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51.
52.
Jang Hye Jin Choi Ji Yeon Kim Kangjoon Yong Seung Hyun Kim Yeon Wook Kim Song Yee Kim Eun Young Jung Ji Ye Kang Young Ae Park Moo Suk Kim Young Sam Cho Young-Jae Lee Sang Hoon 《Respiratory research》2021,22(1):1-9
IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis. 相似文献
53.
The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites. 相似文献
54.
Daniel C. Ilut Alexander E. Lipka Namhee Jeong Dong Nyuk Bae Dong Hyun Kim Ji Hong Kim Neelam Redekar Kiwoung Yang Won Park Sung-Taeg Kang Namshin Kim Jung-Kyung Moon M. A. Saghai Maroof Michael A. Gore Soon-Chun Jeong 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2016,129(3):453-468
55.
Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding affinities to EDG-1, -3, and -5. 相似文献
56.
Wei Choon Alvin Koh Eun Sang Choe Dong Kun Lee Seung-Cheol Chang Yoon-Bo Shim 《Biosensors & bioelectronics》2009,25(1):211-217
An all solid state potentiometric immunosensor (ASPI) has been developed to study the activation process of neuronal nitric oxide synthase (nNOS), the enzyme involved in the synthesis of nitric oxide generated under physiological conditions. At first, an all solid state H+-selective ISE was fabricated with the carboxylated poly(vinyl chloride) (PVC-COOH) film containing H+ ionophore, antibody was then immobilized on the polymer layer. The immunocomplex formation was detected by monitoring pH change due to interaction between urease labeled secondary antibody and antigen. Experimental parameters such as the amount of phosphorylated nNOS immobilized on the electrode surface and pH responses due to the antibody–antigen reaction were studied in detail. The calibration plot of the potentiometric potential vs. phosphorylated nNOS concentration exhibited a linear relationship in the range of 3.4–340.0 μg/ml. The calibration sensitivity of the phosphorylated nNOS immunosensor was −0.073 ± 0.002 mV/μg ml−1. The detection limit of nNOS was determined to be 0.2 μg/ml based on five-time measurements (95% confidence level, k = 3, n = 5). The reliability of the immunosensor was examined with rat brain tissues as well as neuronal cells, and the results shown were good, implying a promising approach for a novel electrochemical immunosensor platform with potential applications to clinical diagnosis. 相似文献
57.
Oxidative stress caused by pyocyanin impairs CFTR Cl(-) transport in human bronchial epithelial cells 总被引:1,自引:0,他引:1
Schwarzer C Fischer H Kim EJ Barber KJ Mills AD Kurth MJ Gruenert DC Suh JH Machen TE Illek B 《Free radical biology & medicine》2008,45(12):1653-1662
Pyocyanin (N-methyl-1-hydroxyphenazine), a redox-active virulence factor produced by the human pathogen Pseudomonas aeruginosa, is known to compromise mucociliary clearance. Exposure of human bronchial epithelial cells to pyocyanin increased the rate of cellular release of H(2)O(2) threefold above the endogenous H(2)O(2) production. Real-time measurements of the redox potential of the cytosolic compartment using the redox sensor roGFP1 showed that pyocyanin (100 microM) oxidized the cytosol from a resting value of -318+/-5 mV by 48.0+/-4.6 mV within 2 h; a comparable oxidation was induced by 100 microM H(2)O(2). Whereas resting Cl(-) secretion was slightly activated by pyocyanin (to 10% of maximal currents), forskolin-stimulated Cl(-) secretion was inhibited by 86%. The decline was linearly related to the cytosolic redox potential (1.8% inhibition/mV oxidation). Cystic fibrosis bronchial epithelial cells homozygous for DeltaF508 CFTR failed to secrete Cl(-) in response to pyocyanin or H(2)O(2), indicating that these oxidants specifically target the CFTR and not other Cl(-) conductances. Treatment with pyocyanin also decreased total cellular glutathione levels to 62% and cellular ATP levels to 46% after 24 h. We conclude that pyocyanin is a key factor that redox cycles in the cytosol, generates H(2)O(2), depletes glutathione and ATP, and impairs CFTR function in Pseudomonas-infected lungs. 相似文献
58.
Young Jun Kim Kwang Pyo Kim Hae Jin Rhee Sudipto Das John D Rafter Youn Sang Oh Wonhwa Cho 《The Journal of biological chemistry》2002,277(11):9358-9365
Mammalian secretory phospholipases A(2) (sPLA(2)) have been implicated in cellular eicosanoid biosynthesis but the mechanism of their cellular action remains unknown. To elucidate the spatiotemporal dynamics of sPLA(2) mobilization and determine the site of its lipolytic action, we performed time-lapse confocal microscopic imaging of fluorescently labeled sPLA(2) acting on human embryonic kidney (HEK) 293 cells the membranes of which are labeled with a fluorogenic phospholipid, N-((6-(2,4-dinitrophenyl)amino)hexanoyl)-1-hexadecanoyl-2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-sn-glycero-3-phosphoethanolamine. The Western blotting analysis of HEK293 cells treated with exogenous sPLA(2)s showed that not only the affinity for heparan sulfate proteoglycan but also other factors, such as sPLA(2) hydrolysis products or cytokines, are necessary for the internalization of sPLA(2) into HEK293 cells. Live cell imaging showed that the hydrolysis of fluorogenic phospholipids incorporated into HEK293 cell membranes was synchronized with the spatiotemporal dynamics of sPLA(2) internalization, detectable initially at the plasma membrane and then at the perinuclear region. Also, immunocytostaining showed that human group V sPLA(2) induced the translocation of 5-lipoxygenase to the nuclear envelope at which they were co-localized. Together, these studies provide the first experimental evidence that the internalized sPLA(2) acts on the nuclear envelope to provide arachidonate for other enzymes involved in the eicosanoid biosynthesis. 相似文献
59.
A study was conducted to determine the efficacy of β-mannanase supplementation to a diet based on corn and soya bean meal (SBM) on growth performance, nutrient digestibility, blood urea nitrogen (BUN), faecal coliforms and lactic acid bacteria, and noxious gas emission in growing pigs. A total of 140 pigs [(Landrace × Yorkshire) × Duroc; average body weight 25 ± 3 kg] were randomly allotted to a 2 × 2 factorial arrangement with dietary treatments consisting of hulled or dehulled SBM without or with supplementation of 400 U β-mannanase/kg. During the 6 weeks of experimental feeding, β-mannanase supplementation had no effect on body weight gain, feed intake and gain:feed (G:F) ratio. Compared with dehulled SBM, feeding hulled SBM caused an increased feed intake of pigs in the entire trial (p = 0.05). The G:F ratio was improved in pigs receiving dehulled SBM (p < 0.05). Dietary treatments did not influence the total tract digestibility of dry matter, nitrogen and gross energy. Enzyme supplementation reduced (p < 0.05) the population of faecal coliforms and tended to reduce the NH3 concentration after 24 h of fermentation in a closed box containing faecal slurry. Feeding hulled SBM tended to reduce NH3 emission on days 3 and 5 of fermentation. In conclusion, mannanase supplementation had no influence on growth performance and nutrient digestibility but showed a positive effect on reducing coliform population and tended to reduce NH3 emission. Dehulled SBM increased G:F ratio and hulled SBM tended to reduce NH3 emission. 相似文献
60.
Hye Ran Park Jae Meen Lee Gwanhee Ehm Hui-Jun Yang In Ho Song Yong Hoon Lim Mi-Ryoung Kim Keyoung Ran Kim Woong-Woo Lee Young Eun Kim Jae Ha Hwang Chae Won Shin Hyeyoung Park Jin Wook Kim Han-Joon Kim Cheolyoung Kim Dong Gyu Kim Beom Seok Jeon Sun Ha Paek 《PloS one》2016,11(1)