A Neutrophil Proteomic Signature in Surgical Trauma Wounds

Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing

Cold Atmospheric Plasma in the Treatment of Osteosarcoma

Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action

Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient’s further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study. Methods: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed. Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Cold atmospheric plasma in orthopaedic and urologic tumor therapy

Cold atmospheric plasma (CAP) is a highly reactive ionized physical state thereby provoking divers biological effects. In medical applications, CAP treatment promotes wound healing, provokes immunostimulation, and is antiseptically active. Moreover, CAP interacts with antiproliferative mechanisms suggesting CAP treatment as a promising anticancer strategy. Here we review the current state of science concerning the so far investigated CAP effects on different cancer entities in orthopaedic and urologic oncology

A Neutrophil Proteomic Signature in Surgical Trauma Wounds

Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing

Cold Atmospheric Plasma in the Treatment of Osteosarcoma

: Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action

Full-body MR imaging: a retrospective study on a novel diagnostic approach for children sustaining high-energy trauma

Purpose!#!Severe accidents are the leading cause of long-term impairment and death in children. A common diagnostic procedure for children exposed to high-injury trauma is full-body contrast-enhanced CT (fbCT). However, the number of fbCT without detected injuries is relevant. In 2007, full-body MRI (fbMRI) was implemented as a diagnostic approach for children sustaining high-energy trauma. The aim of this cross-sectional retrospective study was to analyze fbMRI as a diagnostic tool for children after high-energy trauma focusing on feasibility, radiological findings, and limitations.!##!Methods!#!Diagnostics using fbMRI (from apex of the head to the pelvis) was performed if a child was stable and suffered a high-energy trauma in a Level I Trauma Center in Germany. 105 fbMRIs in patients exposed to high-energy trauma aged ≤ 16 years were performed between January 2007 and December 2018. Four fbMRIs were excluded as conducted for reasons other than trauma. Time between arrival in the emergency department and fbMRI, additional diagnostic procedures, injuries, and non-trauma related pathologies were analyzed.!##!Results!#!Mean time between arrival in the emergency department and fbMRI was 71 min (± SD 132 min). Two scans were discontinued and changed to a faster diagnostic procedure. 45% of children had additional X-rays and 11% CT scans. The MRIs showed intracranial abnormalities in 27%, extremities injuries in 26%, spinal injuries in 18%, pelvic, and thoracic injuries in 7% of the cases.!##!Conclusion!#!Overall fbMRI is a diagnostic alternative for hemodynamically stable, conscious children after high-energy trauma with the advantages of a radiation-free technique. However, MRI diagnostics take longer than CT scans. Prospective studies will be needed to identify the limiting factors of fbMRIs as primary diagnostic procedure compared to CT scans.!##!Trial registration!#!German Clinical Trials Register (DRKS; DRKS00017015).!##!Level of evidence!#!Case series, level of evidence V