Methyl-CpG Binding Protein 2 as a Potential Diagnostic and Prognostic Marker Facilitates Glioma Progression Through Activation of Wnt/ß-Catenin Pathway.

BACKGROUND: Glioma is the primary malignant tumor in the central nervous system and has high malignancy, mortality, and recurrence rates. Because of its heterogeneity and drug resistance, the blood-brain barrier, and other factors, the treatment of glioma has mainly been surgical resection combined with traditional radiotherapy and chemotherapy. However, the therapeutic effect has not been satisfactory. Methyl-CpG binding protein 2 (MeCP2) is an epigenetic regulator that has been reported to regulate the initiation and progression of glioma. However, the underlying mechanism in glioma has remained unclear. METHODS: The gene expression of MeCp2, miR-138-5p, the epithelial-mesenchymal transition, the apoptosis-related gene, and the Wnt/ß-Catenin pathway-related gene and proliferation were detected by reverse transcription-quantitative polymerase chain reaction or Western blot. The cell proliferation and apoptosis of the glioma cell was assessed using the CCK-8 assay and flow cytometry assay. The relationship between miR-138-5p and MeCp2 was measured using the dual luciferase reporter assay. The effect of MeCp2 in U87 cells was examined in a xenograft tumorigenesis model in vivo. RESULTS: In our study, we found that MeCP2 was upregulated in glioma tissues and cell lines and that MeCP2 knockdown repressed cell proliferation and epithelial-mesenchymal transition but boosted cell apoptosis in glioma. Furthermore, MeCP2 knockdown attenuated in vivo glioma growth in a mice model. Mechanistically, miR-138-5p hindered the expression of MeCP2 by target MeCP2 and then inactivated the Wnt/ß-catenin signaling pathway. In addition, subsequent rescue assays disclosed that miR-138-5p repressed the glioma malignant phenotype and MeCP2 overexpression reversed the inhibitory effect of miR-138-5p upregulation. Consistently, overexpression of MeCP2 elevated glioma development. However, inhibition of the Wnt/ß-catenin signaling pathway with XAV-939 rescued the facilitation effect by overexpressing miR-138-5p. CONCLUSIONS: Our results have revealed that miR-138-5p/MeCP2/Wnt/ß-catenin signaling might be a new target axis for glioma treatment strategies.

Effect of reducing iodine excess on children's goiter prevalence in areas with high iodine in drinking water.

The purpose of the study was to evaluate the effect of removing iodized salt on children's goiter prevalence in high iodine area (HIA). A total of 452 and 459 children aged 8-10 years old were selected by simple random sampling method before and after removing iodized salt from their diet in three towns with median water iodine content of 150-300 µg/l in Hengshui city of Hebei province of China. Their goiter status was judged using the thyroid volume (Tvol) reference for body surface area recommended by the WHO. After removing iodized salt, children's overall median urinary iodine content (MUIC) decreased from 518 (IQR 347,735) µg/l to 416 µg/l (IQR 274,609). Children's MUIC across sex and age group decreased significantly. The overall goiter prevalence in the three towns significantly decreased from 32.96 % (149/452) to 6.54 % (30/459) (P < 0.001). The goiter prevalence in 8-, 9-, and 10-year-old children decreased, respectively, from 38.04 % (35/92), 30.57 % (59/193), and 32.93 % (55/167) to 6.10 % (10/164), 6.75 % (11/163), and 6.82 % (9/132). The goiter prevalence in boys and girls decreased from 34.01 % (83/244) and 31.73 % (66/208) to 6.19 % (14/225) and 6.87 % (16/234), respectively. The decreases in children's goiter prevalence across gender and age groups were all statistically significant. The present study revealed that children's goiter prevalence decreased significantly after removing iodized salt from their diet for about one and half years in the HIA in Hebei province.

[Influence of removing iodized salt on children's goiter status in areas with high iodine in drinking water].

OBJECTIVE: To explore the changes of goiter prevalence of children living in areas with high iodine in drinking water after removing iodized salt from their diet. METHODS: Three towns with median water iodine of 150 - 300 µg/L were selected randomly in Hengshui city of Hebei province of China. A total of 452 and 459 children in the 3 towns were randomly selected to measure thyroid volume by ultrasound before and after removing iodized salt, respectively. Their goiter status was judged using the criteria of age-specific thyroid volume recommended by the WHO. RESULTS: After removing iodized salt, the overall goiter prevalence in the three towns significantly decreased from 24.56% (111/452) to 5.88% (27/459) (P < 0.01). The goiter prevalence in 8, 9 and 10 year-old children decreased respectively from 33.70% (31/92), 23.32% (45/193) and 20.96% (35/167) to 6.10% (10/164), 5.52% (9/163) and 6.06% (8/132). The goiter prevalence in boys and girls decreased from 27.05% (66/244) and 21.63% (45/208 ) to 6.66% (15/226 ) and 5.15% (12/233), respectively. The decreases in children's goiter prevalence across gender and age group were all significant. CONCLUSION: Children's goiter prevalence decreased significantly after removing iodized salt from their diet for about one and half years in the HIA in Hebei province.

[Assessing the effectiveness of removing iodized salt on iodine excessive goiter using thyroid volume reference for body surface area].

OBJECTIVE: Using the thyroid volume criteria for body surface area (BSA) to assess more precisely the effectiveness of removing iodized salt on the goiter status of children living in areas with excessive iodine in drinking water. METHODS: Three towns with median water iodine (MWI) of 150-300 µg/L were selected by simple random method in Hengshui city of Hebei province of China in May of 2010. A total of 452 and 459 children in the 3 towns were randomly selected to measure thyroid volume by ultrasound. Iodized salt was removed in July of 2010. In October of 2013, 459 children in these 3 towns were selected by simple random method to measure their thyroid volume by ultrasound again. Their goiter status was judged using the criteria of thyroid volume for BSA recommended by the WHO. RESULTS: After removing iodized salt, the overall BSA specific goiter prevalence in the three towns significantly decreased from 33% (149/452) to 6% (30/459) (χ² = 100.64, P < 0.001). The BSA specific goiter prevalence in 8, 9 and 10 year-old children decreased respectively from 38% (35/92), 31% (59/193) and 33% (55/167) to 6% (10/164), 7% (11/163) and 7% (9/132) (χ² values were 41.35, 31.66, 29.79, P < 0.001). The BSA specific goiter prevalence in boys and girls decreased from 34% (83/244) and 32% (66/208) to 6% (14/225) and 7% (16/234) (χ² values were 55.01, 45.06, P < 0.001) respectively. CONCLUSION: The BSA specific children's goiter prevalence decreased significantly after removing iodized salt from their diet in the HIA in Hebei province.

Impact of removing iodised salt on children's goitre status in areas with excessive iodine in drinking-water.

The impact of removing iodised salt on children's goitre status in a high-iodine area (HIA) remains unclear. The aim of the present study was to explore the changes in the prevalence of goitre in children after removing iodised salt from their diet. For this purpose, three towns with the median water iodine content of 150-300 µg/l were selected randomly in Hengshui City, Hebei Province, China. A total of 452 and 459 children were randomly selected from the three towns in order to measure thyroid volume by ultrasound before and after removing iodised salt, respectively. Their goitre status was judged using the criteria of age-specific thyroid volume recommended by the WHO. After removing iodised salt, the overall median urinary iodine content (MUIC) of children decreased from 518 (interquartile range (IQR) 347-735) to 416 (IQR 274-609) µg/l. The MUIC of children across sex and age group decreased significantly except for the age group of 9 years. The overall prevalence of goitre in the three towns significantly decreased from 24·56% (n 111/452) to 5·88% (n 27/459) (P< 0·001). Goitre prevalence in children aged 8-10 years decreased from 33·70% (n 31/92), 23·32% (n 45/193) and 20·96% (n 35/167) to 6·10% (n 10/164), 5·52% (n 9/163) and 6·06% (n 8/132), respectively. Goitre prevalence in boys and girls decreased from 27·05% (n 66/244) and 21·63% (n 45/208) to 6·66% (n 15/226) and 5·15% (n 12/233), respectively. The decreases in the prevalence of goitre in children across sex and age group were all statistically significant. The present study revealed that goitre prevalence in children decreased significantly after removing iodised salt from their diet for about 1·5 years in the HIA in Hebei Province.

Goitre prevalence and epidemiological features in children living in areas with mildly excessive iodine in drinking-water.

The prevalence of goitre in areas with mildly excessive iodine in drinking-water is still under debate. The aim of the present study was to explore the prevalence of goitre and its epidemiological characteristics in these areas using WHO criteria. To this end, three towns with a median water iodine (MWI) of 150-300 µg/l were selected randomly in Hengshui City of Hebei Province of China, and one town with a MWI of 105 µg/l was chosen as a control. A total of 452 children in the three towns and 120 children in the control town were randomly selected to measure thyroid volume (T vol) by ultrasound. The goitre status of these children was judged using the criteria recommended by the WHO. The overall goitre prevalences in the three towns were 24·6 % (111/452) by age-specific T vol and 33·0 % (149/452) by body surface area (BSA)-adjusted T vol, which were significantly higher than that in the control town by both age-specific T vol (14·0 % (17/120), P= 0·015) and BSA-adjusted T vol (17·5 % (21/120), P= 0·001). Significant differences were found neither in goitre prevalences across sex by both age-specific T vol (P= 0·078) and BSA-adjusted T vol (P= 0·692) nor in that across age group by both BSA-adjusted T vol (P= 0·461) and age-specific T vol (P= 0·183). The present study found a high prevalence of goitre in children living in areas with mildly excessive iodine in drinking-water in Hebei Province. No significant differences were found in goitre prevalences across sex and age group. These results suggest that the T vol reference values recommended by the WHO could be too low for Chinese children.

An epidemiological survey of children's iodine nutrition and goitre status in regions with mildly excessive iodine in drinking water in Hebei Province, China.

OBJECTIVE: To identify children's iodine nutrition and goitre status in areas with mildly excessive iodine in drinking water. DESIGN: A cross-sectional survey. Probability proportional to size sampling was employed to randomly select children from thirty townships where the median iodine content in drinking water ranged from 150 to 300 µg/l; their urinary iodine concentrations were determined and their thyroid volumes were measured by ultrasound. Drinking water samples and salt samples from the villages where the children lived were collected using a systematic sampling method. SETTING: Hebei Province of China. SUBJECTS: A total of 1259 children aged 8-10 years (621 boys and 638 girls). RESULTS: Children's median urinary iodine concentration was found to be 418·8 µg/l, and the iodine concentration was >300 µg/l for 68·3 % (248/363) of the urine samples. Children's median urinary iodine concentration in villages with median salt iodine >10 mg/kg was significantly higher than that in villages with median salt iodine <5 mg/kg (442·9 µg/l v. 305·4 µg/l, P ≈ 0). The goitre rate of 1259 children examined by ultrasound was 10·96 %. CONCLUSIONS: The iodine intake of children living in areas with mildly excessive iodine in drinking water in Hebei Province was found to be excessive. The measured iodine excess in the sampled children is exacerbated by consumption of iodized salt. Goitre was identified in these areas; however, due to the limitation of the current criteria for children's thyroid volume, a comprehensive assessment of the prevalence of goitre in these regions could not be made and further study is required.

[Study on the relation between iodine nutrition of pregnant women in different occasions and thyroid function of their neonates].

OBJECTIVE: To study iodine nutrition of pregnant women in different occasions and thyroid function of their neonates. METHODS: Urinary iodine of pregnant women and their serum T(3), T(4), FT(3), FT(4) were determined by chloric acid-digestion thermostatic assay and RIA, TSH determination by IRMA; neonatal umbilical cord blood TSH was determined by ELISA. RESULTS: Median urinary iodine of pregnant women were 206.3 microg/L, 161.4 microg/L, 203.3 microg/L at 10 - 14 (first occasion), 23 - 27 (second occasion) and 39 - 40 (third occasion) week but the percentage that lower than 100 microg/L were 14.6%, 17.1%, 11.1% respectively. Serum T(3), T(4) of pregnant women was significantly higher than those women of premarital health inspection (PHIW, P < 0.001). The difference of serum T(3), T(4) of pregnant women at 10 - 14 and 39 - 40 week was not significant. Serum FT(3), FT(4) of pregnant women at 39 - 40 week were 2.61 +/- 0.47 pmol/L and 5.50 +/- 1.57 pmol/L respectively. The difference of serum TSH concentration at third occasion and first occasion of pre-pregnancy was significant but the difference of TSH frequency distribution in three groups was not significant (chi(2) = 1.138, P > 0.5). Blood TSH median neonatal umbilical cord was 1.99 mU/L but the percentage that higher than 5 mU/L was 9.4%. CONCLUSION: For those areas with high iodized salt coverage, pregnant women had had sufficient iodine supplement and good thyroid function. The percentage of neonates from iodine sufficient pregnant women with TSH > 5 mU/L was lower than 10%. Using the normal range of nonpregnant FT(3) and FT(4) to estimate the thyroid function of pregnant women could cause mis diagnosis.