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- ItemNaturally drug-loaded chitin: Isolation and applications(Basel : MDPI, 2019) Kovalchuk, Valentine; Voronkina, Alona; Binnewerg, Björn; Schubert, Mario; Muzychka, Liubov; Wysokowski, Marcin; Tsurkan, Mikhail V.; Bechmann, Nicole; Petrenko, Iaroslav; Fursov, Andriy; Martinovic, Rajko; Ivanenko, Viatcheslav N.; Fromont, Jane; Smolii, Oleg B.; Joseph, Yvonne; Giovine, Marco; Erpenbeck, Dirk; Gelinsky, Michael; Springer, Armin; Guan, Kaomei; Bornstein, Stefan R.; Ehrlich, HermannNaturally occurring three-dimensional (3D) biopolymer-based matrices that can be used in different biomedical applications are sustainable alternatives to various artificial 3D materials. For this purpose, chitin-based structures from marine sponges are very promising substitutes. Marine sponges from the order Verongiida (class Demospongiae) are typical examples of demosponges with well-developed chitinous skeletons. In particular, species belonging to the family Ianthellidae possess chitinous, flat, fan-like fibrous skeletons with a unique, microporous 3D architecture that makes them particularly interesting for applications. In this work, we focus our attention on the demosponge Ianthella flabelliformis (Linnaeus, 1759) for simultaneous extraction of both naturally occurring (“ready-to-use”) chitin scaffolds, and biologically active bromotyrosines which are recognized as potential antibiotic, antitumor, and marine antifouling substances. We show that selected bromotyrosines are located within pigmental cells which, however, are localized within chitinous skeletal fibers of I. flabelliformis. A two-step reaction provides two products: treatment with methanol extracts the bromotyrosine compounds bastadin 25 and araplysillin-I N20 sulfamate, and a subsequent treatment with acetic acid and sodium hydroxide exposes the 3D chitinous scaffold. This scaffold is a mesh-like structure, which retains its capillary network, and its use as a potential drug delivery biomaterial was examined for the first time. The results demonstrate that sponge-derived chitin scaffolds, impregnated with decamethoxine, effectively inhibit growth of the human pathogen Staphylococcus aureus in an agar diffusion assay
- ItemSpider chitin: An Ultrafast Microwave-Assisted Method for Chitin Isolation from Caribena versicolor Spider Molt Cuticle(Basel : MDPI, 2019) Machałowski, Tomasz; Wysokowski, Marcin; Tsurkan, Mikhail V.; Galli, Roberta; Schimpf, Christian; Rafaja, David; Brendler, Erica; Viehweger, Christine; Zółtowska-Aksamitowska, Sonia; Petrenko, Iaroslav; Czaczyk, Katarzyna; Kraft, Michael; Bertau, Martin; Bechmann, Nicole; Guan, Kaomei; Bornstein, Stefan R.; Voronkina, Alona; Fursov, Andriy; Bejger, Magdalena; Biniek-Antosiak, Katarzyna; Rypniewski, Wojciech; Figlerowicz, Marek; Pokrovsky, Oleg; Jesionowski, Teofil; Ehrlich, HermannChitin, as a fundamental polysaccharide in invertebrate skeletons, continues to be actively investigated, especially with respect to new sources and the development of effective methods for its extraction. Recent attention has been focused on marine crustaceans and sponges; however, the potential of spiders (order Araneae) as an alternative source of tubular chitin has been overlooked. In this work, we focused our attention on chitin from up to 12 cm-large Theraphosidae spiders, popularly known as tarantulas or bird-eating spiders. These organisms “lose” large quantities of cuticles during their molting cycle. Here, we present for the first time a highly effective method for the isolation of chitin from Caribena versicolor spider molt cuticle, as well as its identification and characterization using modern analytical methods. We suggest that the tube-like molt cuticle of this spider can serve as a naturally prefabricated and renewable source of tubular chitin with high potential for application in technology and biomedicine. © 2019 by the authors.
- ItemNaturally prefabricated marine biomaterials: Isolation and applications of flat chitinous 3D scaffolds from Ianthella labyrinthus (demospongiae: Verongiida)(Basel : Molecular Diversity Preservation International, 2019) Schubert, Mario; Binnewerg, Björn; Voronkina, Alona; Muzychka, Lyubov; Wysokowski, Marcin; Petrenko, Iaroslav; Kovalchuk, Valentine; Tsurkan, Mikhail; Martinovic, Rajko; Bechmann, Nicole; Ivanenko, Viatcheslav N.; Fursov, Andriy; Smolii, Oleg B.; Fromont, Jane; Joseph, Yvonne; Bornstein, Stefan R.; Giovine, Marco; Erpenbeck, Dirk; Guan, Kaomei; Ehrlich, HermannMarine sponges remain representative of a unique source of renewable biological materials. The demosponges of the family Ianthellidae possess chitin-based skeletons with high biomimetic potential. These three-dimensional (3D) constructs can potentially be used in tissue engineering and regenerative medicine. In this study, we focus our attention, for the first time, on the marine sponge Ianthella labyrinthus Bergquist & Kelly-Borges, 1995 (Demospongiae: Verongida: Ianthellidae) as a novel potential source of naturally prestructured bandage-like 3D scaffolds which can be isolated simultaneously with biologically active bromotyrosines. Specifically, translucent and elastic flat chitinous scaffolds have been obtained after bromotyrosine extraction and chemical treatments of the sponge skeleton with alternate alkaline and acidic solutions. For the first time, cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) have been used to test the suitability of I. labyrinthus chitinous skeleton as ready-to-use scaffold for their cell culture. Results reveal a comparable attachment and growth on isolated chitin-skeleton, compared to scaffolds coated with extracellular matrix mimetic Geltrex®. Thus, the natural, unmodified I. labyrinthus cleaned sponge skeleton can be used to culture iPSC-CMs and 3D tissue engineering. In addition, I. labyrinthus chitin-based scaffolds demonstrate strong and efficient capability to absorb blood deep into the microtubes due to their excellent capillary effect. These findings are suggestive of the future development of new sponge chitin-based absorbable hemostats as alternatives to already well recognized cellulose-based fabrics. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemTargeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction([London] : Nature Publishing Group UK, 2022) Klapproth, Erik; Witt, Anke; Klose, Pauline; Wiedemann, Johanna; Vavilthota, Nikitha; Künzel, Stephan R.; Kämmerer, Susanne; Günscht, Mario; Sprott, David; Lesche, Mathias; Rost, Fabian; Dahl, Andreas; Rauch, Erik; Kattner, Lars; Weber, Silvio; Mirtschink, Peter; Kopaliani, Irakli; Guan, Kaomei; Lorenz, Kristina; Saftig, Paul; Wagner, Michael; El-Armouche, AliAfter myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.
- ItemCNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2(New York, NY : Assoc., 2023) Cachorro, Eleder; Günscht, Mario; Schubert, Mario; Sadek, Mirna S.; Siegert, Johanna; Dutt, Fabian; Bauermeister, Carla; Quickert, Susann; Berning, Henrik; Nowakowski, Felix; Lämmle, Simon; Firneburg, Rebecca; Luo, Xiaojing; Künzel, Stephan R.; Klapproth, Erik; Mirtschink, Peter; Mayr, Manuel; Dewenter, Matthias; Vettel, Christiane; Heijman, Jordi; Lorenz, Kristina; Guan, Kaomei; El-Armouche, Ali; Wagner, Michael; Kämmerer, SusanneBackground: Ventricular arrhythmia and sudden cardiac death are the most common lethal complications after myocardial infarction. Antiarrhythmic pharmacotherapy remains a clinical challenge and novel concepts are highly desired. Here, we focus on the cardioprotective CNP (C-type natriuretic peptide) as a novel antiarrhythmic principle. We hypothesize that antiarrhythmic effects of CNP are mediated by PDE2 (phosphodiesterase 2), which has the unique property to be stimulated by cGMP to primarily hydrolyze cAMP. Thus, CNP might promote beneficial effects of PDE2-mediated negative crosstalk between cAMP and cGMP signaling pathways. Methods: To determine antiarrhythmic effects of cGMP-mediated PDE2 stimulation by CNP, we analyzed arrhythmic events and intracellular trigger mechanisms in mice in vivo, at organ level and in isolated cardiomyocytes as well as in human-induced pluripotent stem cell-derived cardiomyocytes. Results: In ex vivo perfused mouse hearts, CNP abrogated arrhythmia after ischemia/reperfusion injury. Upon high-dose catecholamine injections in mice, PDE2 inhibition prevented the antiarrhythmic effect of CNP. In mouse ventricular cardiomyocytes, CNP blunted the catecholamine-mediated increase in arrhythmogenic events as well as in ICaL, INaL, and Ca2+spark frequency. Mechanistically, this was driven by reduced cellular cAMP levels and decreased phosphorylation of Ca2+handling proteins. Key experiments were confirmed in human iPSC-derived cardiomyocytes. Accordingly, the protective CNP effects were reversed by either specific pharmacological PDE2 inhibition or cardiomyocyte-specific PDE2 deletion. Conclusions: CNP shows strong PDE2-dependent antiarrhythmic effects. Consequently, the CNP-PDE2 axis represents a novel and attractive target for future antiarrhythmic strategies.