Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 81
Filtrar
1.
J Cell Physiol ; 235(2): 1001-1012, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31240707

RESUMO

Emerging evidence has indicated that long noncoding RNA (lncRNAs) play crucial roles in regulating thyroid cancer (TC) development. Linc00210 is a newly identified lncRNA which plays an oncogenic role in hepatocellular carcinoma and nasopharyngeal carcinoma, but whether Linc00210 can modulate the development of TC remains elusive. Here, we found that Linc00210 expression was upregulated in TC tissues compared to the matched noncancerous tissues. Overexpression of Linc00210 augmented the proliferation, migration, and invasion of TC cells. Mechanistically, Linc00210 served as a sponge for miR-195-5p, thereby counteracting its ability in downregulating the expression of IGF1R and the activation of PI3K/Akt signaling. Moreover, inhibition of Linc00210 suppressed the growth of TC cells in nude mice. Our findings for the first time uncovered the oncogenic property of Linc00210 in TC.

2.
Mol Genet Genomic Med ; : e1020, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663297

RESUMO

INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) is essential in mediating folate metabolism, and thus plays an important role in diabetes and diabetic complications. MTHFR C677T (rs1801133 C>T) polymorphism has been proposed to be linked with type 2 diabetes mellitus (T2DM) susceptibility. However, the conclusions are inconsistent. Therefore, we rechecked their linkage aiming to obtain a more reliable estimation by performing an updated meta-analysis. METHODS: We searched electronic databases PubMed, EMBASE, CNKI, and Wanfang to obtain studies updated to October 2019. RESULTS: After carefully screening, we finally incorporated 68 studies with 10,812 cases and 8,745 controls. The genotype frequency of C677T polymorphism was analyzed pooled to generate odds ratios (ORs) and 95% confidence intervals (CIs). Pooled results presented that MTHFR C677T polymorphism was significantly associated with T2DM under homozygous (OR = 1.64, 95% CI = 1.39-1.94), heterozygous (OR = 1.38, 95% CI = 1.20-1.59), recessive (OR = 1.41, 95% CI = 1.23-1.61), dominant (OR = 1.47, 95% CI = 1.27-1.70), and allele (OR = 1.37, 95% CI = 1.23-1.52) genetic models. Stratified analysis demonstrated that C677T genotype was associated with T2DM in Asian populations, but not Caucasian and African populations. CONCLUSION: Our results indicated that MTHFR C677T polymorphism confers to T2DM, especially in Asian populations. Much more large-scale case-control studies are needed to strengthen such conclusion in the future.

3.
EBioMedicine ; 48: 491-504, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629675

RESUMO

BACKGROUND: Tubulointerstitial fibrosis (TIF) plays an important role in the progression of diabetic kidney disease (DKD). Forkhead box O1 (FoxO1) is involved in the regulation of metabolism and cell apoptosis, but its function in renal TIF induced by DKD is less well understood. METHODS: Human kidney biopsies with DKD and normal controls were used to detect apoptosis and TIF induced by diabetes. A mouse model with kidney-specific overexpression of Pax2-3aFoxO1 was established to further investigate the functions of FoxO1 in vivo. The in vitro roles of FoxO1 were analyzed in HK-2 cells with 3aFoxO1-knockin (3aFoxO1-KI) or FoxO1-knockdown (FoxO1-KD) via CRISPR/Cas9. Western blot, immunohistochemistry, and chromatin immunoprecipitation were used to explore the underlying mechanisms. FINDINGS: In this study, DKD patients had increased renal TIF and apoptosis. In vivo study showed that kidney-specific overexpression of Pax2-3aFoxO1 significantly reduced the expression of p-STAT1 with resultant renal functional impairment, retarding renal TIF and apoptosis in diabetic mice. Meanwhile, We observed that FoxO1-KD in HK-2 cells aggravated the expression of p-STAT1, leading to activation of epithelial-to-mesenchymal transition (EMT) and intrinsic apoptotic pathway. Conversely, EMT and apoptosis were significantly attenuated in HK-2 cells with 3aFoxO1-KI under hyperglycemic conditions. INTERPRETATION: Taken together, these data suggest that the protection role of FoxO1 against renal TIF and apoptosis in DKD is likely in part to target STAT1 signaling, which may be a promising strategy for long-term treatment of DKD. FUND: This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 81570746 and 81770812).

4.
Anal Cell Pathol (Amst) ; 2019: 7405602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428552

RESUMO

Aims: Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods: To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results: Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions: Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.

5.
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.

6.
PLoS One ; 14(8): e0214776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469836

RESUMO

BACKGROUND: Sleep duration affects health in various ways. The objective of the present study was to investigate the relationships among sleep duration, daytime napping and kidney function in a middle-aged apparently healthy Chinese population. METHODS: According to self-reported total sleep and daytime napping durations, 33,850 participants who were 38-90 years old and recruited from eight regional centers were divided into subgroups. Height, weight, waist circumference, hip circumference, blood pressure, biochemical indexes, fasting blood glucose (FBG), postprandial blood glucose (PBG), HbA1c, creatinine and urinary albumin-creatinine ratio (UACR) were measured and recorded for each subject. Microalbuminuria was defined as UACR ≥30 mg/g, chronic kidney disease (CKD) was defined as eGFR <60 ml/min, and hyperfiltration was defined as eGFR ≥135 ml/min. Multiple logistic regression was applied to investigate the association between sleep and kidney function. RESULTS: Compared to sleeping for 7-8 h/day, the ORs for microalbuminuria for sleeping for >9 h/day, 8-9 h/day 6-7 h/day and <6 h/day were 1.343 (1.228-1.470, P<0.001), 1.223 (1.134-1.320, P<0.001), 1.130 (1.003-1.273, P = 0.045) and 1.140 (0.908-1.431, P = 0.259), respectively. The eGFR levels exhibited a U-shaped association with sleep duration among subjects with an eGFR ≥90 ml/min and an N-shaped association with sleep duration among subjects with an eGFR <90 ml/min. The OR for hyperfiltration for >9 h/day of sleep was 1.400 (1.123-1.745, P = 0.003) among participants with an eGFR ≥90 ml/min. Daytime napping had a negative effect on renal health. Compared to the absence of a napping habit, the ORs for microalbuminuria for 0-1 h/day, 1-1.5 h/day and >1.5 h/day of daytime napping were 1.552 (1.444-1.668, P<0.001), 1.301 (1.135-1.491, P<0.001) and 1.567 (1.353-1.814, P<0.001), respectively. CONCLUSION: The association of total sleep duration with renal health outcomes is U-shaped. Daytime napping has a negative effect on renal health.

7.
J Diabetes Res ; 2019: 7894950, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281852

RESUMO

Objective: In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods: Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 µg/kg/day), high (0.1 µg/kg/day), and high (0.1 µg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 µg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results: Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions: The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

8.
Genet Test Mol Biomarkers ; 23(6): 387-392, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31161820

RESUMO

Background: Diabetic peripheral neuropathy (DPN) affects nearly 50% of the diabetic population. Advanced glycation end products, measured through skin autofluorescence (SAF), play an important role in the diagnosis and prevention of DPN. To date, however, no relevant study has discussed the relationship between SAF and the Chinese population. Objective: We conducted this study to evaluate the association between DPN and SAF among the Chinese population. Methods: In this cross-sectional study, we recruited a total of 820 patients with type 2 diabetes. All of the patients underwent SAF measurements and a nerve conduction study (NCS). Post-SAF characterization, the patients were divided into three groups according to the first and third quartiles of their SAF values (AU) (SAF ≤ 2.2; 2.2 < SAF ≤ 2.7; SAF > 2.7). Based on the results of the NCS, patients were divided into two groups: DPN and non-DPN. Results: When compared with the non-DPN group (n = 275) with the DNP group. The latter had higher SAF values (2.72 ± 0.55 AU vs. 2.17 ± 0.71 AU, P < 0.01). There were significant differences in age, the percentage of DPN, and NCS parameters, including motor nerve conduction velocity, sensory nerve conduction velocity, distal latency, and sensory nerve action potential among the three SAF groups (p < 0.05). The SAF value was positively associated with DPN (r = 0.11, p < 0.01). After adjusting for all potential confounders, the SAF values were still associated with an increased risk of DPN (odds ratio 5.15; 95% confidence interval [1.48-4.53]) (p < 0.01). A receiver operating characteristic analysis indicated that an SAF value >2.57 ng/mL predicts a threefold increased risk of DPN (p < 0.01). Conclusions: SAF is an independent risk factor for DPN, which might be of potential value for screening DPN in Chinese patients with type 2 diabetes.


Assuntos
Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Pele/diagnóstico por imagem , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Imagem Óptica/métodos , Curva ROC , Fatores de Risco , Pele/metabolismo
9.
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.

10.
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.

11.
J Cell Physiol ; 234(12): 22071-22081, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31152442

RESUMO

Epithelial ovarian cancer is one of the leading causes of cancer-related death worldwide. Growing evidence indicates that multiple complex altered pathways play important regulatory roles in the development and progression of a variety of cancers, including epithelial ovarian cancer. However, the underlying mechanisms remain unclear. First, we identified differentially expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in epithelial ovarian cancer by comparing the expression profiles between epithelial ovarian cancer samples and normal tissue samples in different GEO datasets. Then, GO- and KEGG-pathway-enrichment analyses were applied to investigate the primary functions of the overlapped differentially expressed mRNAs. Moreover, the primary enriched genes were used to construct the signal-network with Cytoscape software. In addition, we integrated the relationship among lncRNAs-miRNAs-mRNAs to create a competing endogenous RNA network. Finally, mRNAs that were associated with patient prognosis in epithelial ovarian cancer were selected using univariate Cox regression analysis. A total of 2,225 mRNAs, 336 lncRNAs, and 14 miRNAs were shown to be differentially expressed in epithelial ovarian cancer compared with normal tissues. The dysregulated mRNAs were primarily enriched in cell division and signal transduction, according to Gene Ontology, whereas, according to KEGG, they were primarily enriched in metabolic pathways and pathways in cancer. A total of 10 mRNAs were associated with patient prognosis in ovarian cancer. This study identifies a novel lncRNA-miRNA-mRNA network, which may suggest potential molecular mechanisms underlying the development of epithelial ovarian cancer, providing new insights for survival prediction and interventional strategies for epithelial ovarian cancer.

12.
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.

13.
Cardiovasc Diabetol ; 18(1): 57, 2019 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054570

RESUMO

BACKGROUND: Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. METHODS: The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the < 25% group, the 25-49% group, the 50-74% group, and the ≥ 75% group according to the quartile division of the centre where the subjects visited. The lipid classes were defined according to the guidelines for the prevention and treatment of dyslipidaemia in Chinese adults. Multiple logistic regression analysis was used to evaluate the association of the lipid parameters and UACR. RESULTS: Multivariable regression analysis revealed that compared with the other lipid parameters, triglycerides (TG) showed an adjusted odds ratio that was significant in model 1-4. This relationship was attenuated after adjusting for Haemoglobin A1c (HbA1c) and blood pressure (BP), but TG ≥ 2.3 mmol/L was still significantly associated with UACR in total subjects and in both men and women (OR: 1.131, 95% CI 1.065-1.203, P < 0.001 in total subjects; OR: 1.134, 95% CI 1.022-1.258, P = 0.017 in men; OR: 1.129, 95% CI 1.046-1.219, P = 0.002 in women). In the stratified analysis, elevated TG was significantly associated with increased urinary albumin in subjects with eGFR ≥ 90 mL/min per 1.73 m2, 5.6 ≤ FBG < 7.0 or 7.8 ≤ PBG < 11.1 mmol/L, 24 ≤ BMI < 28 kg/m2, 120 ≤ SBP < 140 and/or 80 ≤ DBP < 90 mmHg. CONCLUSIONS: We conclude that high TG levels rather than total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol levels are associated with UACR in the general population in China.

14.
J Cell Physiol ; 234(12): 22260-22271, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31081124

RESUMO

To better understand the molecular mechanisms of anaplastic thyroid carcinoma (ATC), we aimed to identify the hub genes specifically involved in ATC by integrated bioinformatics analysis. In this study, using three Gene Expression Omnibus data sets with the same platform GPL570, we screened hub genes involved in ATC progression. In vitro experiments, such as western blot analysis, Transwell assays, and coimmunoprecipitation, was performed to verify our findings. By comparing three subtypes of thyroid cancer with normal tissue, we found ATC harbored more changed genes than well and poorly differentiated thyroid cancer. Using specifically differentially expressed genes between ATC and normal thyroid tissues to perform Gene ontology (GO) analysis, ATC showed enrichments of GO terms involved in lymphocyte migration and activation, collagen catabolic and metabolic process, thyroid hormone synthesis, and embolism. Using genes involved in extracellular matrix, coexpression network analysis and protein-protein interaction analysis were performed to identify matrix metalloproteinase 3 (MMP3) and MMP13 as two hub genes. Our experimental data indicated that both MMP3 and MMP13 were upregulated in ATC and knockdown of either of them could notably suppress ATC cell invasion and migration. Mechanistically, Gene Set Enrichment Analysis, coimmunoprecipitation, and rescue experiments revealed MMP3 and MMP13 not only interacted with each other, but also regulated each other through the janus kinase/signal transducer and activator of transcription 3 and mammalian target of rapamycin pathways. In conclusion, we identified a specific molecular mechanisms for the development of ATC by integrated analysis of transcriptome and in vitro experiments, which suggested that MMP3 and MMP13 might be developed as novel therapeutic targets for ATC.

15.
Oxid Med Cell Longev ; 2019: 3286928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30962862

RESUMO

Objective: The generation of hyperglycemia-induced reactive oxygen species (ROS) is a key event in diabetic nephropathy (DN) development. Since forkhead box class O1 (FOXO1) is associated with oxidative stress and shows a positive effect on DN, its role on renal function and the underlying mechanism is still unclear. Methods: We examined the role of FOXO1 in vivo (in a transgenic diabetic mouse model overexpressing Foxo1) and in vitro (in human HK-2 cells with FOXO1 knockin (KI) and knockout (KO) cultured under high glucose). Results: Renal proximal tubular cells of kidney biopsies from patients with DN showed tubulointerstitial fibrosis and apoptosis. Accordingly, these proximal tubular injuries were accompanied by the increase of ROS generation in diabetic mice. Tissue-specific Foxo1 overexpression in transgenic mice had a protective effect on the renal function and partially reversed tubular injuries by attenuating the diabetes-induced increase in TXNIP and decrease in the TRX levels. FOXO1 knockin and knockout HK-2 cells were constructed to identify the associations between FoxO1 and TXNIP-TRX using CRISPR/CAS9. Similarly, the effects of FOXO1 KI and KO under high glucose were significantly modulated by the treatment of TRX inhibitor PX-12 and TXNIP small interfering RNA. In addition, TXNIP and TXN were identified as the direct FOXO1 transcriptional targets by chromatin immunoprecipitation. Conclusion: The regulatory role of FOXO1/TXNIP-TRX activation in DN can protect against the high glucose-induced renal proximal tubular cell injury by attenuating cellular ROS production. Modulating the FOXO1/TXNIP-TRX pathway may be a new therapeutic target in DN.


Assuntos
Proteínas de Transporte/genética , Nefropatias Diabéticas/metabolismo , Fibrose/tratamento farmacológico , Proteína Forkhead Box O1/genética , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/genética , Animais , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais
16.
Biochimie ; 162: 229-238, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30954547

RESUMO

Lipopolysaccharide (LPS) as a component of the outer structure of cell wall of gram-negative bacteria, could induce apoptosis in the intestinal endocrine cell line STC-1. However, the signaling cascades involved in this process have not been elucidated. Hence, we investigated the mechanism of cell apoptosis and hyposecretion of glucagon-like peptide 1 (GLP-1) induced by LPS in the GLUTag enteroendocrine cell line. LPS decreased the cell viability of GLUTag cells, up-regulated the TNF-α level, induced the apoptosis and down-regulated the mRNA and protein levels of GLP-1. In addition, TNF-α promoted LPS-induced apoptosis of GLUTag cells through mediating the formation of the RIP1/RIP3 necrosome. RIP1 and RIP3 knockdown increased cell viability, the mRNA and protein levels of GLP-1 and the mTOR signaling pathway-related proteins (p-mTOR and p-S6), and decreased the relative caspase 3/7 activity, cell apoptosis and ROS production. Further studies showed that ROS inhibited the mTOR signaling pathway. Moreover, the antioxidant N-acetyl-l-cysteine increased cell viability, GLP-1 expressions and the mTOR signaling pathway-related proteins, and inhibited the ROS production. However, the mTOR specific inhibitor (Rapa) reversed all these above effects. Taken together, our result revealed that LPS induced the apoptosis of GLUTag cells and GLP-1 hyposecretion through the RIP/ROS/mTOR pathway.

17.
J Diabetes Res ; 2019: 5874603, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019977

RESUMO

Background: Physical activity is effective in preventing chronic diseases. However, the impact of different durations of exercise on human health is unknown, especially among people with diabetes or prediabetes. Objective: To explore the relationship between high MET hours per week and the change in glomerular filtration rate (eGFR) in the total population and different subgroups. Methods: A total of 43767 individuals from eight provinces, in China, were recruited. Logistic analysis was used to investigate the association. Participants were divided into 3 groups based on MET hours per week. The primary outcome was an eGFR ≤ 90 mL/min/1.73 m2. Results: The average eGFR was 100.10 (92.43-106.43) mL/min/1.732. Logistic regression analysis revealed that more than 7.5 MET hours per week (equivalent to more than 150 minutes of moderate-intensity of exercise) was associated with the higher risk of the decreased eGFR even after adjusting for confounding factors (7.5 to <21: OR = 1.18, 95% CI [1.09, 1.29]; ≥21: OR = 1.12, 95% CI [1.05, 1.19], p for trend: 0.0047). After adjusting for confounding factors, in stratified analyses, there still existed a significant relationship among participants aged from 55 to less than 65 years, but not among participants younger than 55 or older than 65 years. Similarly, there existed a positive association between high MET hours per week and the decreased eGFR in participants without diabetes and prediabetes, but not in participants with diabetes or prediabetes, and the interactions of age and diabetic states were found. However, there was no significant difference in women or men. Conclusions: More than 7.5 MET hours per week (equivalent to more than 150 minutes per week or 60 minutes per day of moderate-intensity exercise) was associated with decreased eGFR among participants aged from 55 to less than 65 years and participants without diabetes and prediabetes, but not among participants aged younger than 55 years and older than 65 years and participants with diabetes or prediabetes. The importance of planning individualized physical activities is highlighted.


Assuntos
Diabetes Mellitus/fisiopatologia , Exercício/fisiologia , Taxa de Filtração Glomerular/fisiologia , Estado Pré-Diabético/fisiopatologia , Adulto , Fatores Etários , Idoso , China , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
18.
Sci Rep ; 9(1): 5281, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30918291

RESUMO

Gastric cancer (GC) is the fourth most common malignant neoplasm and the second leading cause of cancer death. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression facilitates early GC diagnosis and the development of targeted therapies for advanced GC patients. Emerging evidence has revealed a close correlation between forkhead box (FOX) proteins and cancer development. However, the prognostic significance of forkhead box S1 (FOXS1) in patients with GC and the function of FOXS1 in GC progression remain undefined. In this study, we found that upregulation of FOXS1 was frequently detected in GC tissues and strongly correlated with an aggressive phenotype and poor prognosis. Functional assays confirmed that FOXS1 knockdown suppressed cell proliferation and colony numbers, with induction of cell arrest in the G0/G1 phase of the cell cycle, whereas forced expression of FOXS1 had the opposite effect. Additionally, forced expression of FOXS1 accelerated tumor growth in vivo and increased cell migration and invasion through promoting epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, the core promoter region of FOXS1 was identified at nucleotides -660~ +1, and NFKB1 indirectly bind the motif on FOXS1 promoters and inhibit FOXS1 expression. Gene set enrichment analysis revealed that the FOXS1 gene was most abundantly enriched in the hedgehog signaling pathway and that GLI1 expression was significantly correlated with FOXS1 expression in GC. GLI1 directly bound to the promoter motif of FOXS1 and significantly decreased FOXS1 expression. Finally, we found that miR-125a-5p repressed FOXS1 expression at the translational level by binding to the 3' untranslated region (UTR) of FOXS1. Together, these results suggest that FOXS1 can promote GC development and could be exploited as a diagnostic and prognostic biomarker for GC.

19.
Hepatology ; 70(4): 1099-1118, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30820969

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

20.
Biochem Biophys Res Commun ; 510(1): 35-41, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30660367

RESUMO

The effect of glycemic variability (GV) on diabetic neuropathy, including diabetic central neuropathy and diabetic peripheral neuropathy (DPN), and the involved mechanism are not fully understood. In this study, a fluctuant hyperglycemia rat model was induced by alternate intraperitoneal injections of glucose and insulin. To assess diabetic central neuropathy, step-down type passive avoidance tests were conducted, and the expression levels of p-Tau, T-Tau, p-GSK3ß, GSK3ß, p-Akt, and Akt in the hippocampus were measured. To assess DPN, the motor nerve conduction velocity (MNCV) was measured, and the microstructure of the sciatic nerve was observed. Additionally, the expression levels of oxidative stress and inflammation indicators were detected in the sciatic nerve. We observed that both learning and memory abilities were disrupted by GV. GV promoted Tau phosphorylation and inhibited the Akt/GSK3ß pathway in the hippocampus. Additionally, GV weakened the MNCV of the sciatic nerve, and the structures of both the myelin sheath and the axons in the sciatic nerve were disrupted. GV also significantly reduced the expression of superoxide dismutase (SOD) and increased the expression levels of malondialdehyde (MDA), of proinflammatory cytokines (TNF-α and IL-6) and of NF-κB. In conclusion, the present study highlighted that GV might induce diabetic central neuropathy through the hyperphosphorylation of Tau in the hippocampus by inhibiting the Akt/GSK3ß pathway and that it may cause DPN through oxidative stress and inflammatory responses by activating the NF-κB pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA