Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human osteoarthritis synovium and synovial fibroblasts

AbstractObjective: In this study we investigated the effect of interleukin-13 (IL-13), an anti-inflammatory cytokine, for potential therapeutic use in osteoarthritis (OA).Design: We examined the effect of IL-13 on the synthesis and expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-1 receptor antagonist (IL-1Ra) and stromelysin-1 on human OA synovial membrane inex vivocultures. In addition, we explored the effect of IL-13 on both the IL-1 receptor (IL-1R) and TNF-receptor (TNF-R) systems on OA synovial fibroblasts. This included determination of the levels of IL-1β and TNF-α receptor binding, IL-1Ra and TNF-soluble receptors 55 and 75 (TNF-sR55 and TNF-sR75).Results: In OA synovial membrane treated with LPS, IL-13 inhibited the synthesis of IL-1β, TNF-α and stromelysin-1, but increased IL-1Ra production. In addition, IL-13 reduced the level of IL-1β mRNA and stimulated the level of IL-1Ra mRNA. In synovial fibroblasts, IL-13 decreased the level of IL-1 binding, an effect related to the increased production of IL-1Ra. Although IL-13 had no effect on the TNF-R level, this cytokine markedly decreased the shedding of TNF-R75.Conclusion: These experiments suggest that IL-13 is potentially useful in the therapeutic treatment of OA, as it could regulate the major pathological process of this disease by reducing the production of proinflammatory cytokines and metalloproteases, and favoring the production of IL-1Ra

Tree Line Identification and Dynamics under Climate Change in Wuyishan National Park Based on Landsat Images

The alpine tree line ecotone, reflecting interactions between climate and ecology, is very sensitive to climate change. To identify tree line responses to climate change, including intensity and local variations in tree line advancement, the use of Landsat images with long-term data series and fine spatial resolution is an option. However, it is a challenge to extract tree line data from Landsat images due to classification issues with outliers and temporal inconsistency. More importantly, direct classification results in sharp boundaries between forest and non-forest pixels/segments instead of representing the tree line ecotone (three ecological regions—tree species line, tree line, and timber line—are closely related to the tree line ecotone and are all significant for ecological processes). Therefore, it is important to develop a method that is able to accurately extract the tree line from Landsat images with a high temporal consistency and to identify the appropriate ecological boundary. In this study, a new methodology was developed based on the concept of a local indicator of spatial autocorrelation (LISA) to extract the tree line automatically from Landsat images. Tree line responses to climate change from 1987 to 2018 in Wuyishan National Park, China, were evaluated, and topographic effects on local variations in tree line advancement were explored. The findings supported the methodology based on the LISA concept as a valuable classifier for assessing the local spatial clusters of alpine meadows from images acquired in nongrowing seasons. The results showed that the automatically extracted line from Landsat images was the timber line due to the restriction in spatial autocorrelation. The results also indicate that parts of the tree line in the study area shifted upward vertically by 50 m under a 1 °C temperature increase during the period from 1987 to 2018, with local variations influenced by slope, elevation, and interactions with aspect. Our study contributes a novel result regarding the response of the alpine tree line to global warming in a subtropical region. Our method for automatic tree line extraction can provide fundamental information for ecosystem managers

Normal expression of type 1 insulin-like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin-like growth factor binding proteins.

International audienceObjective. Our previous research demonstrated that, in contrast to normal chondrocytes, human osteoarthritic (OA) chondrocytes were hyporesponsive to stimulation by insulin-like growth factor 1 (IGF-1). The aim of the present investigation was to examine whether this finding was due to an alteration in the level of IGF receptors (IGFRs) and/or IGF binding proteins (IGFBP).Methods. A quantitative reverse transcriptase polymerase chain reaction technique (RT-PCR) was used to measure the type 1 IGFR messenger RNA (mRNA) level, and Northern blotting was used to measure type 2 IGFR and IGFBP mRNA levels. Western immunoblotting was used to identify and measure IGFBP levels.Results. There were similar levels of type 1 IGFR mRNA in normal and OA chondrocytes. The level of type 2 IGFR mRNA, in which an increased amount of which can interfere with the biologic effects of IGF-1, was lower in OA chondrocytes compared with normal chondrocytes. Articular chondrocytes produced IGFBP-2, IGFBP-3, and IGFBP-4, and OA chondrocytes secreted and expressed higher amounts than did normal chondrocytes. There was also an increased level of IGFBP-3 in the OA chondrocyte lysates. IGFBPs 1, 5, and 6 were not detectable.Conclusion. OA chondrocytes synthesize and express a larger amount of 3 IGFBPs. This observation, along with a lack of detectable change in type 1 IGFR mRNA level, suggests that the hyporesponsiveness of OA chondrocytes to IGF-1 might implicate the involvement of IGFBPs in this pathologic process

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s

CEPC Technical Design Report -- Accelerator

The Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s