The macrophage in the pathogenesis of severe acute respiratory syndrome coronavirus infection

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Gas-filled microbubbles: a novel susceptibility contrast agent for brain and liver MRI

Theme: Engineering the Future of BiomedicineGas-filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. However, in vivo demonstration of microbubble susceptibility effect is limited so far and microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (AMBs) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue® ), were investigated with in vivo dynamic brain and liver MRI in Sprague-Dawley rats at 7 Tesla. Transverse relaxation rate enhancements (ΔR2*) maps were computed for brain and liver, yielding results similar to those obtained with a common MR blood pool contrast agent. These results indicate that gas-filled microbubbles can serve as an intravascular MR contrast agent at high field. Enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into microbubbles was also investigated at 7 T in vitro. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas-filled microbubble susceptibility effect can be substantially increased using iron oxides nanoparticles. With such approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications. ©2009 IEEE.published_or_final_versionThe 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2009), Minneapolis, MN., 3-6 September 2009. In Proceedings of the 31st EMBC, 2009, p. 4049-405

Service load analysis of unbonded partially prestressed concrete members

In the design of unbonded partially prestressed concrete (UPPC) members, it is necessary to estimate the stresses in steel and concrete in order to satisfy the requirements of the serviceability limit state. A numerical method has been developed to predict the response of UPPC beams under service load, and the results agree well with experimental results reported in the technical literature. A parametric study has been undertaken to evaluate the variation of stress in prestressed steel under service load as well as the ratio of length of equivalent deformation region to the neutral axis depth at critical section. Results show that this ratio is not sensitive to the variation of the combined reinforcement index. From the moment of application of load to the cracking of the beam, and until the yielding of non-prestressed steel, this ratio is fairly stable and it can be taken as a constant. With the determination of this ratio, an approximate cubic equation similar to that used for cracked section analysis of bonded partially prestressed members is established. Predictions of stresses under service load are in good agreement with available test data. © 2005 Thomas Telford Ltd.published_or_final_versio

Cell number quantification of USPIO-labeled stem cells by MRI: An in vitro study

MRI plays an expanding role in stem cell therapies. The non-invasive nature and high spatial resolution of MR imaging make MR imaging a powerful tool to investigate biologic processes at the molecular and cellular level in vivo longitudinally. Quantitative detection of stem cells after transplantation may allow assessment of stem cell localization and migration, and monitoring of the therapeutic effectiveness of stem cell therapy. In this study, we present a technique for MR quantification of magnetically labeled mouse embryonic stem cells distributed or injected in agarose gel phantoms. Apparent transverse relaxation rate enhancements (ΔR2*) were measured by gradient echo sequences. The linear relationship between ΔR2* and the concentration of USPIO-labeled mouse embryonic stem cells was observed and used for quantifying cell density and cell number after injection or transplantation. The MRI acquisition and analysis protocol were validated by good agreement between actual cell numbers and MRI-estimated cell numbers over a wide range of cell numbers. This MR technique for cell number and cell density quantification is applicable to future in vivo studies. © 2006 IEEE.published_or_final_versio

Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

Background: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.postprin

MRI detection of peritoneal adhesion with dialysate enhancement

This study investigated the use of clinical peritoneal dialysis fluid (dialysate) as a peritoneal contrast agent to visualize peritoneal adhesions in rats at 7 Tesla. Intraperitoneal injection of dialysate (~0.1 mL/g) allowed the MR detection of peritoneal adhesions that were surgically induced in all rats studied (N = 6). MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99). T1 and T2 values of undiluted dialysate were found to be 3017.5¡Ó35.3 ms and 108.4¡Ó2.0 ms, respectively. These findings demonstrated dialysate-enhanced MRI as a potentially valuable technique in clinical detection and evaluation of post-surgical peritoneal adhesion and to monitor therapeutic interventions (i.e., against peritoneal adhesion) in future preclinical research.published_or_final_versio

Lipoteichoic acid from an Enterococcus faecalis clinical strain promotes TNF-α expression through the NF-κB and p38 MAPK signaling pathways in differentiated THP-1 macrophages

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Noninvasive fMRI investigation of interaural level difference processing the rat auditory subcortex

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Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.postprin

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl