8 results
Search Results
Now showing 1 - 8 of 8
- ItemIsoquinolinamine FX-9 Exhibits Anti-Mitotic Activity in Human and Canine Prostate Carcinoma Cell Lines(Basel : Molecular Diversity Preservation International, 2019) Schille, Jan Torben; Nolte, Ingo; Packeiser, Eva-Maria; Wiesner, Laura; Hein, Jens Ingo; Weiner, Franziska; Wu, Xiao-Feng; Beller, Matthias; Junghanss, Christian; Escobar, Hugo MuruaCurrent therapies are insufficient for metastatic prostate cancer (PCa) in men and dogs. As human castrate-resistant PCa shares several characteristics with the canine disease, comparative evaluation of novel therapeutic agents is of considerable value for both species. Novel isoquinolinamine FX-9 exhibits antiproliferative activity in acute lymphoblastic leukemia cell lines but has not been tested yet on any solid neoplasia type. In this study, FX-9's mediated effects were characterized on two human (PC-3, LNCaP) and two canine (CT1258, 0846) PCa cell lines, as well as benign solid tissue cells. FX-9 significantly inhibited cell viability and induced apoptosis with concentrations in the low micromolar range. Mediated effects were highly comparable between the PCa cell lines of both species, but less pronounced on non-malignant chondrocytes and fibroblasts. Interestingly, FX-9 exposure also leads to the formation and survival of enlarged multinucleated cells through mitotic slippage. Based on the results, FX-9 acts as an anti-mitotic agent with reduced cytotoxic activity in benign cells. The characterization of FX-9-induced effects on PCa cells provides a basis for in vivo studies with the potential of valuable transferable findings to the benefit of men and dogs. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemReaction of 1-propanol with Ozone in Aqueous Media(Basel : Molecular Diversity Preservation International, 2019) Reisz, Erika; Tekle-Röttering, Agnes; Naumov, Sergej; Schmidt, Winfried; Schmidt, Torsten C.The main aim of this work is to substantiate the mechanism of 1-propanol oxidation by ozone in aqueous solution when the substrate is present in large excess. Further goals are assessment of the products, their formation yields as well as the kinetic parameters of the considered reaction. The reaction of ozone with 1-propanol in aqueous solution occurs via hydride transfer, H-abstraction and insertion. Of these three mechanisms, the largest share is for hydride transfer. This implies the extraction of an hydride ion from the activated C-H group by O3 according to reaction: (C2H5)(H)(HO)C-H + O3 ?[(C2H5)(H)(HO)C-H+O3?]cage ?(C2H5)(H)(HO)C+ + HO3 -. The experimentally determined products and their overall formation yields with respect to ozone are: propionaldehyde-(60 ± 3)%, propionic acid-(27.4 ± 1.0)%, acetaldehyde-(4.9 ± 0.3)%, acetic acid-(0.3 ± 0.1)%, formaldehyde-(1.0 ± 0.1)%, formic acid-(4.6 ± 0.3)%, hydrogen peroxide- (11.1 ± 0.3)% and hydroxyl radical-(9.8 ± 0.3)%. The reaction of ozone with 1-propanol in aqueous media follows a second order kinetics with a reaction rate constant of (0.64±0.02)M-1·s-1 atpH = 7 and 23 °C. The dependence of the second order rate constant on temperature is described by the equation: ln kII = (27.17 ± 0.38)-(8180 ± 120) × T-1, which gives the activation energy, Ea = (68 ± 1) kJ mol-1 and pre-exponential factor, A = (6.3 ± 2.4) × 1011 M-1 s-1. The nature of products, their yields and the kinetic data can be used in water treatment. The fact that the hydride transfer is the main pathway in the 1-propanol/ozone system can probably be transferred on other systems in which the substrate is characterized by C-H active sites only. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemTreatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs(Basel : Molecular Diversity Preservation International, 2019) Bothe, Friederike; Deubel, Anne-Kathrin; Hesse, Eliane; Lotz, Benedict; Groll, Jürgen; Werner, Carsten; Richter, Wiltrud; Hagmann, SebastienDespite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (_CT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemViscoelastic Behavior of Embroidered Scaffolds for ACL Tissue Engineering Made of PLA and P(LA-CL) After In Vitro Degradation(Basel : Molecular Diversity Preservation International, 2019) Hahn, Judith; Schulze-Tanzil, Schulze-Tanzil; Schröpfer, Michaela; Meyer, Michael; Gögele, Clemens; Hoyer, Mariann; Spickenheuer, Axel; Heinrich, Gert; Breier, AnnetteA rupture of the anterior cruciate ligament (ACL) is the most common knee ligament injury. Current applied reconstruction methods have limitations in terms of graft availability and mechanical properties. A new approach could be the use of a tissue engineering construct that temporarily reflects the mechanical properties of native ligament tissues and acts as a carrier structure for cell seeding. In this study, embroidered scaffolds composed of polylactic acid (PLA) and poly(lactic-co-"-caprolactone) (P(LA-CL)) threads were tested mechanically for their viscoelastic behavior under in vitro degradation. The relaxation behavior of both scaffold types (moco: mono-component scaffold made of PLA threads, bico: bi-component scaffold made of PLA and P(LA-CL) threads) was comparable to native lapine ACL. Most of the lapine ACL cells survived 32 days of cell culture and grew along the fibers. Cell vitality was comparable for moco and bico scaffolds. Lapine ACL cells were able to adhere to the polymer surfaces and spread along the threads throughout the scaffold. The mechanical behavior of degrading matrices with and without cells showed no significant differences. These results demonstrate the potential of embroidered scaffolds as an ACL tissue engineering approach. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemThermo-responsive polymer brushes with side graft chains: Relationship between molecular architecture and underwater adherence(Basel : Molecular Diversity Preservation International, 2019) Sidoli, Ugo; Tee, Hisaschi T.; Raguzin, Ivan; Mühldorfer, Jakob; Wurm, Frederik R.; Synytska, AllaDuring the last few decades, wet adhesives have been developed for applications in various fields. Nonetheless, key questions such as the most suitable polymer architecture as well as the most suitable chemical composition remain open. In this article, we investigate the underwater adhesion properties of novel responsive polymer brushes with side graft chain architecture prepared using “grafting through” approach on flat surfaces. The incorporation in the backbone of thermo-responsive poly(N-isopropylacrylamide) (PNIPAm) allowed us to obtain LCST behavior in the final layers. PNIPAm is co-polymerized with poly(methyl ethylene phosphate) (PMEP), a poloyphosphoester. The final materials are characterized studying the surface-grafted polymer as well as the polymer from the bulk solution, and pure PNIPAm brush is used as reference. PNIPAm-g-PMEP copolymers retain the responsive behavior of PNIPAm: when T > LCST, a clear switching of properties is observed. More specifically, all layers above the critical temperature show collapse of the chains, increased hydrophobicity and variation of the surface charge even if no ionizable groups are present. Secondly, effect of adhesion parameters such as debonding rate and contact time is studied. Thirdly, the reversibility of the adhesive properties is confirmed by performing adhesion cycles. Finally, the adhesive properties of the layers are studied below and above the LCST against hydrophilic and hydrophobic substrates. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemThermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib(Basel : Molecular Diversity Preservation International, 2019) Reis, Berthold; Vehlow, David; Rust, Tarik; Kuckling, Dirk; Müller, MartinTo overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly(N-isoproplyacrylamide-co-dimethylaminoethylmethacrylate) (P(NIPAM-co-DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemKey Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells(Basel : Molecular Diversity Preservation International, 2019) Soltan, Marwa Y.; Sumarni, Uly; Assaf, Chalid; Langer, Peter; Reidel, Ulrich; Eberle, JürgenCutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- 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.