| 1. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 2. |
- Chen, Chengshui, et al.
(författare)
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Preventive and Therapeutic Effects of Phosphoinositide 3-Kinase Inhibitors on Acute Lung Injury
- 2011
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 140:2, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biologic responses. Recent preclinical studies demonstrated that the PI3K-dominant signal pathway could play an important role in the development of acute lung injury, although the mechanism remains unclear. Methods: CD-1 mice were administered different PI3K inhibitors either intranasally or intragastrically once a day for 3 days before intratracheal instillation of lipopolysaccharide at 4 h and 24 h. Effects of SHBM1009 on lipopolysaccharide-induced capillary permeability, leukocyte distribution and activation, and epithelial cell function were measured. Therapeutic effects of SHBM1009 on pancreatic elastase-induced lung injury were evaluated in rats. Results: The data demonstrated that the local delivery of PI3K inhibitors played more effective roles in the prevention of endotoxin-induced lung injury than the systemic delivery. The preventive effects of PI3K inhibitors varied most likely because of chemical properties, targeting sites, and pharmacokinetics. The local PI3K inhibitors prevented both endotoxin- and elastase-induced lung injury in mice and rats, possibly through directly inhibiting or inactivating the function of airway epithelial cells, which could not produce chemoattractant factors to activate neutrophils and macrophages. Conclusions: PI3K may be a therapeutic target for lung injury, and local delivery of PI3K inhibitors may be one of the optimal approaches for the therapy. CHEST 2011; 140(2):391-400
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| 3. |
- Kunze, Angelika, 1978, et al.
(författare)
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Ion-mediated changes of supported lipid bilayers and their coupling to the substrate. A case of bilayer slip?
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 7:18, s. 8582-8591
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Tidskriftsartikel (refereegranskat)abstract
- Ion-mediated (Ca(2+)) changes in viscoelastic, structural and optical properties of negatively charged solid supported lipid bilayers (SLBs) on SiO(2) surfaces were studied by means of quartz crystal microbalance with dissipation (QCM-D) monitoring and optical reflectometry. Despite the sensitivity of QCM-D to viscoeleastic/structural variations, it has not often been used to probe such changes for SLBs. SLBs were prepared from binary phospholipid mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC, neutral) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG, negatively charged) on SiO(2) sensor surfaces in a Ca(2+)-containing buffer. Interestingly, for bilayers containing POPG fractions above 35%, large QCM-D dissipation shifts occurred, when Ca(2+) was removed from buffer in contact with the SLB (while maintaining 100 mM NaCl). The accompanying frequency changes were small. These Ca(2+) mediated QCM-D responses are reversible, and a signal for considerable changes in the viscoelastic and structural properties of the SLB. Variation of Ca(2+)-concentration revealed a threshold concentration of around 0.4 mM for the changes in the SLB to occur. Below this value, at >35% POPG concentration in the SLB, the SLB appears to become more weakly attached to the SiO(2) substrate, which is partly attributed to a weakening of the POPG-substrate interaction in the absence of Ca(2+). A consequence of this is an oscillation-amplitude dependent dissipation, which we attribute to slip of the bilayer at higher oscillation amplitudes. Complementary experiments using a combined QCM-D/reflectometry instrument showed that the Ca(2+)-induced changes in the viscoelastic/structural properties of the SLB are accompanied by changes in the optical properties. We discuss different scenarios to explain the observed reversible effect of Ca(2+)-ions on the dissipative and optical properties of the mixed SLBs. Based on our results we propose the observed phenomenon to be a combination of geometric changes, internal structural changes, changes in the interfacial water layer, and a slip mechanism, i.e. friction between the SLB and the substrate.
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| 4. |
- Zhao, Zeng-Ren, et al.
(författare)
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Significance of mRNA and Protein Expression of MAC30 in Progression of Colorectal Cancer
- 2011
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Ingår i: Chemotherapy. - Basel : Karger AG. - 0009-3157 .- 1421-9794. ; 57:5, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- Background: Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The aim of our study was to investigate the expression of MAC30 mRNA and its correlation with clinicopathological variables in human colorectal cancer (CRC). Methods: MAC30 mRNA expression was first examined in 55 CRCs, along with the samples from the matched distant normal and adjacent noncancerous tissue by RT-PCR, further verified in 18 CRCs by quantitative RT-PCR. MAC30 protein expression was detected by Western blot in 10 CRCs, and DNA sequencing was performed in 1 case of the paired CRC and the matched noncancerous specimen. MAC30 mRNA expression in two colon cancer cell lines, HCT-116(p53-/-) and HCT-116(p53+/+), was detected by quantitative RT-PCR. Results: The mRNA expression of MAC30 was increased in CRC when compared with distant normal (p < 0.01) and adjacent noncancerous mucosa (p < 0.01). The mean value of MAC30 mRNA expression in the tumor located in the colon was higher than in the rectum (0.677 +/- 0.419 vs. 0.412 +/- 0.162, p = 0.005). As the tumor penetrated the wall of the colon/rectum, MAC30 mRNA expression notably increased in tumors with T3+T4 stage compared to tumors with T1+T2 stage (0.571 +/- 0.364 vs. 0.404 +/- 0.115, p = 0.014). MAC30 protein expression in CRCs was also remarkably elevated compared to the adjacent noncancerous mucosa. There was no mutation in the coding region of the MAC30 gene either in CRC or in the noncancerous mucosa. mRNA expression of p53 was notably decreased in HCT-116(p53-/-) compared to HCT-116(p53+/+), while MAC30 did not vary greatly. Conclusion: The overexpression of MAC30 might be involved in the development and aggressiveness of CRCs, especially in the colon.
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