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search.filters.applied.f.access: openAccess × Author: Weltmann, Klaus-Dieter × End date: 2024 × Start date: 2020 × DDC: 570 × Has files: Yes × WGL Institute: INP ×

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Now showing 1 - 6 of 6
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    Nonenzymatic post-translational modifications in peptides by cold plasma-derived reactive oxygen and nitrogen species
    (Melville, NY : AIP, 2020) Wenske, Sebastian; Lackmann, Jan-Wilm; Bekeschus, Sander; Weltmann, Klaus-Dieter; Von Woedtke, Thomas; Wende, Kristian
    Cold physical plasmas are emerging tools for wound care and cancer control that deliver reactive oxygen species (ROS) and nitrogen species (RNS). Alongside direct effects on cellular signaling processes, covalent modification of biomolecules may contribute to the observed physiological consequences. The potential of ROS/RNS generated by two different plasma sources (kINPen and COST-Jet) to introduce post-translational modifications (PTMs) in the peptides angiotensin and bradykinin was explored. While the peptide backbone was kept intact, a significant introduction of oxidative PTMs was observed. The modifications cluster at aromatic (tyrosine, histidine, and phenylalanine) and neutral amino acids (isoleucine and proline) with the introduction of one, two, or three oxygen atoms, ring cleavages of histidine and tryptophan, and nitration/nitrosylation predominantly observed. Alkaline and acidic amino acid (arginine and aspartic acid) residues showed a high resilience, indicating that local charges and the chemical environment at large modulate the attack of the electron-rich ROS/RNS. Previously published simulations, which include only OH radicals as ROS, do not match the experimental results in full, suggesting the contribution of other short-lived species, i.e., atomic oxygen, singlet oxygen, and peroxynitrite. The observed PTMs are relevant for the biological activity of peptides and proteins, changing polarity, folding, and function. In conclusion, it can be assumed that an introduction of covalent oxidative modifications at the amino acid chain level occurs during a plasma treatment. The introduced changes, in part, mimic naturally occurring patterns that can be interpreted by the cell, and subsequently, these PTMs allow for prolonged secondary effects on cell physiology. © 2020 Author(s).
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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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    Effects of cold atmospheric pressure plasma and disinfecting agents on Candida albicans in root canals of extracted human teeth
    (Weinheim : Wiley-VCH-Verl., 2020) Kerlikowski, Anne; Matthes, Rutger; Pink, Christiane; Steffen, Heike; Schlüter, Rabea; Holtfreter, Birte; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Kocher, Thomas; Jablonowski, Lukasz
    Reinfection in endodontically treated teeth is linked to the complexity of the root canal system, which is problematic to reach with conventional disinfection methods. As plasma is expected to have the ability to sanitize narrow areas, the aim of this study was to analyze the effect of cold atmospheric pressure plasma (CAP) on Candida albicans in root canals of extracted human teeth. CAP was applied as mono treatment and in combination with standard endodontic disinfectants (sodium hypochlorite, chlorhexidine and octenidine). Disinfection efficiency was evaluated as reduction of the logarithm of colony forming units per milliliter (log10 CFU/mL) supported by scanning electron microscopy as imaging technique. Plasma alone showed the highest reduction of log10 CFU, suggesting the best disinfection properties of all tested agents. © 2020 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.
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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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    Biocompatible Gas Plasma Treatment Affects Secretion Profiles but Not Osteogenic Differentiation in Patient-Derived Mesenchymal Stromal Cells
    (Basel : Molecular Diversity Preservation International (MDPI), 2022) Fischer, Maximilian; Schoon, Janosch; Freund, Eric; Miebach, Lea; Weltmann, Klaus-Dieter; Bekeschus, Sander; Wassilew, Georgi I.
    Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen and nitrogen species, is suggested to provide advantages in regenerative medicine. Intraoperative CPP therapy targeting pathologies related to diminished bone quality could be promising in orthopedic surgery. Assessment of a clinically approved plasma jet regarding cellular effects on primary bone marrow mesenchymal stromal cells (hBM-MSCs) from relevant arthroplasty patient cohorts is needed to establish CPP-based therapeutic approaches for bone regeneration. Thus, the aim of this study was to derive biocompatible doses of CPP and subsequent evaluation of human primary hBM-MSCs’ osteogenic and immunomodulatory potential. Metabolic activity and cell proliferation were affected in a treatment-time-dependent manner. Morphometric high content imaging analyses revealed a decline in mitochondria and nuclei content and increased cytoskeletal compactness following CPP exposure. Employing a nontoxic exposure regime, investigation on osteogenic differentiation did not enhance osteogenic capacity of hBM-MSCs. Multiplex analysis of major hBM-MSC cytokines, chemokines and growth factors revealed an anti-inflammatory, promatrix-assembling and osteoclast-regulating secretion profile following CPP treatment and osteogenic stimulus. This study can be noted as the first in vitro study addressing the influence of CPP on hBM-MSCs from individual donors of an arthroplasty clientele.
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    xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells
    (Amsterdam [u.a.] : Elsevier, 2020) Bekeschus, Sander; Eisenmann, Sebastian; Sagwal, Sanjeev Kumar; Bodnar, Yana; Moritz, Juliane; Poschkamp, Broder; Stoffels, Ingo; Emmert, Steffen; Madesh, Muniswamy; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Gandhirajan, Rajesh Kumar
    Cold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.