Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 147
Filtrar
1.
Thyroid ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806437

RESUMO

BACKGROUND: Despite the implementation of the universal salt iodization (USI) program for correction of iodine deficiency in China for about 20 years, the actual iodine nutrition status of Chinese residents and the prevalence of iodine deficiency and iodine excess are issues that need to be addressed. This nationally representative cross-sectional study was conducted across all 31 provinces of mainland China to gather extensive data on iodine nutrition status and the influential factors. METHODS: This study included 78,470 participants, aged 18 years or older, who were interviewed and asked to answer a questionnaire. Urine iodine concentration (UIC) was measured by the inductively coupled plasma mass spectrometry method, and goiter was examined by thyroid ultrasonography. In addition, sixty 9 -11 years old school-children in each province were randomly selected to evaluate the UIC and thyroid ultrasonography. The iodine nutrition status was determined according to the WHO guidelines. RESULTS: The iodized salt coverage was 95.37%. The median urine iodine (MUI) was 177.89 µg/L (interquartile range [IQR], 117.89-263.90 µg/L) and goiter prevalence was 1.17% (95% CI, 0.95-1.43%) in the adult population. The MUI was 199.75 µg/L (IQR, 128.41-303.37 µg/L) in school-age children, and goiter prevalence was 3.50% (95% CI, 2.93-4.13%). The percentage of individuals with UIC < 50 µg/L was 3.43%, less than 20%. Analysis indicated that sex, age, geographic factors, BMI, smoking habits influence the iodine nutrition level. CONCLUSION: The mandatory USI program has successfully eliminated iodine deficiency disorders, and the findings indicate that the iodine nutrition level in the general population is within the safe range.

2.
Front Endocrinol (Lausanne) ; 12: 666393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616359

RESUMO

Objective: Epigenetic modifications in RNA are known to play critical roles in cell differentiation through regulating expressions of some key genes including members of the suppressor of cytokine signaling (SOCS) family. The present study aimed to unveil the relationship of SOCS mRNA methylation induced by methyltransferase like 3 (METTL3) with Graves' disease (GD). Methods: Differently expressed genes (DEG) in GD tissues were identified using microarray analysis and further validated using CD4+ T cell microarray of GD tissues and isolated peripheral blood mononuclear cells (PBMCs). Furthermore, expressions of METTL3 targeted genes were detected using METTL3 knock-down experiment in RAW264.7 cells. Results: High throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4+T cells of GD compared to the controls. Bioinformatic analysis was undertaken by searching databases of found genes of the SOCS family that possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down. Conclusions: For the first time, the present study revealed the relationship between m6A modification and GD and indicated that METTL3 may be involved in the development of GD by inducing mRNA m6A methylation modification of SOCS family members.

3.
Endocrinol Metab (Seoul) ; 36(4): 778-789, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34372624

RESUMO

BACKGROUND: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. METHODS: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. RESULTS: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. CONCLUSION: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

4.
J Immunol Res ; 2021: 9421720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458379

RESUMO

Objective: Rheumatoid arthritis (RA) is a complex disease with unknown pathogenesis. In recent years, fewer have paid attention to the broad spectrum of systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA. Methods: Totally, 12 specimens of plasma from 6 RA patients and 6 age- and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify exosomal profiles. Results: A total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC ≥ 2.0 and P < 0.05) and 5 proteins were downregulated (FC ≤ 0.5 and P < 0.05). Bioinformatics analysis revealed that transthyretin (TTR), angiotensinogen (AGT), lipopolysaccharide-binding protein (LBP), monocyte differentiation antigen CD14 (CD14), cartilage oligomeric matrix protein (COMP), serum amyloid P (SAP/APCS), and tenascin (TNC) can interact with each other. Subsequently, these cross-linked proteins may be mainly involved in the inflammatory-related pathways to mediate the onset of RA. Noteworthy, the LBP/CD14 complex can promote the expression of IL-8 and TNF-α, eventually leading to the development of RA. Conclusions: Our findings suggest distinct plasmatic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA but also serve as novel biomarkers in RA diagnosis and prognosis.

5.
Diabetes Metab Syndr Obes ; 14: 3691-3701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447259

RESUMO

Purpose: To investigate the relationship between iodine intake status and the prevalence of metabolic syndrome (MetS) through a population-based survey. Patients and Methods: In total, 2691 Chinese adults participated in this cross-sectional study, and they were stratified by urinary iodine concentration (UIC) and sex. Fasting blood samples were used to assess biochemical parameters, including thyroid function and antibodies. Urine samples were collected in the morning to measure UIC. Multivariate regression logistic analysis was performed for the overall population and sex subgroups. Results: An inverse association was observed between iodine intake status and MetS prevalence in Chinese adults. Compared with individuals with adequate iodine status, those with high-iodine status had significantly low MetS risks, and the adjusted odds ratios (95% confidence interval) were 0.70 (0.57-0.86, P <0.01) and 0.75 (0.6-0.95, P <0.05). A high MetS risk was observed in the iodine-deficient group, which did not reach statistical significance. There was a significant inverse linear trend between the risk of MetS and UIC in the total population and male subgroup (P for trend <0.05), which was not observed in the female subgroup (P for trend >0.05). Conclusion: An inverse association was observed between iodine intake status and the risk of developing MetS in Chinese adults. Sufficient iodine status is a potential protective factor for MetS development. Males may benefit from increased iodine intake, while females would need to achieve a more-than-adequate iodine status to gain metabolic benefits.

6.
Adv Med Sci ; 66(2): 351-358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34304114

RESUMO

PURPOSE: RNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD). MATERIAL AND METHODS: A case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated. RESULTS: Compared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD. CONCLUSIONS: Our results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD.

7.
Immunol Invest ; : 1-10, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34325607

RESUMO

BACKGROUND: Autoimmune thyroid disease (AITD) is an inherited, complex gene- and immune-related disorder that mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Psoriasis susceptibility 1 candidate 1 (PSORS1C1) is a susceptibility gene associated with many autoimmune diseases, but its role in an individual's predisposition to AITD is unknown. METHODS: This study included 1065 Chinese Han patients with AITD and 943 matched healthy individuals. The rs3130983, rs3778638, rs3815087, and rs4959053 single nucleotide polymorphisms (SNPs) in PSORS1C1 were determined using multiplex polymerase chain reaction technology. RESULTS: Of the four SNPs, only the distribution of the rs3778638 genotypes was different between the AITD (AA, 2.67%; AG, 19.15%; and GG, 78.18%) and control (AA, 1.52%; AG, 22.2%; and GG, 75.87%) groups (P = .046). An association between rs3778683 and GD was observed (p = .039) but not with HT. No linkage disequilibrium was observed for rs3130983, rs3815087, rs3778638, and rs4959053 in PSORS1C1 among the patients with AITD and controls. CONCLUSION: This study suggests the influence of PSORS1C1 rs3778638 on the susceptibility to GDs, supporting this locus as a common autoimmunity risk factor.

8.
BMC Endocr Disord ; 21(1): 148, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238277

RESUMO

BACKGROUND: Recent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD. METHODS: A total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. RESULTS: There was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66-0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64-0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65-0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63-0.93, P = 0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR = 0.84, 95%CI 0.71-0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60-0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58-0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis. CONCLUSION: This is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.

9.
Int Rev Immunol ; : 1-17, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243694

RESUMO

Autoimmune disease (AID) is a condition in which the immune system breaks down and starts to attack the body. Some common AIDs include systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus and so forth. The changes in T-cell receptor (TCR) repertoire have been found in several autoimmune diseases, and may be responsible for the breakdown of peripheral immune tolerance. In this review, we discussed the processes of TCR revision in peripheral immune environment, the changes in TCR repertoire that occurred in various AIDs, and the specifically expanded T cell clones. We hope our discussion can provide insights for the future studies, helping with the discovery of disease biomarkers and expanding the strategies of immune-targeted therapy. HighlightsRestricted TCR repertoire and biased TCR-usage are found in a variety of AIDs.TCR repertoire shows tissue specificity in a variety of AID diseases.The relationship between TCR repertoire diversity and disease activity is still controversial in AIDs.Dominant TCR clonotypes may help to discover new disease biomarkers and expand the strategies of immune-targeted therapy.

10.
Front Cell Dev Biol ; 9: 685522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124070

RESUMO

Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Methods: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing. Findings: We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment. Interpretation: These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.

11.
Front Endocrinol (Lausanne) ; 12: 651534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122333

RESUMO

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination. Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs. 0.64%, P<0.001; GD: 0.65% vs. 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% vs. 0.81%, P<0.001; GD: 0.38% vs. 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels. Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.

12.
PLoS Biol ; 19(5): e3001229, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34003819

RESUMO

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.


Assuntos
Coração/crescimento & desenvolvimento , Coração/fisiologia , Animais , Cromatina/metabolismo , Ilhas de CpG/genética , DNA/genética , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica/métodos , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Ventrículos do Coração/crescimento & desenvolvimento , Ventrículos do Coração/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Camundongos , Nucleossomos/metabolismo , Especificidade de Órgãos/genética , RNA Longo não Codificante/metabolismo , Especificidade da Espécie , Transcriptoma/genética
13.
DNA Cell Biol ; 40(3): 482-490, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33617351

RESUMO

This research used combined bioinformatic methods to identify differentially methylated regions (DMRs) in newly diagnosed patients with Graves' disease (GD). Peripheral blood from six GD patients and controls was collected and methyl-DNA immunoprecipitation (MeDIP), and NimbleGen Human DNA Methylation 3 × 720 K promoter plus CpG island microarrays were further analyzed. DMRs were categorized into low-methylated genes and high-methylated genes, which were mapped into a protein-protein interaction (PPI) network constructed by a dataset. Then, six candidate genes were validated in an expanded population with 32 GD patients and 30 controls using bisulfite amplicon sequencing. Top 10 hub genes revealed by PPI analysis were CRHR1, CAMK2A, SERPINA1, RANBP9, ICAM1, ADRB2, KRTAP13-1, PTPRA, S100A2, and KPRP. Five CpG sites of CDKN2C (51436061), SERPINA1 (94856657), B3GNT2 (62422532 and 62422689), and IRS4 (107979477) were validated, having significantly different methylation levels between GD patients and controls. Based on gender stratification, nine significant CpG sites of CDKN2C (51436061), SERPINA1 (94855831), and B3GNT2 (62422301, 62422327, 62422356, 62422365, 62422374, 62422532, and 62422689) were detected between female GD patients and controls. The methylation level of 62422532 of B3GNT2 was significantly associated with levels of serum TGAb and TRAb. In addition, the methylation level of 62422689 of B3GNT2 showed significant correlation with the age of GD patients. In the analysis of prediction of transcription factor binding at specific CpG sites in B3GNT2 promoter region, paired box protein 5 (Pax-5) and CCAAT/enhancer-binding protein (C/EBP ß) might be under the influence of methylation at CpG sites 62422365 and 62422532, respectively. CDKN2C, SERPINA1, IRS4, and especially B3GNT2 were potential aberrantly methylated genes related to GD. These findings might supply the latest information of DNA methylation in the GD disease.


Assuntos
Envelhecimento/metabolismo , Ilhas de CpG , Metilação de DNA , Doença de Graves/metabolismo , Adulto , Fatores Etários , Envelhecimento/genética , Feminino , Doença de Graves/diagnóstico , Doença de Graves/genética , Humanos , Masculino , Pessoa de Meia-Idade
14.
Thyroid ; 31(4): 563-571, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33138723

RESUMO

Background: Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Methods: Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Results: Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood (ß = 0.024; p = 0.038), compared with the nonexposed participants. The association was significant among rural participants (ß = 0.039; p = 0.02) but not in urban participants (ß = 0.005; p = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules (p > 0.05). Conclusions: Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.

15.
Endocrine ; 72(2): 495-504, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33025559

RESUMO

PURPOSE: Autoimmune thyroid disease (AITD) is a classic autoimmune disorder that mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this study, we explored the potential relationship between single-nucleotide polymorphisms (SNPs) of methyltransferase like 3 (METTL3) gene and the development of AITD. METHODS: The distribution of METTL3 genotypes at seven loci (rs1139130, rs1263790, rs1263791, rs17197156, rs2242526, rs3752411, and rs4417466) in 960 AITD (599 GD and 361 HT) patients and 732 unrelated healthy volunteers was examined using high-throughput sequencing technology in a case-controlled manner and their correlations with AITD development were statistically analyzed. RESULTS: METTL3 genotypes at these seven SNPs were not correlated with both GD and HT except a borderline association between rs3752411and GD after adjusted for age, sex, and thyroid function under the recessive model. Subgroup analysis demonstrated that the minor allele frequencies of rs2242526 and rs4417466 were higher in male AITD patients than in healthy volunteers before adjusted for confounding factors and the genotype distribution of rs4417466 was significantly different between the two groups. Additionally, the genotype frequencies of rs1139130, rs1263791, rs2242526, and rs4417466 were positively related with GD in male patients. Likewise, the allele distribution of rs1263791, rs2242526, and rs4417466 in male GD patients differed significantly from that in male controls. Multivariate logistic regression analyses revealed a significant association between allele frequencies of these three loci and GD in male patients after adjusted for the confounding factors. Moreover, the genotype of rs3752411 was strongly associated with GD in females as well. Furthermore, distribution of rs3752411 genotype was significantly associated with hypothyroidism in HT patients. CONCLUSION: Our study for the first time revealed a strong correlation between METTL3 mutations and AITD predisposition, implying that METTL3 may be a new candidate gene for AITD treatment.


Assuntos
Doença de Graves , Doença de Hashimoto , Metiltransferases/genética , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Doença de Graves/genética , Doença de Hashimoto/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
16.
Ann Transl Med ; 8(17): 1079, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33145298

RESUMO

Background: Current echocardiographic normal reference values and nomograms in healthy adults are commonly normalized by body surface area (BSA) with simple linear or isometric corrections. However, various lines of evidence suggest this method might be flawed. In this study, we established the normative data of left ventricular internal diameter (LViD) by BSA-correlated regression equations with the calculation of Z-scores in healthy Han Chinese adults. Methods: A total of 577 healthy Han Chinese adults were enrolled (age 44.4±13.0 years, 43% male and 57% female). LViD was acquired from two-dimensional-guided M-mode echocardiography on all participants from the parasternal long-axis view. Linear and nonlinear regression models were built to correlate LViD with BSA in different sexes and age groups. The best-fit models and nomograms are presented with the Z-scores calculated by the models. Residual analysis and reproducibility were evaluated in each best-fit model for reliability. Results: Body surface area showed polynomial (quadric) correlations with left ventricular end-diastolic diameter (LVDd, R2=0.615, P<0.001) and left ventricular end-systolic diameter (LVDs, R2=0.540, P<0.001). Corresponding regression equations and nomograms for computing the Z-scores of the overall LViD and BSA/sex-specific and BSA/age-specific reference values are presented. Reproducibility, residual distribution, autocorrelation and heteroscedasticity were confirmed in each model. Conclusions: This study proposes a comprehensive approach for normal reference values of left ventricular internal diameters with echocardiographic nomograms in healthy Han Chinese adults, which may offer a more precise way to diagnose cardiovascular disease in clinical practice.

17.
Iran J Basic Med Sci ; 23(10): 1340-1345, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33149868

RESUMO

Objectives: To investigate the effect of Ginkgo biloba extract EGb761 in early brain injury (EBI) after subarachnoid hemorrhage (SAH) and its mechanism. Materials and Methods: The SAH rat model was constructed and pre-treated with EGb761.The neurological function, severity of SAH, water content of brain tissue, damage degree of the blood-brain barrier, related indexes of oxidative stress, and the level of inflammatory cytokines were compared among the groups. The expression of TXNIP/NLRP3 signaling pathway-related proteins in brain tissues was detected by Western blot. Results: After SAH modeling, the neurological function score was significantly reduced, the degree of brain injury, levels of oxidative stress, inflammatory factors, expression of NLRP3 and TXNIP were all increased. Compared with the SAH rats, the neurological function score of rats pre-treated by EGb761 was higher, the degree of brain injury, levels of oxidative stress and inflammatory factors, expression of NLRP3 and TXNIP were all lower. Conclusion: EGb761 could protect neurological injury after SAH and its mechanism may be that EGb761 could inhibit the activation of the TXNIP/NLRP3 signaling pathway and inflammatory reaction after oxidative stress.

18.
Autoimmunity ; 53(6): 353-361, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32741222

RESUMO

BACKGROUND: In the past few years, an increasing number of studies have proposed the idea of extending the therapeutic range of metformin from traditional hypoglycaemic to autoimmune diseases, and confirmed in a variety of autoimmune diseases. However, whether metformin can be used to treat Hashimoto's thyroiditis (HT), which is characterised by thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), is unknown. Therefore, we conducted a systematic review and meta-analysis to evaluate whether metformin can reduce the levels of TPOAb and TgAb in patients with HT or subclinical hypothyroidism (SH), so as to provide a theoretical basis for metformin treatment of these diseases. METHODS: PubMed, Web Of Science and Embase were searched for observational studies investigating the changes of TPOAb and TgAb in patients with HT after metformin treatment. Two authors extracted data from eligible studies and classified them as HT and subclinical hypothyroidism subgroups. The calculation was then performed by weighted mean difference (WMD) combined with a fixed-effects model analysis or standard mean difference (SMD) with a random-effects model analysis, based on the measurement of the outcome. RESULTS: Metformin significantly reduced TPOAb levels and TgAb levels in patients with HT and SH, especially TPOAb (HT: p TPOAb = .009, p TgAb = .046; SH: p TPOAb = .034, p TgAb = .066). In addition, metformin also reduced the levels of thyroid stimulating hormone (TSH), homeostasis model assessment of insulin resistance (HOMA-IR) in patients with HT and SH (HT: p TSH = .000 and p HOMA-IR = .000; SH: p TSH = .000 and p HOMA-IR = .000, respectively). CONCLUSION: Metformin significantly reduces TPOAb level and TgAb level in patients with HT and SH, especially TPOAb. This study is the first to provide a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.


Assuntos
Autoanticorpos/sangue , Doença de Hashimoto/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Metformina/administração & dosagem , Autoanticorpos/imunologia , Doença de Hashimoto/sangue , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/imunologia , Estudos Observacionais como Assunto , Tireotropina/sangue , Resultado do Tratamento
19.
Thyroid ; 30(12): 1810-1819, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32762331

RESUMO

Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p-value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.

20.
Biomed Res Int ; 2020: 1378427, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802832

RESUMO

Background: Many studies have shown that NLRC4 inflammasome polymorphisms are associated with a variety of autoimmune diseases, but the associations between NLRC4 polymorphisms and autoimmune thyroid diseases (AITDs) are unclear. Our research was aimed at identifying the correlations between NLRC4 polymorphisms and AITDs. Methods: Hi-SNP high-throughput genotyping technology was used for detecting four single-nucleotide polymorphisms (SNPs) of NLRC4 in 1005 AITDs patients (including 629 Graves' disease and 376 Hashimoto's thyroiditis) and 781 healthy controls. Results: Compared with healthy controls, the allele frequencies and genotype distribution of rs385076 were statistically related to AITDs (P = 0.016 and P = 0.048, respectively) and Hashimoto's thyroiditis (P = 0.022 and P = 0.046, respectively). Before adjusting for age and gender, rs385076 and AITDs had a significant association in three models of allele model, dominant model, and homozygous model. After adjusting for age and gender, in the above three models, there is still a clear relationship between them. Before adjusting for age and gender, there were prominent discrepancy between rs385076 and Hashimoto's thyroiditis in the allele model (OR = 0.81, 95% CI 0.67-0.97; P = 0.021) and the dominant model (OR = 0.73, 95% CI 0.57-0.94; P = 0.014), after adjusting for age and gender, rs385076 and Hashimoto's thyroiditis were significantly related to allele model, dominant model, and homozygous model. However, rs455060, rs212704, and rs675712 were not related to AITDs in our study. Conclusion: NLRC4 rs385076 was found to have a significant association with Hashimoto's thyroiditis for the first time. It laid a foundation for the disclosure of the pathogenesis of AITDs, and provided a possible treatment prospect for HT.


Assuntos
Doenças Autoimunes/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas de Ligação ao Cálcio/genética , Doença de Graves/genética , Doença de Hashimoto/genética , Doenças da Glândula Tireoide/genética , Adulto , Doenças Autoimunes/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Doença de Graves/patologia , Haplótipos , Doença de Hashimoto/patologia , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Doenças da Glândula Tireoide/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...