Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles.

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders.

Oxidized Melanoma Antigens Promote Activation and Proliferation of Cytotoxic T-Cell Subpopulations.

Increasing evidence suggests the role of reactive oxygen and nitrogen species (RONS) in regulating antitumor immune effects and immunosuppression. RONS modify biomolecules and induce oxidative post-translational modifications (oxPTM) on proteins that can alarm phagocytes. However, it is unclear if and how protein oxidation by technical means could be a strategy to foster antitumor immunity and therapy.

Oxidant-modified amylin fibrils and aggregates alter the inflammatory profile of multiple myeloid cell types, but are non-toxic to islet β cells.

Diabetes mellitus currently affects ∼10% of the population worldwide, with Type 2 predominating, and this incidence is increasing steadily. Both Type 1 and 2 are complex diseases, involving β-cell death and chronic inflammation, but the pathways involved are unresolved. Chronic inflammation is characterized by increased oxidant formation, with this inducing protein modification, altered function and immunogenicity.

Medical Gas Plasma Technology Combines with Antimelanoma Therapies and Promotes Immune-Checkpoint Therapy Responses.

Strategies to improve activity and selectivity are major goals in oncological drug development. Medical gas plasma therapy has been subject to intense research in dermatooncology recently. Based on partial gas ionization, this approach is exceptional in generating a variety of reactive oxygen species simultaneously that can be applied locally at the tumor side.

Argon Humidification Exacerbates Antimicrobial and Anti-MRSA kINPen Plasma Activity.

Gas plasma is a medical technology with antimicrobial properties. Its main mode of action is oxidative damage via reactive species production. The clinical efficacy of gas plasma-reduced bacterial burden has been shown to be hampered in some cases.

Oxidized Proteins Differentially Affect Maturation and Activation of Human Monocyte-Derived Cells.

In cancer, antigen-presenting cells (APC), including dendritic cells (DCs), take up and process proteins to mount adaptive antitumor immune responses. This often happens in the context of inflamed cancer, where reactive oxygen species (ROS) are ubiquitous to modify proteins. However, the inflammatory consequences of oxidized protein uptake in DCs are understudied.

Gas Plasma Protein Oxidation Increases Immunogenicity and Human Antigen-Presenting Cell Maturation and Activation.

Protein vaccines rely on eliciting immune responses. Inflammation is a prerequisite for immune responses to control infection and cancer but is also associated with disease onset. Reactive oxygen species (ROSs) are central during inflammation and are capable of inducing non-enzymatic oxidative protein modifications (oxMods) associated with chronic disease, which alter the functionality or immunogenicity of proteins that are relevant in cancer immunotherapy.

Oxidative modifications control aberrant tyrosine kinase activity.

Therapy resistance is a major reason for the fatal consequences of cancer. The tumor microenvironment (TME) often is associated with the production of excess reactive oxygen species (ROS). ROS are capable of introducing oxidative post-translational modifications (oxPTMs) to proteins targeted in cancer therapy, such as tyrosine kinases (TKs), and ROS could render their functionality.

Gas plasma-oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis.

Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma-derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate.

Biological Risk Assessment of Three Dental Composite Materials following Gas Plasma Exposure.

Gas plasma is an approved technology that generates a plethora of reactive oxygen species, which are actively applied for chronic wound healing. Its particular antimicrobial action has spurred interest in other medical fields, such as periodontitis in dentistry. Recent work has indicated the possibility of performing gas plasma-mediated biofilm removal on teeth.

Conductivity augments ROS and RNS delivery and tumor toxicity of an argon plasma jet.

Gas plasma jet technology was recently identified as a potential adjuvant in the palliation of cancer patients. However, a practical point raised is if higher therapeutic efficacy is achieved with the gas plasma applied in direct contact to the tumor tissue (conducting) or during treatment with the remote cloud of reactive oxygen and nitrogen species (ROS/RNS) being expelled. In a bedside-to-bench study, this clinical question was translated into studying these two distinct treatment modalities using a three-dimensional tumor cell-matrix-hydrogel assay with subsequent quantitative confocal imaging.

Therapeutic ROS and Immunity in Cancer-The TRIC-21 Meeting.

The first Therapeutic ROS and Immunity in Cancer (TRIC) meeting was organized by the excellence research center ZIK (with its previous (FiRBaM) and (YPWPM) workshop series in Northern Germany) and the excellence research program ONKOTHER-H (Rostock/Greifswald, Germany). The meeting showcased cutting-edge research and liberated discussions on the application of therapeutic ROS and immunology in cancer treatment, primarily focusing on gas plasma technology. The 2-day hybrid meeting took place in Greifswald and online from 15-16 July 2021, facilitating a wide range of participants totaling 66 scientists from 12 countries and 5 continents.

Singlet-Oxygen-Induced Phospholipase A Inhibition: A Major Role for Interfacial Tryptophan Dioxidation.

Several studies have revealed that various diseases such as cancer have been associated with elevated phospholipase A (PLA ) activity. Therefore, the regulation of PLA catalytic activity is undoubtedly vital. In this study, effective inactivation of PLA due to reactive species produced from cold physical plasma as a source to model oxidative stress is reported.

ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?

Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities.

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.

Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova.

Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells.

Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an immunological dimension, successful antigen presentation and inflammation modulation is a key hallmark to elicit antitumor immunity.

Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection.

Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored.

Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen.

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 (jet) to treat colorectal cancer cells.

Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells.

Skin cancers have the highest prevalence of all human cancers, with the most lethal forms being squamous cell carcinoma and malignant melanoma. Besides the conventional local treatment approaches like surgery and radiotherapy, cold physical plasmas are emerging anticancer tools. Plasma technology is used as a therapeutic agent by generating reactive oxygen species (ROS).

Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion.

Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS).

Synthetic cytokine receptors transmit biological signals using artificial ligands.

Cytokine-induced signal transduction is executed by natural biological switches, which among many others control immune-related processes. Here, we show that synthetic cytokine receptors (SyCyRs) can induce cytokine signaling using non-physiological ligands. High-affinity GFP- and mCherry-nanobodies were fused to transmembrane and intracellular domains of the IL-6/IL-11 and IL-23 cytokine receptors gp130 and IL-12Rβ1/IL-23R, respectively.

Empiric antibiotic treatment of erythema migrans-like skin lesions as a function of geography: a clinical and cost effectiveness modeling study.

The skin lesion of early Lyme disease, erythema migrans (EM), is so characteristic that routine practice is to treat all such patients with antibiotics. Because other skin lesions may resemble EM, it is not known whether presumptive treatment of EM is appropriate in regions where Lyme disease is rare. We constructed a decision model to compare the cost and clinical effectiveness of three strategies for the management of EM: Treat All, Observe, and Serology as a function of the probability that an EM-like lesion is Lyme disease.

The clinical utility index as a practical multiattribute approach to drug development decisions.

We identify some innovative approaches to predicting overall patient benefit from investigational drugs to support development decisions. We then illustrate calculation of a probabilistic clinical utility index (CUI), an implementation of multiattribute utility that focuses on clinical attributes. We recommend use of the CUI for the support of early drug development decisions because of its practicality, reasonable accuracy, and transparency to decision makers, at stages in which financial factors that may dominate later-phase decisions are less critical.

Intracranial pressure concerns in lateral skull base surgery.

This article serves as a concise review of cerebrospinal fluid metabolism and intracranial pressure regulation for otolaryngologists and lateral skull base surgeons. It examines the methodologies for maintaining cerebrospinal fluid homeostasis by preventing and treating acute elevations of intracranial pressure encountered during lateral skull base surgery.