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1.
PLoS One ; 14(11): e0225435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765419

RESUMO

OBJECTIVES: Although several studies have shown that cigarette smoking is associated with thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), the exact relationship between smoking and thyroid function is controversial. As little is known about the effects of smoking on TSH, TPOAb and TgAb in Chinese residents. This study aimed to evaluate the association between cigarette smoking and TSH, TPOAb and TgAb in ten-city residents of China. STUDY DESIGN: This was a population-based cross-sectional study. METHODS: In this cross-sectional study, 15,181 subjects from ten major cities of China were investigated. Data regarding demographic characteristics, smoking status and consumption of iodine status were collected using in-person interviews based on a self-designed structured questionnaire. Serum concentrations of TSH, TPOAb and TgAb were measured using electrochemiluminescence immunoassays. Univariate analysis and multivariate linear stepwise regression analyses were used to analyze the data. RESULTS: The regular smokers had lower concentrations of TSH, TPOAb and TgAb than occasional smokers, former smokers and never smokers. Multivariate analysis demonstrated that regular smoking was associated with the decreased concentrations of TSH (ß = -0.178), TPOAb (ß = -0.287) and TGAb (ß = -0.453) after adjusting other factors. Furthermore, daily smoking number was significantly associated with the decreased level of TSH (ß = -0.045) and TPOAb(ß = -0.080), and smoking duration was associated with the decreased TSH level (ß = -0.030). CONCLUSIONS: Our findings suggest that cigarette smoking is related to a significant decline in the concentrations of TSH, TPOAb and TgAb. In addition, daily smoking number and long-term smoking decrease serum TSH and TPOAb levels. Cigarette smoking plays a significant role in the development of thyroid dysfunction.

2.
Soft Matter ; 15(45): 9224-9232, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31647491

RESUMO

The development of polymer sponges with large adsorption capacity, high oil/water selectivity and mechanical stability is an effective strategy for the separation of oil from oil-polluted water. The improvement in the adsorption performance for polymer sponges should not be accompanied by the sacrifice of mechanical properties and recycling stability, which are fundamental to their long-term operation in the cleanup of oil-spill accidents. In this work, we synthesized a robust and reusable sponge based on a poly(dimethylsiloxane) (PDMS) frame coated stereoscopically with graphene oxide (GO) via the amidation between PDMS and GO. The combination of the PDMS skeleton with the robust macroporous structure and GO nanosheets acting as mechanical fortifiers contributes to the nanocomposite sponge with great integrity and durability. The resultant PDMS/GO nanocomposite sponge exhibited a high compressive strength of 42.7 kPa with a strain of 60% after 50 cycles. The high adsorption capacity for various oils and organic solvents was obtained in the nanocomposite sponge, and the maximum capacity of 14.6 g g-1 was achieved for chloroform, which is ascribed to the large porosity and hydrophobicity caused by the rough PDMS skeleton covered by the GO nanosheets. Furthermore, a vacuum device with the nanocomposite sponge demonstrated effective separation for a large amount of oil/water mixture, with the maximum separation of 724 times the sponge weight during adsorption. This work provides a productive approach to develop porous polymer nanocomposites with high absorption properties and mechanical cycling stability and paves the path for the application of polymer sponges in oil pollution.

3.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365039

RESUMO

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

4.
J Diabetes ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31222955

RESUMO

BACKGROUND: Because there has been no quality improvement initiatives targeting patients with type 2 diabetes (T2D) receiving basal insulin therapy, this study evaluated the effectiveness of physician-targeted education for optimizing glycemic management in these patients in China. METHODS: This multicenter open-label observational study conducted across China had a baseline sample survey, followed by a 6-month education program, and ended with a post-education sample survey. Education based on T2D treatment guidelines was given at Months 1 and 3, and was reinforced by self-audit every month. Each hospital enrolled 100 patients with T2D receiving basal insulin at both the baseline and post-education survey. The primary outcome was the proportion of hospitals meeting individual improvement goals. The goal setting was based on the proportion of patients achieving HbA1c <7.0% in each hospital at the time of the baseline survey. RESULTS: Overall, the individual improvement goal was achieved by 35 centers (49%). Hospitals with poor glycemic management at the baseline survey had higher possibility to improve at post-education survey. Two large sample surveys at baseline and post-education showed improved glucose management among these hospitals. A higher proportion of patients achieved HbA1c <7.0% in the post-education survey (27.2% vs 36.5%; P < 0.001) with reduced HbA1c levels (8.10% vs 7.72%; P < 0.001). Questionnaires from 723 physicians showed that confidence and practice of basal insulin use were significantly improved. CONCLUSIONS: Physician-targeted education improved glycemic management of patients with T2D in 71 hospitals in China, and was more effective at hospitals with poor glycemic management at the baseline survey.

5.
Diabetes Care ; 42(8): 1539-1548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152120

RESUMO

OBJECTIVE: Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association's 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA1c with the outcomes. RESEARCH DESIGN AND METHODS: Baseline medical history, FPG, 2h-PG, and HbA1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011-2012. A follow-up visit was conducted during 2014-2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality. RESULTS: We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100-125 mg/dL, 2h-PG of 140-199 mg/dL, or HbA1c of 5.7-6.4% (39-47 mmol/mol) were 1.60 (1.43-1.79), 2.72 (2.43-3.04), and 1.49 (1.36-1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA1c ≥6.5% (48 mmol/mol) were 1.18 (1.05-1.33), 1.31 (1.18-1.45), and 1.20 (1.07-1.34) for CVD; 1.10 (0.92-1.32), 1.44 (1.25-1.67), and 1.08 (0.92-1.28) for cancer; and 1.37 (1.20-1.57), 1.57 (1.41-1.76), and 1.33 (1.17-1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality. CONCLUSIONS: 2h-PG remains independently predictive of outcomes in models including FPG and HbA1c. Therefore, in addition to FPG and HbA1c, routine testing of 2h-PG should be considered in order to better assess the risks of outcomes.

6.
J Diabetes ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170331

RESUMO

BACKGROUND: This study investigated the association between birth weight and diabetes in a Chinese population, and the effects of body mass index (BMI) and lifestyle factors in later life on this association. METHODS: Data from 49 118 participants aged ≥40 years with recalled birth weight from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, a nationwide population-based cohort, were used. Diabetes diagnosis was based on oral glucose tolerance tests and HbA1c measurements. Logistic regression models were used to evaluate the association of birth weight and risk of diabetes in later life. RESULTS: Increased risk of diabetes was associated with lower or higher birth weight. Compared with individuals with a birth weight of 2500 to 3499 g, the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes for individuals with a birth weight of <2500, between 3500 and 3999, and ≥4000 g were 1.28 (1.11-1.47), 1.11 (1.04-1.19), and 1.20 (1.07-1.34), respectively. Significant associations were prominent in participants with a current BMI ≥24 kg/m2 , but not detected in those with a normal BMI (OR 1.20 [95% CI 0.96-1.49], 1.11 [95% CI 0.98-1.25], and 1.10 [95% CI 0.89-1.37], respectively). Moreover, there was no increased risk of diabetes in individuals with a low birth weight but with healthy dietary habits (OR 0.94; 95% CI 0.68-1.29) or ideal physical activity (OR 1.41; 95% CI 0.97-2.04). CONCLUSIONS: A U-shaped association was observed between birth weight and the risk of diabetes. Healthy lifestyles (healthy dietary habits or ideal physical activity) may eliminate the negative effects of low birth weight in the development of diabetes, but not the effect of high birth weight.

7.
J Exp Med ; 216(5): 1182-1198, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-30940720

RESUMO

Subclinical hypothyroidism is associated with cardiovascular diseases, yet the underlying mechanism remains largely unknown. Herein, in a common population (n = 1,103), TSH level was found to be independently correlated with both carotid plaque prevalence and intima-media thickness. Consistently, TSH receptor ablation in ApoE -/- mice attenuated atherogenesis, accompanied by decreased vascular inflammation and macrophage burden in atherosclerotic plaques. These results were also observed in myeloid-specific Tshr-deficient ApoE -/- mice, which indicated macrophages to be a critical target of the proinflammatory and atherogenic effects of TSH. In vitro experiments further revealed that TSH activated MAPKs (ERK1/2, p38α, and JNK) and IκB/p65 pathways in macrophages and increased inflammatory cytokine production and their recruitment of monocytes. Thus, the present study has elucidated the new mechanisms by which TSH, as an independent risk factor of atherosclerosis, aggravates vascular inflammation and contributes to atherogenesis.

8.
J Diabetes Res ; 2019: 4328975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949514

RESUMO

Aim: It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes. Methods: A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis. Results: The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10-1.52; P = 0.002) or 1.12- (95% CI 1.01-1.27; P = 0.039) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively. Conclusion: Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Obesidade/complicações , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Glicemia/metabolismo , Índice de Massa Corporal , China/epidemiologia , Feminino , Seguimentos , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose , Humanos , Hiperglicemia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Triglicerídeos/sangue
9.
Mol Genet Genomic Med ; 7(6): e671, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968594

RESUMO

BACKGROUND: Steroid 21-hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype-phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. METHODS: Mutation analysis of CYP21A2 gene, 21-hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype-phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. RESULTS: Among the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt-wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459-P464del) were detected and induced a significantly reduced 21-hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%). CONCLUSION: Four novel mutations were identified and a high consistency of genotype-phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease.

10.
J Cell Mol Med ; 23(5): 3140-3150, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30884106

RESUMO

Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16-week feeding period, serum testosterone levels were reduced in a time-dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), were down-regulated. Notably, the HC-fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up-regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)-related unfolded protein response pathway. Further analysis showed that when 4-phenyl butyric acid (4-PBA) was used to block ER stress in HC-fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down-regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.

11.
Medicine (Baltimore) ; 98(11): e14896, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882706

RESUMO

How nonalcoholic fatty liver disease (NAFLD) is linked to atherosclerosis is still disputed. This study aimed to explore the association between NAFLD and atherosclerosis among adults in Shandong province, China.A total of 6849 individuals were enrolled in the final analyses for a community-based study. The relationship between NAFLD and atherosclerosis was evaluated after adjusting for common confounding factors.Hypertension, diabetes, and higher serum low-density lipoprotein cholesterol (LDL-c) level were positively correlated with NAFLD. An odds ratio (OR) (95% confidence interval [CI]) of 1.325 (range 1.157-1.518) for hypertension, 2.153 (range 1.814-2.555) for diabetes, and 1.161 (range 1.071-1.259) for LDL-c was noticed. These factors also were positively correlated with atherosclerosis, with an OR (95% CI) of 1.501 (range 1.286-1.751) for hypertension, 1.716 (range 1.414-2.084) for diabetes, and 1.344 (range 1.231-1.466) for LDL-c. The prevalence of metabolic syndrome was higher in the atherosclerosis+NAFLD group (81.8%) when compared with the NAFLD-only (30.3%), atherosclerosis-only (32.2%), and control (20.3%) groups (P <.01).NAFLD and atherosclerosis have common metabolic characteristics, such as hypertension, diabetes, and higher serum LDL-c level. Patients with NAFLD in combination with atherosclerosis were found to have a more severe metabolic burden and greater chances of having hypertension, diabetes, dyslipidemia, and higher metabolic syndrome scores than those in the other groups.


Assuntos
Aterosclerose/metabolismo , Metabolismo/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Idoso , Aterosclerose/epidemiologia , Aterosclerose/etiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/classificação , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Razão de Chances , Prevalência , Fatores de Risco
12.
Endocr Pract ; 25(5): 454-460, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30720350

RESUMO

Objective: Epidemiologic studies on the relationship between iodine and thyroid antibodies are inconsistent. Iodine nutrition, genetic, and environmental factors have been shown to modify the effects of iodine on thyroid autoimmunity. We investigated the relationship between urinary iodine concentration (UIC) and thyroglobulin antibodies (TgAbs) in individuals living in iodine-sufficient areas in this cross-sectional study. Methods: A total of 15,008 participants were recruited according to the age range of the population of China in our study. An oral questionnaire was administered to collect basic demographic information. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAbs), TgAbs, and UIC were measured, and thyroid ultrasonography was performed in all subjects. Participants were further divided according to the level of UIC and the status of TgAb, and logistic regression was applied to determine the relationship between UIC and TgAbs. Results: The median UIC of the study population was 205.23 (95% confidence interval [CI], 65.7 to 537.67) µg/L. A total of 17.6% of participants had UIC <100 µg/L. With the increase in UIC, the prevalence of positive TgAbs decreased gradually. UIC level was lowest in subjects with high TgAb titer (median, 182.36 µg/L; 95% CI, 52.88 µg/L to 506.71 µg/L) and highest in the TgAb-negative group (median, 207.16 µg/L; 95% CI, 66.94 µg/L to 538.72 µg/L). Multilinear correlation analysis showed that gender (ß = 37.632; P<.001), age (ß = 0.467; P = .038), TSH (ß = 13.107; P<.001), TPOAb (ß = 1.150; P<.001), thyroid volume (ß = 2.883; P<.001), and UIC (ß = -0.047; P = .032) were independent predictors of TgAb variations. Low UIC (<100 µg/L) was associated with increased risk of positive TgAbs (adjusted odds ratio = 1.255 [1.004 to 1.568]). Conclusion: Low UIC is an independent risk factor for positive TgAb in individuals living in iodine-sufficient areas. Abbreviations: CI = confidence interval; CV = coefficient of variation; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odds ratio; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyrotropin; UIC = urinary iodine concentration; USI = universal salt iodization.


Assuntos
Tireoglobulina/imunologia , China , Estudos Transversais , Humanos , Iodo , Tireotropina , Tiroxina
13.
Am J Physiol Endocrinol Metab ; 316(3): E510-E518, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620634

RESUMO

Recent studies revealed the emerging role of excess uptake of lipids in the development of hypothyroidism. However, the underlying mechanism is largely unknown. We investigated the effect of high-fat diet (HFD) on thyroid function and the role of endoplasmic reticulum (ER) in HFD-induced hypothyroidism. Male Sprague-Dawley rats were fed with HFD or control diet for 18 wk. HFD rats showed an impaired thyroid function, with decreased thyroglobulin (Tg) level. We found the ER stress was triggered in HFD rat thyroid glands and palmitate-treated thyrocytes. Luminal swelling of ER in thyroid epithelial cells of HFD rats was also observed. The rate of Tg degradation increased in palmitate-treated thyrocytes. In addition, applying 4-phenyl butyric acid to alleviate ER stress in HFD rats improved the decrease of Tg and thyroid function. Withdrawal of the HFD improved thyroid function . In conclusion, we demonstrate that ER stress mediates the HFD-induced hypothyroidism, probably by impairing the production of Tg, and attenuation of ER stress improves thyroid function. Our study provides the understanding of how HFD induces hypothyroidism.

14.
Cell Res ; 29(2): 151-166, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30559440

RESUMO

Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease. The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH) levels become elevated at menopause. In this study, we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis. First, epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels, even after adjustment by considering the effects of serum estrogen. In addition, the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in pre-menopausal women. Furthermore, we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. Moreover, blocking FSH signaling by anti-FSHß antibody or ablating the FSH receptor (FSHR) gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding. Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/ß-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. This effect, in turn, results in the upregulation of SREBP-2, which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only.

15.
Biomed Pharmacother ; 109: 1112-1119, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551361

RESUMO

MicroRNAs (miRNAs) have recently been recognized to play an important role in bone-associated diseases. This study aims to explore the expression profile and biological function of miR-217, which is known to be related to tumor cell proliferation and migration, to the proliferation and osteogenic differentiation of MSCs from the patients with steroid-associated osteonecrosis (ONFH). Bone marrow was obtained from the proximal femur of 10 patients with ONFH and 10 patients with femoral neck fractures. Bone marrow-derived mesenchymal stem cells (MSCs) were isolated and cultured. The expression profile, biological function of miR-217 and the interaction between miR-217 and DKK1 were assayed using cell viability measurement, western blot, Real-time PCR, luciferase reporter assay, Alizarin Red S (ARS) staining. We noted that the expression level of miR-217 was significantly decreased in the ONFH samples compared to the control samples (P < 0.0001). By targeting DKK1, miR-217 promoted nuclear translocation of ß-catenin, increased expression of RUNX2, COL1A1 and obviously promoted the proliferation and differentiation of MSCs. Restoring the expression of DKK1 in the MSCs partially reversed the role of miR-217. These findings suggest that miR-217 promotes cell proliferation and osteogenic differentiation by inhibiting DKK1 during the development of steroid-associated osteonecrosis.


Assuntos
Medula Óssea/fisiologia , Diferenciação Celular/genética , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/genética , Osteogênese/genética , Idoso , Linhagem Celular , Sobrevivência Celular/genética , Colágeno Tipo I/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides/metabolismo , beta Catenina/genética
17.
Sci Rep ; 8(1): 17399, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30459349

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

18.
Thyroid ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30398407

RESUMO

Background Recent intervention studies have suggested selenium(Se) as an effective treatment in autoimmune thyroiditis (AIT). However, the exact mechanism is still unclear. The aim of the present study was to explore the effect of Se on thyroid peroxidase antibody (TPOAb) titers in patients with AIT and to analyze a potential impact of the genetic background on the effect of Se supplementation Methods Randomized, placebo-controlled, double-blind trial. 364 patients with elevated TPOAb (>300 IU/mL) were recruited and randomized to receive Se yeast 200 µg/day supplementation or placebo. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), TPOAb, Se, malondialdehyde (MDA), and serum glutathione peroxidase (GPX3) activity were measured at baseline and follow-up. 96 patients were genotyped for SNP r25191g/a. Results The median UIC was 182 µg/L. Serum Se increased significantly (p<0.001) after Se treatment. TPOAb titer decreased by 10.0% at 3 months and by 10.7% at 6 months after se supplementation while there was a moderate increase in TPOAb titer over the follow-up period in patients receiving placebo. GPX3 activity significantly increased (p<0.001), and MDA significantly decreased (p<0.001) after 6 months of Se supplementation. TPOAb titer decreased to different extents in patients with different genotypes of SNP r25191g/a after Se supplementation. Serum TPOAb titer in patients with the AA genotype had a more significant decrease (by 46.2%) than those with the GA and GG genotypes (by 14.5 and 9.8% respectively) at 3 months of Se supplementation (P=0.070). Conclusions Se supplementation significantly reduced TPOAb titer in patients with AIT, and there may be an important genetic component influencing interindividual differences in the decrease in TPOAb titer.

19.
Int J Endocrinol ; 2018: 4215848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30416522

RESUMO

Our previous studies suggested that the thyroid might be a target organ affected by lipotoxicity, which might be partially related to the increasing prevalence of subclinical hypothyroidism. However, the underlying molecular mechanism is not yet clearly established. This study aimed to assess the effect of palmitic acid stimulation on thyrocyte function. Upon palmitic acid stimulation, intracellular contents of lipids, as well as the expression and activity of three key molecules in thyroid hormone synthesis (i.e., thyroglobulin, sodium iodide symporter, and thyroperoxidase), were determined in human primary thyrocytes. The contents of BODIPY® FL C16 (the fluorescently labeled palmitic acid analogue) entering into the thyrocytes were gradually increased with time extending. Accordingly, the intracellular accumulation of both triglyceride and free fatty acids increased in dose- and time-dependent manners. The effect of palmitic acid stimulation on thyroid hormone synthesis was then determined. Both the mRNA and protein levels of thyroglobulin, sodium iodide symporter, and thyroperoxidase were decreased following palmitic acid stimulation. Consistently, upon palmitic acid stimulation, the secreted thyroglobulin levels in supernatants, 131I uptake, and extracellular thyroperoxidase activity were all decreased in a dose-dependent manner. Our results demonstrated that upon palmitic acid stimulation, the expressions of the key molecules (thyroglobulin, sodium iodide symporter, and thyroperoxidase) were reduced and their activities were suppressed, which might lead to impaired thyroid hormone synthesis.

20.
Hepatol Commun ; 2(11): 1356-1368, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30411082

RESUMO

Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re-induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined in situ hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell-specific markers in the livers of cholestatic mouse models and patients with cholestasis. H19RNA+ cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19)+ cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5-diethoxycarbony1-1,4-dihydrocollidine (DDC), and multidrug-resistant gene 2 knockout ( Mdr2 -/- ) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens. In contrast, double-positive H19RNA+/sex-determining region Y (SRY)-box 9 (SOX9)+ ductal progenitor cells, H19RNA+/hepatocyte nuclear factor 4α (HNF4α)+ hepatocytes, H19RNA+/F4/80+ Kupffer cells, HNF4α+/SOX9+ hybrid hepatocytes, as well as triple-positive H19 RNA+/HNF4α+/SOX9+ periportal hepatocytes were identified. In addition, H19 RNA could not be detected in mesenchymal cell marker desmin+ cells. Furthermore, H19 RNA was predominately detected in cytoplasm with a small amount at the interspace with neighboring cells. Conclusion: H19RNA is localized in HNF4α+ periportal hepatocytes, SOX9+ ductal progenitor cells, and F4/80+ Kupffer cells but not in CK19+ cholangiocytes and desmin+ stellate cells in cholestatic livers.

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