The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform

Mark J Kushner - One of the best experts on this subject based on the ideXlab platform.

  • atmospheric pressure Plasma jets onto a reactive water layer over tissue pulse repetition rate as a control mechanism
    Journal of Physics D, 2019
    Co-Authors: Seth Norberg, Eric Johnsen, Guy Parsey, Amanda M Lietz, Mark J Kushner
    Abstract:

    The use of Plasma jets to treat tissue in the context of Plasma Medicine often involves a thin intervening liquid layer on top of the tissue. Plasma activated species first transport through and react in the liquid layer prior to reaching the tissue. Of the many parameters that can be used to control this process, pulse repetition frequency (PRF) stands out. Results from a computational investigation of multiple pulses at varying PRF from an atmospheric pressure Plasma jet (APPJ) onto a reactive liquid layer are discussed, and three key trends are made clear. First, a high PRF (short time between pulses) enables the gaseous species produced during the previous pulse to remain in the vicinity of the Plasma at the onset of the next pulse, thereby increasing the inventory of (H)N x O y and O3 in the gas phase. These species then solvate into the liquid, water in this case, and produce higher densities of aqueous ozone, nitrate, and peroxynitrite. With a lower PRF, reactants produced on a previous pulse are convected away prior to the next discharge pulse with more spatial separation of reactants both above and within the water. As a result, more of the hydroxyl anion (), ozone anion () and nitric oxide (NOaq) reach the tissue beneath the water. The second trend is that the production of H2O2aq and its fluence to the underlying tissue are relatively independent of the PRF. The precursors for H2O2aq are primarily produced by the surface ionization wave (SIW) on the top of the liquid, which then directly solvate into the liquid. Lastly, when the Plasma plume touches the liquid, the SIW on the water layer increases the production of all aqueous species compared to configurations where the Plasma plume does not touch the liquid. These trends are true for all PRF.

  • Helium atmospheric pressure Plasma jets interacting with wet cells: Delivery of electric fields
    Journal of Physics D: Applied Physics, 2016
    Co-Authors: Seth A. Norberg, Eric Johnsen, Mark J Kushner
    Abstract:

    © 2016 IOP Publishing Ltd. The use of atmospheric pressure Plasma jets (APPJs) in Plasma Medicine have produced encouraging results in wound treatment, surface sterilization, deactivation of bacteria, and treatment of cancer cells. It is known that many of the reactive oxygen and nitrogen species produced by the APPJ are critical to these processes. Other key components to treatment include the ion and photon fluxes, and the electric fields produced in cells by the ionization wave of the APPJ striking in the vicinity of the cells. These relationships are often complicated by the cells being covered by a thin liquid layer - wet cells. In this paper, results from a computational investigation of the interaction of APPJs with tissue beneath a liquid layer are discussed. The emphasis of this study is the delivery of electric fields by an APPJ sustained in He/O 2 = 99.8/0.2 flowing into humid air to cells lying beneath water with thickness of 200 μm. The water layer represents the biological fluid typically covering tissue during treatment. Three voltages were analyzed - two that produce a Plasma effluent that touches the surface of the water layer and one that does not touch. The effect of the liquid layer thickness, 50 μm to 1 mm, was also examined. Comparisons were made of the predicted intracellular electric fields to those thresholds used in the field of bioelectronics.

  • helium atmospheric pressure Plasma jets touching dielectric and metal surfaces
    Journal of Applied Physics, 2015
    Co-Authors: Seth Norberg, Eric Johnsen, Mark J Kushner
    Abstract:

    Atmospheric pressure Plasma jets (APPJs) are being investigated in the context Plasma Medicine and biotechnology applications, and surface functionalization. The composition of the surface being treated ranges from plastics, liquids, and biological tissue, to metals. The dielectric constant of these materials ranges from as low as 1.5 for plastics to near 80 for liquids, and essentially infinite for metals. The electrical properties of the surface are not independent variables as the permittivity of the material being treated has an effect on the dynamics of the incident APPJ. In this paper, results are discussed from a computational investigation of the interaction of an APPJ incident onto materials of varying permittivity, and their impact on the discharge dynamics of the Plasma jet. The computer model used in this investigation solves Poisson's equation, transport equations for charged and neutral species, the electron energy equation, and the Navier-Stokes equations for the neutral gas flow. The APPJ ...

  • formation of reactive oxygen and nitrogen species by repetitive negatively pulsed helium atmospheric pressure Plasma jets propagating into humid air
    Plasma Sources Science and Technology, 2015
    Co-Authors: Seth Norberg, Eric Johnsen, Mark J Kushner
    Abstract:

    Atmospheric pressure Plasma jets have many beneficial effects in their use in surface treatment and, in particular, Plasma Medicine. One of these benefits is the controlled production of reactive oxygen and nitrogen species (RONS) in the active discharge through the molecular gases added to the primary noble gas in the input mixture, and through the interaction of reactive species in the Plasma effluent with the ambient air. In this computational investigation, a parametric study was performed on the production of RONS in a multiply pulsed atmospheric pressure Plasma jet sustained in a He/O2 mixture and flowing into ambient humid air. The consequences of flow rate, O2 fraction, voltage, and repetition rate on reactant densities after a single discharge pulse, after 30 pulses, and after the same total elapsed time were investigated. At the end of the first discharge pulse, voltage has the greatest influence on RONS production. However, the systematic trends for production of RONS depend on repetition rate and flow rate in large part due to the residence time of RONS in the Plasma zone. Short residence times result in reactive species produced by the previous pulse still being in the discharge tube or in the path of the ionization wave at the next pulse. The RONS therefore accumulate in the tube and in the near effluent on a pulse-to-pulse basis. This accumulation enables species requiring multiple reactions among the primary RONS species to be produced in greater numbers.

  • interaction of multiple atmospheric pressure micro Plasma jets in small arrays he o2 into humid air
    Plasma Sources Science and Technology, 2014
    Co-Authors: Natalia Yu Babaeva, Mark J Kushner
    Abstract:

    Arrays of atmospheric-pressure Plasma jets are being considered as a means to increase the area being treated in surface modification and in Plasma Medicine in particular. A unique challenge of scaling Plasma jet arrays is that individual Plasma jets in an array tend to interact with each other, which can lead to quenching of some individual jets. To investigate these potential interactions, a computational study of one-, two- and three-tube arrays of micro-Plasma jet arrays was performed. An atmospheric-pressure He/O2 = 99.8/0.2 mixture was flowed through the tubes into humid room air. We found that the jets interact through electrostatic, hydrodynamic and photolytic means. The hydrodynamic interactions result from the merging of individual He channels emerging from individual tubes as air diffuses into the extended gas jets. Ionization waves (IWs) or Plasma bullets, which form the jets on the boundaries of an array, encounter higher mole fractions of air earlier compared with the center jet and so are slower or are quenched earlier. The close proximity of the jets produces electrostatic repulsion, which affects the trajectories of the IWs. If the jets are close enough, photoionizing radiation from their neighbors is an additional form of interaction. These interactions are sensitive to the spacing of the jets.

Klaus-dieter Weltmann - One of the best experts on this subject based on the ideXlab platform.

  • perspectives on cold atmospheric Plasma cap applications in Medicine
    Physics of Plasmas, 2020
    Co-Authors: Thomas Von Woedtke, Steffen Emmert, Hansrobert Metelmann, Stefan Rupf, Klaus-dieter Weltmann
    Abstract:

    Plasma Medicine is an innovative research field combining Plasma physics, life science, and clinical Medicine. It is mainly focused on the application cold atmospheric Plasma (CAP) in therapeutic settings. Based on its ability to inactivate microorganisms but also to stimulate tissue regeneration, current medical applications are focused on the treatment of wounds and skin diseases. Since CAP is also able to inactivate cancer cells, its use in cancer therapy is expected to be the next field of clinical Plasma application. Other promising applications are expected in oral Medicine and ophthalmology. It is the current state of knowledge that biological CAP effects are mainly based on the action of reactive oxygen and nitrogen species supported by electrical fields and UV radiation. However, continuing basic research is not only essential to improve, optimize, and enlarge the spectrum of medical CAP applications and their safety, but it is also the basis for identification and definition of a single parameter or set of parameters to monitor and control Plasma treatment and its effects. In the field of CAP Plasma devices, research and application are currently dominated by two basic types: dielectric barrier discharges and Plasma jets. Its individual adaptation to specific medical needs, including its combination with technical units for continuous and real-time monitoring of both Plasma performance and the target that is treated, will lead to a new generation of CAP-based therapeutic systems.

  • Plasma Medicine a field of applied redox biology
    in Vivo, 2019
    Co-Authors: Thomas Von Woedtke, Anke Schmidt, Sander Bekeschus, Kristian Wende, Klaus-dieter Weltmann
    Abstract:

    Plasma Medicine comprises the application of physical Plasma directly on or in the human body for therapeutic purposes. Three most important basic Plasma effects are relevant for medical applications: i) inactivation of a broad spectrum of microorganisms, including multidrug-resistant pathogens, ii) stimulation of cell proliferation and angiogenesis with lower Plasma treatment intensity, and iii) inactivation of cells by initialization of cell death with higher Plasma treatment intensity, above all in cancer cells. Based on own published results as well as on monitoring of relevant literature the aim of this topical review is to summarize the state of the art in Plasma Medicine and connect it to redox biology. One of the most important results of basic research in Plasma Medicine is the insight that biological Plasma effects are mainly mediated via reactive oxygen and nitrogen species influencing cellular redox-regulated processes. Plasma Medicine can be considered a field of applied redox biology.

  • high throughput image cytometry micronucleus assay to investigate the presence or absence of mutagenic effects of cold physical Plasma
    Environmental and Molecular Mutagenesis, 2018
    Co-Authors: Sander Bekeschus, Thomas Von Woedtke, Klaus-dieter Weltmann, Anke Schmidt, Felix Niessner, Axel Kramer, Hansrobert Metelmann, Frank Adler, Kristian Wende
    Abstract:

    Promising cold physical Plasma sources have been developed in the field of Plasma Medicine. An important prerequisite to their clinical use is lack of genotoxic effects in cells. During optimization of one or even different Plasma sources for a specific application, large numbers of samples need to be analyzed. There are soft and easy-to-assess markers for genotoxic stress such as phosphorylation of histone H2AX (γH2AX) but only few tests are accredited by the OECD with regard to mutagenicity detection. The micronucleus (MN) assay is among them but often requires manual counting of many thousands of cells per sample under the microscope. A high-throughput MN assay is presented using image flow cytometry and image analysis software. A human lymphocyte cell line was treated with Plasma generated with ten different feed gas conditions corresponding to distinct reactive species patterns that were investigated for their genotoxic potential. Several millions of cells were automatically analyzed by a MN quantification strategy outlined in detail in this work. Our data demonstrates the absence of newly formed MN in any feed gas condition using the atmospheric pressure Plasma jet kINPen. As positive control, ionizing radiation gave a significant 5-fold increase in micronucleus frequency. Thus, this assay is suitable to assess the genotoxic potential in large sample sets of cells exposed chemical or physical agents including Plasmas in an efficient, reliable, and semiautomated manner. Environ. Mol. Mutagen., 2018. © 2018 Wiley Periodicals, Inc.

  • basic research in Plasma Medicine a throughput approach from liquids to cells
    Journal of Visualized Experiments, 2017
    Co-Authors: Sander Bekeschus, Klaus-dieter Weltmann, Anke Schmidt, Felix Niessner, Torsten Gerling, Kristian Wende
    Abstract:

    In Plasma Medicine, ionized gases with temperatures close to that of vertebrate systems are applied to cells and tissues. Cold Plasmas generate reactive species known to redox regulate biological processes in health and disease. Pre-clinical and clinical evidence points to beneficial effects of Plasma treatment in the healing of chronic ulcer of the skin. Other emerging topics, such as Plasma cancer treatment, are receiving increasing attention. Plasma medical research requires interdisciplinary expertise in physics, chemistry, and bioMedicine. One goal of Plasma research is to characterize Plasma-treated cells in a variety of specific applications. This includes, for example, cell count and viability, cellular oxidation, mitochondrial activity, cytotoxicity and mode of cell death, cell cycle analysis, cell surface marker expression, and cytokine release. This study describes the essential equipment and workflows required for such research in Plasma bioMedicine. It describes the proper operation of an atmospheric pressure argon Plasma jet, specifically monitoring its basic emission spectra and feed gas settings to modulate reactive species output. Using a high-precision xyz-table and computer software, the jet is hovered in millisecond-precision over the cavities of 96-well plates in micrometer-precision for maximal reproducibility. Downstream assays for liquid analysis of redox-active molecules are shown, and target cells are Plasma-treated. Specifically, melanoma cells are analyzed in an efficient sequence of different consecutive assays but using the same cells: measurement of metabolic activity, total cell area, and surface marker expression of calreticulin, a molecule important for the immunogenic cell death of cancer cells. These assays retrieve content-rich biological information about Plasma effects from a single plate. Altogether, this study describes the essential steps and protocols for Plasma medical research.

  • the Plasma jet kinpen a powerful tool for wound healing
    Clinical Plasma Medicine, 2016
    Co-Authors: Sander Bekeschus, Klaus-dieter Weltmann, A Schmidt, Thomas Von Woedtke
    Abstract:

    Abstract The development of cold atmospheric pressure Plasma sources was the starting point for the innovative field of Plasma Medicine many years ago. Today, a large body of information is available on the biomedical and clinical applications of Plasma. Among the latter, wound healing is of special interest as there have been promising studies demonstrating a benefit of Plasma in the treatment of chronic wounds. Wound healing is tightly regulated by redox mechanisms. This creates an exciting opportunity as we and others have identified reactive oxygen and nitrogen species to be the central components mediating biological effects of cold Plasma. A directed delivery of the Plasma-generated species to cells and tissues may therefore commence new therapeutic options not only in the healing of pathological wounds but also related to other redox-based diseases. The literature covers numerous findings on the biological effects of cold physical Plasma sources. However, Plasma sources strongly differ from each other making it challenging to summarize or even compare results from different types of sources from a physical and biological point of view. The aim of this comprehensive review is to provide a unique compendium of studies assessing the pre-clinical and clinical relevance as well as potential health risks related to the exposure to the atmospheric pressure argon Plasma jet kINPen. This well-investigated and promising Plasma source demonstrates a strong potential to be of clinical significance in the near future. Also, the collection of studies investigating its biological effects may serve as a role model for similar Plasma sources and applications in the field of Plasma Medicine.

Thomas Von Woedtke - One of the best experts on this subject based on the ideXlab platform.

  • perspectives on cold atmospheric Plasma cap applications in Medicine
    Physics of Plasmas, 2020
    Co-Authors: Thomas Von Woedtke, Steffen Emmert, Hansrobert Metelmann, Stefan Rupf, Klaus-dieter Weltmann
    Abstract:

    Plasma Medicine is an innovative research field combining Plasma physics, life science, and clinical Medicine. It is mainly focused on the application cold atmospheric Plasma (CAP) in therapeutic settings. Based on its ability to inactivate microorganisms but also to stimulate tissue regeneration, current medical applications are focused on the treatment of wounds and skin diseases. Since CAP is also able to inactivate cancer cells, its use in cancer therapy is expected to be the next field of clinical Plasma application. Other promising applications are expected in oral Medicine and ophthalmology. It is the current state of knowledge that biological CAP effects are mainly based on the action of reactive oxygen and nitrogen species supported by electrical fields and UV radiation. However, continuing basic research is not only essential to improve, optimize, and enlarge the spectrum of medical CAP applications and their safety, but it is also the basis for identification and definition of a single parameter or set of parameters to monitor and control Plasma treatment and its effects. In the field of CAP Plasma devices, research and application are currently dominated by two basic types: dielectric barrier discharges and Plasma jets. Its individual adaptation to specific medical needs, including its combination with technical units for continuous and real-time monitoring of both Plasma performance and the target that is treated, will lead to a new generation of CAP-based therapeutic systems.

  • Plasma Medicine a field of applied redox biology
    in Vivo, 2019
    Co-Authors: Thomas Von Woedtke, Anke Schmidt, Sander Bekeschus, Kristian Wende, Klaus-dieter Weltmann
    Abstract:

    Plasma Medicine comprises the application of physical Plasma directly on or in the human body for therapeutic purposes. Three most important basic Plasma effects are relevant for medical applications: i) inactivation of a broad spectrum of microorganisms, including multidrug-resistant pathogens, ii) stimulation of cell proliferation and angiogenesis with lower Plasma treatment intensity, and iii) inactivation of cells by initialization of cell death with higher Plasma treatment intensity, above all in cancer cells. Based on own published results as well as on monitoring of relevant literature the aim of this topical review is to summarize the state of the art in Plasma Medicine and connect it to redox biology. One of the most important results of basic research in Plasma Medicine is the insight that biological Plasma effects are mainly mediated via reactive oxygen and nitrogen species influencing cellular redox-regulated processes. Plasma Medicine can be considered a field of applied redox biology.

  • high throughput image cytometry micronucleus assay to investigate the presence or absence of mutagenic effects of cold physical Plasma
    Environmental and Molecular Mutagenesis, 2018
    Co-Authors: Sander Bekeschus, Thomas Von Woedtke, Klaus-dieter Weltmann, Anke Schmidt, Felix Niessner, Axel Kramer, Hansrobert Metelmann, Frank Adler, Kristian Wende
    Abstract:

    Promising cold physical Plasma sources have been developed in the field of Plasma Medicine. An important prerequisite to their clinical use is lack of genotoxic effects in cells. During optimization of one or even different Plasma sources for a specific application, large numbers of samples need to be analyzed. There are soft and easy-to-assess markers for genotoxic stress such as phosphorylation of histone H2AX (γH2AX) but only few tests are accredited by the OECD with regard to mutagenicity detection. The micronucleus (MN) assay is among them but often requires manual counting of many thousands of cells per sample under the microscope. A high-throughput MN assay is presented using image flow cytometry and image analysis software. A human lymphocyte cell line was treated with Plasma generated with ten different feed gas conditions corresponding to distinct reactive species patterns that were investigated for their genotoxic potential. Several millions of cells were automatically analyzed by a MN quantification strategy outlined in detail in this work. Our data demonstrates the absence of newly formed MN in any feed gas condition using the atmospheric pressure Plasma jet kINPen. As positive control, ionizing radiation gave a significant 5-fold increase in micronucleus frequency. Thus, this assay is suitable to assess the genotoxic potential in large sample sets of cells exposed chemical or physical agents including Plasmas in an efficient, reliable, and semiautomated manner. Environ. Mol. Mutagen., 2018. © 2018 Wiley Periodicals, Inc.

  • the Plasma jet kinpen a powerful tool for wound healing
    Clinical Plasma Medicine, 2016
    Co-Authors: Sander Bekeschus, Klaus-dieter Weltmann, A Schmidt, Thomas Von Woedtke
    Abstract:

    Abstract The development of cold atmospheric pressure Plasma sources was the starting point for the innovative field of Plasma Medicine many years ago. Today, a large body of information is available on the biomedical and clinical applications of Plasma. Among the latter, wound healing is of special interest as there have been promising studies demonstrating a benefit of Plasma in the treatment of chronic wounds. Wound healing is tightly regulated by redox mechanisms. This creates an exciting opportunity as we and others have identified reactive oxygen and nitrogen species to be the central components mediating biological effects of cold Plasma. A directed delivery of the Plasma-generated species to cells and tissues may therefore commence new therapeutic options not only in the healing of pathological wounds but also related to other redox-based diseases. The literature covers numerous findings on the biological effects of cold physical Plasma sources. However, Plasma sources strongly differ from each other making it challenging to summarize or even compare results from different types of sources from a physical and biological point of view. The aim of this comprehensive review is to provide a unique compendium of studies assessing the pre-clinical and clinical relevance as well as potential health risks related to the exposure to the atmospheric pressure argon Plasma jet kINPen. This well-investigated and promising Plasma source demonstrates a strong potential to be of clinical significance in the near future. Also, the collection of studies investigating its biological effects may serve as a role model for similar Plasma sources and applications in the field of Plasma Medicine.

  • research on Plasma Medicine relevant Plasma liquid interaction what happened in the past five years
    Clinical Plasma Medicine, 2015
    Co-Authors: Helena Jablonowski, Thomas Von Woedtke
    Abstract:

    Abstract During the last five years mechanisms of Plasma-induced change of liquid chemistry have drawn huge attention in basic research in Plasma Medicine because liquid phase processes have been identified to be the main key to understand detailed mechanisms of atmospheric pressure Plasma effects on living systems. Moreover, Plasma-activated liquids are considered to be useful for several applications also in the medical field. This review gives a compilation of the work done in the past five years mainly from an analytical point of view to reveal both the actual knowledge and the still missing parts for a more complete understanding of the Plasma–liquid-tissue interaction. In general, independent both on the different atmospheric pressure Plasma sources (dielectric barrier discharges, Plasma jets; different working gases) and the different liquid systems (water, non-buffered and buffered saline solutions, cell culture media) investigated, hydrogen peroxide (H2O2) as well as nitrite (NO2−) and nitrate (NO3−) were detected as stable reactive oxygen and nitrogen species (ROS, RNS/RONS). In non-buffered systems, pH decrease was found. It is hypothesized that the basic pathways of generation of reactive species in liquids after treatment with atmospheric pressure Plasmas can be generalized. These stable and easy to detect ROS and RNS/RONS are considered to be representative for more or less complex reactions chains with the participation of other more reactive and short-lived reactive oxygen and nitrogen “precursor” species which are induced in liquids by Plasma treatment and may play dominant roles in biological Plasma effects. As most important precursors of hydrogen peroxide as well as nitrite and nitrate, hydroxyl radicals (•OH), superoxide anion radicals (O2•−), singlet oxygen (1O2), and nitric oxide (•NO) were identified and partially detected in different Plasma treated liquids. By combination of experimental data and theoretical considerations including modeling approaches first steps to identify reaction pathways were realized yet. Above all, peroxynitrite (ONOO–) was identified to play a crucial role for biological effects of Plasma-treated liquids. In future, innovative and sophisticated analytics possibly at least partially beyond the classical chemical and pharmaceutical techniques have to found to improve the fundamental understanding of liquid phase-transmitted mechanisms of Plasma effects on living cells and tissue and its consequences for complex physiological as well as pathophysiological processes in the organism. This is essential both for the consolidation of Plasma Medicine on a sound scientific basis and to open up innovative fields of Plasma application in Medicine.

Masaru Hori - One of the best experts on this subject based on the ideXlab platform.

  • non thermal atmospheric pressure Plasma activates lactate in ringer s solution for anti tumor effects
    Scientific Reports, 2016
    Co-Authors: Hiromasa Tanaka, Kae Nakamura, Hiroaki Kajiyama, Masaaki Mizuno, Fumitaka Kikkawa, Fumi Utsumi, Kenji Ishikawa, Keigo Takeda, Masaru Hori
    Abstract:

    Non-thermal atmospheric pressure Plasma is a novel approach for wound healing, blood coagulation, and cancer therapy. A recent discovery in the field of Plasma Medicine is that non-thermal atmospheric pressure Plasma not only directly but also indirectly affects cells via Plasma-treated liquids. This discovery has led to the use of non-thermal atmospheric pressure Plasma as a novel chemotherapy. We refer to these Plasma-treated liquids as Plasma-activated liquids. We chose Ringer’s solutions to produce Plasma-activated liquids for clinical applications. In vitro and in vivo experiments demonstrated that Plasma-activated Ringer’s lactate solution has anti-tumor effects, but of the four components in Ringer’s lactate solution, only lactate exhibited anti-tumor effects through activation by non-thermal Plasma. Nuclear magnetic resonance analyses indicate that Plasma irradiation generates acetyl and pyruvic acid-like groups in Ringer’s lactate solution. Overall, these results suggest that Plasma-activated Ringer’s lactate solution is promising for chemotherapy.

  • cancer therapy using non thermal atmospheric pressure Plasma with ultra high electron density
    Physics of Plasmas, 2015
    Co-Authors: Hiromasa Tanaka, Tetsuo Adachi, Masaaki Mizuno, Shinya Toyokuni, Shoichi Maruyama, Yasuhiro Kodera, Hiroko Terasaki, Masashi Kato, Fumitaka Kikkawa, Masaru Hori
    Abstract:

    Cancer therapy using non-thermal atmospheric pressure Plasma is a big challenge in Plasma Medicine. Reactive species generated from Plasma are key factors for treating cancer cells, and thus, non-thermal atmospheric pressure Plasma with high electron density has been developed and applied for cancer treatment. Various cancer cell lines have been treated with Plasma, and non-thermal atmospheric Plasma clearly has anti-tumor effects. Recent innovative studies suggest that Plasma can both directly and indirectly affect cells and tissues, and this observation has widened the range of applications. Thus, cancer therapy using non-thermal atmospheric pressure Plasma is promising. Animal experiments and understanding the mode of action are essential for clinical application in the future. A new academic field that combines Plasma science, the biology of free radicals, and systems biology will be established.

  • Plasma activated medium induces a549 cell injury via a spiral apoptotic cascade involving the mitochondrial nuclear network
    Free Radical Biology and Medicine, 2015
    Co-Authors: Tetsuo Adachi, Saho Nonomura, Hirokazu Hara, Shinichi Kondo, Hiromasa Tanaka, Masaru Hori
    Abstract:

    Abstract Plasma Medicine is a rapidly expanding new field of interdisciplinary research that combines physics, chemistry, biology, and Medicine. Nonthermal atmospheric pressure Plasma can be applied to living cells and tissues and has emerged as a novel technology for cancer therapy. Plasma has recently been shown to affect cells not only directly, but also by indirect treatment with previously prepared Plasma-activated medium (PAM). The objective of this study was to demonstrate the inhibitory effects of PAM on A549 cell survival and elucidate the signaling mechanisms responsible for cell death. PAM maintained its ability to suppress cell viability for at least 1 week when stored at −80 °C. The severity of PAM-triggered cell injury depended on the kind of culture medium used to prepare the PAM, especially that with or without pyruvate. Hydrogen peroxide (H2O2) and/or its derived or cooperating reactive oxygen species reduced the mitochondrial membrane potential, downregulated the expression of the antiapoptotic protein Bcl2, activated poly(ADP-ribose) polymerase-1, and released apoptosis-inducing factor from mitochondria with endoplasmic reticulum stress. However, the activation of caspase 3/7 and attenuation of cell viability by the addition of caspase inhibitor were not observed. The accumulation of adenine 5′-diphosphoribose as a product of the above reactions activated transient receptor potential melastatin 2, which elevated intracellular Ca2+ levels and subsequently led to cell death. These results demonstrated that H2O2 and/or other reactive species in PAM disturbed the mitochondrial–nuclear network in cancer cells through a caspase-independent apoptotic pathway. Moreover, damage to the Plasma membrane by H2O2-cooperating charged species not only induced apoptosis, but also increased its permeability to extracellular reactive species. These phenomena were also detected in PAM-treated HepG2 and MCF-7 cells.

  • selective cytotoxicity of indirect nonequilibrium atmospheric pressure Plasma against ovarian clear cell carcinoma
    SpringerPlus, 2014
    Co-Authors: Fumi Utsumi, Kae Nakamura, Hiroaki Kajiyama, Hiromasa Tanaka, Masaru Hori, Fumitaka Kikkawa
    Abstract:

    Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid carcinoma. Non-thermal atmospheric pressure Plasma which produces reactive species has recently led to an explosion of research in Plasma Medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to Plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to Plasma. In this study, we confirmed whether this indirect Plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure Plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure Plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.

  • Plasma interactions with aminoacid l alanine as a basis of fundamental processes in Plasma Medicine
    Current Applied Physics, 2013
    Co-Authors: Yuichi Setsuhara, Ken Cho, Masaharu Shiratani, Makoto Sekine, Masaru Hori
    Abstract:

    Abstract Plasma interactions with l -alaine have been studied as a basis of fundamental processes in Plasma Medicine. The Plasma interactions with l -alaine have been examined for investigations of molecular degradations induced by direct exposures with Ar Plasma and exposures with UV–VUV photons emitted from the Ar Plasma via chemical bonding states analyses using X-ray photoelectron spectroscopy (XPS). The direct Ar-Plasma exposure resulted in significant degradations of COOH group and CNH 2 group. Separate experiments via irradiation with photons in UV and VUV regions from the Ar Plasma showed that the molecular degradation via irradiation with photons in VUV region was much more significant than via irradiation with photons in UV region. These experiments have indicated that the causality of the molecular degradation of the l -alanine during the Ar Plasma exposure is considered to be significant in the following order; ions > VUV photons > UV photons ∼ meta-stable radicals. Furthermore, the exposure with Ar–O 2 mixture Plasma resulted in insignificant change in the XPS C1s spectra for variation of the exposure time ranging from 30 s to 300 s, indicating that the surface etching process is much more considerable than the chemical degradation process.

Annemie Bogaerts - One of the best experts on this subject based on the ideXlab platform.

  • synergistic effect of electric field and lipid oxidation on the permeability of cell membranes
    Biochimica et Biophysica Acta, 2017
    Co-Authors: Maksudbek Yusupov, Erik C Neyts, J Van Der Paal, Annemie Bogaerts
    Abstract:

    Abstract Background Strong electric fields are known to affect cell membrane permeability, which can be applied for therapeutic purposes, e.g., in cancer therapy. A synergistic enhancement of this effect may be accomplished by the presence of reactive oxygen species (ROS), as generated in cold atmospheric Plasmas. Little is known about the synergy between lipid oxidation by ROS and the electric field, nor on how this affects the cell membrane permeability. Method We here conduct molecular dynamics simulations to elucidate the dynamics of the permeation process under the influence of combined lipid oxidation and electroporation. A phospholipid bilayer (PLB), consisting of di-oleoyl-phosphatidylcholine molecules covered with water layers, is used as a model system for the Plasma membrane. Results and conclusions We show how oxidation of the lipids in the PLB leads to an increase of the permeability of the bilayer to ROS, although the permeation free energy barriers still remain relatively high. More importantly, oxidation of the lipids results in a drop of the electric field threshold needed for pore formation (i.e., electroporation) in the PLB. The created pores in the membrane facilitate the penetration of reactive Plasma species deep into the cell interior, eventually causing oxidative damage. General significance This study is of particular interest for Plasma Medicine, as Plasma generates both ROS and electric fields, but it is also of more general interest for applications where strong electric fields and ROS both come into play.

  • structural modification of the skin barrier by oh radicals a reactive molecular dynamics study for Plasma Medicine
    Journal of Physics D, 2015
    Co-Authors: Jonas Van Der Paal, Maksudbek Yusupov, Christof C W Verlackt, Erik C Neyts, Annemie Bogaerts
    Abstract:

    While Plasma treatment of skin diseases and wound healing has been proven highly effective, the underlying mechanisms, and more generally the effect of Plasma radicals on skin tissue, are not yet completely understood. In this paper, we perform ReaxFF-based reactive molecular dynamics simulations to investigate the interaction of Plasma generated OH radicals with a model system composed of free fatty acids, ceramides, and cholesterol molecules. This model system is an approximation of the upper layer of the skin (stratum corneum). All interaction mechanisms observed in our simulations are initiated by H-abstraction from one of the ceramides. This reaction, in turn, often starts a cascade of other reactions, which eventually lead to the formation of aldehydes, the dissociation of ceramides or the elimination of formaldehyde, and thus eventually to the degradation of the skin barrier function.

  • reactive molecular dynamics simulations for a better insight in Plasma Medicine
    Plasma Processes and Polymers, 2014
    Co-Authors: Annemie Bogaerts, Maksudbek Yusupov, Jonas Van Der Paal, Christof C W Verlackt, Erik C Neyts
    Abstract:

    In this review paper, we present several examples of reactive molecular dynamics simulations, which contribute to a better understanding of the underlying mechanisms in Plasma Medicine on the atomic scale. This includes the interaction of important reactive oxygen Plasma species with the outer cell wall of both gram-positive and gram-negative bacteria, and with lipids present in human skin. Moreover, as most biomolecules are surrounded by a liquid biofilm, the behavior of these Plasma species in a liquid (water) layer is presented as well. Finally, a perspective for future atomic scale modeling studies is given, in the field of Plasma Medicine in general, and for cancer treatment in particular.

  • computer simulations of Plasma biomolecule and Plasma tissue interactions for a better insight in Plasma Medicine
    Journal of Physics D, 2014
    Co-Authors: Erik C Neyts, Christof C W Verlackt, Maksudbek Yusupov, Annemie Bogaerts
    Abstract:

    Plasma Medicine is a rapidly evolving multidisciplinary field at the intersection of chemistry, biochemistry, physics, biology, Medicine and bioengineering. It holds great potential in medical, health care, dentistry, surgical, food treatment and other applications. This multidisciplinary nature and variety of possible applications come along with an inherent and intrinsic complexity. Advancing Plasma Medicine to the stage that it becomes an everyday tool in its respective fields requires a fundamental understanding of the basic processes, which is lacking so far. However, some major advances have already been made through detailed experiments over the last 15 years. Complementary, computer simulations may provide insight that is difficult—if not impossible—to obtain through experiments. In this review, we aim to provide an overview of the various simulations that have been carried out in the context of Plasma Medicine so far, or that are relevant for Plasma Medicine. We focus our attention mostly on atomistic simulations dealing with Plasma–biomolecule interactions. We also provide a perspective and tentative list of opportunities for future modelling studies that are likely to further advance the field.

  • interaction of o and oh radicals with a simple model system for lipids in the skin barrier a reactive molecular dynamics investigation for Plasma Medicine
    Journal of Physics D, 2013
    Co-Authors: Jonas Van Der Paal, Erik C Neyts, Stefaan Aernouts, Adri C T Van Duin, Annemie Bogaerts
    Abstract:

    Plasma Medicine has been claimed to provide a novel route to heal wounds and regenerate skin, although very little is currently known about the elementary processes taking place. We carried out a series of ReaxFF-based reactive molecular dynamics simulations to investigate the interaction of O and OH radicals with lipids, more specifically with α-linolenic acid as a model for the free fatty acids present in the upper skin layer. Our calculations predict that the O and OH radicals most typically abstract a H atom from the fatty acids, which can lead to the formation of a conjugated double bond, but also to the incorporation of alcohol or aldehyde groups, thereby increasing the hydrophilic character of the fatty acids and changing the general lipid composition of the skin. Within the limitations of the investigated model, no formation of possibly toxic products was observed. (Some figures may appear in colour only in the online journal)