排序方式: 共有183条查询结果,搜索用时 31 毫秒
91.
Iliana Herrera José Cisneros Mariel Maldonado Remedios Ramírez Blanca Ortiz-Quintero Elena Anso Navdeep S. Chandel Moisés Selman Annie Pardo 《The Journal of biological chemistry》2013,288(36):25964-25975
Idiopathic pulmonary fibrosis is a devastating lung disorder of unknown etiology. Although its pathogenesis is unclear, considerable evidence supports an important role of aberrantly activated alveolar epithelial cells (AECs), which produce a large variety of mediators, including several matrix metalloproteases (MMPs), which participate in fibroblast activation and lung remodeling. MMP-1 has been shown to be highly expressed in AECs from idiopathic pulmonary fibrosis lungs although its role is unknown. In this study, we explored the role of MMP-1 in several AECs functions. Mouse lung epithelial cells (MLE12) transfected with human Mmp-1 showed significantly increased cell growth and proliferation at 36 and 48 h of culture (p < 0.01). Also, MMP-1 promoted MLE12 cell migration through collagen I, accelerated wound closing, and protected cells from staurosporine- and bleomycin-induced apoptosis compared with mock cells (p < 0.01). MLE12 cells expressing human MMP-1 showed a significant repression of oxygen consumption ratio compared with the cells with the empty vector. As under hypoxic conditions hypoxia-inducible factor-1α (HIF-1α) mediates a transition from oxidative to glycolytic metabolism, we analyzed activation of HIF-1α. Ηigher activation of this factor was detected in MMP-1-transfected cells under normoxia and hypoxia. Likewise, a significant decrease of both total and mitochondrial reactive oxygen species was observed in MMP-1-transfected cells. Paralleling these findings, attenuation of MMP-1 expression by shRNA in A549 (human) AECs markedly reduced proliferation and migration (p < 0.01) and increased the oxygen consumption ratio. These findings indicate that epithelial expression of MMP-1 inhibits mitochondrial function, increases HIF-1α expression, decreases reactive oxygen species production, and contributes to a proliferative, migratory, and anti-apoptotic AEC phenotype. 相似文献
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Idiopathic pulmonary fibrosis: new insights in its pathogenesis 总被引:9,自引:0,他引:9
Idiopathic pulmonary fibrosis (IPF) is a unique type of chronic fibrosing lung disease of unknown etiology. The sequence of the pathogenic mechanisms is unknown, but the disease is characterized by epithelial injury and activation, the formation of distinctive subepithelial fibroblast/myofibroblast foci, and excessive extracellular matrix accumulation. These pathological processes usually lead to progressive and irreversible changes in the lung architecture resulting in progressive respiratory insufficiency and an almost universally terminal outcome in a relatively short period of time. While research has largely focused on inflammatory mechanisms for initiating the fibrotic response, recent evidence strongly suggests that disruption of the alveolar epithelium is an underlying pathogenic event. Although treatment to date has proved largely ineffective, this new approach has opened up several promising therapeutic avenues. 相似文献
94.
Da Silva-Grigoletto ME De Hoyo M Sañudo B Carrasco L García-Manso JM 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(12):3326-3333
Da Silva-Grigoletto, ME, de Hoyo, M, Sa?udo, B, Corrales, L, and García-Manso, JM. Determining the optimal whole-body vibration dose-response relationship for muscle performance. J Strength Cond Res 25(12): 3326-3333, 2011-The aim of this investigation was twofold: first, to determine the optimal duration of a single whole-body vibration (WBV) exposure (phase 1) and second to find out the ideal number of sets per intervention to maximize muscle performance (phase 2). All participants were young (age: 19.4 ± 1.6 years), healthy, physically active men. In both studies, a 30-Hz frequency and a 4-mm peak-to-peak displacement were used. In phase 1, subjects (n = 30) underwent 3 sets of different durations (30, 60, and 90 seconds), whereas in phase 2, subjects (n = 27) underwent 3 interventions where the duration remained fixed at 60 seconds, and the number of sets performed (3, 6, or 9) was modified. The recovery time between sets was set at 2 minutes. In all interventions, each set consisted of 1 isometric repetition in a squat position with knees flexed at 100°. Before and after each session, jump height (countermovement jump [CMJ] and squat jump [SJ]) and power output in half squat (90° knee flexion) were assessed. In phase 1, an improvement in jump ability and power output was observed after the 30- and 60-second intervention (p < 0.01), whereas the 90 second intervention, participants just experienced a decrease in SJ and CMJ (p < 0.05). When comparing the different protocols, the greatest response was achieved using 60 seconds (p < 0.05), which was therefore considered as the optimal duration to be used in phase 2. In the second phase, improvements in jump ability and power output were found with 3 and 6 sets (p < 0.05), whereas with 9 sets, participants actually experienced a decrease in these variables. Intergroup comparison showed a greater effect for the program of 6 sets (p < 0.05). In conclusion, a WBV intervention consisting of six 60-second sets produces improved muscle performance measured by SJ, CMJ, and power output. 相似文献
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Campelo MW Oriá RB Lopes LG Brito GA Santos AA Vasconcelos RC Silva FO Nobrega BN Bento-Silva MT Vasconcelos PR 《Neurochemical research》2012,37(4):749-758
Rut-bpy is a novel nitrosyl–ruthenium complex releasing NO into the vascular system. We evaluated the effect of Rut-bpy (100 mg/kg)
on a rat model of brain stroke. Forty rats were assigned to four groups (Saline solution [SS], Rut-bpy, SS+ischemia–reperfusion
[SS+I/R] and Rut-bpy+ischemia–reperfusion [Rut-bpy+I/R]) with their mean arterial pressure (MAP) continuously monitored. The
groups were submitted (SS+I/R and Rut-bpy+I/R) or not (SS and Rut-bpy) to incomplete global brain ischemia by occlusion of
the common bilateral carotid arteries during 30 min followed by reperfusion for further 60 min. Thirty minutes before ischemia,
rats were treated pairwise by intraperitoneal injection of saline solution or Rut-bpy. At the end of experiments, brain was
removed for triphenyltetrazolium chloride staining in order to quantify the total ischemic area. In a subset of rats, hippocampus
was obtained for histopathology scoring, nitrate and nitrite measurements, immunostaining and western blotting of the nuclear
factor- κB (NF-κB). Rut-bpy pre-treatment decreased MAP variations during the transition from brain ischemia to reperfusion
and decreased the fractional injury area. Rut-bpy pre-treatment reduced NF-κB hippocampal immunostaining and protein expression
with improved histopathology scoring as compared to the untreated operated control. In conclusion, Rut-bpy improved the total
brain infarction area and hippocampal neuronal viability in part by inhibiting NF-κB signaling and helped to stabilize the
blood pressure during the transition from ischemia to reperfusion. 相似文献
97.
Chronic myeloid leukemia (CML) is a pluripotent hematopoietic disorder that is currently considered incurable. The tyrosine kinase product of the Philadelphia chromosome, P210 BCR-ABL, provided a pathogenetic explanation for the initiation of the CML chronic phase and is the molecular therapeutic target for the disease. Imatinib mesylate, an orally available BCR-ABL kinase inhibitor, can induce haematologic and cytogenetic remission of CML. However, imatinib resistance occurs frequently, resulting in relapse. New treatment strategies are focusing on resistant CML stem cells and the bone marrow stroma. The identification of novel pathways and mechanisms in the bone marrow microenvironment could significantly contribute to the development of such strategies. In this work, we used a high-resolution label-free MS(E) proteomic approach to identify differential protein expression in the CML bone marrow plasma of responsive and resistant patients. Oxidative lipid metabolism and regulation of the switch from canonical to noncanonical WNT signaling may contribute to CML resistance in the bone marrow compartment. 相似文献
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Ana M. González‐Di Pierro Moisés Méndez‐Toribio Isela Zermeño Víctor Arroyo‐Rodríguez Kathryn E. Stoner Alejandro Estrada 《Biotropica》2011,43(4):459-466
The regeneration of many tropical trees is threatened by forest fragmentation because it produces major physical, biological and ecological changes that limit seed germination and seedling establishment. We analyzed the regenerative potential of an old growth forest tree species—Ampelocera hottlei (Ulmaceae)—in three contrasting habitats located in the Lacandona rain forest, southeastern Mexico: continuous forest, fragments occupied by black howler monkeys (Alouatta pigra) and fragments unoccupied by howlers. We tested if germination of A. hottlei seeds among habitats was affected by understory temperature, light incidence and ingestion by A. pigra. We compared seedling survival and relative growth rate in height (RGRH) for 20 d among habitats and between ingested and control seeds (from mature fruits). Germination was higher in continuous forest than in fragments (occupied or not), with higher germination rates for ingested seeds in fragments. Temperature and light incidence were lower in continuous forest than in fragments. Germination decreased with increasing temperature and light incidence with this relationship being significantly higher for ingested seeds. Seedling survival was higher in continuous forest than in fragments, whereas RGRH did not differ among habitats. In addition, survival and RGRH were higher in seedlings originating from ingested seeds. Overall, our results suggest that the populations of A. hottlei can be limited in fragments where changes in the understory physical environment and the extirpation of A. pigra will likely have deleterious consequences for the regeneration of A. hottlei and possibly for other tree species, ultimately affecting forest composition and structure. Abstract in Spanish is available at http://www.blackwell‐synergy.com/loi/btp . 相似文献
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Suzana Gispert Filomena Ricciardi Alexander Kurz Mekhman Azizov Hans-Hermann Hoepken Dorothea Becker Wolfgang Voos Kristina Leuner Walter E. Müller Alexei P. Kudin Wolfram S. Kunz Annabelle Zimmermann Jochen Roeper Dirk Wenzel Marina Jendrach Moisés García-Arencíbia Javier Fernández-Ruiz Leslie Huber Hermann Rohrer Miguel Barrera Andreas S. Reichert Udo Rüb Amy Chen Robert L. Nussbaum Georg Auburger 《PloS one》2009,4(6)