HMGA2 promotes adipogenesis by activating C/EBPβ-mediated expression of PPARγ

AbstractAdipogenesis is orchestrated by a highly ordered network of transcription factors including peroxisome-proliferator activated receptor-gamma (PPARγ) and CCAAT-enhancer binding protein (C/EBP) family proteins. High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has been reported to play an essential role in preadipocyte proliferation, and its overexpression has been implicated in obesity in mice and humans. However, the direct role of HMGA2 in regulating the gene expression program during adipogenesis is not known. Here, we demonstrate that HMGA2 is required for C/EBPβ-mediated expression of PPARγ, and thus promotes adipogenic differentiation. We observed a transient but marked increase of Hmga2 transcript at an early phase of differentiation of mouse 3T3-L1 preadipocytes. Importantly, Hmga2 knockdown greatly impaired adipocyte formation, while its overexpression promoted the formation of mature adipocytes. We found that HMGA2 colocalized with C/EBPβ in the nucleus and was required for the recruitment of C/EBPβ to its binding element at the Pparγ2 promoter. Accordingly, HMGA2 and C/EBPβ cooperatively enhanced the Pparγ2 promoter activity. Our results indicate that HMGA2 is an essential constituent of the adipogenic transcription factor network, and thus its function may be affected during the course of obesity

MACT: A Manageable Minimization Allocation System

Background. Minimization is a case allocation method for randomized controlled trials (RCT). Evidence suggests that the minimization method achieves balanced groups with respect to numbers and participant characteristics, and can incorporate more prognostic factors compared to other randomization methods. Although several automatic allocation systems exist (e.g., randoWeb, and MagMin), the minimization method is still difficult to implement, and RCTs seldom employ minimization. Therefore, we developed the minimization allocation controlled trials (MACT) system, a generic manageable minimization allocation system. System Outline. The MACT system implements minimization allocation by Web and email. It has a unified interface that manages trials, participants, and allocation. It simultaneously supports multitrials, multicenters, multigrouping, multiple prognostic factors, and multilevels. Methods. Unlike previous systems, MACT utilizes an optimized database that greatly improves manageability. Simulations and Results. MACT was assessed in a series of experiments and evaluations. Relative to simple randomization, minimization produces better balance among groups and similar unpredictability. Applications. MACT has been employed in two RCTs that lasted three years. During this period, MACT steadily and simultaneously satisfied the requirements of the trial. Conclusions. MACT is a manageable, easy-to-use case allocation system. Its outstanding features are attracting more RCTs to use the minimization allocation method

Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy

The correlation between diabetes and systematic well-being on human life has long established. As a common complication of diabetes, the prevalence of diabetic nephropathy (DN) has been increasing globally. DN is known to be a major cause of end-stage kidney disease (ESKD). Till now, the molecular mechanisms for DN have not been fully explored and the effective therapies are still lacking. Noncoding RNAs are a class of RNAs produced by genome transcription that cannot be translated into proteins. It has been documented that ncRNAs participate in the pathogenesis of DN by regulating inflammation, apoptosis, autophagy, cell proliferation, and other pathological processes. In this review, the pathological roles and diagnostic and therapeutic potential of three types of ncRNAs (microRNA, long noncoding RNA, and circular RNA) in the progression of DN are summarized and illustrated

Evaluating cellular uptake of gold nanoparticles in HL-7702 and HepG2 cells for plasmonic photothermal therapy

A novel method is proposed for quantifying the Raman intensity as a function of gold mass in a single cell based on the Raman mapping and inductively coupled plasma-mass spectrometry techniques. And a high-efficiency plasmonic photothermal therapy has also been achieved by adjusting the laser wavelength, laser power and exposure time, resulting in most of the HL-7702 cells survive, whereas most of the HepG2 cells get damaged

Prevalence of Pre-Diabetes and Its Associated Risk Factors in Rural Areas of Ningbo, China

Objective: The aims of the study were to investigate the prevalence of pre-diabetes and explore its associated risk factors in rural areas of Ningbo, China. Methods: A cross-sectional survey was conducted with 4583 adult residents in rural areas of Ningbo, China between March and May 2013. The survey used a multi-stage, stratified, cluster sampling method. Data collected included demographics and medical history, anthropometric measurements, blood pressure, blood lipid, and plasma glucose. After at least 10 h of overnight fasting, participants underwent an oral glucose tolerance test (OGTT) to identify pre-diabetes. Univariate and multivariate logistic regression analyses were used to evaluate the associated risk factors for pre-diabetes, and to estimate the effect of interaction between the factors. Results: There were 1307 survey participants having pre-diabetes (28.52%) and the age-standardized prevalence was 30.53%. Multivariate logistic regression results showed that overweight/obesity, hypertension, and higher triglycerides were the risk factors for developing pre-diabetes. There were positive interactions between overweight/obesity and triglycerides, and also between hypertension and triglycerides on the multiplicative scale, suggesting that they synergistically influenced the development of pre-diabetes. Conclusions: The rural areas in Ningbo had a high prevalence of pre-diabetes. Overweight and obesity, hypertension, and elevated triglycerides were the major risk factors. There is a need of early intervention for preventing pre-diabetes

Hsa_circRNA_0054633 is highly expressed in gestational diabetes mellitus and closely related to glycosylation index

Abstract Background Circular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM). Methods A retrospective case–control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018. We collected serum samples from 40 healthy pregnant women (controls) and 40 women with GDM (cases) during the second trimester as well as 65 controls and 65 cases during the third trimester of pregnancy. Placenta tissues and neonatal cord blood were each from another 20 cases and 20 controls. We selected six circRNAs (hsa_circRNA_0054633, hsa_circRNA_103410, hsa_circRNA_063981, hsa_circRNA_102682, hsa_circRNA_0018508, and hsa_circRNA_406918) as candidate biomarkers and used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure their concentrations in the serum and placental tissues. The Pearson correlation test was used to assess the correlation between various circRNAs and between circRNA and clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs for GDM at each stage. Results Hsa_circRNA_0054633 was highly expressed in the blood during the second and third trimesters; its expression was also high in the placenta but low in the cord blood (P < 0.05). Hsa_cirRNA_0054633 was highly correlated with GHBA1 and GHBA1c levels in maternal blood samples at various stages of the GDM group (including placental tissue and umbilical cord blood) (P < 0.05). Hsa_circRNA_063981, hsa_circRNA_102682, and hsa_circRNA_103410 were also differentially expressed between the case and control groups at different stages (P < 0.05). There was a strong correlation between hsa_circRNA_0054633 and hsa_circRNA_103410 levels in third-trimester maternal blood (P = 0.000, r = 0.554) and in neonatal umbilical cord blood (P = 0.000, r = 0.866). Hsa_circRNA_0054633 showed a significant diagnostic value in the second and third trimesters of pregnancy, placenta, and cord blood (AUC = 0.793, 0.664, 0.747, and 0.783, respectively, P < 0.001). Conclusion This study suggests that hsa_cirRNA_0054633 is abnormally expressed in GDM patients and may play a potential role in the development of GDM. The possibility of using circRNAs for the diagnosis of GDM requires additional investigation in future studies

PPARα-dependent Increase of Mouse Urine Output by Gemfibrozil and Fenofibrate

While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. 24-hour urine output was monitored, and urine, serum, liver and kidney tissues were subjected to toxicity assessment. A two month challenge followed by a two week wash-out was performed for gemfibrozil to determine urine output and the potential toxicicity. A therapeutically equivalent dose of gemfibrozil was more effective than fenofibrate in increasing urine output. This regulatory effect was not observed in Pparα-null mice. In contrast, hepatomegaly induced by fenofibrate was more pronounced than that of gemfibrozil. No significant toxicity was observed in liver or kidney in the 2-month treatment with gemfibrozil. These data demonstrated PPARα mediates the increased urine output by fibrates. Considering the relative action on hepatomegaly and the regulatory effect on urine output, gemfibrozil may be the preferable drug to increase urine output. These results revealed a new pharmacodynamic effect of clinically-prescribed PPARα agonists and suggested the potential value of gemfibrozil in modification of blood pressure.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author