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31.
Koletsis E Chatzimichalis A Apostolakis E Kokkinis K Fotopoulos V Melachrinou M Chorti M Crockett J Marinos E Bellenis I Dougenis D 《Experimental biology and medicine (Maywood, N.J.)》2006,231(8):1410-1420
Experimental models for studying transplantation have up to now been unable to isolate reperfusion injury with minimal surgical manipulation and without the interference of graft rejection. Six pigs were subjected to left hilum preparation only (control group), and eight pigs were subjected to left hilum preparation plus in situ cooling ischemia and reperfusion of the lung (experimental group). The hilum was dissected free from other tissues in both groups. Lung preservation was achieved by antegrade flush perfusion via the left pulmonary artery. Pulmonary veins were clamped at the left atrium and a vent was created. The left main bronchus was clamped. Lung temperature was maintained at 4 degrees -8 degrees C, while core temperature was kept at 38 degrees C. After 3 hrs of cold ischemia the clamps were removed and the lung was reperfused. Elevated pulmonary vascular resistance and local and systemic aspects of ischemia-reperfusion syndrome were consistently reproduced. This large-animal model of in situ unilateral lung cold ischemia with warm reperfusion proved to be very reliable in reproducing all aspects of ischemia-reperfusion injury. It excludes the interference of rejection and extensive surgical manipulation. We therefore propose its use in experimental studies investigating pharmaceutical or cooling modifications affecting lung ischemia-reperfusion outcomes. 相似文献
32.
Injectable nanocomposites of single-walled carbon nanotubes and biodegradable polymers for bone tissue engineering 总被引:1,自引:0,他引:1
We have investigated the dispersion of single-walled carbon nanotubes (SWNTs) and functionalized SWNTs (F-SWNTs) in the unsaturated, biodegradable polymer poly(propylene fumarate) (PPF) and examined the rheological properties of un-cross-linked nanocomposite formulations as well as the electrical and mechanical properties of cross-linked nanocomposites. F-SWNTs were produced from individual SWNTs by a diazonium-based method and dispersed better than unmodified SWNTs in both un-cross-linked and cross-linked PPF matrix. Cross-linked nanocomposites with F-SWNTs were superior to those with unmodified SWNTs in terms of their mechanical properties. Specifically, nanocomposites with 0.1 wt % F-SWNTs loading resulted in a 3-fold increase in both compressive modulus and flexural modulus and a 2-fold increase in both compressive offset yield strength and flexural strength when compared to pure PPF networks, whereas the use of 0.1 wt % SWNTs gained less than 37% mechanical reinforcement. These extraordinary mechanical enhancements considered together with Raman scattering and sol fraction measurements indicate strong SWNT-PPF interactions and increased cross-linking densities resulting in effective load transfer. With enhanced mechanical properties and capabilities of in situ injection and cross-linking, these SWNT/polymer nanocomposites hold significant implications for the fabrication of bone tissue engineering scaffolds. 相似文献
33.
34.
Setaki D Tataridis D Stamatiou G Kolocouris A Foscolos GB Fytas G Kolocouris N Padalko E Neyts J De Clercq E 《Bioorganic chemistry》2006,34(5):248-273
The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H(3)N(2) virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2-C2' bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N-C2' distance is 3.7, 3.8 A for 27, 30 and 2.5 A for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages. 相似文献
35.
Highly dynamic exon shuffling in candidate pathogen receptors ... what if brown algae were capable of adaptive immunity? 总被引:1,自引:0,他引:1
Zambounis A Elias M Sterck L Maumus F Gachon CM 《Molecular biology and evolution》2012,29(4):1263-1276
Pathogen recognition is the first step of immune reactions. In animals and plants, direct or indirect pathogen recognition is often mediated by a wealth of fast-evolving receptors, many of which contain ligand-binding and signal transduction domains, such as leucine-rich or tetratricopeptide repeat (LRR/TPR) and NB-ARC domains, respectively. In order to identify candidates potentially involved in algal defense, we mined the genome of the brown alga Ectocarpus siliculosus for homologues of these genes and assessed the evolutionary pressures acting upon them. We thus annotated all Ectocarpus LRR-containing genes, in particular an original group of LRR-containing GTPases of the ROCO family, and 24 NB-ARC-TPR proteins. They exhibit high birth and death rates, while a diversifying selection is acting on their LRR (respectively TPR) domain, probably affecting the ligand-binding specificities. Remarkably, each repeat is encoded by an exon, and the intense exon shuffling underpins the variability of LRR and TPR domains. We conclude that the Ectocarpus ROCO and NB-ARC-TPR families are excellent candidates for being involved in recognition/transduction events linked to immunity. We further hypothesize that brown algae may generate their immune repertoire via controlled somatic recombination, so far only known from the vertebrate adaptive immune systems. 相似文献
36.
Aliprantis AO Stolina M Kostenuik PJ Poliachik SL Warner SE Bain SD Gross TS 《FASEB journal》2012,26(3):1110-1118
A unilateral injection of botulinum toxin A (BTxA) in the calf induces paralysis and profound loss of ipsalateral trabecular bone within days. However, the cellular mechanism underlying acute muscle paralysis-induced bone loss (MPIBL) is poorly understood. We hypothesized that MPIBL arises via rapid and extensive osteoclastogenesis. We performed a series of in vivo experiments to explore this thesis. First, we observed elevated levels of the proosteoclastogenic cytokine receptor activator for nuclear factor-κB ligand (RANKL) within the proximal tibia metaphysis at 7 d after muscle paralysis (+113%, P<0.02). Accordingly, osteoclast numbers were increased 122% compared with the contralateral limb at 5 d after paralysis (P=0.04) and MPIBL was completely blocked by treatment with human recombinant osteoprotegerin (hrOPG). Further, conditional deletion of nuclear factor of activated T-cells c1 (NFATc1), the master regulator of osteoclastogenesis, completely inhibited trabecular bone loss (-2.2±11.9%, P<0.01). All experiments included negative control assessments of contralateral limbs and/or within-animal pre- and postintervention imaging. In summary, transient muscle paralysis induced acute RANKL-mediated osteoclastogenesis resulting in profound local bone resorption. Elucidation of the pathways that initiate osteoclastogenesis after paralysis may identify novel targets to inhibit bone loss and prevent fractures. 相似文献
37.
Vardinoyannis K Demetropoulos S Mylonas M A Triantis K Makris C Georgiou G Wiktor A Demetropoulos A 《ZooKeys》2012,(174):63-77
Terrestrial slugs of the Island of Cyprus were recently studied in the framework of a study of the whole terrestrial malacofauna of the island. The present work was carried out in the Natura 2000 conservation areas of the island in 155 sampling sites over three years (2004-2007). Museum collections as well as literature references were included. In total six species are present in the Natura 2000 areas of the island, belonging to three families: Limacidae, Agriolimacidae and Milacidae. One of the species, Milax riedeli, is a new record for the island. The distribution of the species across the island and in the surrounding areas is discussed. 相似文献
38.
Nikolaidis MG Kyparos A Dipla K Zafeiridis A Sambanis M Grivas GV Paschalis V Theodorou AA Papadopoulos S Spanou C Vrabas IS 《Biomarkers》2012,17(1):28-35
Twenty males ran either on a level treadmill (nonmuscle-damaging condition) or on a downhill treadmill (muscle-damaging condition). Blood and urine samples were collected before and after exercise (immediately after, 1h, 4h, 24h, 48h, and 96h). The following assays were performed: F(2)-isoprostanes in urine, protein carbonyls in plasma, glutathione, superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes. The main finding was that monophasic redox responses were detected after nonmuscle-damaging exercise compared to the biphasic responses detected after muscle-damaging exercise. Based on these findings, muscle-damaging exercise may be a more appropriate experimental model to induce physiological oxidative stress. 相似文献
39.
Gargalionis AN Piperi C Adamopoulos C Papavassiliou AG 《The international journal of biochemistry & cell biology》2012,44(8):1276-1289
Epigenetic regulation of gene expression has provided colorectal cancer (CRC) pathogenesis with an additional trait during the past decade. In particular, histone post-translational modifications set up a major component of this process dictating chromatin status and recruiting non-histone proteins in complexes formed to "handle DNA". In CRC, histone marks of aberrant acetylation and methylation levels on specific residues have been revealed, along with a plethora of deregulated enzymes that catalyze these reactions. Mutations, deletions or altered expression patterns transform the function of several histone-modifying proteins, further supporting the crucial role of epigenetic effectors in CRC oncogenesis, being closely associated to inactivation of tumor suppressor genes. Elucidation of the biochemical basis of these new tumorigenic mechanisms allows novel potential prognostic factors to come into play. Moreover, the detection of these changes even in early stages of the multistep CRC process, along with the reversible nature of these mechanisms and the technical capability to detect such alterations in cancer cells, places this group of covalent modifications as a further potential asset for clinical diagnosis or treatment of CRC. This review underlines the biochemistry of histone modifications and the potential regulatory role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the underlying mechanisms of the emerging epigenetic interplay along with the chemical compounds that are candidates for clinical use are discussed, offering new insights for further investigation of key histone enzymes and new therapeutic targets. 相似文献
40.
Wang H Liu Z Li D Guo X Kasper FK Duan C Zhou J Mikos AG Wang C 《Journal of cellular and molecular medicine》2012,16(6):1310-1320
In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation. 相似文献