available. This study aimed to clarify whether iodine deficiency or excess is associated with SH, especially, when test results for anti-thyroid autoantibodies are negative. METHODS: A total of 115 women with SH and 104 women with euthyroidism (EH) in early pregnancy in Tianjin, China were investigated, and their serum thyroid-stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), anti-thyroid globulin antibody (TGAb), urinary iodine (UIC), and urinary creatinine (UCr) concentrations were measured. Thyroid ultrasonography was performed to determine thyroid echogenicity and volume. The UIC, UIC/UCr ratio, prevalence of TPOAb and TGAb positivity, and thyroid gland volume were compared between the EH and SH groups. UIC and ultrasonographic features were analysed in subjects in the SH group who were negative for TPOAb and TGAb. RESULTS: Median UIC of SH (154.0 µg/L) and EH (150.1 µg/L) met the World Health Organization criterion for iodine sufficiency in pregnant women. Neither UIC nor the UIC/UCr ratio differed significantly between groups. The prevalence of TPOAb and TGAb positivity in the SH group was significantly higher than that in the EH group (P < 0.01). The percentage of subjects with UIC ≥ 250 µg/L in the SH group was significantly higher than that in the EH group (p = 0.004). The percentage of subjects negative for autoantibodies and UIC ≥ 250 µg/L in the SH group tended to be higher than that in subjects in the EH group negative for autoantibodies, but the difference was not statistically significant (p = 0.025, adjusted test level α = 0.0167). Eight of 18 subjects in the SH group with negative results for TPOAb and TGAb were diagnosed with Hashimoto thyroiditis by means of thyroid ultrasonography. CONCLUSIONS: Women in early pregnancy with SH in Tianjin were iodine sufficient, but still at risk of iodine deficiency as pregnancy progressed. UIC ≥ 250 µg/L was associated with increased risk of SH. Serological negative autoimmune thyroiditis and UIC ≥ 250 µg/L may play a role in pathogenesis of SH cases with negative results for autoantibodies.

[Impact of deep slow-wave sleep deprivation on oxidative stress response of the testis tissue in rats].

OBJECTIVE: To investigate the influence of deep slow-wave sleep deprivation on the oxidative stress of testicular tissue in rats. METHODS: Thirty-six 5-week-old male Wistar rats were equally randomized into deep slow-wave sleep deprivation group (SD1), deep slow-wave sleep and duration sleep deprivation group ( SD2), and a cage control group (CC). The rat model of deep slow-wave sleep deprivation was established using the flowerpot technique. The rats in the SD1 group were interfered every 24 minutes and deprived of 12 hours of sleep at night, those in the SD2 group deprived of 8 minutes of sleep at an interval of 24 minutes and 12 hours of sleep at night, and those in the CC group exposed to 12 hours of daylight and 12 hours of darkness. After 28 days, all the rats were executed for measurement of the testis volume and protein content, determination of the methane dicarboxylic aldehyde (MDA) level and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observation of the pathological changes in the testicular tissue under the microscope. RESULTS: Compared with the CC group, the rats in the SD1 and SD2 groups showed significantly reduced body weight (ï¼»268.5 ± 1.6ï¼½ vs ï¼»248.1 ± 25.1ï¼½andï¼»232.9 ± 10.1ï¼½g, P<0.05) and increased relative testis mass (ï¼»50.0 ± 1.3ï¼½ vs ï¼»57.9 ± 6.1ï¼½ and ï¼»54.9 ± 3.5ï¼½ ×10⁻², P<0.05). Statistically significant differences were found between the CC and SD2 groups in the contents of protein (ï¼»6.3 ± 1.4ï¼½ vs ï¼»4.5 ± 0.9ï¼½ gpro/L, P<0.05) and MDA (ï¼»1.1 ± 0.1ï¼½ vs ï¼»1.3 ± 0.3ï¼½ nmol/mgpro, P<0.05) and the activities of SOD (ï¼»104.3 ± 33.1ï¼½ vs ï¼»135.2 ± 26.9ï¼½ U/mgpro, P<0.05) and GSH-Px (ï¼»15.6 ± 4.0ï¼½ vs ï¼»21.7 ± 4.3ï¼½ U/mgpro, P<0.05), but not between the CC and SD1 groups (P>0.05). The lumens in the testis were narrowed, with obvious hyperplasia, hyperemia and edema in the peripheral interstitial tissue, but no significant pathologic changes were observed in the testis tissue of the SD1 group. CONCLUSIONS: Long-term deprivation of deep slow-wave sleep impairs the structure of the testis tissue and induces oxidative stress response in rats.

24-Hour Urine Samples Are More Reproducible Than Spot Urine Samples for Evaluation of Iodine Status in School-Age Children.

BACKGROUND: Variation in different urinary measurements for evaluation of iodine status is of concern to clinicians and researchers. OBJECTIVE: This study evaluated variations between urine iodine concentration (UIC), spot and 24-h urine sample creatinine concentrations, and 24-h urine iodine excretion (24-h UIE) in repeated samples from school-age children. METHODS: Urine samples (24 h and morning spot) were collected on 2 occasions from 981 children in Ningjin and Lingxian counties, China. Samples from Ningjin were collected in October and November 2013, and samples from Lingxian were collected in April and May 2014. Morning spot urine iodine concentration (MUIC), morning spot urine creatinine, 24-h UIC, and 24-h urine creatinine were measured in all samples. The 24-h UIE was calculated by multiplying the 24-h UIC by the 24-h urine volume. RESULTS: In Ningjin County, the 24-h UIC and 24-h UIE did not differ between repeated collections [192 and 172 µg/L, respectively, for 24-h UIC (P = 0.08); 123 and 120 µg/L, respectively, for 24-h UIE (P = 0.56)], whereas the MUIC was lower in November 2013 than in October 2013 (170 and 190 µg/L, respectively; P = 0.034). In Lingxian County, no significant differences were observed in 24-h UIC between the repeated collections (230 and 218 µg/L, respectively; P = 0.79), whereas the 24-h UIE and MUIC were higher in the samples collected in May 2014 than in April 2014 [161 and 155 µg/L, respectively, for 24-h UIE (P = 0.002); 244 and 203 µg/L, respectively, for MUIC (P < 0.001)]. When data from both counties were combined, no difference was observed between repeated 24-h UIC (214 compared with 196 µg/L; P = 0.17) and 24-h UIE (143 compared with 143 µg/d; P = 0.06), but MUICs were lower in the first collection than in the second collection (199 and 207 µg/L, respectively; P = 0.002). The κ values were >0.4 for 24-h UIC and mean UIE, whereas relatively low κ values were observed for MUIC and mean UIE. CONCLUSION: The 24-h UIC was more accurate and reproducible than the MUIC in evaluating iodine status in a large-scale population study of school-age children.

Unmyelinated axon loss with postnatal hypertonia after fetal hypoxia.

OBJECTIVE: White matter (WM) injury due to myelination defects is believed to be responsible for the motor deficits seen in cerebral palsy. We tested the hypothesis that the predominant injury is to functional electrical connectivity in unmyelinated WM fibers by conducting a longitudinal study of central WM tracts in newborn rabbit kits with hypertonia in our model of cerebral palsy. METHODS: Pregnant rabbits at 70% gestation underwent 40-minute uterine ischemia. Motor deficits in newborn kits, including muscle hypertonia, were assessed by neurobehavioral testing. Major central WM tracts, including internal capsule, corpus callosum, anterior commissure, and fimbria hippocampi, were investigated for structural and functional injury using diffusion tensor magnetic resonance imaging (MRI), electrophysiological recordings of fiber conductivity in perfused brain slices, electron microscopy, and immunohistochemistry of oligodendrocyte lineage. RESULTS: Motor deficits were observed on postnatal day 1 (P1) when WM tracts were unmyelinated. Myelination occurred later and was obvious by P18. Hypertonia was associated with microstructural WM injury and unmyelinated axon loss at P1, diagnosed by diffusion tensor MRI and electron microscopy. Axonal conductivity from electrophysiological recordings in hypertonic P18 kits decreased only in unmyelinated fibers, despite a loss in both myelinated and unmyelinated axons. INTERPRETATION: Motor deficits in cerebral palsy were associated with loss of unmyelinated WM tracts. The contribution of injury to myelinated fibers that was observed at P18 is probably a secondary etiological factor in the motor and sensory deficits in the rabbit model of cerebral palsy.

Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals.

OBJECTIVE: The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester- and method-specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer's methodology, euthyroid definition and iodine status. DESIGN: Cross-sectional dataset analysis. SUBJECTS: Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). MEASUREMENTS: Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti-TPOAb and anti-TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. RESULTS: All participants had long-term consumption of iodized salt and median urinary iodine of 150-200 µg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03-4·51, 0·05-4·50 and 0·47-4·54 mIU/l and FT4 11·8-21·0, 10·6-17·6 and 9·2-16·7 pmol/l. The manufacturer's method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. CONCLUSIONS: The trimester- and method-based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.

Defending Effects of Iodide Transfer in Placental Barrier Against Maternal Iodine Deficiency.

Objective: Placental iodide transport is necessary for maintaining an adequate iodide supply to the developing fetus. We hypothesized that compounds from the placental barrier can compensate for decreases in maternal iodine intake and normalize fetal iodine levels. Methods: Pregnant rats administered different amounts of iodine (1.24, 2.5, 5, or 10 µg/day) were evaluated on gestational day (gd) 16 and 20. The iodine levels in maternal blood, amniotic fluid (AF), and placental tissue were estimated using As-Ce catalytic spectrophotometry. The protein and/or messenger RNA (mRNA) levels of sodium iodide symporter (NIS), pendrin, alpha-smooth muscle actin (α-SMA), and CD31 in the placental labyrinth, trophoblast cells isolated using laser capture microdissection (LCM), and/or fetomaternal thyroid were detected using immunoblotting, real-time polymerase chain reaction, and/or immunohistochemistry. Results: When iodine intake was reduced, iodine levels in maternal blood gradually decreased; however, placental iodine levels were not significantly different between groups on gd16 and gd20. Minimal changes were observed in AF iodine levels on gd16, and a mild decreasing trend was observed (iodine dose, 10 to 1.24 µg/day) on gd20. NIS protein, which was linearly distributed along the basolateral membrane of maternal-fetal thyroid follicles, gradually increased with decreasing iodine levels. Regarding iodine deficiency in the placental labyrinth on gd16 and gd20, pendrin and glycosylated NIS proteins were significantly upregulated in a dose-dependent manner. However, the mRNA levels were unchanged. Furthermore, the conversion of NIS protein from the nonglycosylated to the glycosylated form increased. In trophoblast cells isolated using LCM, PDS mRNA levels increased in the 1.24-µg/day group on gd16 but not NIS mRNA levels. There was a smaller α-SMA+ area in the labyrinth zone on gd16 and gd20; however, the proportional CD31+ area increased on gd16 and reduced on gd20 with decreased iodine levels. Conclusions: All mechanisms upregulating the expression of iodine transporters and changes in villous stroma and microvessel area in the placental labyrinth can promote iodide transfer from mother to fetus in iodine deficiency, especially before the onset of fetal thyroid function. Compensatory NIS protein regulation in the placenta against decreased iodine intake mainly occurs during translation and glycosylation modification after translation. Pendrin may be more important than NIS in the mediation of placental iodide transport.

Imbalance of Autophagy and Apoptosis Induced by Oxidative Stress May Be Involved in Thyroid Damage Caused by Sleep Deprivation in Rats.

Many studies have shown that sleep deprivation can affect a wide range of tissues and organs, and most of these effects are related to oxidative stress. Oxidative stress can cause functional and morphological changes in cells, which are closely related to autophagy and apoptosis. In this study, we examined changes in thyroid morphology and function, oxidative stress, autophagy, and apoptosis in rats after sleep deprivation. Thyroid hormones, thyroid-stimulating hormone, functional substances required for the synthesis of thyroid hormones, and thyroid morphological observations were used to evaluate the changes and impairment of thyroid function. Methane dicarboxylic aldehyde and total antioxidant capacity were measured to assess oxidative stress in the thyroid. To evaluate the balance of autophagy and apoptosis, the expression of autophagy- and apoptosis-related proteins was examined by western blotting, and apoptotic cells were labeled with TUNEL staining. The body weight of rats in the sleep deprivation group decreased, but the relative weight of the thyroid gland increased. Sleep deprivation led to morphological changes in the thyroid. The levels of thyroid hormones and thyroid-stimulating hormone increased after sleep deprivation. Total antioxidant capacity decreased, and methane dicarboxylic aldehyde levels increased in the thyroid in the sleep deprivation group. Analysis of autophagy- and apoptosis-related proteins indicated that the microtubule-associated protein 1 light chain 3 beta- (LC3B-) and LC3A-II/I ratio and Beclin 1 levels significantly decreased in the sleep deprivation group and P62 levels significantly increased. The number of apoptotic cells in the thyroid gland of sleep-deprived rats increased significantly. Taken together, these results indicate that sleep deprivation can lead to oxidative stress in the thyroid and ultimately cause thyroid damage, which may be related to the imbalance of autophagy and apoptosis.

High catalytic efficiency from Er3+-doped CeO2-x nanoprobes for in vivo acute oxidative damage and inflammation therapy.

Cerium oxide nanoparticles (NPs) due to their advanced catalytic performance have been widely used to treat oxidative damage. However, Ce2O3 NPs have not been further investigated in the treatment of acute oxidative injury in vivo. It is meaningful to improve the efficiency for treatment of acute oxidative injury with NPs in vivo. In this report, we designed Er3+-doped Ce2O3 (Er/Ce2O3) NPs with a size of 7.9 nm, which were used to treat acute liver injury. Er/Ce2O3 NPs realized high-efficiency catalysis of hydrogen peroxide (H2O2) at room temperature. An acute liver damage model was established through intraperitoneal injection of lipopolysaccharide (LPS) in C57 mice. By analyzing histopathological and biochemical indexes, Er/Ce2O3 NPs showed a significant improvement in LPS-induced acute liver injury. Acute liver oxidative damage can be treated within 24 hours, which proved the high catalytic efficiency of Er/Ce2O3 NPs in vivo. The activities of SOD, GPx and CTA increased and production of ROS decreased with Er/Ce2O3 NP treatment in comparison with LPS-induced injury, indicating that the mechanism of Er/Ce2O3 NPs in the treatment of acute oxidative damage of liver was mainly via catalysis of ROS products. Moreover, the protein expression levels of TNF-α, CD45 and IL-1ß in liver decreased in the Er/Ce2O3 NPs-treated group, which indicated that Er/Ce2O3 NPs have the function of anti-inflammation property. Therefore, Er/Ce2O3 NPs can be applied to treat and prevent diseases caused by acute oxidative damage.

Semiconductor ZnO based photosensitizer core-shell upconversion nanoparticle heterojunction for photodynamic therapy.

Photodynamic therapy (PDT) as a noninvasive technique is widely used to treat cancer diseases due to its low side effects. PDT based on upconversion nanoparticles (UCNPs) improved tissue penetration and photo-stability. However, traditional photosensitizers and UCNPs were difficult to incorporate, which limited the circulation of the UCNPs in blood and decreased the PDT effect. Herein, we designed NaErF4@ZnO UCNPs for potential application in thyroid tumor cell PDT. With ZnO coated on NaErF4, the blue (415 nm), green (525 nm/545 nm) and red (661 nm) upconversion luminescence enhanced compared with that of NaErF4 core nanoparticles. Particularly, the generation of UV upconversion emission by NaErF4 sensitized ZnO, which catalyzed H2O and O2 to produce ROS reactive oxygen species (ROS) to induce papillary thyroid carcinoma (PTC) cell lines BHP 5-16. With 1000 µg mL-1 of NaErF4@ZnO UCNPs, the viability of BHP 5-16 cells decreased to about 41% as measured by CCK8 assay with 980 nm NIR irradiation. Moreover, it was confirmed that NaErF4@ZnO UCNPs had low toxicity for BHP 5-16 cells. All these results indicated that NaErF4@ZnO upconversion nanoparticles were an excellent platform for PDT treatment.

Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice.

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats.

Sleep deprivation adversely affects the digestive system. Multiple studies have suggested sleep deprivation and oxidative stress are closely related. Autophagy can be triggered by oxidative stress as a self-defense strategy to promote survival. In this study, we investigated the effects of sleep deprivation on liver functions, oxidative stress, and concomitant hepatocyte autophagy, as well as the associated pathways. Enzymatic and nonenzymatic biochemical markers in the serum were used to assess hepatic function and damage. To evaluate the occurrence of autophagy, expression of autophagy-related proteins was tested and autophagosomes were labeled. Additionally, methane dicarboxylic aldehyde (MDA), antioxidant enzymes, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed using chemical methods and a Western blot. Serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase increased in sleep-deprived rats. Total protein and albumin abundance was also abnormal. Sleep deprivation induced histopathological changes in the liver. The superoxide dismutase level decreased significantly in the liver of sleep-deprived rats. In contrast, the MDA content increased in the sleep deprivation group. Moreover, the microtubule-associated protein 1 light chain 3 beta (LC3B) II/I ratio and Beclin I content increased considerably in the sleep-deprived rats, while p62 levels decreased. Sleep deprivation apparently inhibited the AKT/mTOR signaling pathway. We conclude that sleep deprivation can induce oxidative stress and ultimately cause liver injury. Autophagy triggered by oxidative stress appears to be mediated by the AKT/mTOR pathway and plays a role in relieving oxidative stress caused by sleep deprivation.

Variation of iodine concentration in breast milk and urine in exclusively breastfeeding women and their infants during the first 24 wk after childbirth.

OBJECTIVE: The aim of this study was to observe the variation of iodine concentration in breast milk and urine in exclusively breastfeeding women and their infants during the first 24 wk after childbirth. METHODS: In all, 634 exclusively breastfeeding mother-infant pairs were enrolled at hospital and followed at the 1, 4, 8, 12, 16, and 24 wk postpartum. Spot infant urinary iodine concentration (I-UIC), maternal urinary iodine concentration UIC (M-UIC), and breast milk iodine concentration (BMIC) in bilateral breasts were measured. RESULTS: During the first 24 wk, the median I-UIC was 216 (139-362) and 122 (68-217) µg/L in lactating mothers, both indicating iodine sufficiency. A strong correlation and no difference were found between BMIC in bilateral breasts. The mean BMIC (M-BMIC) of the two breasts was 165 (112-257) µg/L with a Bland-Altman index of 2.1%. Positive correlations were found between M-BMIC and I-UIC (r = 0.353, P < 0.001), between M-BMIC and M-UIC (r = 0.339, P < 0.001), and between I-UIC and M-UIC (r = 0.222, P < 0.001). M-BMIC was significantly higher than M-UIC (P < 0.001) and lower than I-UIC (P < 0.001). M-BMIC declined from week 1 to week 8 postpartum, both I-UIC and M-UIC dropped from week 1 to week 4 postpartum and stabilized thereafter. CONCLUSION: The iodine nutrition in lactating women and infants were adequate during the first 24 wk after childbirth. M-BMIC declined from week 1 to week 8 postpartum. Both I-UIC and M-UIC dropped from week 1 to week 4 postpartum. Further studies are needed to explore a more definitive BMIC and UIC range for an optimal iodine status in lactating women and breastfed infants.

Excessive iodine intake is associated with formation of thyroid nodules in pregnant Chinese women.

In recent decades, the prevalence of thyroid nodules (TNs) has steadily increased in pregnant women. Therefore, this study aimed to investigate associations between TNs and iodine intake in pregnant women. From March 2016 to May 2017, serum and spot urine samples, as well as demographic data and medical history, were collected from 2353 pregnant women. Urine iodine concentration (UIC) and creatinine (Cr) level were determined in spot urine samples; serum thyroid hormones and thyroid autoantibodies were also determined. We examined the hypothesis that excess iodine intake influences incidence of TNs. Herein, TNs were diagnosed by ultrasonography, whereas demographic data and medical history were collected by questionnaire. Multivariate logistic regression models were used to calculate the odds ratios and their corresponding confidence intervals for TN risk factors. Generalized linear mixed model was used to assess the random effects of the regions. The UIC and UIC to creatinine ratio (I/Cr ratio) were significantly higher in pregnant women with TNs (168 and 190 µg/L, respectively, for UIC [P < .01]; 139 and 155 µg/g, respectively, for I/Cr ratio [P < .01]). Thyroglobulin, age, pre-pregnancy body mass index, and iodine-excessive region were associated with TNs (odds ratio = 1.01, 1.06, 1.04, and 2.38, respectively). Whereas I/Cr ratio was not a significant risk factor for TNs in pregnant women when adjusted for potential confounders, iodine excess (I/Cr ratio >500 µg/g) was a risk factor in pregnant women in their second trimester. People living in areas with excessive iodine in drinking water should decrease their iodine intake, and a safe water source should be provided to ensure that the I/Cr ratio of pregnant women can be maintained at an optimal level.

Inhibition of SphK2 Stimulated Hepatic Gluconeogenesis Associated with Dephosphorylation and Deacetylation of STAT3.

BACKGROUND: Sphingosine kinase (SphK) is considered as a potential target for developing novel therapeutics of cancer and other diseases including diabetes. As the major SphK isoform in the liver, much less is known the role of SphK2 involved in regulating hepatic glucose metabolism. METHOD: In this study, RNA interference, real time RT-PCR, western blot and immunoprecipitation method was used to investigate the regulation of SphK2 in hepatic glucose metabolism. RESULTS: Both siRNA and SphK2 inhibitor ABC294640 stimulated expression of gluconeogenetic gene PEPCK and G6Pase but not enzymes of hepatic glycogenolysis, glycolysis and glycogen synthesis. Inhibition of SphK2 also prevented insulin repressed PEPCK and G6Pase expression as well as glucose production levels. Furtherly, inhibition of SphK2 inactivated STAT3 by decreasing both phosphorylation on Tyr705 and acetylation on lysine residue, and led to stimulation of PEPCK and G6Pase expression. Inhibition of SphK2 also prevented IL-6 dependent activation of STAT3 and suppression of PEPCK and G6pase expression both in vitro and in vivo. CONCLUSION: Our study suggests that SphK2 participates in hepatic glucose metabolism related to activation of STAT3.

Thyroid function alterations attributed to high iodide supplementation in maternal rats and their offspring.

OBJECTIVE: Our aim was to investigate thyroid function alterations attributed to high iodide supplementation in maternal rats and their offspring. METHODS: Depending on their iodide intake, the pregnant rats were randomly divided into three groups: normal iodide intake (NI), 10 times high iodide intake (10 HI) and 100 times high iodide intake (100 HI) groups. Iodine concentration in the urine and maternal milk; iodine content and mitochondrial superoxide production; expression of TRα1, TRß1, NIS and Dio1 in both the thyroid and mammary glands were all measured. The offspring were exposed to different iodide-containing water (NI, 10 HI and 100 HI) from weaning to postnatal day 180 (PN180). Serum thyroid hormone levels were measured in both maternal rats and their offspring. RESULTS: Iodine concentration in the urine and maternal milk, as well as iodine content in the thyroid and mammary glands was significantly increased in both the 10 HI and 100 HI groups (p < .05). In the 100 HI group of maternal rats, low FT3 levels, high FT4, TPOAb and TgAb levels were detected. In addition, an increased mitochondrial superoxide production and decreased expression of TRα1, TRß1, NIS and Dio1 in the thyroid and mammary glands was found (p < .05). A positive staining of CD4+ that co-localized with TRß1 in the infiltrated cells within the thyroid follicles was observed. At PN180 in the offspring, the FT3 and FT4 levels showed a significant decrease, while the levels of serum TSH, TPOAb and TgAb were significantly increased in both 10 HI and 100 HI groups (p < .05). CONCLUSION: In maternal rats, although normal thyroid function can be maintained following 10 HI, thyroiditis can be induced following 100 HI on lactation days 7, 14, and 21. In the offspring at PN180, hypothyroidism complicated with thyroiditis can occur in both the 10 HI and 100 HI groups.

Anthropometry-based 24-h urinary creatinine excretion reference for Chinese children.

To establish 24-h urinary creatinine excretion reference ranges based on anthropometry in healthy Chinese children, a cross-sectional survey was conducted using twice-sampled 24-h urine and anthropometric variables. Age- and sex-specific 24-h creatinine excretion reference ranges (crude and related to individual anthropometric variables) were derived. During October 2013 and May 2014, urine samples were collected. Anthropometric variables were measured in the first survey. Data of 710 children (377 boys and 333 girls) aged 8-13 years who completed the study were analyzed. No significant difference was observed in 24-h urine volumes between the two samples (median [interquartile range): 855.0 [600.0-1272.0) mL vs. 900.0 [660.0-1220.0) mL, P = 0.277). The mean 24-h urine creatinine excretion was regarded as representative of absolute daily creatinine excretion in children. Sex-specific, body-weight-adjusted creatinine excretion reference values were 15.3 mg/kg/day (0.1353 mmol/kg/day) for boys and 14.3 mg/kg/day (0.1264 mmol/kg/day) for girls. Differences were significant between boys and girls within the same age group but not across different age groups within the same sex. Ideal 24-h creatinine excretion values for height were derived for potential determination of the creatinine height index. These data can serve as reference ranges to calculate ratios of analyte to creatinine. The creatinine height index can be used to assess somatic protein status.

ß-Sheet Breaker Peptide-HPYD for the Treatment of Alzheimer's Disease: Primary Studies on Behavioral Test and Transcriptional Profiling.

Background: Alzheimer's disease (AD), is a progressive neurodegenerative disease that is characterized by cognitive loss. Most researchers believe that aggregation and accumulation of ß-amyloid peptides (Aß) in brain cells are the central pathological hallmark of this disease. Methods: Based on the amyloid hypothesis, a 10 amino acids ß-sheet breaker peptide HPYD (His-Lys-Gln-Leu-Pro-Phe-Tyr-Glu-Glu-Asp) was designed according to the structure and sequence of the previous designed peptide H102. Accelerated stability test, thioflavine T (ThT) fluorescence spectral analysis and transmission electron microscopy (TEM) imaging were performed to detect the stability and inhibitory effects on the aggregation of Aß1-42 by H102 and HPYD. FITC-labeled HPYD was first tested to determine whether it could be transferred along the olfactory pathway to the brain after nasal administration to mice. Subsequently, the Morris Water Maze (MWM) test for behavioral analysis was used to investigate the learning and memory ability of APP/PS1 transgenic mice by HPYD. Immunohistochemistry and western blot analysis was performed to determine the role of HPYD on Aß and APP protein levels. In addition, microarray analysis was used to evaluate the effect of HPYD on gene expression in AD mouse models. Results: Our in vitro results demonstrated that HPYD had enhanced stability and inhibitory effects on Aß1-42 aggregation compared to H102. HPYD could be delivered into the brain through nasal administration and improved the learning and memory ability in APP/PS1 transgenic mouse models by reducing Aß and APP protein levels. In addition, microarray analyses suggested that several genes related to the inflammatory pathway, AD and gluco-lipid metabolism were dysregulated and could be restored to almost normal levels after HPYD administration to mice. Conclusions: Our results demonstrated that HPYD could be a potential therapeutic drug candidate for the treatment of AD.

Activation of the Nrf2-Keap 1 Pathway in Short-Term Iodide Excess in Thyroid in Rats.

Wistar rats were randomly divided into groups of varying iodide intake: normal iodide; 10 times high iodide; and 100 times high iodide on Days 7, 14, and 28. Insignificant changes were observed in thyroid hormone levels (p > 0.05). Urinary iodine concentration and iodine content in the thyroid glands increased after high consumption of iodide from NI to 100 HI (p < 0.05). The urinary iodine concentration of the 100 HI group on Days 7, 14, and 28 was 60-80 times that of the NI group. The mitochondrial superoxide production and expressions of Nrf2, Srx, and Prx 3 all significantly increased, while Keap 1 significantly decreased in the 100 HI group when compared to the NI or 10 HI group on Days 7, 14, and 28 (p < 0.05). Immunofluorescence staining results showed that Nrf2 was localized in the cytoplasm in NI group. Although Nrf2 was detected in both cytoplasm and nucleus in 10 HI and 100 HI groups, a stronger positive staining was found in the nucleus. We conclude that the activation of the Nrf2-Keap 1 antioxidative defense mechanism may play a crucial role in protecting thyroid function from short-term iodide excess in rats.