Mir34a constrains pancreatic carcinogenesis

Several studies have shown that over 70 different microRNAs are aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC), affecting proliferation, apoptosis, metabolism, EMT and metastasis. The most important genetic alterations driving PDAC are a constitutive active mutation of the oncogene Kras and loss of function of the tumour suppressor Tp53 gene. Since the MicroRNA 34a (Mir34a) is a direct target of Tp53 it may critically contribute to the suppression of PDAC. Mir34a is epigenetically silenced in numerous cancers, including PDAC, where Mir34a down-regulation has been associated with poor patient prognosis. To determine whether Mir34a represents a suppressor of PDAC formation we generated an in vivo PDAC-mouse model harbouring pancreas-specific loss of Mir34a (Kras(G12D);Mir34a(Delta/Delta)). Histological analysis of Kras(G12D);Mir34a(Delta/Delta) mice revealed an accelerated formation of pre-neoplastic lesions and a faster PDAC development, compared to Kras(G12D) controls. Here we show that the accelerated phenotype is driven by an early up-regulation of the pro-inflammatory cytokines TNFA and IL6 in normal acinar cells and accompanied by the recruitment of immune cells. Our results imply that Mir34a restrains PDAC development by modulating the immune microenvironment of PDAC, thus defining Mir34a restauration as a potential therapeutic strategy for inhibition of PDAC development

Big Data Validity Evaluation Based on MMTD

Big data has been studied extensively in recent years. With the increase in data size, data quality becomes a priority. Evaluation of data quality is important for data management, which influences data analysis and decision making. Data validity is an important aspect of data quality evaluation. Based on 3V properties of big data, dimensions that have a major influence on data validity in a big data environment are analyzed. Each data validity dimension is analyzed qualitatively using medium logic. The measuring of medium truth degree is used to propose models to measure single and multiple dimensions of big data validity. The validity evaluation method based on medium logic is more reasonable and scientific than general methods

Compaction and Breakage Characteristics of Crushed Stone Used as the Backfill Material of Urban Pavement Subsidence

The subsidence of urban pavement is becoming frequent accidents, and backfill is the primary means of remedy. Crushed stone is a commonly used aggregate for backfill material in engineering, and its compaction behavior under load needs to be well understood. In this work, a series of compaction tests were carried out on the same batch of crushed stone samples with the same gradation. The content changes of particles with different sizes were analyzed, the particle breakage characteristics during the compaction process were discussed, and the difference in particle breakage caused by loading speed and loading mode was examined. It shows the following: (1) For all samples, the content of particles that were crushed during compaction was always less than 40%. The particles with the strongest breakage varied with sample gradation. (2) The particle breakage could be divided into four categories: complete fragmentation, complete rupture, local fragmentation, and surface grinding. They affected the particle size distribution after compaction to varying degrees. (3) The particle breakage could be expressed as a cubical parabola of loading speed, whose coefficients are related to the sample gradation. (4) Stepwise loading rendered stronger particle breakage than direct loading, and the increase of particle breakage due to loading mode was more evident for continuous grading samples than discontinuous grading samples. This study will provide an experimental basis and reference for the selection and use of backfill aggregate in urban subsidence areas

Hepatocellular Brg1 promotes CCl4-induced liver inflammation, ECM accumulation and fibrosis in mice.

IntroductionHepatic fibrosis is a progressive pathological process involving the exhaustion of hepatocellular regenerative capacity and ultimately leading to the development of cirrhosis and even hepatocellular carcinoma. Brg1, the core subunit of the SWI/SNF chromatin-remodeling complex, was recently identified as important for liver regeneration. This study investigates the role of Brg1 in hepatic fibrosis development.MethodsHepatocyte-specific Brg1 knockout mice were generated and injected with carbon tetrachloride (CCl4) for 4, 6, 8, and 12 weeks to induce liver fibrosis. Afterwards, liver fibrosis and liver damage were assessed.ResultsBrg1 expression was significantly increased in the fibrotic liver tissue of wild-type mice, as compared to that of untreated wild-type mice. The livers of the Brg1 knockout animals showed reduced liver inflammation, extracellular matrix accumulation, and liver fibrosis. TNF-α and NF-κB-mediated inflammatory response was reduced in Brg1 knockout animals.ConclusionBrg1 promotes the progression of liver fibrosis in mice and may therefore be used as a potential therapeutic target for treating patients with liver fibrosis due to chronic injury

BRG1 promotes hepatocarcinogenesis by regulating proliferation and invasiveness.

The chromatin remodeler complex SWI/SNF plays an important role in physiological and pathological processes. Brahma related gene 1(BRG1), a catalytic subunit of the SWI/SNF complex, is known to be mutated in hepatocellular carcinoma (HCC). However, its role in HCC remains unclear. Here, we investigate the role of BRG1 on cell growth and invasiveness as well as its effect on the expression of putative target genes. Expression of BRG1 was examined in human liver tissue samples and in HCC cell lines. In addition, BRG1 was silenced in human HCC cell lines to analyse cell growth and invasiveness by growth curves, colony formation assay, invasion assay and the expression of putative target genes. BRG1 was found to be significantly increased in HCC samples compared to non-HCC samples. In addition, a declined proliferation rate of BRG1-silenced human HCC cell lines was associated with a decrease of expression of cyclin family members. In line with a decreased invasiveness of BRG1-siRNA-treated human HCC cell lines, down-regulation of MMP7 was detected. These results support the hypothesis that overexpression of BRG1 increases cell growth and invasiveness in HCC. Furthermore, the data highlight cyclin B, E and MMP7 to be associated with BRG1 during hepatocarcinogenesis