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Angeliki Datsi Martin Steinhoff Fareed Ahmad Majid Alam Joerg Buddenkotte 《Allergy》2021,76(10):2982-2997
The cytokine interleukin-31 has been implicated in the pathophysiology of multiple atopic disorders such as atopic dermatitis (AD), allergic rhinitis, and airway hyper-reactivity. In AD, IL-31 has been identified as one of the main “drivers” of its cardinal symptom, pruritus. Here, we summarize the mechanisms by which IL-31 modulates inflammatory and allergic diseases. TH2 cells play a central role in AD and release high levels of TH2-associated cytokines including IL-31, thereby mediating inflammatory responses, initiating immunoregulatory circuits, stimulating itch, and neuronal outgrowth through activation of the heterodimeric receptor IL-31 receptor A (IL31RA)/Oncostatin M receptor (OSMRβ). IL31RA expression is found on human and murine dorsal root ganglia neurons, epithelial cells including keratinocytes and various innate immune cells. IL-31 is a critical cytokine involved in neuroimmune communication, which opens new avenues for cytokine modulation in neuroinflammatory diseases including AD/pruritus, as validated by recent clinical trials using an anti-IL-31 antibody. Accordingly, inhibition of IL-31-downstream signaling may be a beneficial approach for various inflammatory diseases including prurigo. However, as to whether downstream JAK inhibitors directly block IL-31-mediated-signaling needs to be clarified. Targeting the IL-31/IL31RA/OSMRβ axis appears to be a promising approach for inflammatory, neuroinflammatory, and pruritic disorders in the future. 相似文献
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Eli E. Machtei Georgios Romanos Philip Kang Suncica Travan Stephan Schmidt Evangelos Papathanasiou Nikolaos Tatarakis Moshik Tandlich Leila H. Liberman Jacob Horwitz Seyed Hossein Bassir Srinivas Myneni Harlan J. Shiau Lior Shapira Nikos Donos Athena Papas Joerg Meyle William V. Giannobile Panos N. Papapanou David M. Kim 《Journal of periodontology》2021,92(1):11-20
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Devon L. Drey Eric C. O'Quinn Tamilarasan Subramani Kristina Lilova Gianguido Baldinozzi Igor M. Gussev Antonio F. Fuentes Joerg C. Neuefeind Michelle Everett David Sprouster Alexandra Navrotsky Rodney C. Ewing Maik Lang 《RSC advances》2020,10(57):34632
Pyrochlore (A2B2O7) is an important, isometric structure-type because of its large variety of compositions and structural derivatives that are generally related to different disordering mechanisms at various spatial scales. The disordering is key to understanding variations in properties, such as magnetic behavior or ionic conduction. Neutron and X-ray total scattering methods were used to investigate the degree of structural disorder in the Ho2Ti2−xZrxO7 (x = 0.0–2.0, Δx = 0.25) solid solution series as a function of the Zr-content, x. Ordered pyrochlores (Fdm) disorder to defect fluorite (Fmm) via cation and anion disordering. Total scattering experiments with sensitivity to the cation and anion sublattices provide unique insight into the underlying atomic processes. Using simultaneous Rietveld refinement (long-range structure) and small-box refinement PDF analysis (short-range structure), we show that the series undergoes a rapid transformation from pyrochlore to defect fluorite at x ≈ 1.2, while the short-range structure exhibits a linear increase in a local weberite-type phase, C2221, over the entire composition range. Enthalpies of formation from the oxides determined using high temperature oxide melt solution calorimetry support the structural data and provide insight into the effect of local ordering on the energetics of disorder. The measured enthalpies of mixing are negative and are fit by a regular solution parameter of W = −31.8 ± 3.7 kJ mol−1. However, the extensive short-range ordering determined from the structural analysis strongly suggests that the entropies of mixing must be far less positive than implied by the random mixing of a regular solution. We propose a local disordering scheme involving the pyrochlore 48f to 8a site oxygen Frenkel defect that creates 7-coordinated Zr sites contained within local weberite-type coherent nanodomains. Thus, the solid solution is best described as a mixture of two phases, with the weberite-type nanodomains triggering the long-range structural transformation to defect fluorite after accumulation above a critical concentration (50% Ti replaced by Zr).Combined neutron and X-ray total scattering with calorimetric measurements of the solid solution series Ho2Ti2−xZrxO7 reveals a complex order–disorder transition across short, intermediate, and long length scales induced by chemical substitution. 相似文献
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Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community
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Philipp Houben Giulia Manzini Michael Kremer Joerg Arend Gabriela A. Berlakovich Ernst Klar Jürgen Klempnauer Jan Lerut Gerd Otto Jacques Pirenne Xavier Rogiers Daniel Seehofer Dirk L. Stippel Peter Schemmer 《Transplant international》2015,28(11):1291-1298
Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty‐four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community. 相似文献
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Schuettrumpf J Herzog RW Schlachterman A Kaufhold A Stafford DW Arruda VR 《Blood》2005,105(6):2316-2323
Intramuscular injection of adeno-associated viral (AAV) vector to skeletal muscle of humans with hemophilia B is safe, but higher doses are required to achieve therapeutic factor IX (F.IX) levels. The efficacy of this approach is hampered by the retention of F.IX in muscle extracellular spaces and by the limiting capacity of muscle to synthesize fully active F.IX at high expression rates. To overcome these limitations, we constructed AAV vectors encoding F.IX variants for muscle- or liver-directed expression in hemophilia B mice. Circulating F.IX levels following intramuscular injection of AAV-F.IX-K5A/V10K, a variant with low-affinity to extracellular matrix, were 2-5 fold higher compared with wild-type (WT) F.IX, while the protein-specific activities remained similar. Expression of F.IX-R338A generated a protein with 2- or 6-fold higher specific activity than F.IX-WT following vector delivery to skeletal muscle or liver, respectively. F.IX-WT and variant forms provide effective hemostasis in vivo upon challenge by tail-clipping assay. Importantly, intramuscular injection of AAV-F.IX variants did not trigger antibody formation to F.IX in mice tolerant to F.IX-WT. These studies demonstrate that F.IX variants provide a promising strategy to improve the efficacy for a variety of gene-based therapies for hemophilia B. 相似文献