Objective. Nuclear factor-B (NF-B) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-B, might have antiarthritic effects.Methods. An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally.Results. In vitro experiments demonstrated that AdA20 suppressed NF-B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor ␣ in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus-injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-B signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-B. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study.Conclusion. These results suggest that using A20 to block the NF-B pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA.
Objective. Insulin-like growth factor binding protein 3 (IGFBP-3) is known to interfere with the NF-B signaling pathway, and it effectively promotes apoptosis in tumor cells by a variety of mechanisms. NF-B activation and apoptosis resistance of fibroblast-like synoviocytes (FLS) play pivotal roles in rheumatoid arthritis (RA). This study was undertaken to evaluate whether IGFBP-3 has antiarthritic effects.Methods. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 complementary DNA (AdIGFBP-3) or IGFBP-3 mutant that is devoid of IGF binding affinity but retains IGFBP-3 receptor binding ability (AdmtIGFBP-3). The regulatory roles of IGFBP-3 in inflammation and bone destruction were investigated in mice with collagen-induced arthritis (CIA).Results. IGFBP-3 levels were significantly higher in patients with RA than in those with osteoarthritis (OA) and were notably higher in patients with active RA. AdIGFBP-3 suppressed NF-B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor ␣ (TNF␣) in RA FLS. AdIGFBP-3 sensitized RA FLS to TNF␣-induced apoptosis in vitro and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice. AdIGFBP-3-injected mice with CIA had attenuated arthritis severity and reduced radiologic and pathologic abnormalities. Moreover, AdIGFBP-3 down-regulated local and systemic levels of NF-B-targeted proinflammatory cytokines. Of note, RA FLS and mice with CIA treated with AdmtIGFBP-3 exhibited similar effects as those treated with AdIGFBP-3.Conclusion. Our results suggest that both the inflammatory response and bone destruction are reduced with blockage of NF-B activation and induction of apoptosis in RA FLS by IGFBP-3. Therefore, IGFBP-3 may have therapeutic potential in RA.
Recent satellite missions have provided new perspectives by offering high spatial resolution, a variety of spectral properties, and fast revisit rates to the same regions. In this study, we examined the utility of both broadband red-edge spectral information and texture features for classifying paddy rice crops in South Korea into three different growth stages. The rice grown in South Korea can be grouped into earlymaturing, medium-maturing, and medium-late-maturing cultivars, and each cultivar is known to have a minimum and maximum productivity. Therefore, the accurate classification of paddy rice crops into a certain time line enables pre-estimation of the expected rice yields. For the analysis, two seasons of RapidEye satellite image data were used. The results showed that the broadband red-edge information slightly improved the classification accuracy of the paddy rice crops, particularly when single-season image data were used. In contrast, texture information resulted in only minor improvement or even a slight decline in accuracy, although it is known to be advantageous for object-based classification. This was due to the homogeneous nature of paddy rice fields, as different rice cultivars are similar in terms of their morphology. Based on these results, we conclude that the additional spectral information such as the red-edge band is more useful than the texture features to detect different crop conditions in relatively homogeneous rice paddy environments. We therefore confirm the potential of broadband red-edge information to improve the classification of paddy rice crops. However, there is still a need to examine the relationship between textural properties and paddy rice crop parameters in greater depth.
ObjectiveSIRT1 modulates the acetylation of the p65 subunit of nuclear factor-κB (NF-κB) and plays a pivotal role in the inflammatory response. This study sought to assess the role of SIRT1 in rheumatoid arthritis (RA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse.MethodsmSIRT1 KO mice were generated using the loxP/Cre recombinase system. K/BxN serum transfer arthritis was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical and pathological scoring. The levels of inflammatory cytokines in the serum and joints were measured by ELISA. Migration, M1 polarization, cytokine production, osteoclastogenesis, and p65 acetylation were assessed in bone marrow-derived monocytes/macrophages (BMMs).ResultsmSIRT1 KO mice showed more severe inflammatory arthritis and aggravated pathological findings than control mice. These effects were paralleled by increases in IL-1, TNF-α, TRAP-positive osteoclasts, and F4/80+ macrophages in the ankles of mSIRT1 KO mice. In addition, BMMs from mSIRT1 KO mice displayed hyperacetylated p65 and increased NF-κB binding activity when compared to control mice, which resulted in increased M1 polarization, migration, pro-inflammatory cytokine production, and osteoclastogenesis.ConclusionOur study provides in vivo evidence that myeloid cell-specific deletion of SIRT1 exacerbates inflammatory arthritis via the hyperactivation of NF-κB signaling, which suggests that SIRT1 activation may be beneficial in the treatment of inflammatory arthritis.
Abstract:The monitoring of crop development can benefit from the increased frequency of observation provided by modern geostationary satellites. This paper describes a four-year testing period from 2010 to 2014, during which satellite images from the world's first Geostationary Ocean Color Imager (GOCI) were used for spectral analyses of paddy rice in South Korea. A vegetation index was calculated from GOCI data based on the bidirectional reflectance distribution function (BRDF)-adjusted reflectance, which was then used to visually analyze the seasonal crop dynamics. These vegetation indices were then compared with those calculated using the Moderate-resolution Imaging Spectroradiometer (MODIS)-normalized difference vegetation index (NDVI) based on Nadir BRDF-adjusted reflectance. The results show clear advantages of GOCI, which provided four times better temporal resolution than the combined MODIS sensors, interpreting subtle characteristics of the vegetation development. Particularly in the rainy season, when data acquisition under clear weather conditions was very limited, it was possible to find cloudless pixels within the study sites by compiling GOCI images obtained from eight acquisition periods per day, from which the vegetation index could be calculated. In this study, ground spectral measurements from CROPSCAN were also compared with satellite-based vegetation products, despite their different index magnitude, according to systematic discrepancy, showing a similar crop development pattern to the GOCI products. Consequently, we conclude that the very high temporal resolution of GOCI is very beneficial for monitoring crop development, and has potential for providing improved information on phenology. OPEN ACCESSRemote Sens. 2015, 7 11327
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