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Now showing 1 - 10 of 48
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    Activation of murine immune cells upon co-culture with plasma-treated B16F10 melanoma cells
    (Basel : MDPI, 2019) Rödder, Katrin; Moritz, Juliane; Miller, Vandana; Weltmann, Klaus-Dieter; Metelmann, Hans-Robert; Gandhirajan, Rajesh; Bekeschus, Sander
    Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells' activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone. © 2019 by the authors.
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    The kINPen—a review on physics and chemistry of the atmospheric pressure plasma jet and its applications
    (Bristol : IOP Publ., 2018-5-16) Reuter, Stephan; von Woedtke, Thomas; Weltmann, Klaus-Dieter
    The kINPen® plasma jet was developed from laboratory prototype to commercially available non-equilibrium cold plasma jet for various applications in materials research, surface treatment and medicine. It has proven to be a valuable plasma source for industry as well as research and commercial use in plasma medicine, leading to very successful therapeutic results and its certification as a medical device. This topical review presents the different kINPen plasma sources available. Diagnostic techniques applied to the kINPen are introduced. The review summarizes the extensive studies of the physics and plasma chemistry of the kINPen performed by research groups across the world, and closes with a brief overview of the main application fields.
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    Plasma treatment limits cutaneous squamous cell carcinoma development in vitro and in vivo
    (Basel : MDPI AG, 2020) Pasqual-Melo, Gabriella; Nascimento, Thiago; Sanches, Larissa Juliani; Blegniski, Fernanda Paschoal; Bianchi, Julya Karen; Sagwal, Sanjeev Kumar; Berner, Julia; Schmidt, Anke; Emmert, Steffen; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Gandhirajan, Rajesh Kumar; Cecchini, Alessandra Lourenço; Bekeschus, Sander
    Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Combining Biocompatible and Biodegradable Scaffolds and Cold Atmospheric Plasma for Chronic Wound Regeneration
    (Basel : Molecular Diversity Preservation International (MDPI), 2021) Emmert, Steffen; Pantermehl, Sven; Foth, Aenne; Waletzko-Hellwig, Janine; Hellwig, Georg; Bader, Rainer; Illner, Sabine; Grabow, Niels; Bekeschus, Sander; Weltmann, Klaus-Dieter; Jung, Ole; Boeckmann, Lars
    Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin wounds include venous and/or arterial circulatory disorders, diabetes, or constant pressure to the skin (decubitus). The hallmarks of modern wound treatment include debridement of dead tissue, disinfection, wound dressings that keep the wound moist but still allow air exchange, and compression bandages. Despite all these efforts there is still a huge treatment resistance and wounds will not heal. This calls for new and more efficient treatment options in combination with novel biocompatible skin scaffolds. Cold atmospheric pressure plasma (CAP) is such an innovative addition to the treatment armamentarium. In one CAP application, antimicrobial effects, wound acidification, enhanced microcirculations and cell stimulation can be achieved. It is evident that CAP treatment, in combination with novel bioengineered, biocompatible and biodegradable electrospun scaffolds, has the potential of fostering wound healing by promoting remodeling and epithelialization along such temporarily applied skin replacement scaffolds.
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    Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing
    (New York [u.a.] : Hindawi, 2015) Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian
    Background. The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. Methods. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Results. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. Conclusions. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine.
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    Abschlussbericht zum Verbundprojekt Campus PlasmaMed, Teilvorhaben Campus PlasmaMed 6
    (Hannover : Technische Informationsbibliothek (TIB), 2011) Weltmann, Klaus-Dieter
    [no abstract available]
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    Quantification of the ozone and singlet delta oxygen produced in gas and liquid phases by a non-thermal atmospheric plasma with relevance for medical treatment
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2018-8-15) Jablonowski, Helena; Santos Sousa, Joao; Weltmann, Klaus-Dieter; Wende, Kristian; Reuter, Stephan
    In the field of plasma medicine, the identification of relevant reactive species in the liquid phase is highly important. To design the plasma generated species composition for a targeted therapeutic application, the point of origin of those species needs to be known. The dominant reactive oxygen species generated by the plasma used in this study are atomic oxygen, ozone, and singlet delta oxygen. The species density changes with the distance to the active plasma zone, and, hence, the oxidizing potential of this species cocktail can be tuned by altering the treatment distance. In both phases (gas and liquid), independent techniques have been used to determine the species concentration as a function of the distance. The surrounding gas composition and ambient conditions were controlled between pure nitrogen and air-like by using a curtain gas device. In the gas phase, in contrast to the ozone density, the singlet delta oxygen density showed to be more sensitive to the distance. Additionally, by changing the surrounding gas, admixing or not molecular oxygen, the dynamics of ozone and singlet delta oxygen behave differently. Through an analysis of the reactive species development for the varied experimental parameters, the importance of several reaction pathways for the proceeding reactions was evaluated and some were eventually excluded.
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    Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen
    (London : Nature Publishing Group, 2021) Miebach, Lea; Freund, Eric; Horn, Stefan; Niessner, Felix; Sagwal, Sanjeev Kumar; von Woedtke, Thomas; Emmert, Steffen; Weltmann, Klaus-Dieter; Clemen, Ramona; Schmidt, Anke; Gerling, Torsten; Bekeschus, Sander
    Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
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    Periodic Exposure of Plasma-Activated Medium Alters Fibroblast Cellular Homoeostasis
    (Basel : Molecular Diversity Preservation International (MDPI), 2022) Bhartiya, Pradeep; Kaushik, Neha; Nguyen, Linh N.; Bekeschus, Sander; Masur, Kai; Weltmann, Klaus-Dieter; Kaushik, Nagendra Kumar; Choi, Eun Ha
    Excess amounts of redox stress and failure to regulate homeostatic levels of reactive species are associated with several skin pathophysiologic conditions. Nonmalignant cells are assumed to cope better with higher reactive oxygen and nitrogen species (RONS) levels. However, the effect of periodic stress on this balance has not been investigated in fibroblasts in the field of plasma medicine. In this study, we aimed to investigate intrinsic changes with respect to cellular proliferation, cell cycle, and ability to neutralize the redox stress inside fibroblast cells following periodic redox stress in vitro. Soft jet plasma with air as feeding gas was used to generate plasma-activated medium (PAM) for inducing redox stress conditions. We assessed cellular viability, energetics, and cell cycle machinery under oxidative stress conditions at weeks 3, 6, 9, and 12. Fibroblasts retained their usual physiological properties until 6 weeks. Fibroblasts failed to overcome the redox stress induced by periodic PAM exposure after 6 weeks, indicating its threshold potential. Periodic stress above the threshold level led to alterations in fibroblast cellular processes. These include consistent increases in apoptosis, while RONS accumulation and cell cycle arrest were observed at the final stages. Currently, the use of NTP in clinical settings is limited due to a lack of knowledge about fibroblasts’ behavior in wound healing, scar formation, and other fibrotic disorders. Understanding fibroblasts’ physiology could help to utilize nonthermal plasma in redox-related skin diseases. Furthermore, these results provide new information about the threshold capacity of fibroblasts and an insight into the adaptation mechanism against periodic oxidative stress conditions in fibroblasts.
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    Cold physical plasma-induced oxidation of cysteine yields reactive sulfur species (RSS)
    (Amsterdam [u.a.] : Elsevier, 2019) Bruno, Giuliana; Heusler, Thea; Lackmann, Jan-Wilm; Woedtke, Thomas von; Weltmann, Klaus-Dieter; Wende, Kristian
    Purpose: Studying plasma liquid chemistry can reveal insights into their biomedical effects, i.e. to understand the direct and indirect processes triggered by the treatment in a model or clinical application. Due to the reactivity of the sulfur atom, thiols are potential targets for plasma- derived reactive species. Being crucial for protein function and redox signaling pathways, their controllable modification would allow expanding the application range. Additionally, models to control and standardize CAP sources are desired tools for plasma source design. Methods: Cysteine, a ubiquitous amino acid, was used as a tracer compound to scavenge the reactive species produced by an argon plasma jet (kINPen). The resulting product pattern was identified via high-resolution mass spectrometry. The Ellman´s assay was used to screen CAP derived thiol consumption, and long-lived species deposition (hydrogen peroxide, nitrite, nitrate) was monitored in relation to the presence of cysteine. Results: The intensity of cysteine oxidation increased with treatment time and availability of oxygen in the feed gas. A range of products from cysteine was identified, in part indicative for certain treatment conditions. Several non-stable products occur transiently during the plasma treatment. Bioactive reactive sulfur species (RSS) have been found for mild treatment conditions, such as cysteine sulfoxides and cysteine-S-sulfonate. Considering the number of cysteine molecules in the boundary layer and the achieved oxidation state, short-lived species dominate in cysteine conversion. In addition, a boundary layer depletion of the tracer was observed. Conclusion: Translating these data into the in-vivo application, strong direct oxidation of protein thiol groups with subsequent changes in protein biochemistry must be considered. Plasma-derived RSS may in part contribute to the observed biomedical effects of CAP. Care must be taken to control the discharge parameter tightly as chemical dynamics at or in the liquid are subject to change easily. © 2019