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      Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice.

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          Abstract

          Excessive production of inflammatory chemokines can cause chronic inflammation and thus impair cutaneous wound healing. Capturing chemokine signals using wound dressing materials may offer powerful new treatment modalities for chronic wounds. Here, a modular hydrogel based on end-functionalized star-shaped polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG) heparin was customized for maximal chemokine sequestration. The material is shown to effectively scavenge the inflammatory chemokines MCP-1 (monocyte chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1α (macrophage inflammatory protein-1α) and MIP-1β (macrophage inflammatory protein-1β) in wound fluids from patients suffering from chronic venous leg ulcers and to reduce the migratory activity of human monocytes and polymorphonuclear neutrophils. In an in vivo model of delayed wound healing (db/db mice), starPEG-GAG hydrogels outperformed the standard-of-care product Promogran with respect to reduction of inflammation, as well as increased granulation tissue formation, vascularization, and wound closure.

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          Most cited references 67

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          ClusPro: an automated docking and discrimination method for the prediction of protein complexes.

          Predicting protein interactions is one of the most challenging problems in functional genomics. Given two proteins known to interact, current docking methods evaluate billions of docked conformations by simple scoring functions, and in addition to near-native structures yield many false positives, i.e. structures with good surface complementarity but far from the native. We have developed a fast algorithm for filtering docked conformations with good surface complementarity, and ranking them based on their clustering properties. The free energy filters select complexes with lowest desolvation and electrostatic energies. Clustering is then used to smooth the local minima and to select the ones with the broadest energy wells-a property associated with the free energy at the binding site. The robustness of the method was tested on sets of 2000 docked conformations generated for 48 pairs of interacting proteins. In 31 of these cases, the top 10 predictions include at least one near-native complex, with an average RMSD of 5 A from the native structure. The docking and discrimination method also provides good results for a number of complexes that were used as targets in the Critical Assessment of PRedictions of Interactions experiment. The fully automated docking and discrimination server ClusPro can be found at http://structure.bu.edu
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            Chemokines and disease.

            We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.
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              Heparin-Protein Interactions

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                Author and article information

                Journal
                Sci Transl Med
                Science translational medicine
                American Association for the Advancement of Science (AAAS)
                1946-6242
                1946-6234
                Apr 19 2017
                : 9
                : 386
                Affiliations
                [1 ] Department of Dermatology, Venerology, and Allergology, Leipzig University, 04103 Leipzig, Germany.
                [2 ] Collaborative Research Center (SFB-TR67) "Functional Biomaterials for Controlling Healing Processes in Bone and Skin-From Material Science to Clinical Application," Leipzig and Dresden, Germany.
                [3 ] Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, 01069 Dresden, Germany.
                [4 ] Technische Universität Dresden, Center for Regenerative Therapies Dresden, Fetscherstraße 105, 01307 Dresden, Germany.
                [5 ] Department of Dermatology, Venerology, and Allergology, Leipzig University, 04103 Leipzig, Germany. sandra.franz@medizin.uni-leipzig.de freudenberg@ipfdd.de.
                [6 ] Collaborative Research Center (SFB-TR67) "Functional Biomaterials for Controlling Healing Processes in Bone and Skin-From Material Science to Clinical Application," Leipzig and Dresden, Germany. sandra.franz@medizin.uni-leipzig.de freudenberg@ipfdd.de.
                Article
                9/386/eaai9044
                10.1126/scitranslmed.aai9044
                28424334

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