Search Results
Ring-Closure Mechanisms Mediated by Laccase to Synthesize Phenothiazines, Phenoxazines, and Phenazines
The green and environmentally friendly synthesis of highly valuable organic substances is one possibility for the utilization of laccases (EC 1.10.3.2). As reactants for the herein described syntheses, different o-substituted arylamines or arylthiols and 2,5-dihydroxybenzoic acid and its derivatives were used. In this way, the formation of phenothiazines, phenoxazines, and phenazines was achieved in aqueous solution mediated by the laccase of Pycnoporus cinnabarinus in the presence of oxygen. Two types of phenothiazines (3-hydroxy- and 3-oxo-phenothiazines) formed in one reaction assay were described for the first time. The cyclization reactions yielded C–N, C–S, or C–O bonds. The syntheses were investigated with regard to the substitution pattern of the reaction partners. Differences in C–S and C–N bond formations without cyclization are discussed.
Singlet-Oxygen-Induced Phospholipase A2 Inhibition: A Major Role for Interfacial Tryptophan Dioxidation
Several studies have revealed that various diseases such as cancer have been associated with elevated phospholipase A2 (PLA2) activity. Therefore, the regulation of PLA2 catalytic activity is undoubtedly vital. In this study, effective inactivation of PLA2 due to reactive species produced from cold physical plasma as a source to model oxidative stress is reported. We found singlet oxygen to be the most relevant active agent in PLA2 inhibition. A more detailed analysis of the plasma-treated PLA2 identified tryptophan 128 as a hot spot, rich in double oxidation. The significant dioxidation of this interfacial tryptophan resulted in an N-formylkynurenine product via the oxidative opening of the tryptophan indole ring. Molecular dynamics simulation indicated that the efficient interactions between the tryptophan residue and phospholipids are eliminated following tryptophan dioxidation. As interfacial tryptophan residues are predominantly involved in the attaching of membrane enzymes to the bilayers, tryptophan dioxidation and indole ring opening leads to the loss of essential interactions for enzyme binding and, consequently, enzyme inactivation. © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH
Uncertainty Quantification and Sensitivity Analysis for the Electrical Impedance Spectroscopy of Changes to Intercellular Junctions Induced by Cold Atmospheric Plasma
The influence of pertinent parameters of a Cole-Cole model in the impedimetric assessment of cell-monolayers was investigated with respect to the significance of their individual contribution. The analysis enables conclusions on characteristics, such as intercellular junctions. Especially cold atmospheric plasma (CAP) has been proven to influence intercellular junctions which may become a key factor in CAP-related biological effects. Therefore, the response of rat liver epithelial cells (WB-F344) and their malignant counterpart (WB-ras) was studied by electrical impedance spectroscopy (EIS). Cell monolayers before and after CAP treatment were analyzed. An uncertainty quantification (UQ) of Cole parameters revealed the frequency cut-off point between low and high frequency resistances. A sensitivity analysis (SA) showed that the Cole parameters, R0 and α were the most sensitive, while Rinf and τ were the least sensitive. The temporal development of major Cole parameters indicates that CAP induced reversible changes in intercellular junctions, but not significant changes in membrane permeability. Sustained changes of τ suggested that long-lived ROS, such as H2O2, might play an important role. The proposed analysis confirms that an inherent advantage of EIS is the real time observation for CAP-induced changes on intercellular junctions, with a label-free and in situ method manner.
Combined toxicity of gas plasma treatment and nanoparticles exposure in melanoma cells in vitro
Despite continuous advances in therapy, cancer remains a deadly disease. Over the past years, gas plasma technology emerged as a novel tool to target tumors, especially skin. Another promising anticancer approach are nanoparticles. Since combination therapies are becoming increas-ingly relevant in oncology, both gas plasma treatment and nanoparticle exposure were combined. A series of nanoparticles were investigated in parallel, namely, silica, silver, iron oxide, cerium oxide, titanium oxide, and iron-doped titanium oxide. For gas plasma treatment, the atmospheric pressure argon plasma jet kINPen was utilized. Using three melanoma cell lines, the two murine non-metastatic B16F0 and metastatic B16F10 cells and the human metastatic B-Raf mutant cell line SK-MEL-28, the combined cytotoxicity of both approaches was identified. The combined cytotoxicity of gas plasma treatment and nanoparticle exposure was consistent across all three cell lines for silica, silver, iron oxide, and cerium oxide. In contrast, for titanium oxide and iron-doped titanium oxide, significantly combined cytotoxicity was only observed in B16F10 cells.
Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer’s Lactate Solutions in a Model of Peritoneal Carcinomatosis
Reactive species generated by medical gas plasma technology can be enriched in liquids for use in oncology targeting disseminated malignancies, such as metastatic colorectal cancer. Notwithstanding, reactive species quantities depend on the treatment mode, and we recently showed gas plasma exposure in conductive modes to be superior for cancer tissue treatment. However, evidence is lacking that such a conductive mode also equips gas plasma-treated liquids to confer augmented intraperitoneal anticancer activity. To this end, employing atmospheric pressure argon plasma jet kINPen-treated Ringer’s lactate (oxRilac) in a CT26-model of colorectal peritoneal carcinomatosis, we tested repeated intraabdominal injection of such remotely or conductively oxidized liquid for antitumor control and immunomodulation. Enhanced reactive species formation in conductive mode correlated with reduced tumor burden in vivo, emphasizing the advantage of conduction over the free mode for plasma-conditioned liquids. Interestingly, the infiltration of lymphocytes into the tumors was equally enhanced by both treatments. However, significantly lower levels of interleukin (IL)4 and IL13 and increased levels of IL2 argue for a shift in intratumoral T-helper cell subpopulations correlating with disease control. In conclusion, our data argue for using conductively over remotely prepared plasma-treated liquids for anticancer treatment.
Self-Activation of Inorganic-Organic Hybrids Derived through Continuous Synthesis of Polyoxomolybdate and para-Phenylenediamine Enables Very High Lithium-Ion Storage Capacity
Inorganic-organic hybrid materials with redox-active components were prepared by an aqueous precipitation reaction of ammonium heptamolybdate (AHM) with para-phenylenediamine (PPD). A scalable and low-energy continuous wet chemical synthesis process, known as the microjet process, was used to prepare particles with large surface area in the submicrometer range with high purity and reproducibility on a large scale. Two different crystalline hybrid products were formed depending on the ratio of molybdate to organic ligand and pH. A ratio of para-phenylenediamine to ammonium heptamolybdate from 1 : 1 to 5 : 1 resulted in the compound [C6H10N2]2[Mo8O26] ⋅ 6 H2O, while higher PPD ratios from 9 : 1 to 30 : 1 yielded a composition of [C6H9N2]4[NH4]2[Mo7O24] ⋅ 3 H2O. The electrochemical behavior of the two products was tested in a battery cell environment. Only the second of the two hybrid materials showed an exceptionally high capacity of 1084 mAh g−1 at 100 mA g−1 after 150 cycles. The maximum capacity was reached after an induction phase, which can be explained by a combination of a conversion reaction with lithium to Li2MoO4 and an additional in situ polymerization of PPD. The final hybrid material is a promising material for lithium-ion battery (LIB) applications.
Biological Risk Assessment of Three Dental Composite Materials following Gas Plasma Exposure
Gas plasma is an approved technology that generates a plethora of reactive oxygen species, which are actively applied for chronic wound healing. Its particular antimicrobial action has spurred interest in other medical fields, such as periodontitis in dentistry. Recent work has indicated the possibility of performing gas plasma-mediated biofilm removal on teeth. Teeth frequently contain restoration materials for filling cavities, e.g., resin-based composites. However, it is unknown if such materials are altered upon gas plasma exposure. To this end, we generated a new in-house workflow for three commonly used resin-based composites following gas plasma treatment and incubated the material with human HaCaT keratinocytes in vitro. Cytotoxicity was investigated by metabolic activity analysis, flow cytometry, and quantitative high-content fluorescence imaging. The inflammatory consequences were assessed using quantitative analysis of 13 different chemokines and cytokines in the culture supernatants. Hydrogen peroxide served as the control condition. A modest but significant cytotoxic effect was observed in the metabolic activity and viability after plasma treatment for all three composites. This was only partially treatment time-dependent and the composites alone affected the cells to some extent, as evident by differential secretion profiles of VEGF, for example. Gas plasma composite modification markedly elevated the secretion of IL6, IL8, IL18, and CCL2, with the latter showing the highest correlation with treatment time (Pearson’s r > 0.95). Cell culture media incubated with gas plasma-treated composite chips and added to cells thereafter could not replicate the effects, pointing to the potential that surface modifications elicited the findings. In conclusion, our data suggest that gas plasma treatment modifies composite material surfaces to a certain extent, leading to measurable but overall modest biological effects.
Application of scanning electrochemical microscopy for topography imaging of supported lipid bilayers
Oxidative stress in cellular environments may cause lipid oxidation and membrane degradation. Therefore, studying the degree of lipid membrane morphological changes by reactive oxygen and nitrogen species will be informative in oxidative stress-based therapies. This study introduces the possibility of using scanning electrochemical microscopy as a powerful imaging technique to follow the topographical changes of a solid-supported lipid bilayer model induced by reactive species produced from gas plasma. The introduced strategy is not limited to investigating the effect of reactive species on the lipid bilayer but could be extended to understand the morphological changes of the lipid bilayer due to the action of membrane proteins or antimicrobial peptides.
Highly active heterogeneous hydrogenation catalysts prepared from cobalt complexes and rice husk waste
The utilization and valorization of agricultural waste is a key strategy for the implementation of a sustainable economy to lessen the environmental footprint of human activities on Earth. This work describes the use of rice husk (RH) from agricultural waste to prepare a highly active catalyst for the reduction of nitro compounds. RH was impregnated with various cobalt complexes bearing N-donor ligands, then pyrolyzed and the resulting composite was etched with a base to remove the silica domains. The composition and morphology of the prepared materials were investigated by IR, AAS, ICP-OES, XRD, BET, XPS and SEM technics. The material showed excellent activity and selectivity in the hydrogenation of nitro groups in aromatic and aliphatic substrates. A remarkable selectivity towards nitro groups was found in the presence of various reactive functionalities, including halogens, carbonyls, borates, and nitriles. Apart from their excellent activity and selectivity, these catalysts showed remarkable stability, allowing their easy recovery and multiple reuse without requiring re-activation.
Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine
The loss of skin integrity is inevitable in life. Wound healing is a necessary sequence of events to reconstitute the body’s integrity against potentially harmful environmental agents and restore homeostasis. Attempts to improve cutaneous wound healing are therefore as old as humanity itself. Furthermore, nowadays, targeting defective wound healing is of utmost importance in an aging society with underlying diseases such as diabetes and vascular insufficiencies being on the rise. Because chronic wounds’ etiology and specific traits differ, there is widespread polypragmasia in targeting non-healing conditions. Reactive oxygen and nitrogen species (ROS/RNS) are an overarching theme accompanying wound healing and its biological stages. ROS are signaling agents generated by phagocytes to inactivate pathogens. Although ROS/RNS’s central role in the biology of wound healing has long been appreciated, it was only until the recent decade that these agents were explicitly used to target defective wound healing using gas plasma technology. Gas plasma is a physical state of matter and is a partially ionized gas operated at body temperature which generates a plethora of ROS/RNS simultaneously in a spatiotemporally controlled manner. Animal models of wound healing have been vital in driving the development of these wound healing-promoting technologies, and this review summarizes the current knowledge and identifies open ends derived from in vivo wound models under gas plasma therapy. While gas plasma-assisted wound healing in humans has become well established in Europe, veterinary medicine is an emerging field with great potential to improve the lives of suffering animals.