Browsing by Author "Stankevich, Ksenia S."

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Composite Ferroelectric Membranes Based on Vinylidene Fluoride-Tetrafluoroethylene Copolymer and Polyvinylpyrrolidone for Wound Healing
(MDPI AG, 2020-12) Tverdokhlebova, Tamara S.; Antipina, Ludmila S.; Kudryavtseva, Valeriya L.; Stankevich, Ksenia S.; Kolesnik, Ilya M.; Senokosova, Evgenia A.; Velikanova, Elena A.; Antonova, Larisa V.; Vasilchenko, Dmitry V.; Dambaev, Georgiy T.; Plotnikov, Evgenii V.; Bouznik, Vyacheslav M.; Bolbasov, Evgeny N.
Wound healing is a complex process and an ongoing challenge for modern medicine. Herein, we present the results of study of structure and properties of ferroelectric composite polymer membranes for wound healing. Membranes were fabricated by electrospinning from a solution of vinylidene fluoride/tetrafluoroethylene copolymer (VDF–TeFE) and polyvinylpyrrolidone (PVP) in dimethylformamide (DMF). The effects of the PVP content on the viscosity and conductivity of the spinning solution, DMF concentration, chemical composition, crystal structure, and conformation of VDF–TeFE macromolecules in the fabricated materials were studied. It was found that as PVP amount increased, the viscosity and conductivity of the spinning solutions decreased, resulting in thinner fibers. Using FTIR and XRD methods, it was shown that if the PVP content was lower than 50 wt %, the VDF–TeFE copolymer adopted a flat zigzag conformation (TTT conformation) and crystalline phases with ferroelectric properties were formed. Gas chromatography results indicated that an increase in the PVP concentration led to a higher residual amount of DMF in the material, causing cytotoxic effects on 3T3L1 fibroblasts. In vivo studies demonstrated that compared to classical gauze dressings impregnated with a solution of an antibacterial agent, ferroelectric composite membranes with 15 wt % PVP provided better conditions for the healing of purulent wounds.
Design, synthesis and biological evaluation of novel O-substituted tryptanthrin oxime derivatives as c-Jun N-terminal kinase inhibitors
(Frontiers Media SA, 2022-09) Schepetkin, Igor A.; Kovrizhina, Anastasia R.; Stankevich, Ksenia S.; Khlebnikov, Andrei I.; Kirpotina, Liliya N.; Quinn, Mark T.; Cook, Matthew J.
The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNK represents an attractive target for therapeutic intervention. Herein, a panel of novel tryptanthrin oxime analogs were synthesized and evaluated for JNK1-3 binding (Kd) and inhibition of cellular inflammatory responses (IC50). Several compounds exhibited submicromolar JNK binding affinity, with the most potent inhibitor being 6-(acetoxyimino)indolo[2,1-b]quinazolin-12(6H)-one (1j), which demonstrated high JNK1-3 binding affinity (Kd = 340, 490, and 180 nM for JNK1, JNK2, and JNK3, respectively) and inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcription activity in THP-1Blue cells and interleukin-6 (IL-6) production in MonoMac-6 monocytic cells (IC50 = 0.8 and 1.7 μM, respectively). Compound 1j also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Likewise, 1j inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. Molecular modeling suggested modes of binding interaction of selected compounds in the JNK3 catalytic site that were in agreement with the experimental JNK3 binding data. Our results demonstrate the potential for developing anti-inflammatory drugs based on these nitrogen-containing heterocyclic systems.
Modification of PCL Scaffolds by Reactive Magnetron Sputtering: A Possibility for Modulating Macrophage Responses
(2020) Stankevich, Ksenia S.; Kudryavtseva, Valeriya L.; Bolbasov, Evgeny N.; Shesterikov, Evgeny V.; Larionova, Irina V.; Shapovalova, Yelena G.; Domracheva, Liubov V.; Volokhova, Apollinariya A.; Kurzina, Irina A.; Zhukov, Yuri M.; Malashicheva, Anna B.; Kzhyshkowska, Julia G.; Tverdokhlebov, Sergei I.
Direct current (DC) reactive magnetron sputtering is as an efficient method for enhancing the biocompatibility of poly(ε-caprolactone) (PCL) scaffolds. However, the PCL chemical bonding state, the composition of the deposited coating, and their interaction with immune cells remain unknown. Herein, we demonstrated that the DC reactive magnetron sputtering of the titanium target in a nitrogen atmosphere leads to the formation of nitrogen-containing moieties and the titanium dioxide coating on the scaffold surface. We have provided the possible mechanism of PCL fragmentation and coating formation supported by XPS results and DFT calculations. Our preliminary biological studies suggest that DC reactive magnetron sputtering of the titanium target could be an effective tool to control macrophage functional responses toward PCL scaffolds as it allows to inhibit respiratory burst while retaining cell viability and scavenging activity.