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Juan I. Moliva Murugesan V. S. Rajaram Sabeen Sidiki Smitha J. Sasindran Evelyn Guirado Xueliang Jeff Pan Shu-Hua Wang Patrick Ross Jr. William P. Lafuse Larry S. Schlesinger Joanne Turner Jordi B. Torrelles 《Age (Dordrecht, Netherlands)》2014,36(3):1187-1199
As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population. 相似文献
53.
The management of osteoarthritis (OA) is a major challenge. Most published recommendations aim to control OA symptoms, i.e. reduce pain and improve joint function. However, the main aim of the treatment of OA is to halt or delay disease progression. In line with this aim, the various therapies should help to preserve articular structure by controlling cartilage degradation, synovitis and sclerosis of subchondral bone, the three tissues involved in the physiopathology of OA. This aim should be kept in mind both in the development of future treatments and in currently available drugs. Chondroitin sulfate is a symptomatic slow-acting drug for osteoarthritis (SYSADOA). There is, however, an increasing body of evidence showing the effect of disease modifying osteoarthritis drugs (DMOAD), i.e. slow-acting drugs for OA able to modify structure. This review aims to synthesize the information on the protective effect of chondroitin sulfate on cartilage, as well as its ability to preserve the structure of subchondral bone. 相似文献
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Ke Zheng Jordi Xiol Michael Reuter Sigrid Eckardt N. Adrian Leu K. John McLaughlin Alexander Stark Ravi Sachidanandam Ramesh S. Pillai Peijing Jeremy Wang 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(26):11841-11846
Piwi-interacting RNAs (piRNAs) are essential for silencing of transposable elements in the germline, but their biogenesis is poorly understood. Here we demonstrate that MOV10L1, a germ cell–specific putative RNA helicase, is associated with Piwi proteins. Genetic disruption of the MOV10L1 RNA helicase domain in mice renders both MILI and MIWI2 devoid of piRNAs. Absence of a functional piRNA pathway in Mov10l1 mutant testes causes loss of DNA methylation and subsequent derepression of retrotransposons in germ cells. The Mov10l1 mutant males are sterile owing to complete meiotic arrest. This mouse mutant expresses Piwi proteins but lacks piRNAs, suggesting that MOV10L1 is required for piRNA biogenesis and/or loading to Piwi proteins. 相似文献
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Francisco J. Padillo Juan F. Ruiz‐Rabelo Adolfo Cruz María D. Perea Inmaculada Tasset Pedro Montilla Isaac Túnez Jordi Muntané 《Journal of pineal research》2010,49(3):264-270
Abstract: Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin (MEL) has antioxidant activity and prevents experimental genotoxicity. The specific inhibitor of cyclooxygenase‐2 (COX‐2), celecoxib (CEL), increases the efficacy of chemoradiotherapy in advanced pancreatic cancer. The objective of the study was the comparison and synergic effect of MEL and CEL during either the induction or progression phases of the tumor process, measuring parameters of oxidative stress, number of tumor nodules and survival of animals with pancreatic cancer. Pancreatic cancer was induced by N‐nitrosobis (2‐oxopropyl)amine) (BOP) in Syrian hamsters. Melatonin and/or CEL were administered during the induction, postinduction as well as during both phases. The presence of tumor nodules were observed macroscopically in pancreatic and splenic areas, and the levels of lipoperoxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) in pancreatic tissue were measured. The increases in tumor nodules and LPO as well as the reductions in GSH and enzymatic antioxidants in the pancreas induced by BOP were related to a lower survival rate of animals. The administration of MEL exerted a more potent beneficial effect than CEL treatment on the reduction in tumor nodules, oxidative stress and death of experimental BOP‐treated animals. The combined treatment only exerted a synergistic beneficial effect when administered during the induction phase. Melatonin by itself had significant beneficial actions in improving the survival of hamsters. 相似文献
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Peran L Camuesco D Comalada M Nieto A Concha A Diaz-Ropero MP Olivares M Xaus J Zarzuelo A Galvez J 《World journal of gastroenterology : WJG》2005,11(33):5185-5192
AIM: To investigate the intestinal anti-inflammatory effect and mechanism of a probiotic Lactobacillus salivarius ssp. salivarius CECT5713 in the TNBS model of rat colitis. METHODS: Female Wistar rats (180-200 g) were used in this study. A group of rats were administered orally the probiotic L. salivarius ssp. salivarius(5×108 CFU suspended in 0.5 mL of skimmed milk) daily for 3 wk. Two additional groups were used for reference, a non-colitic and a control colitic without probiotic treatment, which received orally the vehicle used to administer the probiotic. Two weeks after starting the experiment, the rats were rendered colitic by intracolonic administration of 10 mg of TNBS dissolved in 0.25 mL of 500 mL/L ethanol. One week after colitis induction, all animals were killed and colonic damage was evaluated both histologically and biochemically. The biochemical studies performed in colonic homogenates include determination of myeloperoxidase (MPO) activity, glutathione (GSH) content, leukotriene B4 (LTB4) and tumor necrosis factor a (TNF-α) levels, as well as inducible nitric oxide synthase (iNOS) expression. In addition, the luminal contents obtained from colonic samples were used for microbiological studies, in order to determine Lactobacilli and Bifidobacteria counts. RESULTS: Treatment of colitic rats with L salivarius ssp. salivarius resulted in amelioration of the inflammatory response in colitic rats, when compared with the corresponding control group without probiotic treatment. This anti-inflammatory effect was evidenced macroscopically by a significant reduction in the extent of colonic necrosis and/or inflammation induced by the administration of TNBS/ethanol (2.3±0.4 cm vs 53.4±0.3 cm in control group, P<0.01) and histologically by improvement of the colonic architecture associated with a reduction in the neutrophil infiltrate in comparison with non-treated colitic rats. The latter was confirmed biochemically by a significant reduction of colonic MPO activity (105.3±26.0 U/g vs 180.6±21.9 U/g, P<0.05) a marker of neutrophil infiltration. The beneficial effect was associated with an increase of the colonic GSH content (1 252±42 nmol/g vs 1 087±51 nmol/g,P<0.05), which is depleted in colitic rats, as a consequence of the oxidative stress induced by the inflammatory process. In addition, the treatment of colitic rats with L. salivarius resulted in a significant reduction of colonic TNF-α levels (509.4±68.2 pg/g vs 782.9±60.1 pg/g, P<0.01) and in a lower colonic iNOS expression, when compared to TNBS control animals without probiotic administration. Finally, treated colitic rats showed higher counts of Lactobacilli species in colonic contents than control colitic rats, whereas no differences were observed in Bifidobacteria counts. CONCLUSION: Administration of the probiotic L. salivarius ssp. salivarius CECT5713 facilitates the recovery of the inflamed tissue in the TNBS model of rat colitis, an effect associated with amelioration of the production of some of the mediators involved in the inflammatory response in the intestine, such as cytokines, including TNF-α and NO. This beneficial effect could be ascribed to its effect on the altered immune response that occurs in this inflammatory condition. 相似文献