Publications by authors named "Hongmei Shen"

90 Publications

Chloroplast genomes in Populus (Salicaceae): comparisons from an intensively sampled genus reveal dynamic patterns of evolution.

Sci Rep 2021 May 4;11(1):9471. Epub 2021 May 4.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

The chloroplast is one of two organelles containing a separate genome that codes for essential and distinct cellular functions such as photosynthesis. Given the importance of chloroplasts in plant metabolism, the genomic architecture and gene content have been strongly conserved through long periods of time and as such are useful molecular tools for evolutionary inferences. At present, complete chloroplast genomes from over 4000 species have been deposited into publicly accessible databases. Despite the large number of complete chloroplast genomes, comprehensive analyses regarding genome architecture and gene content have not been conducted for many lineages with complete species sampling. In this study, we employed the genus Populus to assess how more comprehensively sampled chloroplast genome analyses can be used in understanding chloroplast evolution in a broadly studied lineage of angiosperms. We conducted comparative analyses across Populus in order to elucidate variation in key genome features such as genome size, gene number, gene content, repeat type and number, SSR (Simple Sequence Repeat) abundance, and boundary positioning between the four main units of the genome. We found that some genome annotations were variable across the genus owing in part from errors in assembly or data checking and from this provided corrected annotations. We also employed complete chloroplast genomes for phylogenetic analyses including the dating of divergence times throughout the genus. Lastly, we utilized re-sequencing data to describe the variations of pan-chloroplast genomes at the population level for P. euphratica. The analyses used in this paper provide a blueprint for the types of analyses that can be conducted with publicly available chloroplast genomes as well as methods for building upon existing datasets to improve evolutionary inference.
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http://dx.doi.org/10.1038/s41598-021-88160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096831PMC
May 2021

Protective effect of Achyranthes bidentata polypeptides on NMDA-mediated injury is developmentally regulated via modulating NR2A and NR2B differentially.

Ann Transl Med 2021 Feb;9(3):248

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Background: Achyranthes bidentata polypeptides (ABPPs) are a potent intervention for excitotoxicity-related disorders such as Parkinson's disease and ischemic stroke. Previous work suggests that overstimulation of N-methyl-D-aspartate (NMDA) receptors plays a critical role in excitotoxicity, and expression of NR2 subunit variations is developmentally regulated. Our current study focused on neuroprotection of ABPPs on cultured neurons by modulation of NR2A and NR2B differentially.

Methods: Primary cultured neurons were treated with NVP-AAM077, Ro-256981, ABPPs, and then the neurons were exposed to NMDA to induce excitotoxicity. Cellular viability was detected promptly and 24-hour after exposure to NMDA by MTT assay. Patch-clamp recording was applied to evaluate the effect of ABPPs on NMDA-evoked current and the differential modulation of ABPPs on NR2A and NR2B subunits in conjunction with NVP-AAM077 and Ro-256981.

Results: ABPPs (10 µg/mL) blocked neuronal injury by NMDA in mature cultures, and the peptides conferred neuroprotection in immature cultures unless co-applied with NVP-AAM077. Furthermore, ABPPs enhanced NMDA current in mature cultures, while decreasing NMDA current in immature cultures. On the other hand, we showed that ABPPs increased NMDA current when Ro-256981 was present and decreased NMDA current when NVP-AAM007 was present.

Conclusions: Neuroprotection of ABPPs on NMDA-mediated injury differentially in immature and mature cultures involves enhancement of NR2A subunits and prevention of NR2B subunits, indicating that dosage of ABPP should be considered in treatment with patients at different developmental stages.
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http://dx.doi.org/10.21037/atm-20-581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940890PMC
February 2021

DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis.

Neoplasma 2021 May 14;68(3):482-489. Epub 2021 Jan 14.

Institute of Iodine Deficiency Disorders, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention,, Harbin Medical University, Harbin, China.

Bladder cancer (BCa) is a common carcinoma of the urinary tract, which occurs in the bladder mucosa. In recent years, people have recognized that epigenetic changes such as DNA methylation play important roles in the development of BCa but the specific mechanism is unclear. In this study, we detected the methylation rates in the SOCS1 gene of 490 subjects (including 247 patients with BCa and 243 healthy controls) using the MassARRAY EpiTYPER system. Principal component analysis (PCA) was conducted with the aim of identifying common underlying patterns that could explain the largest part of common variance in methylation across units. A logistic regression model was used to assess the relation of SOCS1 methylation patterns with factors related to BCa risk. The methylation rates varied for different CpG units and were significantly different in BCa patients compared to controls. Six principal component factors were extracted by combining initial eigenvalue, explanatory power, and Scree Plot. After adjusting for age, gender, family history of bladder cancer, smoking, and drinking, we observed that Factor 1 (OR=0.051, 95% CI: 0.015-0.178, p<0.001), Factor 2 (OR=0.146, 95% CI: 0.073-0.295, p<0.001), Factor 3 (OR=0.346, 95% CI: 0.198-0.606, p<0.001), and Factor 4 (OR=0.270, 95% CI: 0.135-0.537, p<0.001) were associated with BCa. Based on follow-up results, we found that the 1-, 3-, 5-year survival rates in the hypermethylated group were lower than in the hypomethylated group. We found that several CpG units in methylation patterns were associated with the incidence of BCa showing the important DNA methylation patterns for BCa pathogenesis. Our findings provided new insights into understanding this disease and new potential targets for therapeutic intervention for BCa patients in the future.
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http://dx.doi.org/10.4149/neo_2020_200928N1035DOI Listing
May 2021

Predicted CD4 T cell infiltration levels could indicate better overall survival in sarcoma patients.

J Int Med Res 2021 Jan;49(1):300060520981539

The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Objective: The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations.

Methods: Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined.

Results: Levels of CD4 T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4 T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4 T cell infiltration levels.

Conclusions: This data mining study indicated that CD4 T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4 T cells infiltration indicated a better chance of survival.
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http://dx.doi.org/10.1177/0300060520981539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809305PMC
January 2021

Relationship between TSHR, BRAF and PIK3CA gene copy number variations and thyroid nodules.

Endocrine 2021 Jul 11;73(1):116-124. Epub 2021 Jan 11.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Purpose: This study aims to investigate the relationship between the TSHR, BRAF, and PIK3CA gene copy number variations (CNVs) and thyroid nodules by analyzing gene CNVs, and to explore the interaction between iodine status and the above genes CNVs in the occurrence of thyroid nodules.

Methods: Three hundred and ninety-five subjects were selected from 3 regions with different iodine status in Shanxi Province of China, including 192 patients with thyroid nodules and 203 healthy controls. The basic information about subjects had been obtained through a questionnaire. B ultrasound was utilized to check thyroid nodules. Blood and urine samples were harvested to detect the thyroid function and urinary iodine concentration. Real-time quantitative polymerase chains reaction (RT-PCR) served to detect CNVs in DNA from human blood.

Results: There was an association between TSHR gene CNV and thyroid nodules (χ = 8.403, P = 0.004). The prevalence of BRAF and PIK3CA gene CNVs was not statistically significant between the case group and the control group. Differences in the TSHR gene CNV rates for cases of the 3 areas were statistically significant (χ = 10.072, P = 0.007). No statistical difference in the prevalence rates of the 3 genes CNVs between diverse characteristics of thyroid nodules was observed. UIC > 300 μg/L (OR = 1.74, 95% CI: 1.02-2.96, P = 0.041) and TSHR gene CNV (OR = 3.53, 95% CI: 1.40-8.92, P = 0.008) were risk factors for thyroid nodules. There was no significant interaction between the UIC and the examined genes CNVs.

Conclusions: TSHR gene CNV and high urinary iodine levels can increase the risk of thyroid nodules. But the interactions between the 3 above genes CNVs and iodine nutrition were not found in the occurrence of thyroid nodules.
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http://dx.doi.org/10.1007/s12020-020-02587-9DOI Listing
July 2021

Relationship between excess iodine, thyroid function, blood pressure, and blood glucose level in adults, pregnant women, and lactating women: A cross-sectional study.

Ecotoxicol Environ Saf 2021 Jan 10;208:111706. Epub 2020 Dec 10.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, People's Republic of China. Electronic address:

High water iodine concentration in drinking water can lead to excessive iodine, which will affect normal thyroid function, blood glucose, and blood pressure, especially among pregnant and lactating women. The aim of the present study was to determine the relationship between iodine, thyroid function, blood pressure, and blood glucose level among adults, and pregnant and lactating women in areas that are iodine-adequate (IA) and iodine-excess (IE) with respect to iodine concentrations in drinking water. A cross-sectional survey was conducted involving 144 pregnant and 237 lactating women in Shanxi Province, and 828 adults in Shandong Province. Water iodine, urinary iodine, thyroid function, blood pressure, and blood glucose were measured. Compared with the IA area, the water iodine concentration (WIC) in the IE area was higher (adults, 325.00 µg/L vs. 71.40 µg/L; pregnant and lactating women, 464.80 µg/L vs. 57.50 µg/L). For adults, and pregnant and lactating women, in the IE area, the urinary iodine concentration (UIC), free thyroxine (FT [except for lactating women]), and systolic blood pressure (only adults 18-40 years of age) were significantly higher, while the blood glucose level and the prevalence of hyperglycemia (except for adults) was lower, and the free triiodothyronine (FT), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and hypertension-positive rates of the three populations were not significantly different. For adults, systolic and diastolic pressure were positively correlated with FT and FT, respectively, while the blood glucose level were inversely associated with the WIC. For pregnant women, systolic pressure and the WIC, diastolic pressure and FT, blood glucose level and FT were all positively correlated, while the blood glucose level was inversely associated with TSH, WIC and UIC. For lactating women, systolic pressure was positively correlated with WIC and UIC, while blood glucose level were inversely associated with WIC and UIC. Pregnant and lactating women in the IE area were at lower risk for an association with hyperglycemia. Collectively, our research showed that long-term exposure to high water iodine is a high-risk factor for abnormal blood pressure and a low-risk factor for abnormal blood glucose level, especially for special populations such as pregnant and lactating women. Moreover, enhanced monitoring of blood pressure and blood glucose level in people with abnormal thyroid function in areas with high water iodine is important.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111706DOI Listing
January 2021

Associations between water iodine concentration and the prevalence of dyslipidemia in Chinese adults: A cross-sectional study.

Ecotoxicol Environ Saf 2021 Jan 5;208:111682. Epub 2020 Dec 5.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, People's Republic of China. Electronic address:

Iodine is important in both thyroid function and lipid metabolism. Some studies have explored the effect of thyroid hormones (THs) and urinary iodine concentration (UIC) on serum lipid levels. However, the association between iodine intake and dyslipidemia has not been well established. This study aimed to investigate the relationship between water iodine concentration (WIC) and dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C). A cross-sectional survey was conducted involving 409, 390 and 436 adults (≥18 years) from the iodine-deficient (median water iodine, MWI < 10 µg/L), iodine-adequate (MWI between 40 and 100 µg/L) and iodine-excess (MWI > 100 µg/L) areas, respectively. WIC, total cholesterol (TC), triglyceride (TRIG), HDL-C and LDL-C were measured. The prevalence of dyslipidemia were calculated based on the level of WIC using the chi-square method. To further explore whether prevalence was associated with WIC, simple linear regressions and multiple logistic regression models were used. Compared to those with WIC of 40-100 µg/L, a WIC of >100 µg/L was found to be protective associated with against the occurrence of hypertriglyceridemia [adjusted odds ratio (AOR) = 0.649, 95% confidence interval (CI): 0.455-0.924] and low HDL-C (AOR = 0.429, 95% CI: 0.264-0.697). The prevalence of hypertriglyceridemia, low HDL-C and high LDL-C as a function of WIC was found to be an inverted U-shaped association with a zenith at a WIC of 40-100 µg/L. Collectively, our research showed that serum lipid levels are related to WIC. The benefit effect association between WIC and dyslipidemia appears in cases of iodine excess (>100 µg/L).
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http://dx.doi.org/10.1016/j.ecoenv.2020.111682DOI Listing
January 2021

[Reuse process of positive pressure powered air-filter protective hoods].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 Oct;49(5):603-608

Central Sterile Supply Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Objective: To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic.

Methods: The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method.

Results: Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing.

Conclusions: The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.
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http://dx.doi.org/10.3785/j.issn.1008-9292.2020.10.09DOI Listing
October 2020

The Relationship between PTPN22 R620W Polymorphisms and the Susceptibility to Autoimmune Thyroid Diseases: An Updated Meta-analysis.

Immunol Invest 2020 Oct 26:1-14. Epub 2020 Oct 26.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

The protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W polymorphism has been related to susceptibility to autoimmune thyroid disease (AITD) with inconsistent results. Therefore, this meta-analysis was designed to assess a more accurate association between the PTPN22 R620W polymorphism and AITD susceptibility. A systematic search of the EMBASE, PubMed, Web of Science, CBM, CNKI, and WanFang databases was performed to determine relevant publications. Statistical analyses of the odds ratios (ORs), 95% confidence intervals (CIs), and values were performed using STATA software. Our meta-analysis included 18 separate studies comprised of 4,726 cases and 4,220 controls. In the allele and all genetic models, PTPN22 R620W polymorphism and Graves' disease (GD) (allele model TvsC: OR = 1.573; 95% CI = 1.378-1.795; < .001) and Hashimoto's thyroiditis (HT) (allele model TvsC: OR = 1.737; 95% CI = 1.230-2.454; = .002) susceptibility was positively associated. A racial subgroup analysis showed that the T allele significantly increased AITD susceptibility in all genetic models involving Caucasians, but not in Asians. This meta-analysis showed that the PTPN22 R620W polymorphism is associated with the risk of GD and HT in the overall study population. In addition, the PTPN22 R620W polymorphism is associated with elevated AITD risk in Caucasians, but not in Asians.
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http://dx.doi.org/10.1080/08820139.2020.1837154DOI Listing
October 2020

Iodine nutrition status of women after 10 years of Lipiodol supplementation: a cross-sectional study in Xinjiang, China.

Br J Nutr 2021 Jul 8;126(1):9-21. Epub 2020 Oct 8.

Institute for Iodine Deficiency Disorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin City, Heilongjiang Province 150081, People's Republic of China.

This study examined the contribution of long-term use of Lipiodol capsules, as a supplement to iodised salt to the control of iodine deficiency disorders among women in Xinjiang of China. A total of 1220 women across Kashgar, Aksu, Turpan and Yili Prefectures were surveyed in 2017. Lipiodol capsules were administered twice yearly in Kashgar and once yearly in Aksu and Turpan, but not in Yili. Urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody, thyroid peroxidase antibody and thyroid volume values were assessed. All the women in the four areas were in a state of non-iodine deficiency by UIC. The UIC were higher than adequate in Kashgar and Aksu (619·4 v. 278·6 μg/l). Thyroid hormone levels differed significantly in Turpan and Yili (FT3: 4·4 v. 4·6 pmol/l, FT4: 13·8 v. 14·2 pmol/l, TSH: 2·0 v. 2·7 mIU/l), but did not differ significantly in Kashgar, Aksu and Yili. The four areas did not differ significantly with regard to thyroid nodules, autoimmune thyroiditis or goitre. However, the detection rates of subclinical hypothyroidism (16·6 %) and total thyroid dysfunction (25·4 %) were higher among women in Yili. The supplementation with Lipiodol capsules had improved the iodine nutrition status of women in iodine-deficient areas of Xinjiang since 2006. To avoid negative effects of excess iodine, we suggest a gradual discontinuation of Lipiodol capsules in women with special needs based on the existing iodine nutrition level of local women.
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http://dx.doi.org/10.1017/S0007114520003918DOI Listing
July 2021

Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling.

Nat Commun 2020 06 12;11(1):2979. Epub 2020 Jun 12.

Section on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA.

NMDA receptor-dependent long-term depression (NMDAR-LTD) is a long-lasting form of synaptic plasticity. Its expression is mediated by the removal of AMPA receptors from postsynaptic membranes. Under basal conditions, endocytosed AMPA receptors are rapidly recycled back to the plasma membrane. In NMDAR-LTD, however, they are diverted to late endosomes for degradation. The mechanism for this switch is largely unclear. Additionally, the inducibility of NMDAR-LTD is greatly reduced in adulthood. The underlying mechanism and physiological significance of this phenomenon are elusive. Here, we report that autophagy inhibition is essential for the induction and developmental dampening of NMDAR-LTD. Autophagy is inhibited during NMDAR-LTD to decrease endocytic recycling. Autophagy inhibition is both necessary and sufficient for LTD induction. In adulthood, autophagy is up-regulated to make LTD induction harder, thereby preventing the adverse effect of excessive LTD on memory consolidation. These findings reveal the unrecognized functions of autophagy in synaptic plasticity, endocytic recycling, and memory.
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http://dx.doi.org/10.1038/s41467-020-16794-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293213PMC
June 2020

Study on the cleaning effect of medical protective positive pressure air supply respirator during COVID-19.

Panminerva Med 2020 Jun 4. Epub 2020 Jun 4.

Central Sterile Supply Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

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http://dx.doi.org/10.23736/S0031-0808.20.03971-3DOI Listing
June 2020

Autoimmune thyroid diseases after 25 years of universal salt iodisation: an epidemiological study of Chinese adults in areas with different water iodine levels.

Br J Nutr 2020 10 21;124(8):853-864. Epub 2020 May 21.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin150081, People's Republic of China.

The present study aimed to evaluate the status of iodine nutrition and thyroid function in adults, to understand the distribution of thyroid disease in people with autoimmune thyroid disease (AITD) in different water iodine areas and to explore the relationship between serum iodine, urine iodine and thyroid function in people with AITD. A cross-sectional survey was conducted in areas of Shandong Province with different water iodine levels, and subsequently 1225 adults were enrolled from iodine-deficient (ID), iodine-adequate (IA) and iodine-excess (IE) areas. Urinary iodine, water iodine, salt iodine, serum iodine and thyroid function were measured. According to the urine iodine concentration, the ID and IA areas were defined as iodine sufficient and the IE area as iodine excessive. Urine iodine, serum iodine, free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were comparatively higher in the IE area. The positive rate of thyroglobulin antibody (19·1 %) and the prevalence of AITD (21·8 %) were higher in the ID areas; the prevalence of subclinical hypothyroidism was lowest in the ID areas (7·3 %) and highest in the IE area (16·3 %). Among the AITD population, urinary iodine concentration, free triiodothyronine, FT4 and TSH had a non-linear correlation with serum iodine; abnormal TSH level, serum iodine concentration > 110 µg/l and goitre were risk factors for AITD in adults, especially females. Our data collectively suggest that universal salt iodisation has improved the iodine nutritional status of the population in ID areas in China. Non-step-by-step iodine fortification may induce the transformation of thyroid autoimmune diseases from recessive-to-dominant in susceptible people. Moreover, enhanced monitoring of thyroid function in people with AITD is important.
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http://dx.doi.org/10.1017/S0007114520001786DOI Listing
October 2020

Aberrant Methylation of Suppressor of Cytokine Signaling 1 (SOCS1) Gene as a Biomarker for Early Prediction and Diagnosis of Bladder Cancer.

Clin Lab 2020 May;66(5)

Background: SOCS1 protein, the negative regulatory protein of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway, may inhibit signaling of JAK-STAT pathway by several cytokines and has tumor suppressor activity. Methylation of CpG island in the promoter region of SOCS1 gene has often been shown to inactivate the SOCS1 gene in certain human cancers. However, the precise role of SOCS1 in bladder cancer is unclear.

Methods: Two hundred forty-seven patients with BCa and 243 healthy controls were enrolled from Tumour Hospital Affiliated to Harbin Medical University, Hongqi Hospital Affiliated to Mudanjiang Medical University, and Mudanjiang Tumour Hospital from September 2013 to March 2019. The methylation rate in the promoter region of the SOCS1 among all participants were detected using the MassARRAY EpiTYPER system. A ROC curve was set out to analyze SOCS1 gene promoter CpG island methylation for BCa diagnosis.

Results: There was a significantly higher methylation rate in BCa compared to controls. Then we assessed the methylation rate of different CpG islands in SOCS1 gene among BCa cases and normal controls. Methylation rate was shown to vary among different CpG islands. The methylation rates of CpG islands were shown to vary among different grades. We observed that the methylation rate of different CpG islands vary according to pathological grades.

Conclusions: Our study demonstrates that aberrant methylation of CpG island in the promoter region of SOCS1 gene may be involved in occurrence, progression, and prognosis of BCa and, thus, may serve as an independent diagnosis and prognostic biomarker.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190926DOI Listing
May 2020

Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis.

Endocrine 2020 09 11;69(3):508-515. Epub 2020 Apr 11.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Purpose: To explore the association between the thyroid stimulating hormone receptor (TSHR) gene methylation and human papillary thyroid cancer (PTC), as well as PTC related clinicopathological indicators.

Methods: We searched PubMed, Embase, Medline, and Web of Science databases through computer for articles published in English on association between methylation of TSHR gene and PTC. Articles published in Chinese were searched in China National Knowledge Infrastructure (CNKI), WanFang, China Biology Medicine (CBM) disc, and WeiPu databases. Database search took place in the 4th week of October.

Results: Totally 914 samples from 14 case-control studies were included in our meta-analysis. The methylation rate of TSHR gene in PTC group was significantly greater than that in control group (OR = 6.45, 95% CI 3.03, 13.71, P < 0.001). The subgroup analysis results showed the incidence of TSHR gene methylation was higher in autologous controls (OR = 16.39, 95% CI 8.83, 30.42, P < 0.001), Asian races (OR = 8.26, 95% CI 3.54, 19.23, P < 0.001), and Chinese (OR = 11.40, 95% CI 5.56, 23.39, P < 0.001). Hierarchical analysis of PTC related clinicopathological indicators showed that TSHR gene methylation rate are higher in PTC patients over 45 years (OR = 1.65, 95% CI 1.07, 2.55, P < 0.05) and lymph node metastasis (OR = 5.36, 95% CI 1.54, 18.67, P < 0.01). In addition, the occurrence of TSHR gene methylation had also been shown to be related to the clinical stage (OR = 0.23, 95% CI 0.07, 0.70, P < 0.05) and size (OR = 0.19, 95% CI 0.11, 0.32, P < 0.01) of tumors. The result of sensitivity analysis showed the combined results of the studies included in the meta-analysis were fairly stable. Begg's and Egger's tests also suggested that there was no significance publication bias (P > 0.1).

Conclusions: The rate of TSHR gene methylation is higher in PTC and it may be associated with the pathogenesis of human PTC, suggesting that TSHR gene may be a candidate marker for PTC diagnosis. In addition, the occurrence of TSHR gene methylation in PTC patients is closely related to age, lymph node metastasis, clinical stage, and tumor size, suggesting that TSHR gene may be used as an index to judge the severity of PTC.
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http://dx.doi.org/10.1007/s12020-020-02284-7DOI Listing
September 2020

The Relationship between High Iodine Consumption and Levels of Autoimmune Thyroiditis-Related Biomarkers in a Chinese Population: a Meta-Analysis.

Biol Trace Elem Res 2020 Aug 11;196(2):410-418. Epub 2019 Nov 11.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

To comprehensively evaluate the relationship between high iodine concentration and biomarker abnormalities related to autoimmune thyroiditis in a Chinese population. Medline, PubMed, and Embase electronic databases were searched for articles published domestically and internationally on the relationship between high iodine concentrations and thyroid hormone antibodies and thyroid-stimulating hormone in China before March 2019. Articles published in Chinese were searched in the China Biology Medicine (CBM) disc, Wanfang Database, and China National Knowledge Infrastructure (CNKI). A total of 16 cross-sectional articles were included in this study, including 9061 participants. A meta-analysis was conducted in Stata 14.0. The binary categorical and continuous variables used odds ratios (ORs) and standardized mean differences (SMDs) with the corresponding 95% confidence intervals (CIs) as the effect statistics, respectively. The results showed that high iodine concentrations had a minimal association with the abnormal rates of thyroid peroxidase antibody (TPOAb) (OR = 1.274, 95% CI (0.957, 1.695), P > 0.05) and thyroglobulin antibody (TGAb) (OR = 1.217, 95% CI (0.911, 1.626), P > 0.05) in the entire population. The thyroid-stimulating hormone (TSH) level in the high iodine group was greater than that in the adaptive iodine group (SMD = 0.202, 95% CI (0.096, 0.309), P < 0.05). The results of the subgroup analysis showed that the abnormal TPOAb rate in pregnant women (OR = 1.519, 95% CI (1.007, 2.291), P < 0.05) and children (OR = 3.365, 95% CI (1.966, 5.672), P < 0.05) in the high iodine group was greater than that in the adaptive iodine group, and the abnormal TGAb rate of children in the high iodine group was greater than that in the adaptive iodine group. The TSH levels of lactating women (SMD = 0.24, 95% CI (0.053, 0.427), P < 0.05), pregnant women (SMD = 0.301, 95% CI (0.176, 0.426), P < 0.05), and children (SMD = 0.25, 95% CI(0.096, 0.309), P < 0.05) in the high iodine group were higher than those in the adaptive iodine group. Egger's and Begg's tests showed no significant (P > 0.1) publication bias. High iodine can increase the risk of abnormal levels of TPOAb, TGAb, and TSH related to autoimmune thyroiditis in pregnant women, lactating women, and children in China.
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http://dx.doi.org/10.1007/s12011-019-01951-9DOI Listing
August 2020

The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease.

Biol Trace Elem Res 2020 Jun 7;195(2):409-416. Epub 2019 Sep 7.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.

Autoimmune thyroid disease (AITD) is a recurrent and refractory clinical endocrine disease. Some studies have shown that the incidence of AITD is not only related to iodine, a kind of environmental factor, but that susceptibility genes also play a crucial role in its pathogenesis. Since research on susceptibility genes is still underway, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related to susceptibility to AITD, and to explore the risk factors in the occurrence of AITD. Blood samples from five AITD patients and five controls from each area were assessed by chromosome microarray to identify candidate genes. The copy number (CN) of the candidate genes and urinary iodine levels were determined in adults, including 158 AITD patients and 181 controls, from areas having different iodine statuses. The cell growth-related genes, glypican 5 (GPC5), B9 domain containing 2 (B9D2), and ankyrin repeat and suppressor of cytokine signaling [SOCS] box-containing protein family 11 (ASB11), were selected as the candidate genes. The distribution of GPC5, B9D2, and ASB11 CNVs in AITD patients and controls was significantly different, and high urinary iodine levels and GPC5 CNVs are risk factors for AITD. There was no significant association between urinary iodine level and CNVs of the candidate genes. High urinary iodine levels and GPC5 CNVs are risk factors for AITD, but an association with the occurrence of AITD was not found.
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http://dx.doi.org/10.1007/s12011-019-01880-7DOI Listing
June 2020

Effect of Urinary Iodine Concentration in Pregnant and Lactating Women, and in Their Infants Residing in Areas with Excessive Iodine in Drinking Water in Shanxi Province, China.

Biol Trace Elem Res 2020 Feb 14;193(2):326-333. Epub 2019 Apr 14.

Institute for Endemic Disease Prevention and Treatment of Shanxi Province, Linfen, Shanxi, China.

It is uncertain how many factors affect urinary iodine concentration. The aim of this study was to determine the effect of consumption of drinking water with high iodine concentration on urinary iodine concentration in pregnant and lactating women, and infants. We included 218 lactating women and their infants and 142 pregnant women in areas with suitable and high water iodine content. Urine, serum, and water iodine concentration were assessed. Breastfeeding women living in areas with high water iodine content had a greater likelihood of iodine sufficiency or iodine excess [odds ratio (P = 0.044, P < 0.001)] compared with women living in areas with suitable water iodine content. Older women were less likely to have higher urinary iodine concentration (P = 0.041). Pregnant women who consumed milk > 4 times weekly during pregnancy were more likely to be iodine sufficient (P = 0.028). Living in areas with high water iodine content for > 5 years is a risk factor for iodine excess (P < 0.001, P = 0.007). There is a probability of higher urinary iodine concentration in pregnant and lactating women and their infants living in areas with high water iodine content. Age had an effect on iodine excess in lactating women. Consumption of milk > 4 times a week during pregnancy and living in an area with high iodine water content for > 5 years were associated with iodine sufficiency and iodine excess in pregnant women.
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http://dx.doi.org/10.1007/s12011-019-01716-4DOI Listing
February 2020

Applying Situational Theory of Problem Solving in Cancer Information Seeking: A Cross-Sectional Analysis of 2014 HINTS Survey.

J Health Commun 2019 8;24(2):165-173. Epub 2019 Mar 8.

c Assistant Director, Statistical Unit, Center for Health Policy Research , University of California , Los Angeles , California USA.

Informed by the Situational Theory of Problem Solving (STOPS), this study used data from the Health Information National Trends Survey, a large and representative national sample, to examine predictors of information seeking and information accessing of health information, including cancer-related information. We found that the independent variables in STOPS-problem recognition, involvement recognition, and referent criterion- well predicted people's information seeking of cancer-related information and accessing of health information on line. However, the impact of trust in online health information was more complicated than anticipated. Our study demonstrated the utility of the STOPS in the health information context. Theoretical and practical implications are discussed.
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http://dx.doi.org/10.1080/10810730.2019.1587111DOI Listing
February 2020

Effects of Excessive Iodine Intake on Blood Glucose, Blood Pressure, and Blood Lipids in Adults.

Biol Trace Elem Res 2019 Dec 23;192(2):136-144. Epub 2019 Feb 23.

Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

To understand the effects of excess iodine intake on blood glucose, blood pressure, and blood lipids in adults. We selected three villages from Shanxi Province to conduct cross-sectional survey: Maxi [median water iodine concentration (MWIC) 6.3 μg/L, median urinary iodine concentration (MUIC) 126.6 μg/L, 320 adults]; Xiwenzhuang (MWIC 79.8 μg/L, MUIC 221.2 μg/L, 264 adults); and Gaoche (MWIC 506.0 μg/L, MUIC 421.3 μg/L, 241 adults). According to the urinary iodine levels in adults, the three villages were defined as iodine-adequate, iodine-sufficient, and iodine-excess. Urinary iodine, water iodine, thyroid function, blood glucose, blood pressure, and blood lipids were measured. Compared with the iodine-adequate area, blood glucose and systolic and diastolic pressure of adults in iodine-sufficient and iodine-excess areas increased and high-density lipoprotein-cholesterol decreased (all P < 0.001). Urinary iodine, thyroid-stimulating hormone, and free thyroxine have a nonlinear correlation with blood glucose (R = 0.8174, 0.8264, and 0.8520, respectively). Excessive iodine intake may result in elevated blood glucose and blood pressure and has some influence on blood lipids, and may increase the risk of hypertension and diabetes.
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http://dx.doi.org/10.1007/s12011-019-01668-9DOI Listing
December 2019

SYKT Alleviates Doxorubicin-Induced Cardiotoxicity via Modulating ROS-Mediated p53 and MAPK Signal Pathways.

Evid Based Complement Alternat Med 2018 26;2018:2581031. Epub 2018 Aug 26.

Department of Radiotherapy, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, China.

Doxorubicin (DOX) is an effective therapeutic drug for malignant tumors; however, its clinical applications were limited by its side effects, especially the cardiotoxicity caused by ROS-mediated p53 and MAPK signal pathways' activation-induced cell apoptosis. Sanyang Xuedai mixture (SYKT) has been reported as an antioxidant agent and attenuated DOX-induced cardiotoxicity by targeting ROS-mediated apoptosis, but the mechanisms are still not fully delineated. This study aimed at investigating whether SYKT alleviated DOX-induced cardiotoxicity by inhibiting ROS-mediated apoptosis and elucidating the role of ROS-mediated p53 and MAPK signal pathways' activation in this process. Identification, separation, and culture of mouse primary cardiomyocytes. Cells were treated with DOX (1 M), SYKT (30 mg/mL), or SYKT coupled with DOX. The p53 inhibitor Pifithrin- (PFT-), p38/MAPK inhibitor SB203583 (SB), and JNK inhibitor SP600125 (SP) were used as positive control. Western blot was employed to detected p53 and p38 as well as JNK expressions and the activation and translocation of Bax and cytochrome C. Flow cytometer (FCM) was used to detect the mitochondrial membrane potential and cell apoptosis. After separation and culture, 95% of cells showed positive cTnI expression, which indicated that mouse primary cardiomyocytes were successfully identified in our research. DOX activated p53 and MAPK signal pathways in a time-dependent manner, which were inactivated by being cotreated with SYKT, PFT-, or SB, respectively. DOX significantly decreased Bax and increased cytochrome c expressions in the cytoplasm, whereas Bax was upregulated and cytochrome c was downregulated in the mitochondria, which were reversed by SYKT treatment. Besides, DOX reduced mitochondria membrane potential (MMP) in cardiomyocytes compared to the control group; SYKT recovered its MMP and attenuated DOX-induced cardiomyocyte injury. Of note, DOX increased the expression levels of cleaved caspase-3 as well as poly ADP-ribose polymerase (PARP) and promoted cell apoptosis, which were also reversed by SYKT treatment. Our results indicated that SYKT alleviated DOX-induced cardiotoxicity by inhibiting p53 and MAPK signal pathways' activation-mediated apoptosis, and it might serve as a potential therapeutic agent for DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1155/2018/2581031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129364PMC
August 2018

Copy Number Variation of Immune-Related Genes and Their Association with Iodine in Adults with Autoimmune Thyroid Diseases.

Int J Endocrinol 2018 11;2018:1705478. Epub 2018 Mar 11.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Background: Autoimmune thyroid diseases (AITD) are complex conditions that are caused by an interaction between genetic susceptibility and environmental triggers. Iodine is already known to be an environmental trigger for AITD, but genes associated with susceptibility need to be further assessed. Therefore, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related with susceptibility to AITD, and to investigate the interaction between iodine status and CNVs in the occurrence of AITD.

Methods: Blood samples from 15 patients with AITD and 15 controls were assessed by chromosome microarray to identify candidate genes. The copy number of candidate genes and urinary iodine level was determined in adults from areas of different iodine statuses including 158 patients and 181 controls.

Results: The immune-related genes, and , were selected as candidate genes. The distribution of CNV in AITD patients and controls was significantly different and was considered a risk factor for AITD. There was no significant association between urinary iodine level and candidate gene CNVs.

Conclusion: CNV and an excess of iodine were risk factors for AITD, but an association with the occurrence of AITD was not found.
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http://dx.doi.org/10.1155/2018/1705478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866896PMC
March 2018

Assessment of thyroid function in children, adults and pregnant and lactating women after long-term salt iodisation measurements.

Br J Nutr 2018 06 27;119(11):1245-1253. Epub 2018 Mar 27.

1Key Lab of Etiology and Epidemiology,Education Bureau of Heilongjiang Province & Ministry of Health,Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention,Harbin Medical University,No. 157Baojian Road,Nangang District,Harbin 150081,People's Republic of China.

Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.
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http://dx.doi.org/10.1017/S0007114518000570DOI Listing
June 2018

Association of TSHR Gene Copy Number Variation with TSH Abnormalities.

Biol Trace Elem Res 2018 Nov 15;186(1):85-90. Epub 2018 Mar 15.

Key Laboratory of Etiology and Epidemiology, National Health and Family Planning Commission, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As-Ce catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p = 0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC > 200 μg/l (OR = 1.49, 95% CI = 1.01-2.22) and the TSHR gene (OR = 6.01, 95% CI = 1.96-18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.
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http://dx.doi.org/10.1007/s12011-018-1300-7DOI Listing
November 2018

The application of serum iodine in assessing individual iodine status.

Clin Endocrinol (Oxf) 2017 Dec 4;87(6):807-814. Epub 2017 Aug 4.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Context: The prevalence of thyroid disease in China is on the rise, and this could be partly associated with excessive iodine intake in some individuals; therefore, increased attention is being paid to individual iodine status. However, current indices are not appropriate for evaluating individual iodine status.

Objective: To evaluate the association between serum iodine and urinary iodine (UI), as well as thyroid diseases, and provide an excellent base for future individual iodine status assessment.

Design, Subjects And Measurements: A total of 902 adults were enrolled in this study including 325, 286 and 291 subjects from regions in China where iodine is adequate, sufficient and in excess, respectively. Serum iodine, UI and thyroid function were assessed, and ultrasonography performed in all subjects.

Results: The median serum iodine values of adults with subclinical hypothyroidism, high serum autoantibody and thyroid nodules were significantly higher than those of euthyroid adults (P<0.05). A serum iodine level higher than 100 μg/L was considered as a risk factor for thyroid diseases. Serum iodine had strong nonlinear correlations with UI and thyroid function. When thyroid function was taken as a gold standard, the area under the receiver operating characteristic (ROC) curve for serum iodine was 0.752 and UI was 0.507 for subjects with lower serum iodine and UI levels. The area for serum iodine was 0.773 and UI was 0.638 for subjects with higher serum iodine and UI levels. The areas under these curves were significantly different (P<0.001).

Conclusion: In adults, serum iodine had a strong nonlinear correlation with UI and a high level of serum iodine was a risk factor for thyroid diseases.
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http://dx.doi.org/10.1111/cen.13421DOI Listing
December 2017

Eliminating Iodine Deficiency in China: Achievements, Challenges and Global Implications.

Nutrients 2017 Apr 5;9(4). Epub 2017 Apr 5.

Parasitic and Endemic Disease Prevention and Control Division of the National Health and Family Planning Commission of China, 14 Zhichun Road, Beijing 100088, China.

The prevention of iodine deficiency through salt iodization has been recognized as a global success story, and China stands at the forefront of this achievement with one of the most successful programs in the world. High level political commitment, national mandatory legislation, a state-managed edible salt industry and a complex and highly sophisticated surveillance system have facilitated the success of the program. Challenges have arisen however, including: (i) concern that adequate iodine status in pregnant women cannot be achieved without causing above adequate iodine intakes in children; (ii) declining iodine intake as a result of reductions in salt consumption and increased consumption of processed foods, which may not be made with iodized salt; (iii) the existence of areas with high iodine content in the water; and (iv) declines in household use of iodized salt due to concerns about excess iodine intake and thyroid disease. This article reviews the achievements and challenges of the Chinese Iodine Deficiency Disorders (IDD) Elimination Program and reflects on lessons learned and implications for other national salt iodization programs.
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http://dx.doi.org/10.3390/nu9040361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409700PMC
April 2017

Should urinary iodine concentrations of school-aged children continue to be used as proxy for different populations? Analysis of data from Chinese national surveys.

Br J Nutr 2016 09 8;116(6):1068-76. Epub 2016 Aug 8.

1Key Lab of Etiology and Epidemiology,Education Bureau of Heilongjiang Province & Ministry of Health,Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin 150081,People's Republic of China.

I deficiency is a worldwide public health problem. Median urinary I concentration in school-aged children has been used globally as a proxy for all populations. This study aims to determine whether median urinary I concentration of school-aged children is an appropriate indicator of I nutritional status in different adult populations. This is a secondary data analysis of two national I Deficiency Disorder surveys (2011, 2014) and two regional surveys (in coastal areas, 2009, and in high-risk areas, 2009-2014). Population groups included in these surveys were school-aged children (8-10 years), pregnant women, lactating women, women of childbearing age and adults (men and women, 18-45 years). All participants were self-reported healthy without history of thyroid diseases or were not using thyroid medicines. The median urinary I concentration of school-aged children was matched with that of the other population at the county level. The matched populations had similar iodised salt supply, food and water I, food composition and I content in salt. Weak or moderate correlation of median urinary I concentrations was observed between school-aged children and pregnant women and between children and lactating women. However, the agreement was stronger between children and women of childbearing age and between children and adult men and women. The results could be affected by cut-off values, data aggregation level and sample size. Using median urinary I concentration of school-aged children tends to overestimate that of pregnant women and lactating women. Median urinary I concentration of school-aged children can be used for assessing I nutrition in the adult population.
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http://dx.doi.org/10.1017/S0007114516002828DOI Listing
September 2016

miRNAs in NMDA receptor-dependent synaptic plasticity and psychiatric disorders.

Clin Sci (Lond) 2016 07;130(14):1137-46

Section on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, U.S.A.

The identification and functional delineation of miRNAs (a class of small non-coding RNAs) have added a new layer of complexity to our understanding of the molecular mechanisms underlying synaptic plasticity. Genome-wide association studies in conjunction with investigations in cellular and animal models, moreover, provide evidence that miRNAs are involved in psychiatric disorders. In the present review, we examine the current knowledge about the roles played by miRNAs in NMDA (N-methyl-D-aspartate) receptor-dependent synaptic plasticity and psychiatric disorders.
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http://dx.doi.org/10.1042/CS20160046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582542PMC
July 2016

The relationship between iodine nutrition and thyroid disease in lactating women with different iodine intakes.

Br J Nutr 2015 Nov 14;114(9):1487-95. Epub 2015 Sep 14.

1Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin City,Heilongjiang Province 150081,People's Republic of China.

Areas with low, adequate and excessive I content in water co-exist in China. Limited data are currently available on I nutrition and thyroid disease in lactating women and their breast-fed infants with different I intakes. This study aimed to evaluate I nutrition in both lactating women and their infants and the prevalence of thyroid disease in areas with different levels of I in water. From January to June 2014, a total of 343 healthy lactating women (excluding those taking anti-thyroid drugs or I supplements within a year of the study, consuming seafood at the time of the study or those diagnosed with congenital thyroid disease) from Beihai in Guangxi province and Jiajiazhuang, Yangcheng, Jicun and Pingyao townships in Shanxi province were selected. Compared with the I-sufficient group, median urinary I concentrations in both lactating women and infants as well as breast milk I levels were significantly lower in the I-deficient group (P<0·001). The prevalence of thyroid disease in lactating women, particularly subclinical hypothyroidism, was higher in the I-excess group than in the I-sufficient group (P<0·05). In areas with excessive water I content, high thyroid peroxidase antibody and high thyroglobulin levels were risk factors for abnormal thyroid-stimulating hormone levels. Our data collectively suggest that excessive I intake potentially causes subclinical hypothyroidism in lactating women. Moreover, enhanced monitoring of I status is important to avoid adverse effects of I deficiency or excess, particularly in susceptible populations such as pregnant or lactating women and infants.
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http://dx.doi.org/10.1017/S0007114515003128DOI Listing
November 2015

Small-molecule inhibitors targeting INK4 protein p18(INK4C) enhance ex vivo expansion of haematopoietic stem cells.

Nat Commun 2015 Feb 18;6:6328. Epub 2015 Feb 18.

1] Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, School of Pharmacy, NIH National Center of Excellence for Drug Abuse Research, Drug Discovery Institute, Pittsburgh, Pennsylvania 15260, USA [2] Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Among cyclin-dependent kinase inhibitors that control the G1 phase in cell cycle, only p18 and p27 can negatively regulate haematopoietic stem cell (HSC) self-renewal. In this manuscript, we demonstrate that p18 protein is a more potent inhibitor of HSC self-renewal than p27 in mouse models and its deficiency promoted HSC expansion in long-term culture. Single-cell analysis indicated that deleting p18 gene favoured self-renewing division of HSC in vitro. Based on the structure of p18 protein and in-silico screening, we further identified novel smallmolecule inhibitors that can specifically block the activity of p18 protein. Our selected lead compounds were able to expand functional HSCs in a short-term culture. Thus, these putative small-molecule inhibitors for p18 protein are valuable for further dissecting the signalling pathways of stem cell self-renewal and may help develop more effective chemical agents for therapeutic expansion of HSC.
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http://dx.doi.org/10.1038/ncomms7328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508125PMC
February 2015