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INTRODUCTION: Diabetic osteoporosis (DOP) is a chronic diabetic complication, which is attributed to high glucose (HG)-induced dysfunction of bone marrow mesenchymal stem cells (BMSCs). Studies have revealed that microRNAs (miRNAs) play critical roles in osteogenic differentiation of BMSCs in DOP. Here, the role of miR-9-5p in DOP progression was explored. MATERIALS AND METHODS: The rat model of DOP was established by intraperitoneal injection of streptozotocin (STZ). BMSCs were treated with high glucose (HG) to establish in vitro models. Gene expression in BMSCs and bone tissues of rats was tested by RT-qPCR. The degree of osteogenic differentiation of BMSCs was examined by Alizarin Red staining and ALP activity analysis. The protein levels of collagen-I (COL1), osteocalcin (OCN), osteopontin (OPN), runt-related transcription factor-2 (RUNX2), and DEAD-Box Helicase 17 (DDX17) in BMSCs were evaluated by western blotting. The interaction between miR-9-5p and DDX17 was identified by luciferase reporter assay. H&E staining was used to test morphological structure of femurs of rats with STZ treatment. RESULTS: MiR-9-5p was overexpressed in HG-treated BMSCs, while DDX17 was downregulated. Functionally, miR-9-5p knockdown promoted BMSCs osteogenic differentiation under HG condition. Mechanically, miR-9-5p targeted DDX17. DDX17 knockdown reversed the effect of miR-9-5p silencing on osteogenic differentiation of HG-treated BMSCs. In in vivo studies, miR-9-5p downregulation ameliorated the DOP condition of rats and miR-9-5p expression was negatively correlated with DDX17 expression in bone tissues of rats with STZ treatment. CONCLUSION: MiR-9-5p knockdown promotes HG-induced osteogenic differentiation BMSCs in vitro and mitigates the DOP condition of rats in vivo by targeting DDX17.
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Células-Tronco Mesenquimais , MicroRNAs , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Glucose/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , RatosRESUMO
BACKGROUND: Diabetic nephropathy (DN), a common microvascular complication of type 2 diabetes mellitus (T2DM), is an important factor causing chronic kidney disease. However, the relationship between miR-29a and DN remains unknown. Therefore, a cross-sectional study was conducted to identify a potential molecular biomarker for DN prevention and management by detecting the serum miR-29a levels. METHODS: The serum miR-29a levels were measured in 360 subjects (180 T2DM patients and 180 healthy controls) using quantitative reverse transcription PCR (qRT-PCR), and other conventional indicators were measured and analysed. A binary logistic regression was used to evaluate the DN risk factors; a receiver operating characteristic (ROC) curve was applied to analyse the diagnostic efficacy of miR-29a for DN, and a Spearman's rank correlation analysis was used to evaluate the correlation between serum miR-29a and cystatin C. RESULTS: The serum miR-29 levels in the T2DM patients were higher than those in the healthy subjects and significantly increased with the progression of DN (p < 0.05). Serum miR-29a and cystatin C are independent predictors of the occurrence of DN. Compared with a single indicator, the combination of serum miR-29a and cystatin C has better DN diagnostic performance. In addition, the serum miR-29a levels were positively correlated with cystatin C in the patients with DN (r = 0.521, p < 0.001). CONCLUSION: The expression of serum miR-29a was significantly associated with the occurrence and progression of DN and is expected to become a potential biomarker for the diagnosis of DN.
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Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , MicroRNAs/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Cistatina C/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Voluntários Saudáveis , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
BACKGROUND: The present study investigated the relationships between serum amyloid A (SAA), 25-hydroxyvitamin D (25(OH)VD) and diabetic nephropathy (DN) to provide evidence for the prevention and management of DN. METHODS: A total of 182 patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. The levels of SAA, 25(OH)VD, and other conventional indicators were measured and analyzed. Receiver operating characteristic curve analysis was applied for the combined measurement of SAA and 25(OH)VD, and risk factors for DN were evaluated using binary logistic regression analysis. RESULTS: The levels of SAA in T2DM patients were significantly higher than those in healthy subjects, and the level significantly increased with the progression of DN (p < 0.05). In contrast, the level of 25(OH)VD in T2DM patients was significantly lower than that in healthy subjects, and the level significantly decreased with the progression of DN (p < 0.05). The combined measurement of SAA and 25(OH)VD distinguished DN patients from T2DM patients better than the measurement of SAA or 25(OH)VD alone. SAA was an independent risk factor for DN, and 25(OH)VD was an independent protective factor for DN. CONCLUSION: SAA and 25(OH)VD might be used as potential markers to identify patients at increased risk of developing DN.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Humanos , Proteína Amiloide A Sérica , Vitamina D/análogos & derivadosRESUMO
Traditionally, hyperthyroid-associated osteoporosis has been considered to be the result of increased thyroid hormone levels. The pathogenesis of hyperthyroid-associated osteoporosis remains unclear. Thyroid stimulating hormone receptor (TSHR) is closely associated with osteoporosis. Our study aimed to explore the role of TSHR and its upstream microRNA (miRNA) in hyperthyroid-associated osteoporosis. Bioinformatics analysis (starBase and Targetscan) and a wide range of experiments including reverse-transcription quantitative polymerase chain reaction, luciferase reporter, western blot analysis of osteogenic differentiation markers including OSX, OCN, ALP, OPN, and COL1, hematoxylin and eosin staining, Alizarin Red staining assays were used to explore the function and mechanism of TSHR in hyperthyroid-associated osteoporosis. First, we observed that TSHR was downregulated in bone marrow mesenchymal stem cells (BMSCs) isolated from rats after culture in osteogenic medium for 7 days. Functionally, overexpression of TSHR accelerates BMSC osteogenic differentiation. Mechanistically, we predicted four potential miRNAs for TSHR. MiR-577 was validated to bind with TSHR. Rescue assays showed that miR-577 overexpression inhibited BMSC osteogenic differentiation via targeting TSHR. In vivo experiments showed that miR-577 aggravated bone loss and bone remodeling and our data showed that it is achieved by targeting TSHR in hyperthyroid-associated osteoporosis. This finding may deep our understanding of the pathogenesis of hyperthyroid-associated osteoporosis.
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Hipertireoidismo , MicroRNAs , Osteoporose , Animais , Remodelação Óssea , Diferenciação Celular , Células Cultivadas , Hipertireoidismo/complicações , Hipertireoidismo/genética , MicroRNAs/genética , Osteogênese , Osteoporose/genética , Ratos , Receptores da Tireotropina/genéticaRESUMO
BACKGROUND: Serum amyloid A (SAA) plays a critical role in acute or chronic and is used in clinical laboratories as an indicator of inflammation. The elevated SAA is closely related to inflammation-mediated diseases, such as liver diseases, autoimmune diseases, metabolism-related diseases, amyloidosis, and tumors. However, there is no unified population reference interval for SAA. This study aimed to investigate the distribution of SAA in healthy Chinese adults 20-79 years of age and to establish its population reference interval. METHODS: A total of 2365 healthy subjects met the requirements of this study. The levels of SAA were detected using an AU5821 automatic biochemical analyzer and its original reagents. According to the recommended methods of CLSI C28-A3 and WS/T 402-2012, the population reference interval of SAA was established using the unilateral 95th percentile (P95 ), and the 90% confidence interval of upper limits was calculated. RESULTS: The distributions of SAA levels were not significantly different between sexes (P> .05) and also did not differ by age (P> .05). Therefore, the population reference interval for SAA was established as an upper limit of 11.0 mg/L (90% confidence interval: 9.3-12.3 mg/L) by using the method of latex immunoturbidimetry. CONCLUSIONS: Serum amyloid A is closely related to the occurrence and progression of various diseases. The preliminary establishment of a population reference interval for SAA can fully exert its potential clinical value.
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Proteína Amiloide A Sérica/análise , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
Introduction: A few past experimental studies have indicated that exposure to volatile organic compounds (VOCs) might be a potential risk factor for diabetes retinopathy (DR). However, these findings lack substantial support from extensive epidemiological research. This large-scale cross-sectional study aimed to examine whether exposure to low levels of VOCs in the general population is associated with diabetes mellitus (DM) and DR. Methods: The analytical data was from the National Health and Nutrition Examination Survey (NHANES) dataset (2011-2018). To minimize the potential impact of gender and age on the findings, propensity score matching was utilized to align the data selection. Relationships between blood VOCs and DM and DR were assessed in a sample of 2,932 adults using the logistic regression models. Additionally, Bayesian kernel machine regression (BKMR) models and Weighted Quantile Sum (WQS) were conducted for mixture exposure analysis. Results: The result shows VOCs were positive associated with DM and DR in US adults, as assessed by WQS model, and the calculated odd ratios (ORs) [95% confidence interval (C.I)] were 53.91(34.11 ~ 85.22) and 7.38(3.65 ~ 14.92), respectively. Among the components of VOCs, 1,2-Dibromoethane, Carbon Tetrachloride and 2,5-Dimethylfuran were positive related with the DR, and ORs (95%C.I) were 2.91(2.29 ~ 3.70), 2.86(2.25 ~ 3.65) and 2.19(1.79 ~ 2.94), respectively. BKMR model shows that there was a dose-response relationship between combined VOCs and DR, although the relationship was non-linearly. Conclusion: This study suggested that exposure to VOCs may increase the risk of DR, which had important public health implications.
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Diabetes Mellitus , Retinopatia Diabética , Compostos Orgânicos Voláteis , Adulto , Humanos , Inquéritos Nutricionais , Estudos Transversais , Compostos Orgânicos Voláteis/efeitos adversos , Exposição Ambiental/efeitos adversos , Teorema de Bayes , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Fatores de RiscoRESUMO
Objective: It's well known that γ-Glutamyltransferase (γ-GGT) and obesity plays an important role in the development of preHT. However, the effect of γ-GGT on preHT in populations with different obesity status remains unclear. Methods: From February 2014 to January 2018, a total of 20,368 participants were enrolled in this study after excluding those with hypertension and liver diseases. Fasting blood samples were collected to measure γ-GGT and blood lipid levels and glucose indices. Demographic and clinical parameters such as sex, age, height, weight, neck circumference (NC), waist circumference (WC), hip circumference (HC), and body fat ratio (BFR); and information on smoking and alcohol consumption were collected by trained medical professionals. Results: Participants were divided into three groups based on obesity status. The prevalence of preHT was 83.5 % in the obesity group was higher than that in the overweight group (58.9 %) and the normal group (47.1 %). γ-GGT in different categories of obesity indices were significantly different, and higher obesity indices were found with higher γ-GGT levels. The interaction of γ-GGT and obesity indices such as NC, WC, HC, and BFR on the prevalence of preHT was significant (P = 0.028, 0.002, 0.007, and 0.034, respectively). Serum γ-GGT was found to be positively associated with preHT in participants with normal and overweight body mass indices. Conclusion: Our results indicate that γ-GGT is a risk factor for preHT in participants who are nonobese, and that the obesity indices NC, WC, HC, BFR, and γ-GGT were contributing factors in increasing the risk of preHT.
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BACKGROUND: Thyroid carcinoma (THCA) is the most frequent endocrine malignancy. Papillary thyroid carcinoma (PTC) is the major subtype of THCA, accounting for over 80% of all THCA cases. LncRNA PAX8-AS1, a tumor suppressor associated with various human cancers, has been reported to be relevant to the regulation of all sorts of cellular processes. The purpose of this study was to verify the role of PAX8-AS1 in PTC. METHODS: Three human PTC cell lines (K1, TPC-1, and IHH4) and one normal human thyroid cell line, Nthy-ori3-1, were used in our study. The expression of genes was detected by qRT-PCR. The bioinformatic analysis and luciferase reporter assay were used to confirm the binding relationship of PAX8-AS1 to miR-96-5p, and the targeting relationship of miR-96-5p to PKN2 was also predicted. Cell proliferation and apoptosis capacities were assessed by MTT and flow cytometry, respectively. EdU assay was used to detect cell proliferation. Western blot assay was employed to examine protein expression. RESULTS: The expression of PAX8-AS1 was decreased in PTC tissues and cells. PAX8-AS1 overexpression inhibited the proliferation of PTC cells and promoted cell apoptosis. In addition, PAX8-AS1 bonds with miR-96-5p, whose downregulation elevated the expression of PKN2 in PTC cells. Importantly, according to the rescue experiments, PKN2 silencing partially reversed the inhibitory effects of PAX8-AS1 expression on PTC cell proliferation and apoptosis. CONCLUSIONS: We found that the PAX8-AS1/miR-96-5p/PKN2 axis was closely related to the progression of PTC, which could be a potential target for treating PTC patients.