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Subject: cold atmospheric pressure plasma (CAP) ×

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    Cold Physical Plasma Modulates p53 and Mitogen-Activated Protein Kinase Signaling in Keratinocytes
    (London: Hindawi, 2019) Schmidt, Anke; Bekeschus, Sander; Jarick, Katja; Hasse, Sybille; von Woedtke, Thomas; Wende, Kristian
    Small reactive oxygen and nitrogen species (ROS/RNS) driven signaling plays a significant role in wound healing processes by controlling cell functionality and wound phase transitions. The application of cold atmospheric pressure plasma (CAP), a partially ionized gas expelling a variety of ROS and RNS, was shown to be effective in chronic wound management and contrastingly also in malignant diseases. The underlying molecular mechanisms are not well understood but redox signaling events are involved. As a central player, the cellular tumor antigen p53 governs regulatory networks controlling proliferation, death, or metabolism, all of which are grossly modulated by anti- and prooxidant signals. Using a human skin cell model, a transient phosphorylation and nuclear translocation of p53, preceded by the phosphorylation of upstream serine- (ATM) and serine/threonine-protein kinase (ATR), was detected after CAP treatment. Results indicate that ATM acts as a direct redox sensor without relevant contribution of phosphorylation of the histone A2X, a marker of DNA damage. Downstream events are the activation of checkpoint kinases Chk1/2 and several mitogen-activated (MAP) kinases. Subsequently, the expression of MAP kinase signaling effectors (e.g., heat shock protein Hsp27), epithelium derived growth factors, and cytokines (Interleukins 6 + 8) was increased. A number of p53 downstream effectors pointed at a decrease of cell growth due to DNA repair processes. In summary, CAP treatment led to an activation of cell repair and defense mechanisms including a modulation of paracrine inflammatory signals emphasizing the role of prooxidant species in CAP-related cell signaling. © 2019 Anke Schmidt et al.
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    Foundations of plasmas for medical applications
    (Bristol : IOP Publ., 2022) von Woedtke, T.; Laroussi, M.; Gherardi, M.
    Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids like water or physiological saline by a CAP source is performed in order to study specific biological activities. A basic understanding of the interaction between plasma and liquids and bio-interfaces is essential to follow biological plasma effects. Charged species, metastable species, and other atomic and molecular reactive species first produced in the main plasma ignition are transported to the discharge afterglow to finally be exposed to the biological targets. Contact with these liquid-dominated bio-interfaces generates other secondary reactive oxygen and nitrogen species (ROS, RNS). Both ROS and RNS possess strong oxidative properties and can trigger redox-related signalling pathways in cells and tissue, leading to various impacts of therapeutic relevance. Dependent on the intensity of plasma exposure, redox balance in cells can be influenced in a way that oxidative eustress leads to stimulation of cellular processes or oxidative distress leads to cell death. Currently, clinical CAP application is realized mainly in wound healing. The use of plasma in cancer treatment (i.e. plasma oncology) is a currently emerging field of research. Future perspectives and challenges in plasma medicine are mainly directed towards the control and optimization of CAP devices, to broaden and establish its medical applications, and to open up new plasma-based therapies in medicine.