RESUMEN
Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic. A large and growing unmet therapeutic need has inspired numerous studies in the field. Integrating the published genomic data available in the Gene Expression Omnibus (GEO) with NAFLD samples from rodents, we discovered that interferon regulatory factor 6 (IRF6) is significantly downregulated in high-fat diet (HFD)-induced fatty liver. In the current study, we identified IRF6 in hepatocytes as a protective factor in liver steatosis (LS). During HFD challenge, hepatic Irf6 was suppressed by promoter hypermethylation. Severity of HFD-induced LS was exacerbated in hepatocyte-specific Irf6 knockout mice, whereas hepatocyte-specific transgenic mice overexpressing Irf6 (IRF6-HTG) exhibited alleviated steatosis and metabolic disorder in response to HFD feeding. Mechanistic studies in vitro demonstrated that hepatocyte IRF6 directly binds to the promoter of the peroxisome proliferator-activated receptor γ (PPARγ) gene and subsequently halts the transcription of Pparγ and its target genes (e.g., genes that regulate lipogenesis and lipid acid uptake) under physiological conditions. Conclusion: Irf6 is downregulated by promoter hypermethylation upon metabolic stimulus exposure, which fail to inhibit Pparγ and its targets, driving abnormalities of lipid metabolism.
Asunto(s)
Regulación de la Expresión Génica , Factores Reguladores del Interferón/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , PPAR gamma/genética , Animales , Metilación de ADN/genética , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hepatocitos/citología , Humanos , Factores Reguladores del Interferón/metabolismo , Metabolismo de los Lípidos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Distribución Aleatoria , Sensibilidad y EspecificidadRESUMEN
With the rapid advancement of urbanization and industrialization, ecological patches within cities and towns are fragmented and ecological corridors are cut off, regional ecological security is threatened and sustainable development is hindered. Building an ecological network that conforms to regional realities can connect fragmented patches, protect biodiversity and regional characteristics, and provide scientific reference for regional ecological protection and ecological network planning. By taking Qilin District, the main urban area of Qujing City as an example, and using geospatial data as the main data source, based on morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR), this study identified ecological source areas, extracted ecological corridors, and build & optimize ecological networks. (1) All landscape types are identified based on MSPA, the proportion of core area was the highest among all landscape types, which was 80.69%, combined with the connectivity evaluation, 14 important ecological source areas were selected. (2) 91 potential ecological corridors were extracted through MCR and gravity models, there were 16 important ones. (3) The network connectivity analysis method is used to calculate the α, ß, and γ indexes of the ecological network before optimization, which were 2.36, 6.5, and 2.53, while after optimization, α, ß and γ indices were 3.8, 9.5 and 3.5, respectively. The combined application of MSPA-MCR model and ecological network connectivity analysis evaluation is conducive to improving the structure and functionality of ecological network.
RESUMEN
The aim of this study was to evaluate the effects of at-home and in-office bleaching agents on esthetic CAD-CAM materials after red wine immersion by measuring their optical properties. Sixty specimens were prepared out of three esthetic CAD-CAM materials: Vita Enamic, Celtra Duo, and Ceresmart (n = 20). All specimens were immersed in a red wine solution, and color measurements were performed. Specimens were randomly divided (n = 10) according to the bleaching procedure (in office, at home), bleaching durations were set to 3 time points, and color measurements were performed. According to the Commission Internationale de l'Eclairage (CIE) L* a* b* parameters, CIEDE2000 color differences (ΔE00), translucency parameters (TP00), and whiteness index values (ΔWID) after wine staining and after bleaching were calculated. Data were analyzed using the Mann−Whitney U-test, the Kruskal−Wallis test, and a two-way analysis of variance (ANOVA) (α = 0.05). ΔE00, ΔTP00, and ΔWID decreased with an increase in bleaching treatment. ΔE00 after the final bleaching treatment of in-office bleaching ranged from 1.7 to 2.0, whereas those of in-office treatment ranged from 0.4 to 1.1. All ΔTP00 and ΔWID after the final treatment were below the 50:50% perceptibility thresholds (ΔTP00 < 0.6, and ΔWID < 0.7). Significant differences in ΔE00, ΔTP00, and ΔWID among esthetic CAD-CAM materials were found between CD and CE. In the present study, color recovery after at-home and in-office bleaching appeared to be material-dependent. In-office bleaching showed more effective recovery comparing to at-home bleaching.
RESUMEN
OBJECTIVE: This study aimed to construct a 5-year survival prediction model of coronary heart disease (CHD) induced chronic heart failure (CHF), which is supported by the traditional Chinese medicine (TCM) factor, and to verify the model. METHODS: Inpatients from January 1, 2012, to December 31, 2017, in seven hospitals in Shandong Province were studied. The random number table was used to randomly divide the seven hospitals into two groups (training set and verification set). In the training set, the least absolute shrinkage selection operator regression was first used to screen the independent variables. Logistic regression was then applied to construct a survival prediction model. The following nomogram visualizes the prediction model results. Finally, C-indices, calibration curves, and decision curves were used to discriminate and calibrate the established model and evaluate its practicability in the clinic. Bootstrap resampling and the verification set were used for internal and external verification, respectively. RESULTS: A total of 424 eligible patients were included in the model construction and verification. In this 5-year survival prediction model of patients with CHF induced by CHD, eight independent predictors were included. The series of C-indices for the training set, bootstrap resamples, and verification set was 0.885, 0.867, and 0.835, respectively, demonstrating the credibility of our model. Additionally, the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis of the training and verification sets showed that this 5-year survival prediction model was good in discrimination, calibration, and clinical practicability. CONCLUSION: This work highlights eight independent factors affecting 5-year mortality in patients with CHF induced by CHD after discharge and further helps reallocate medical resources rationally by precisely identifying high-risk groups. The constructed prediction model not only plays a credible role in prediction but also demonstrates TCM intervention as a protective factor for the 5-year death of patients with CHF induced by CHD, thereby advancing the use of TCM in CHF.
RESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a common liver disease and a major cause of related complications such as cirrhosis and hepatocellular carcinoma (HCC). NAFLD progresses through the stages of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and HCC. However, NAFLD usually cannot be diagnosed in a timely manner, which is largely attributed to the asymptomatic features of NAFLD patients and the lack of an effective and accurate noninvasive screening approach. Although liver biopsy has been recognized as a gold standard for diagnosing NAFLD, this approach is not suitable for screening and monitoring NAFLD because of its high cost and invasiveness. Several noninvasive screening and diagnostic systemic assessments have been developed in recent years for NAFLD evaluation. Here we summarize the current status and methods for NAFLD diagnosis, including both noninvasive (imaging, biomarkers) and invasive (liver biopsy) assessments. We further discuss the advantages and disadvantages of these developed diagnostic approaches for NAFLD.