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- ItemImpedimetric Analysis of Trabecular Bone Based on Cole and Linear Discriminant Analysis(Lausanne : Frontiers Media, 2021) Wei, Wenzuo; Shi, Fukun; Kolb, Juergen F.A spatially unambiguous characterization of electrical properties of osseous tissues is important for the therapy of osteopathy via electrical stimulation. Accordingly, the study aimed to characterize the highly inhomogeneous composition and structures of different anatomical regions of trabecular bone based on their electrical properties. The electrical properties of 64 porcine trabecular bone samples were analyzed in a parallel plate electrode configuration and compared with published results. Therefore, a novel method, combining traditional Cole model with a linear discriminant analysis (LDA), was developed to discriminate the different regions, i.e., femur head, greater trochanter, and femur neck. Possible mechanisms behind the distinction for different regions could be interpreted from both methods. Respective adjacent regions with similar structure and composition could be distinguished from statistically significant differences of Cole parameters, i.e., α (p < 0.01) and R∞ (p < 0.05). The latter was correlated especially with water content, indicating an association of individual differences in microstructures in particular with conductivity. Conversely, different regions were unambiguously discriminated with LDA based on permittivity or conductivity. Contributions to the discrimination were explicitly reflected by the coefficients of the derived LDA features. A clear distinction was obtained especially for a frequency response at 950 kHz. Moreover, predictions for the classification of unspecified samples assigned them correctly to their origin with a success of 92.9%. The combination of both methods offers the possibility for a spatially resolved and eventually patient specific discrimination and evaluation of bone tissues and their response to therapies, notably electrical stimulation.
- ItemRisk Evaluation of EMT and Inflammation in Metastatic Pancreatic Cancer Cells Following Plasma Treatment(Lausanne : Frontiers Media, 2020) Freund, Eric; Spadola, Chiara; Schmidt, Anke; Privat-Maldonado, Angela; Bogaerts, Annemie; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Heidecke, Claus-Dieter; Partecke, Lars-Ivo; Käding, André; Bekeschus, SanderThe requirements for new technologies to serve as anticancer agents go far beyond their toxicity potential. Novel applications also need to be safe on a molecular and patient level. In a broader sense, this also relates to cancer metastasis and inflammation. In a previous study, the toxicity of an atmospheric pressure argon plasma jet in four human pancreatic cancer cell lines was confirmed and plasma treatment did not promote metastasis in vitro and in ovo. Here, these results are extended by additional types of analysis and new models to validate and define on a molecular level the changes related to metastatic processes in pancreatic cancer cells following plasma treatment in vitro and in ovo. In solid tumors that were grown on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM), plasma treatment induced modest to profound apoptosis in the tissues. This, however, was not associated with a change in the expression levels of adhesion molecules, as shown using immunofluorescence of ultrathin tissue sections. Culturing of the cells detached from these solid tumors for 6d revealed a similar or smaller total growth area and expression of ZEB1, a transcription factor associated with cancer metastasis, in the plasma-treated pancreatic cancer tissues. Analysis of in vitro and in ovo supernatants of 13 different cytokines and chemokines revealed cell line-specific effects of the plasma treatment but a noticeable increase of, e.g., growth-promoting interleukin 10 was not observed. Moreover, markers of epithelial-to-mesenchymal transition (EMT), a metastasis-promoting cellular program, were investigated. Plasma-treated pancreatic cancer cells did not present an EMT-profile. Finally, a realistic 3D tumor spheroid co-culture model with pancreatic stellate cells was employed, and the invasive properties in a gel-like cellular matrix were investigated. Tumor outgrowth and spread was similar or decreased in the plasma conditions. Altogether, these results provide valuable insights into the effect of plasma treatment on metastasis-related properties of cancer cells and did not suggest EMT-promoting effects of this novel cancer therapy. © Copyright © 2020 Freund, Spadola, Schmidt, Privat-Maldonado, Bogaerts, von Woedtke, Weltmann, Heidecke, Partecke, Käding and Bekeschus.
- ItemRadiation Driven Chemistry in Biomolecules—is (V)UV Involved in the Bioactivity of Argon Jet Plasmas?(Lausanne : Frontiers Media, 2021) Bruno, G.; Wenske, S.; Mahdikia, H.; Gerling, T.; von Woedtke, T.; Wende, K.Cold physical plasmas, especially noble gas driven plasma jets, emit considerable amounts of ultraviolet radiation (UV). Given that a noble gas channel is present, even the energetic vacuum UV can reach the treated target. The relevance of UV radiation for antimicrobial effects is generally accepted. It remains to be clarified if this radiation is relevant for other biomedical application of plasmas, e.g., in wound care or cancer remediation. In this work, the role of (vacuum) ultraviolet radiation generated by the argon plasma jet kINPen for cysteine modifications was investigated in aqueous solutions and porcine skin. To differentiate the effects of photons of different wavelength and complete plasma discharge, a micro chamber equipped with a MgF2, Suprasil, or Borosilicate glass window was used. In liquid phase, plasma-derived VUV radiation was effective and led to the formation of cysteine oxidation products and molecule breakdown products, yielding sulfite, sulfate, and hydrogen sulfide. At the boundary layer, the impact of VUV photons led to water molecule photolysis and formation of hydroxyl radicals and hydrogen peroxide. In addition, photolytic cleavage of the weak carbon-sulfur bond initiated the formation of sulfur oxy ions. In the intact skin model, protein thiol modification was rare even if a VUV transparent MgF2 window was used. Presumably, the plasma-derived VUV radiation played a limited role since reactions at the boundary layer are less frequent and the dense biomolecules layers block it effectively, inhibiting significant penetration. This result further emphasizes the safety of physical plasmas in biomedical applications.