Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oxid Med Cell Longev ; 2019: 9151067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583050

RESUMO

Background/Aims: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males. Methods: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence. Results: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs). Conclusion: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.

2.
J Cell Mol Med ; 23(10): 6859-6871, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373170

RESUMO

OBJECTIVE: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD. METHODS: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif-/- ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays. RESULTS: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif-/- mice with HFD. CONCLUSIONS: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.

3.
PLoS One ; 14(5): e0216151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048873

RESUMO

Type 2 diabetes [T2D] and thyroid dysfunction [TD] often co-occur, have overlapping pathologies, and their risk increases with age. Since 1995, universal salt iodization has been implemented in China to prevent disorders caused by iodine deficiency. However, after two decades of implementation of universal salt iodization, the prevalence of TD in elderly Chinese patients with T2D is not well described and may have been underestimated. We conducted a questionnaire-based survey across 24 endocrinology centers in China between December 2015 and July 2016. Demographic and clinical data from 1677 patients with T2D were obtained and analyzed to examine the prevalence of TD along with T2D in these patients. We assessed TD prevalence according to the four TD subtypes [subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism], TD history, gender, and age. The diagnosis rates were calculated for TD and also for the TD subtype. The number of patients reaching treatment goals for T2D [hemoglobin A1c <7%] and TD [normal free thyroxine and thyroid-stimulating hormone [TSH]] and the incidences of complications and comorbidities were recorded. Among the enrolled patients with T2D [N = 1677], TD was diagnosed in 23.79% [399/1677] out of which 61% (245/399) were previously diagnosed and 38.59% (154/399) were newly diagnosed cases. Subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism were reported in 4.89%, 9.3%, 1.13%, and 3.16% of the total population, respectively. Among patients previously diagnosed with TD, the incidence in women [166/795; 20.88%] was higher than in men [79/882; 8.96%]. The treatment goals for TD and T2D were attained in 39.6% [97/245] and 34.41% [577/1677] of the cases, respectively. Diabetic complications and comorbidities were reported in 99.7% of patients, with peripheral neuropathy being the most common [43.46%] followed by cataract [24.73%]. We had found that the incidences of dyslipidemia, elevated LDL levels, and osteoporosis were significantly higher in patients with TD than those without TD. TD is underdiagnosed in elderly Chinese patients with T2D.

4.
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
5.
Life Sci ; 228: 215-220, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002916

RESUMO

AIMS: Small-for-gestational-age (SGA) fetus is an important public health issue because of its high mortality and long-term effects on health. Maternal hyperuricemia is associated with diverse adverse pregnant outcomes and neonatal disturbance. We aimed to evaluate whether maternal hyper-uric acid (HUA) is associated with the risk of SGA fetus and to explore whether it can modify the association between maternal hyper-blood pressure (HBP) and SGA fetus. MATERIALS AND METHODS: We performed a population-based cross-section retrospective study, a total of 6715 pregnant females were recruited. Multiple logistic regression analysis was performed to identify risk factors significantly correlated with SGA fetus, and then studied the effect of maternal HUA on the association between maternal HBP and SGA fetus. KEY FINDINGS: We collected 537 SGA fetuses among 6715 pregnant females. Maternal HUA was an independent risk factor for SGA delivery (odds ratio (OR), 2.737; 95% confidence interval (CI), 2.110-3.551). A dose-response association between maternal uric acid and SGA delivery was found among normotensive and hypertensive group. Compared with those whose uric acid was lower than 270 µmo/L with normal-blood pressure (NBP), the risk for SGA delivery in those whose uric acid was higher than 370 µmo/L with stage 2 or 3 hypertension increased 12.695-fold. SIGNIFICANCE: Our results suggest that maternal HUA could increase the risk of neonatal SGA, and maternal HUA could be superimposed upon pre-existing maternal HBP and increase the risk for SGA fetus.


Assuntos
Hipertensão/complicações , Hiperuricemia/complicações , Recém-Nascido Pequeno para a Idade Gestacional , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Adulto , Pressão Sanguínea , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco
6.
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.

7.
Mol Med Rep ; 19(6): 4603-4612, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957178

RESUMO

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross­sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high­cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross­linking (beta­CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta­CTX and PINP and were negatively correlated with BMD and positively correlated with beta­CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro. Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol­induced osteoporosis in men.


Assuntos
Remodelação Óssea , Hipercolesterolemia/sangue , Osteoporose/sangue , Adulto , Animais , Biomarcadores/sangue , Reabsorção Óssea/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Estudos Transversais , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Sprague-Dawley
8.
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
9.
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.

10.
Metab Syndr Relat Disord ; 17(4): 217-222, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30741593

RESUMO

Background: Given its high incidence, thyroid nodule (TN) warrants public attention. Thyroid volume (TV) has also been associated with multiple factors, such as iodine deficiency and supply and body mass index. It is well known that metabolic syndrome (MetS) comprises many metabolic disturbances, with insulin resistance being its major component. Materials and Methods: The aim of this study was to investigate the relationship between TN and TV and MetS and its components in an iodine-adequate area in Asia. All participants were asked to complete a questionnaire. After excluding 938 individuals based on the exclusion criteria, we reviewed data from 927 of 1865 participants. Adopting MetS diagnostic criteria, we found 437 subjects to be MetS positive [MetS(+)] and 490 subjects to be MetS negative [MetS(-)], respectively. Multivariate linear regression was used to assess the relationship between TNs and MetS. Moreover, univariate binary logistic regression analyses were used to calculate odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the associations between different variables and TNs. Results: A total of 232 females and 205 males were MetS(+), as diagnosed using the International Diabetes Federation criteria. However, there were 330 females and 160 males in the group of MetS(-) individuals. The prevalence of TNs was 38.29% in the MetS(+) group and 17.79% in the MetS(-) group. After adjusting for systolic blood pressure, diastolic blood pressure, and gender, only high-density lipoprotein, waist circumference (WC), and age were related to TNs (OR = 0.45, 95% CI 0.27-0.75, P = 0.0023; OR = 1.04, 95% CI 1.02-1.06, P = 0.0036). The TV of all participants was 13.98 (11.24, 17.01) mL; 13.26 (10.62, 16.17) mL for females and 14.96 (11.83, 18.01) mL for males. It was found that only WC was related to TV, after controlling for sex and age (P = 0.02). Conclusions: The morbidity among TN patients in the MetS(+) group was higher than that among the MetS(-) group. High-density lipoprotein cholesterol emerged as a protective factor, and WC was a risk factor for TN. Moreover, TV was related to MetS, and WC was an independent risk factor for TV.

11.
Life Sci ; 220: 69-75, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30685450

RESUMO

OBJECTIVE: To explore the correlation of the viscus fat area (VFA) with the Framingham 10-year general cardiovascular disease risk in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 202 patients with T2DM were divided into two groups based on VFA (a VFA ≥ 100 cm2 group and a VFA < 100 cm2 group), or four groups based on sex and age (a middle-aged male group, an elderly male group, a middle-aged female group, and an elderly female group). The correlation between the Framingham 10-year general cardiovascular disease risk and body fat indexes was analyzed. RESULTS: Patients in the VFA ≥ 100 cm2 group had higher body fat indexes and Framingham Risk Scores (FRSs) and lower levels of high density lipoprotein-cholesterol (HDL-C) when compared to the VFA < 100 cm2 group (P < 0.05). Female patients had higher body fat mass (BFM) and body fat percentage (BFP) levels and a lower VFA when compared to male patients. The VFA was significantly higher in the elderly than in the middle-aged patients. The waist hip fat ratio (WHFR) was significantly higher in elderly females than in elderly males (P < 0.05). Elderly females had the highest FRS of all patients. Multiple stepwise regression analysis revealed the VFA as a contributor to the Framingham 10-year general cardiovascular disease risk after statistical correction for other multiple factors affecting cardiovascular disease risk. CONCLUSION: The VFA is an independent factor that contributes to the Framingham 10-year general cardiovascular disease risk in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Tecido Adiposo , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , HDL-Colesterol/análise , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/metabolismo , Gordura Intra-Abdominal/citologia , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fatores de Risco
12.
Med Sci Monit ; 25: 590-597, 2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30698163

RESUMO

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.


Assuntos
Desidroepiandrosterona/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Atorvastatina/uso terapêutico , China , Desidroepiandrosterona/análise , Desidroepiandrosterona/fisiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/sangue , Sinvastatina/uso terapêutico
13.
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.

14.
Oncol Lett ; 16(4): 4291-4296, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214563

RESUMO

The aim of the study was to investigate the expression of tumor suppressor gene p53 and MMP-9 in non-small cell lung cancer (NSCLC) before and after chemotherapy, and investigate its association with the effect of chemotherapy and prognosis. Fifty-eight elderly NSCLC patients comprised the observation group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of p53 and MMP-9 in lung cancer tissues before and after chemotherapy. Immunohistochemistry and western blot analysis were used to detect the expression of p53 and MMP-9 proteins in NSCLC tissue before and after chemotherapy. Terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) was used to detect apoptotic cells. The association between the effect of chemotherapy and the expression of p53 and MMP-9 in lung cancer tissues was analysed. RT-qPCR results showed that the expression of p53 and MMP-2 mRNA in the tumor tissue after chemotherapy was significantly lower than that in the tumor tissue before chemotherapy. Western blot analysis revealed that the expression of p53 and MMP-2 protein in the tumor tissue after chemotherapy was significantly decreased. The positive expression of p53 and MMP-2 in lung cancer tissues before chemotherapy was 76.25 and 71.25%, respectively, and were reduced to 27.50 and 23.75%, respectively, after chemotherapy. After chemotherapy, the positive rates of p53 and MMP-2 were significantly lower than those before chemotherapy. TUNEL results showed that the apoptosis index increased significantly after chemotherapy. Efficiency of chemotherapy in patients with a negative expression of p53 and MMP-2 in lung cancer before chemotherapy was significantly higher than that in patients with a positive p53 and MMP-2 expression. A significant difference was found in the expression levels of p53 and MMP-2 in lung cancer before and after chemotherapy. The findings of the present study indicate that the expression levels of p53 and MMP-2 can be used as a predictor of chemotherapy sensitivity.

15.
Gene ; 676: 73-78, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30201105

RESUMO

OBJECTIVE: The study aimed to ascertain the correlation between AKR1B1 polymorphism rs759853 and the risk of diabetic retinopathy (DR) through a meta-analysis. METHODS: Crude odds ratios (ORs) and the corresponding 95% confidence interval (95% CIs) were calculated to assess the association of AKR1B1 rs759853 polymorphism with DR risk. Stratification analyses were further conducted based on ethnicity, diabetes mellitus (DM) type, Hardy-Weinberg equilibrium (HWE) status, and genotyping method. Heterogeneity was detected by Q test. Sensitivity analysis was implemented to check the robustness of final results. Additionally, Begg's funnel plot and Egger's test were used to evaluate underlying publication bias. RESULTS: Our meta-analysis ultimately incorporated 21 eligible publications with 22 independent case-control studies. The overall results demonstrated that AKR1B1 rs759853 polymorphism had no association with DR risk under all genetic models. However, after subgroup analysis by DM type, the rs759853 polymorphism was a protective factor against the DR onset in patients with type 1 DM (TT vs. CC: OR = 0.33, 95% CI = 0.17-0.67; TT + CT vs. CC: OR = 0.49, 95% CI = 0.36-0.68; TT vs. CC + CT: OR = 0.48, 95% CI = 0.28-0.83; allele T vs. allele C: OR = 0.56, 95% CI = 0.44-0.72; CT vs. CC: OR = 0.52, 95% CI = 0.37-0.74). Furthermore, subgroup analysis by genotyping method suggested that rs759853 genotyped using MassARRAY assay was significantly correlated with decreased risk of DR under dominate model (TT + CT vs. CC: OR = 0.71, 95%CI = 0.52-0.96). CONCLUSION: AKR1B1 polymorphism rs759853 may inhibit the occurrence of DR in patients with type 1 DM.


Assuntos
Aldeído Redutase/genética , Retinopatia Diabética/genética , Aldeído Redutase/metabolismo , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
16.
J Diabetes Res ; 2018: 7198274, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30155489

RESUMO

The main aim of this study is to quantitatively describe the status of physical activity and evaluate its levels in a rural population and to investigate the association between the quantifiable physical activity and type 2 diabetes and metabolic syndrome. In total, 2076 participants aged over 40 years were included in a cross-sectional analysis. Physical activity status and the contributions of different types of activity were evaluated. The association between social behaviors and physical activities was analyzed. In addition, the impact of physical activities on type 2 diabetes mellitus and metabolic syndrome was also analyzed by logistic regression. Approximately half of the total activity in rural areas consisted of work-related activity (49.3%) followed by commuting (30.2%) and recreational activity (20.5%). In rural areas, the prevalence of physical activity levels was 28.6% for low levels, 47.3% for moderate levels, and 24.1% for high levels. Educational level showed a significant negative association with the physical activity level. Lower physical activity shows a strong and significant association with type 2 diabetes and metabolic syndrome. In conclusion, insufficient physical activity among rural people over 40 years old increases the risk of type 2 diabetes and metabolic syndrome. Population-wide and individualized guidelines for physical activities especially recreational physical activities should be developed.

17.
Horm Metab Res ; 50(9): 661-670, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30081425

RESUMO

Obesity is associated with decreased testosterone levels in males. Testosterone is synthesized by testosterone synthetic enzymes, which are stimulated by luteinizing hormone (LH). Testosterone can also be converted to estradiol via the aromatase. The objective of this study was to examine the factors related to testosterone synthesis and conversion, and to systematically evaluate the key processes that influence testosterone levels in male obesity. Three hundred and two male subjects (aged 25-45 years old) were divided according to BMI into normal weight (18.5-23.9 kg/m2), overweight (24-27.9 kg/m2), and obese (≥28 kg/m2) groups; or divided following WHR into non-abdominal obesity and abdominal obesity groups (WHR: ≥0.9). Male C57BL/6 mice were divided into normal diet (ND) and high-fat diet (HFD)-induced obesity group. Serum sex hormones and aromatase levels were measured using ELISAs. Testosterone synthetic enzymes in the testes were measured by qRT-PCR. The testosterone levels in obese men and abdominal obesity men were lower than normal men. In abdominal obesity men serum LH levels were decreased and associated with testosterone levels after multivariate regression analysis. Serum aromatase levels were increased in abdominal obesity males. In mice, compared to the ND group, the HFD group had decreased steroidogenic acute regulatory protein (StAR). However, aromatase levels in subcutaneous adipose tissue were higher in the ND group than HFD group. In conclusion, according to this study decreased testicular synthesis function and the conversion of testosterone may explain the reduction in testosterone levels in male obesity, and the decrease of testicular synthesis may change first.

18.
PLoS One ; 13(6): e0198343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29856828

RESUMO

Diabetes mellitus ranks high on the international health agenda as a global pandemic and as a threat to human health and global economies. A total of 10851 participants aged over 40 years were included in the cross-sectional analysis. This observational study analyzed the prevalence of diabetes mellitus and the awareness, treatment and glycemic control of diabetes in a rural Chinese population. Approximately 25% of middle-aged and elderly rural Chinese residents had diabetes in 2010-2011. The prevalence was higher with older age, dyslipidemia, higher body mass index and larger waist circumference. Among the subjects with diabetes, 40.3% were aware of their condition; 62.9% were receiving treatment, and 16.9% had controlled diabetes. Metformin was the majority oral antidiabetic drug treatment most often prescribed, for either monotherapy or combined therapy. These results indicate that diabetes has become an urgent public health problem in the Chinese rural population because of its high prevalence and low rates of awareness, treatment and control. The management and prevention of diabetes mellitus should be considered an essential strategy at the level of public health.

19.
Wien Klin Wochenschr ; 130(11-12): 390-397, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29845362

RESUMO

Nonalcoholic fatty liver disease (NAFLD) currently represents the most common hepatic disease worldwide and is closely linked to cardiovascular disease, obesity and diabetes mellitus. This study aimed to investigate NAFLD and its influence on different monocyte subpopulations to determine the presence of significant associations. A total of 3 monocyte subpopulations were investigated, i.e. classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). Of the participants 261 were included in this study (n = 53 with NAFLD, n = 208 controls). Ultrasonography was used to diagnose NAFLD and exclude other morphologic causes of liver diseases and other tests (including medical history inquiries and detection of hepatitis virus) were performed to exclude other causes of parenchymal liver disease. Classical inflammatory and metabolic-related NAFLD biomarkers were also determined. In contrast to the healthy control group, the intermediate monocyte fraction was increased in NAFLD patients (p = 0.032), while the classical monocyte fraction was decreased (p = 0.025). Intermediate monocyte fraction, body mass index (BMI) and tumor necrosis factor alpha (TNF-α) were independent risk factors for NAFLD. Classical, non-classical and intermediate monocytes fraction were strongly associated with age, triglyceride, and waist circumference. This study suggests that the intermediate monocyte fraction in peripheral blood is likely related to the aggravation of NAFLD.

20.
Lipids Health Dis ; 17(1): 78, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29642923

RESUMO

BACKGROUND: Macrosomia is a serious public health problem worldwide due to its increasing prevalence and adverse influences on maternal and neonatal outcomes. Maternal dyslipidemia exerts potential and adverse impacts on pregnant women and newborns. However, the association between maternal serum lipids and the risk of macrosomia has not yet been clearly elucidated. We explored the association between the maternal lipids profile at late gestation and the risk of having macrosomia among women without diabetes mellitus (DM). METHODS: The medical records of 5407 pregnant women giving birth to single live babies at term were retrospectively analyzed. Subjects with DM, hypertension, thyroid disorders and fetal malformation were excluded. Maternal fasting serum lipids were measured during late pregnancy. Logistic regression analysis was used to analyze the variables associated with the risk of macrosomia. RESULTS: Maternal serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were related to macrosomia; each 1 mmol/L increase in TG resulted in a 27% increase in macrosomia risk, while each 1 mmol/L increase in HDL-C level resulted in a 37% decrease in macrosomia risk, even after adjusting for potential confounders. Notably, the risk of macrosomia increased progressively with increased maternal serum TG levels and decreased HDL-C levels. Compared with women with serum TG levels < 2.5 mmol/L, women with TG levels greater than 3.92 mmol/L had an approximately 2.8-fold increased risk of macrosomia. Compared with women with serum HDL-C levels above 2.23 mmol/L, women with HDL-C levels of less than 1.62 mmol/L had a 1.9-fold increased risk of giving birth to an infan with macrosomia. In addition, a higher risk of macrosomia was observed in women with simultaneous hypertriglyceridemia and low serum HDL-C levels (odds ratio [OR] 2.400, 95% confidence interval [CI]: 1.760-3.274) compared to those with hypertriglyceridemia or low serum HDL-C alone (OR 2.074, 95% CI: 1.609-2.673 and OR 1.363, 95% CI: 1.028-1.809, respectively). CONCLUSIONS: Maternal serum TG levels and HDL-C levels at late gestation are independent predictors of macrosomia in women without DM.


Assuntos
Diabetes Gestacional/sangue , Macrossomia Fetal/sangue , Lipídeos/sangue , Adulto , Peso ao Nascer , HDL-Colesterol/sangue , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Análise Multivariada , Gravidez , Fatores de Risco , Triglicerídeos/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA