FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients

Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

<p>Abstract</p> <p>Background</p> <p>The anaplastic lymphoma kinase (<it>ALK</it>) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of <it>ALK </it>include <it>NPM</it>, <it>EML4</it>, <it>TPM3</it>, <it>ATIC</it>, <it>TFG</it>, <it>CARS</it>, and <it>CLTC</it>. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer.</p> <p>Results</p> <p>RACE-coupled PCR sequencing was used to assess <it>ALK </it>fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the <it>EML4</it>-<it>ALK </it>fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that <it>EML4</it>-<it>ALK </it>was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking <it>EGFR </it>and <it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion was associated with non-smokers (<it>P </it>= 0.03), younger age of onset (<it>P </it>= 0.03), and adenocarcinomas without <it>EGFR</it>/<it>KRAS </it>mutations (<it>P </it>= 0.04). A trend towards improved survival was observed for patients with the <it>EML4</it>-<it>ALK </it>fusion, although it was not statistically significant (<it>P </it>= 0.20). Concurrent deletion in <it>EGFR </it>exon 19 and fusion of <it>EML4</it>-<it>ALK </it>was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the <it>EML</it>-<it>ALK </it>fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; <it>P </it>= 0.0018). However, expression of EML4 did not differ between the groups.</p> <p>Conclusions</p> <p>The <it>EML4</it>-<it>ALK </it>fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking <it>EGFR</it>/<it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of <it>EML4</it>-<it>ALK</it>-positive patients.</p

An Upscaling–Downscaling Optimal Seamline Detection Algorithm for Very Large Remote Sensing Image Mosaicking

For the mosaicking of multiple remote sensing images, obtaining the optimal stitching line in the overlapping region is a key step in creating a seamless mosaic image. However, for very large remote sensing images, the computation of finding seamlines involves a huge amount of image pixels. To handle this issue, we propose a stepwise strategy to obtain pixel-level optimal stitching lines for large remote sensing images via an upscaling–downscaling image sampling procedure. First, the resolution of the image is reduced and the graph cut algorithm is applied to find an energy-optimal seamline in the reduced image. Then, a stripe along the preliminary seamline is identified from the overlap area to remove the other inefficient nodes. Finally, the graph cut algorithm is applied nested within the identified stripe to seek the pixel-level optimal seamline of the original image. Compared to the existing algorithms, the proposed method produces fewer spectral differences between stitching lines and less-crossed features in the experiments. For a wide range of remote sensing images involving large data, the new method uses less than 10 percent of the time needed by the SLIC+ graph cut method

Building pedotransfer functions for estimating soil erodibility in southeastern China

Soil erodibility (K) reflects the sensitivity of soil to detachment and transport and is a key factor for estimating the loss of soil. Most of the models for estimating K are complex and experiential, simple and local estimation model in the hilly and mountainous southeastern China is rare. This study aims to build local pedotransfer functions (PTFs) for soil erodibility estimation and evaluate the performance of the built PTFs, i.e. multiple linear regression (MLR), MLR with deformed forms of variables (MLR-DFV) and artificial neutral network with deformed forms of variables (ANN-DFV) to estimating K in southeastern China. The local true K values were obtained by a comprehensive method that considering the optimization prediction model and runoff-plot monitoring data. The best predictive variables were determined using correlation analysis, principal component analysis, importance evaluation and minimum variable-set determination. Mean K in the study area was 0.043 t ha h ha−1 MJ−1 mm−1, ranging from 0.019 to 0.060 t ha h ha−1 MJ−1 mm−1, showed a moderate spatial variability. Soil organic-matter content (SOM) was the most important factor influencing K and accounted for 17.5 % of the total importance. Soil sand content, geometric mean diameter of aggregates, SOM and synthetic curvature were identified as the best predictive variables representing soil physical properties, aggregate characteristics, nutrient and topographical conditions, respectively. The accuracies of MLR-DFV and ANN-DFV were high and similar but higher than the accuracy of MLR. K estimated using ANN-DFV was more similar in magnitude, distribution, and spatial variability to the true K data than K estimated using MLR-DFV. We developed the first local PTFs for estimating K in the hilly and mountainous southeastern China, which could provide empirical basis and method support for studying K in similar regions

Progress and prospect of studies of Benggang erosion in southern China

Benggangs are a special type of severely eroded landform in southern China. They cause severe damage to soil resources, which has had a large negative impact on local ecological environments and people’s lives. Benggang erosion has received abundant attention in the past few decades, but few studies have systematically summarized and analyzed the progress, deficiencies and future directions of research of Benggang erosion. The purpose of this paper is therefore to analyze the progress of research on Benggang erosion, summarize the research deficiencies and propose future research directions and priorities. Benggangs gained attention in the 1960s, and studies of Benggang erosion have achieved rich results, including the characteristics of parental materials, spatial variation of soil properties in Benggang areas, mechanisms of the occurrence and process of Benggang erosion, dynamic monitoring of Benggang erosion, estimation of erosion volume, measures for controlling Benggang erosion and evaluation of their effectiveness. These studies have improved our knowledge and understanding of the basic attributes, occurrence, development, and factors influencing Benggang erosion and have provided a scientific basis for the optimal arrangement of measures for conserving soil and water and the rational development and effective management of Benggangs. We nevertheless believe that deficiencies remain in the aspects of the optimization of monitoring methods, mechanism of composite erosion, control of erosion and evaluation of the effectiveness of controlling Benggang erosion under the current level of development of research on soil erosion and the high standard of ecological protection. Further studies are necessary in the following areas: space-air-ground integrated technology for optimizing the monitoring of Benggang erosion; mechanism of hydraulic-gravitational composite erosion and the construction of models; research, development and application of new material for the prevention and control of Benggang erosion and development of a system for evaluating the effectiveness of erosion control. These research topics can supplement and enrich the content of traditional research on Benggang erosion and are very important for the restoration of ecological environments and improving ecological services and functions in areas with Benggang erosion

A RBM47 and IGF2BP1 mediated circular FNDC3B-FNDC3B mRNA imbalance is involved in the malignant processes of osteosarcoma

Abstract Background Circular RNAs (circRNAs) are a class of noncoding RNAs that are involved in the progression of many human cancers. The precise gene locus and the roles of circular RNA from Fibronectin type III domain containing 3B (FNDC3B) in OS and its mechanisms of action have not been fully explored. Materials and methods qRT-qPCR assay was used to determine gene expressions. CCK8 Assay, EdU assay, wound-healing assay, transwell invasion assay and in vivo xenograft assay were used to perform functional investigations. RNA-FISH, immunofluorescence, RIP assay, RNA stability analysis were applied in mechanistic studies. Results We found that circFNDC3B downregulated and FNDC3B mRNA upregulated in OS, and might be potential biomarkers for indicating disease progression and prognosis of OS patients. CircFNDC3B acted as a tumor suppressor gene to restrain OS progression and FNDC3B functioned as an oncogene to promote OS progression in vitro and in vivo. RNA binding protein RNA binding motif protein 47 (RBM47) could bind to the flanking introns of circFNDC3B to facilitate the generation of circFNDC3B, resulting in the reduction of FNDC3B mRNA and the circFNDC3B-FNDC3B mRNA imbalance. CircFNDC3B also inhibited FNDC3B mRNA expression by reducing its stability via competitively binding to Insulin-like growth-factor-2 mRNA binding protein (IGF2BP1). Conclusion This study demonstrated that RBM47 and IGF2BP1 mediated circular FNDC3B/FNDC3B mRNA imbalance was involved in the malignant processes of OS

Study on the Quality Evaluation of Compound Danshen Preparations Based on the xCELLigence Real-Time Cell-Based Assay and Pharmacodynamic Authentication

Objective: To perform a preliminary study on the quality evaluation of compound Danshen preparations based on the xCELLigence Real-Time Cell-based Assay (RTCA) system and make a pharmacodynamics verification. Methods: The compound Danshen was discussed as a methodological example, and the bioactivity of the compound Danshen preparations were evaluated by real-time cell electronic analysis technology. Meanwhile, an in vivo experiment on an acute blood stasis rat model was performed in order to verify this novel evaluation through the curative effect of dissipating blood stasis. Results: We determined the cell index (CI) and IC50 of the compound Danshen preparations and produced time/dose-dependent cell response profiles (TCRPs). The quality of the three kinds of compound Danshen preparations was evaluated through the RTCA data. The trend of CI and TCRPs reflected the effect of drugs on the cell (promoting or inhibiting), and it was verified that the results correlated with the biological activity of the drugs using a pharmacodynamics experiment. Conclusion: The RTCA system can be used to evaluate the quality of compound Danshen Preparations, and it can provide a new idea and new method for quantitatively characterizing the biological activity of traditional Chinese medicines (TCMs)

Carambolaside W Inhibited H1N1 Influenza Virus-Induced Oxidative Stress through STAT-3/BCL-XL Signaling Pathway

The H1N1 influenza virus is highly infectious and pathogenic, and in recent years, it has often presented seasonal mass outbreaks of infection. People infected with H1N1 will develop a high fever and other respiratory infection symptoms. If not treated in time, complications such as pneumonia may occur. In this study, we focused on developing drugs that can effectively fight against with H1N1 virus. A flavonoid glycoside was extracted from the carambola, then characterized by HR-ESI-MS with the molecular formula C47H58O2, and named carambolaside W. The flavonoid glycosides were found to have good anti-H1N1 influenza virus effects. In this study, we verified that carambolaside W has low toxicity and can effectively inhibit influenza virus replication in vitro. H1N1 virus infection induces intracellular oxidative stress damage to accelerate disease progression. The results showed that carambolaside W effectively inhibited the oxidative stress caused by H1N1 infection. The Western blot assay also revealed that carambolaside W alters the expression of apoptosis-related proteins in vitro and exerts a good anti-H1N1 influenza virus effect. In summary, carambolaside W is a low-toxicity natural flavonoid that can effectively treat the H1N1 influenza virus as a potential anti-H1N1 virus agent

MicroRNA-130a Targets MAP3K12 to Modulate Diabetic Endothelial Progenitor Cell Function

Aims: The aim of the present study was to explore the influence of microRNA (miR)-130a dysregulation on the JNK signal pathway through its target MAP3K12 in diabetic endothelial progenitor cells (EPCs). Methods: The expression of miR-130a was compared between diabetic and normal EPCs. Computational target prediction was performed to identify MAP3K12 as a functionally relevant target of miR-130a in EPCs. The role of miR-130a was investigated regarding its anti-apoptotic effects and its role on the regulation of EPC function was evaluated through the negative regulation of the JNK signal pathway Results: MiR-130a expression was significantly downregulated in diabetic EPCs, and cell proliferation was reduced in EPCs under high glucose condition. miR-130a inhibited the JNK pathway by targeting MAP3K12, contributing to its anti-apoptotic effect and the maintenance of EPC function. In diabetic EPCs, high glucose affects the expression of miR-130a, inducing sustained JNK activation and promoting EPC apoptosis and dysfunction. Conclusions: Downregulation of miR-130a may underlie endothelial dysfunction in diabetes through the activation of JNK signal pathway