Alzheimer’s Disease and Rheumatoid Arthritis: A Mendelian Randomization Study

Alzheimer’s disease (AD) is the most common neurodegenerative disease. In recent years, multiple pathway analyses of AD genome-wide association studies (GWAS) have been conducted, and provided strong support for immune pathways in AD. Rheumatoid arthritis (RA) is a chronic autoimmune disease. It is reported that antirheumatic drugs had protective effect on dementia in RA patients. However, observational studies have reported a controversial inverse relationship between AD and RA. In addition, Mendelian randomization studies have also been performed to evaluate the association of RA with AD. However, these studies reported inconsistent association of RA with AD. Until now, it is still unclear that AD is a causally associated with RA. Here, we performed a Mendelian randomization study to investigate the causal association of AD with RA. We analyzed the large-scale AD GWAS dataset (74,046 individuals) and RA GWAS dataset (58,284 individuals) from the European descent. However, we did not identify any significant association of AD with RA using inverse-variance weighted meta-analysis (IVW), weighted median regression and MR-Egger regression

Hot deformation behavior and 3D processing map of super austenitic stainless steel containing 7Mo–0.46N–0.02Ce: Effect of the solidification direction orientation of columnar crystal to loading direction

In the present paper, hot compression tests on a super austenitic stainless steel (SASS) containing 7Mo–0.46N–0.02Ce were performed at temperatures of 900 °C-1200 °C and strain rates of 0.01–10 s−1. The effect of angle between solidification direction of columnar crystal and loading direction (0°, 30°, 60°, and 90°) on the flow behavior and microstructure evolution of SASS was studied. Results showed that, samples with different columnar crystal characteristics and test conditions displayed various flow behaviors due to the difference in dynamic restoration softening mechanism, flow localization, and shear band formation. With the decrease of the angle between the solidification direction of columnar crystal and loading direction, the deformation activation energy (Q) and the ln Z value of SASS decreased at the true strain of 0.7. It indicates that dynamic recovery (DRV) and dynamic recrystallization (DRX) are more likely to happen in the samples with low angles. The location and range of high efficiency of power dissipation (η) region and instability region of the samples differed much with different columnar crystal characteristics. This means obviously different hot workability and microstructure evolution behaviors. At the true strain of 0.7, no negative η-value region was observed in the 0° sample, and the range of instability region was relatively small. On the whole, SASS presented the optimum hot workability when the angle between the solidification direction of columnar crystal and loading direction was 0°

Construction and analysis of circular RNA molecular regulatory networks in liver cancer

<p>Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we used a <i>systems biology approach</i> to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. Quantitative real-time PCR was performed to verify the top-five circRNAs. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets.</p

Taraxasterol Inhibits LPS-Induced Inflammatory Response in BV2 Microglia Cells by Activating LXRα

Neuroinflammation plays a critical role in the development of neurodegenerative diseases. Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have anti-inflammatory effect. The aim of this study was to investigate the anti-inflammatory effects and mechanism of taraxasterol in LPS-stimulated BV2 microglia cells. BV2 microglia cells were treated with taraxasterol 12 h before LPS stimulation. The effects of taraxasterol on LPS-induced TNF-α and IL-1β production were detected by ELISA. The effects of taraxasterol on LXRα, ABCA1, TLR4, and NF-κB expression were detected by western blot analysis. The results showed that taraxasterol dose-dependently inhibited LPS-induced TNF-α and IL-1β production and NF-κB activation. Taraxasterol also disrupted the formation of lipid rafts and inhibited translocation of TLR4 into lipid rafts. Furthermore, taraxasterol was found to activate LXRα-ABCA1 signaling pathway which induces cholesterol efflux from cells. In addition, our results showed that the anti-inflammatory effect of taraxasterol was attenuated by transfection with LXRα siRNA. In conclusion, these results suggested that taraxasterol inhibits LPS-induced inflammatory response in BV2 microglia cells by activating LXRα-ABCA1 signaling pathway

Platycodin D Inhibits Inflammatory Response in LPS-Stimulated Primary Rat Microglia Cells through Activating LXRα–ABCA1 Signaling Pathway

Platycodin D (PLD), an effective triterpenesaponin extracted from Platycodon grandiflorum, has been known to have anti-inflammatory effect. In the present study, we investigate the anti-inflammatory effects of PLD on LPS-induced inflammation in primary rat microglia cells. The results showed that PLD significantly inhibited LPS-induced ROS, TNF-α, IL-6, and IL-1β production in primary rat microglia cells. PLD also inhibited LPS-induced NF-κB activation. Furthermore, our results showed that PLD prevented LPS-induced TLR4 translocation into lipid rafts via disrupting the formation of lipid rafts by inducing cholesterol efflux. In addition, PLD could activate LXRα–ABCA1 signaling pathway which induces cholesterol efflux from cells. The inhibition of inflammatory cytokines by PLD could be reversed by SiRNA of LXRα. In conclusion, these results indicated that PLD prevented LPS-induced inflammation by activating LXRα–ABCA1 signaling pathway, which disrupted lipid rafts and prevented TLR4 translocation into lipid rafts, thereby inhibiting LPS-induced inflammatory response

Transcription Factors and microRNA-Co-Regulated Genes in Gastric Cancer Invasion in <i>Ex Vivo</i>

<div><p>Aberrant miRNA expression abnormally modulates gene expression in cells and can contribute to tumorigenesis in humans. This study identified functionally relevant differentially expressed genes using the transcription factors and miRNA-co-regulated network analysis for gastric cancer. The TF-miRNA co-regulatory network was constructed based on data obtained from cDNA microarray and miRNA expression profiling of gastric cancer tissues. The network along with their co-regulated genes was analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Transcriptional Regulatory Element Database (TRED). We found eighteen (17 up-regulated and 1 down-regulated) differentially expressed genes that were co-regulated by transcription factors and miRNAs. KEGG pathway analysis revealed that these genes were part of the extracellular matrix-receptor interaction and focal adhesion signaling pathways. In addition, qRT- PCR and Western blot data showed an increase in COL1A1 and decrease in NCAM1 mRNA and protein levels in gastric cancer tissues. Thus, these data provided the first evidence to illustrate that altered gene network was associated with gastric cancer invasion. Further study with a large sample size and more functional experiments is needed to confirm these data and contribute to diagnostic and treatment strategies for gastric cancer.</p></div