Redox for Repair: Cold Physical Plasmas and Nrf2 Signaling Promoting Wound Healing

Chronic wounds and ulcers are major public health threats. Being a substantial burden for patients and health care systems alike, better understanding of wound pathophysiology and new avenues in the therapy of chronic wounds are urgently needed. Cold physical plasmas are particularly effective in promoting wound closure, irrespective of its etiology. These partially ionized gases deliver a therapeutic cocktail of reactive oxygen and nitrogen species safely at body temperature and without genotoxic side effects. This field of plasma medicine reanimates the idea of redox repair in physiological healing. This review compiles previous findings of plasma effects in wound healing. It discusses new links between plasma treatment of cells and tissues, and the perception and intracellular translation of plasma-derived reactive species via redox signaling pathways. Specifically, (i) molecular switches governing redox-mediated tissue response; (ii) the activation of the nuclear E2-related factor (Nrf2) signaling, together with antioxidative and immunomodulatory responses; and (iii) the stabilization of the scaffolding function and actin network in dermal fibroblasts are emphasized in the light of wound healing

Geschichten urbaner Landschaften : Formate des Erzählens für kollaborative Entwurfsprozesse

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Medical gas plasma-stimulated wound healing: Evidence and mechanisms

Defective wound healing poses a significant burden on patients and healthcare systems. In recent years, a novel reactive oxygen and nitrogen species (ROS/RNS) based therapy has received considerable attention among dermatologists for targeting chronic wounds. The multifaceted ROS/RNS are generated using gas plasma technology, a partially ionized gas operated at body temperature. This review integrates preclinical and clinical evidence into a set of working hypotheses mainly based on redox processes aiding in elucidating the mechanisms of action and optimizing gas plasmas for therapeutic purposes. These hypotheses include increased wound tissue oxygenation and vascularization, amplified apoptosis of senescent cells, redox signaling, and augmented microbial inactivation. Instead of a dominant role of a single effector, it is proposed that all mechanisms act in concert in gas plasma-stimulated healing, rationalizing the use of this technology in therapy-resistant wounds. Finally, addressable current challenges and future concepts are outlined, which may further promote the clinical utilization, efficacy, and safety of gas plasma technology in wound care in the future

Hyperspectral Imaging of Wounds Reveals Augmented Tissue Oxygenation following Cold Physical Plasma Treatment in Vivo

Efficient vascularization of skin tissue supports wound healing in response to injury. This includes elevated blood circulation, tissue oxygenation, and perfusion. Cold physical plasma promotes wound healing in animal models and humans. Physical plasmas are multicomponent systems that generate several physicochemical effectors, such as ions, electrons, reactive oxygen and nitrogen species, and UV radiation. However, the consequences of plasma treatment on wound oxygenation and perfusion, vital processes to promote tissue regeneration, are largely unexplored. We used a novel hyperspectral imaging (HSI) system and a murine dermal full-thickness wound model in combination with kINPen argon plasma jet treatment to address this question. Plasma treatment promoted tissue oxygenation in superficial as well as deep (6 mm) layers of wound tissue. In addition to perfusion changes, we found a wound healing stage-dependent shift of tissue hemoglobin and tissue water index during reactive species-driven wound healing. Contactless, fast monitoring of medical parameters in real-time using HSI revealed a plasma-supporting effect in wound healing together with precise information about biological surface-specific features

Visual Processing in Rapid-Chase Systems: Image Processing, Attention, and Awareness

Visual stimuli can be classified so rapidly that their analysis may be based on a single sweep of feedforward processing through the visuomotor system. Behavioral criteria for feedforward processing can be evaluated in response priming tasks where speeded pointing or keypress responses are performed toward target stimuli which are preceded by prime stimuli. We apply this method to several classes of complex stimuli. (1) When participants classify natural images into animals or non-animals, the time course of their pointing responses indicates that prime and target signals remain strictly sequential throughout all processing stages, meeting stringent behavioral criteria for feedforward processing (rapid-chase criteria). (2) Such priming effects are boosted by selective visual attention for positions, shapes, and colors, in a way consistent with bottom-up enhancement of visuomotor processing, even when primes cannot be consciously identified. (3) Speeded processing of phobic images is observed in participants specifically fearful of spiders or snakes, suggesting enhancement of feedforward processing by long-term perceptual learning. (4) When the perceived brightness of primes in complex displays is altered by means of illumination or transparency illusions, priming effects in speeded keypress responses can systematically contradict subjective brightness judgments, such that one prime appears brighter than the other but activates motor responses as if it was darker. We propose that response priming captures the output of the first feedforward pass of visual signals through the visuomotor system, and that this output lacks some characteristic features of more elaborate, recurrent processing. This way, visuomotor measures may become dissociated from several aspects of conscious vision. We argue that “fast” visuomotor measures predominantly driven by feedforward processing should supplement “slow” psychophysical measures predominantly based on visual awareness

Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to plasma treatment have not yet been identified. To this end, we screened eight human cancer cell lines to investigate effects of low-dose, tumor-static plasma-treated medium (PTM) on cellular activity, immune-modulatory properties, and transcriptional levels of 22 redox-related genes. With PTM, a moderate reduction of metabolic activity and modest modulation of chemokine/cytokine pattern and markers of immunogenic cell death was observed. Strikingly, the Nuclear factor (erythroid-derived 2)-like 2 (nrf2) target heme oxygenase 1 (hmox1) was upregulated in all cell lines 4 h post PTM-treatment. nrf2 was not changed, but its baseline expression inversely and significantly correlated with hmox1 expression after exposure to PTM. Besides awarding hmox1 a central role with plasma-derived oxidants, we present a transcriptional redox map of 22 targets and chemokine/cytokine secretion map of 13 targets across eight different human tumor cell lines of four tumor entities at baseline activity that are useful for future studies in this field

Ideen, Interessen und Zusammenarbeit in der Stadtentwicklung : auf dem Weg zu einer lokalen Kultur der Partizipation

Unter der Annahme, dass nachhaltige Stadtentwicklung nur möglich ist, wenn vielfältige Lebensinteressen berücksichtigt und auch bürgerschaftliche Potenziale einbezogen werden, fragt dieser Beitrag nach notwendigen Rahmenbedingungen der Handlungsfähigkeit für und ggf. durch bürgerschaftliche Projekte. Grundlage sind zwei Projekte zur Altstadtentwicklung in einer kleineren deutschen Stadt, die im Rahmen des Praxisforschungsprojekts „Transformation urbaner Zentren“ durchgeführt wurden. Die Analyse erfolgt auf Grundlage von Konzepten zu Governance, Partizipation, Empowerment und Selbstwirksamkeit. Aus der Betrachtung der Motive und Interessen der beteiligten Personen sowie deren Erwartungen an die Projektbegleitung und einer Reflexion der Projektarbeit vor Ort werden begünstigende Rahmenbedingungen für bürgerschaftliche Projekte im Rahmen der Stadtentwicklung benannt

With or without the EU? Understanding EU member states’ motivations for dealing with Russia at the European or the national level

This thesis seeks to explain why European Union (EU) member states choose to pursue their foreign policy objectives regarding Russia at the EU level or bilaterally. It explores the idea in the literature that national governments engage in ‘venue shopping’ to achieve national foreign policy objectives. The thesis examines the question of how EU member states engage with Russia by examining different policy case studies (energy relations, democracy and human rights promotion, bilateral disputes). It analyses member governments’ choice of policy route from two contrasting, but complementary perspectives, exploring both rational choice arguments from a 'logic of expected consequences' perspective (focusing on the anticipated costs and benefits of national governments' choice of policy route) and social constructivist arguments from a 'logic of appropriateness' perspective (focusing on the effects of EU membership and the socialisation of national representatives into the rules and norms of behaviour in the EU on the political elites' choice of policy route). With a systematic analysis of national governments’ choices across different policy issues it helps clarify the motivations underpinning the decision to pursue national foreign policy objectives at the European or the national level. It thereby contributes to filling a lacuna in the existing literature on EU-Russia relations and the extant research on member states’ foreign policies in the EU context. The contributions to existing scholarship that the thesis makes are: first, it demonstrates that the decision to cooperate, or act at the bilateral level, is not as clear cut as it is often depicted. I show that in most cases it is not a question of either-or. Member states frequently pursue cooperation at the EU level to achieve foreign policy objectives that they also pursue at the bilateral level. Second, I show that member states’ choices are predominantly influenced by their assessment of the utility of the European and the national route. There is considerably less evidence to suggest that the European level is being privileged as a result of a socialisation in the EU, so the length of membership, and thus the duration of national decision-makers' exposure to EU policy-making processes does not determine a member government’s choice and influences it only to a limited extent. Third, I show that the size/capacity of the member state they represent is but one factor influencing national governments in their choice of foreign policy route. Whether a state is large or small gives indications of a national government's likely choice, but it does not offer definitive insights into which policy route will be chosen on a particular issue. Fourth, I concur with existing research that argues that a distinction between policy issues in terms of their hierarchy (‘first order’ or ‘second order’) provides insights into member states’ likely choice, but I argue that it is necessary to not just focus on the policy domain, but also to differentiate within a policy domain between the pursuit of broader framework objectives that deliver benefits to all member states and those objectives on which individual states accrue gains in the absence of a common EU agreement with Russia. Fifth, this thesis highlights the importance of how member states perceive Russia - as a threat or as an opportunity – and the importance they attribute to maintaining ‘friendly’, ‘pragmatic’ relations for whether they cooperate at the EU level or opt for the pursuit of their individual relations with Russia at the bilateral level. Finally, on the basis of the findings from the three analytically and empirically significant cases I argue that member states’ choices are highly contingent and can only be explained by considering the interplay between the different factors that enter into national governments’ calculus regarding the utility of the EU route versus the bilateral pursuit of national foreign policy objectives