Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis

AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis. METHODS Acute colitis was induced in C57BL/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon. RESULTS Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in proinflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80+, T helper CD4+ (Th), T cytotoxic CD8+ (Tcyt) and T regulatory CD25+ (Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/ or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut. These results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS

MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation

G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development

Communication Interconnection Network Architecture and Logical Devices Application

Recently launched a communication standard, communication architecture for network protocol design technique, defined by International Electrotechnical Commission(IEC), the need is to implement communication interconnection network architecture with logical devices, it’s a challenging task. The choice of logical device is to attain the critical time requirement of data transmission for Protective Relaying of 3ms without complicating the real-time implementation, processing power and data interconnection requirement. We are confirmed that the speed is only depends on the interconnection architecture design so as to prove the effectiveness of network design

Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

Abstract Diblock copolymers of poly(q-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5 -24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 Ag ml À 1 , while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 jC demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells

Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro-1

<p><b>Copyright information:</b></p><p>Taken from "Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro"</p><p></p><p>International Journal of Nanomedicine 2006;1(2):155-162.</p><p>Published online Jan 2006</p><p>PMCID:PMC2426783.</p><p>© 2006 Dove Medical Press Limited. All rights reserved</p

Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro-0

<p><b>Copyright information:</b></p><p>Taken from "Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro"</p><p></p><p>International Journal of Nanomedicine 2006;1(2):155-162.</p><p>Published online Jan 2006</p><p>PMCID:PMC2426783.</p><p>© 2006 Dove Medical Press Limited. All rights reserved</p

Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro-3

<p><b>Copyright information:</b></p><p>Taken from "Efficient suppression of secretory clusterin levels by polymer-siRNA nanocomplexes enhances ionizing radiation lethality in human MCF-7 breast cancer cells in vitro"</p><p></p><p>International Journal of Nanomedicine 2006;1(2):155-162.</p><p>Published online Jan 2006</p><p>PMCID:PMC2426783.</p><p>© 2006 Dove Medical Press Limited. All rights reserved</p