Long noncoding RNA (lnc RNA ) DLEU 2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU 2 in pancreatic cancer ( PC ) progression are poorly understood. In this study, we found that the DLEU 2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU 2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU 2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU 2 directly bond to microRNA‐455 (miR‐455) and functioned as an endogenous sponge for miR‐455, which could remarkably suppress cell growth and invasion. We also determined that SMAD 2 was a direct target of miR‐455, and the restoration of SMAD 2 rescued cell growth and invasion that were reduced by DLEU 2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high SMAD 2 expression was correlated with poor patient survival. These results indicate that DLEU 2 is an important promoter of PC development, and targeting the DLEU 2/miR‐455/ SMAD 2 pathway could be a promising therapeutic approach in the treatment of PC .

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A b s t r a c t As immune sentinels of the central nervous system (CNS), microglia is pivotal cellular mediator of neuroinflammatory processes. Activation of microglia might elicit the expression of proinflammatory cytokines involved in the progression of neuroinflammatory diseases. Numerous studies have demonstrated that propofol (2,6-diisopropylphenol) has an effective anti-inflammatory property. Intermittent hypoxia (IH), as a result of obstructive sleep apnoea (OSA), could lead to neuron damage and neuroinflammation in the CNS. Here, we determined the effects of propofol on the inflammatory response in microglia during IH. The levels of nuclear factor-κB (NF-κB) inhibitor (IκB) and activated p38 mitogen-activated protein kinase (MAPK) exposed to IH with or without propofol treatment were detected by Western blot. The viability of cells exposed to various concentrations of propofol was monitored with MTT assay. The production and mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by qRT-PCR

1. High-dose systemic or intralesional steroids are the first-line pharmacological treatments for haemangioma. However, the mechanism of action of steroids is unknown. Using the in vitro model developed by us, the present study examined some of the effects of five commonly used glucocorticoids on haemangioma biopsies taken from two patients. 2. At 12 micro mol/L, triamcinolone and dexamethasone consistently exhibited capillary growth inhibition, whereas methylprednisolone displayed an inhibitory effect during the first 7 days of culture. At this concentration, inhibition of capillary growth was observed in betamethasone-treated cultures derived from one patient but not in those derived from the other. However, hydrocortisone had a negligible effect on capillary growth. 3. Transcription of various factors considered important for haemangioma development were studied by reverse transcription-polymerase chain reaction. Neither vascular endothelial growth factor nor fibroblast growth factor-2 played a vital role in steroid-induced inhibition of capillary growth. All glucocorticoids induced a marked decrease of interleukin (IL)-6 transcripts. 4. Capillary growth inhibition in cultures treated with all glucocorticoids, except triamcinolone, was associated with an increased transcription of clusterin/apolipoprotein J (clust/apoJ), an apoptotic gene. There was increased transcription of mitochondrial cytochrome (cyt) b in the inhibited cultures resulting from triamcinolone, dexamethasone or methylprednisolone treatment that was associated with capillary growth inhibition, suggesting an important role of mitochondria in glucocorticoid-induced regression of haemangioma. 5. Our results indicate that glucocorticoids may modulate haemangiogenesis via an upregulation of cyt b, clust/apoJ and/or IL-6. The variable effects of different glucocorticoids on one or more of these factors may explain the interindividual variation in the in vivo response of haemangioma to the steroids.

Background: Blood-brain barrier (BBB) disruption and neuroinflammation are considered key mechanisms of pathogenic Escherichia coli invasion of the brain. However, the specific molecules involved in meningitic E. coliinduced BBB breakdown and neuroinflammatory response remain unclear. Our previous RNA-sequencing data from human brain microvascular endothelial cells (hBMECs) revealed two important host factors: platelet-derived growth factor-B (PDGF-B) and intercellular adhesion molecule-1 (ICAM-1), which were significantly upregulated in hBMECs after meningitic E. coli infection. Whether and how PDGF-B and ICAM-1 contribute to the development of E. coli meningitis are still unclear. Methods: The western blot, real-time PCR, enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence were applied to verify the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in vivo and in vitro. Evan's blue assay and electric cell-substrate impedance sensing assay were combined to identify the effects of PDGF-B on BBB permeability. The CRISPR/Cas9 technology, cell-cell adhesion assay, and electrochemiluminescence assay were used to investigate the role of ICAM-1 in neuroinflammation subversion. Results: We verified the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in mouse as well as monolayer hBMECs models. Functionally, we showed that the increase of PDGF-B may directly enhance the BBB permeability by decreasing the expression of tight junction proteins, and the upregulation of ICAM-1 contributed to neutrophils or monocytes recruitment as well as neuroinflammation subversion in response to meningitic E. coli infection. Conclusions: Our findings demonstrated the roles of PDGF-B and ICAM-1 in mediating bacterial-induced BBB damage as well as neuroinflammation, providing new concepts and potential targets for future prevention and treatment of bacterial meningitis.