Zobrazení zdroje stránky Vogelogden7863

Dynamic interactions between the gastrointestinal epithelium and the mucosal immune system normally contribute to ensuring intestinal homeostasis and optimal immunosurveillance, but destabilisation of these interactions in genetically predisposed individuals can lead to the development of chronic inflammatory diseases. Ulcerative colitis is one of the main types of inflammatory diseases that affect the bowel, but its pathogenesis has yet to be completely defined. Several genetic factors and other inflammation-related genes are implicated in mediating the inflammation and development of the disease. Some susceptibility loci associated with increased risk of ulcerative colitis are found to be implicated in mucosal barrier function. Different biomarkers that cause damage to the colonic mucosa can be detected in patients, including perinuclear ANCA, which is also useful in distinguishing ulcerative colitis from other colitides. The choice of treatment for ulcerative colitis depends on disease severity. Therapeutic strategies include anti-tumour necrosis factor alpha (TNF-α) monoclonal antibodies used to block the production of TNF-α that mediates intestinal tract inflammation, an anti-adhesion drug that prevents lymphocyte infiltration from the blood into the inflamed gut, inhibitors of JAK1 and JAK3 that suppress the innate immune cell signalling and interferons α/β which stimulate the production of anti-inflammatory cytokines, as well as faecal microbiota transplantation. Although further research is still required to fully dissect the pathophysiology of ulcerative colitis, understanding its cellular pathology and molecular mechanisms has already proven beneficial and it has got the potential to identify further novel, effective targets for therapy and reduce the burden of this chronic disease. © The Author(s) 2020.Background Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are being found to play crucial roles in ATC progression. Herein, we focused on the role of nuclear paraspeckle assembly transcript 1 (NEAT1) on ATC progression under hypoxia and underlying mechanisms governing it. Methods The expression levels of NEAT1, miR-206 and miR-599 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were detected using transwell assays. Glucose consumption and lactate production were determined using a corresponding commercial assay kit. Western blot was performed to evaluate the level of hexokinase 2 (HK2). The targeted interplays between NEAT1 and miR-206 or miR-599 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model was established to observe the effect of NEAT1 on tumor growth in vivo. Results Our data indicated that NEAT1 was highly expressed in ATC tissues and cells, and hypoxia induced NEAT1 expression in ATC cells. NEAT1 depletion repressed ATC cell migration, invasion and glycolysis under hypoxia. Mechanistically, NEAT1 acted as a molecular sponge of miR-206 and miR-599. Moreover, the repressive effects of NEAT1 knockdown on ATC cell migration, invasion and glycolysis under hypoxia were mediated by miR-206 or miR-599. Additionally, NEAT1 knockdown weakened tumor growth in vivo. Conclusion In conclusion, our study suggested that a low NEAT1 expression suppressed the migration, invasion, and glycolysis in ATC cells under hypoxia at least partially through modulating miR-206 and miR-599, providing new therapeutic strategies for ATC treatment. © The Author(s) 2020.Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. Accordingly, this kind of biological therapy can potentially be used as a promising approach in the field of cancer management. Given the failure of traditional monitoring strategies (such as immunohistochemical analysis (in providing sufficient safety and efficacy necessary for virotherapy and continual pharmacologic monitoring to track pharmacokinetics in real-time, the development of alternative strategies for ongoing monitoring of oncolytic treatment in a live animal model seems inevitable. [https://www.selleckchem.com/products/picropodophyllin-ppp.html AXL1717] Three-dimensional molecular imaging methods have recently been considered as an attractive approach to overcome the limitations of oncolytic therapy. These noninvasive visualization systems provide real-time follow-up of viral progression within the cancer tissue by the ability of engineered oncolytic viruses (OVs) to encode reporter transgenes based on recombinant technology. Human sodium/iodide symporter (hNIS) is considered as one of the most prevalent nuclear imaging reporter transgenes that provides precise information regarding the kinetics of gene expression, viral biodistribution, toxicity, and therapeutic outcomes using the accumulation of radiotracers at the site of transgene expression. Here, we provide an overview of pre-clinical and clinical applications of hNIS-based molecular imaging to evaluate virotherapy efficacy. Moreover, we describe different types of reporter genes and their potency in the clinical trials. © The Author(s) 2020.Background Cholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. Methods The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. Results Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients.