51 results
Search Results
Now showing 1 - 10 of 51
- ItemCharacterisation of Methicillin-Resistant Staphylococcus aureus from Alexandria, Egypt(Basel : MDPI, 2023) Monecke, Stefan; Bedewy, Amira K.; Müller, Elke; Braun, Sascha D.; Diezel, Celia; Elsheredy, Amel; Kader, Ola; Reinicke, Martin; Ghazal, Abeer; Rezk, Shahinda; Ehricht, RalfThe present study aims to characterise clinical MRSA isolates from a tertiary care centre in Egypt’s second-largest city, Alexandria. Thirty isolates collected in 2020 were genotypically characterised by microarray to detect their resistance and virulence genes and assign them to clonal complexes (CC) and strains. Isolates belonged to 11 different CCs and 14 different strains. CC15-MRSA-[V+fus] (n = 6), CC1-MRSA-[V+fus+tir+ccrA/B-1] (PVL+) (n = 5) as well as CC1-MRSA-[V+fus+tir+ccrA/B-1] and CC1153-MRSA-[V+fus] (PVL+) (both with n = 3) were the most common strains. Most isolates (83%) harboured variant or composite SCCmec V or VI elements that included the fusidic acid resistance gene fusC. The SCCmec [V+fus+tir+ccrA/B-1] element of one of the CC1 isolates was sequenced, revealing a presence not only of fusC but also of blaZ, aacA-aphD and other resistance genes. PVL genes were also common (40%). The hospital-acquired MRSA CC239-III strain was only found twice. A comparison to data from a study on strains collected in 2015 (Montelongo et al., 2022) showed an increase in fusC and PVL carriage and a decreasing prevalence of the CC239 strain. These observations indicate a diffusion of community-acquired strains into hospital settings. The beta-lactam use in hospitals and the widespread fusidic acid consumption in the community might pose a selective pressure that favours MRSA strains with composite SCCmec elements comprising mecA and fusC. This is an unsettling trend, but more MRSA typing data from Egypt are required.
- ItemPancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate(Basel : MDPI, 2023) Miebach, Lea; Mohamed, Hager; Wende, Kristian; Miller, Vandana; Bekeschus, SanderSurvival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective treatments. Gas plasma-oxidized liquid treatment showed promising preclinical results in other gastrointestinal and gynecological tumors by targeting the tumor redox state. Here, carrier solutions are enriched with reactive oxygen (ROS) and nitrogen (RNS) species that can cause oxidative distress in tumor cells, leading to a broad range of anti-tumor effects. Unfortunately, clinical relevance is often limited, as many studies have forgone the use of medical-grade solutions. This study investigated the efficacy of gas plasma-oxidized Ringer’s lactate (oxRilac), a physiological solution often used in clinical practice, on two pancreatic cancer cell lines to induce tumor toxicity and provoke immunogenicity. Tumor toxicity of the oxRilac solutions was further confirmed in three-dimensional tumor spheroids monitored over 72 h and in ovo using stereomicroscope imaging of excised GFP-expressing tumors. We demonstrated that cell death signaling was induced in a dose-dependent fashion in both cell lines and was paralleled by the increased surface expression of key markers of immunogenic cell death (ICD). Nuclear magnetic resonance (NMR) spectroscopy analysis suggested putative reaction pathways that may cause the non-ROS related effects. In summary, our study suggests gas plasma-deposited ROS in clinically relevant liquids as an additive option for treating pancreatic cancers via immune-stimulating and cytotoxic effects.
- ItemChemotherapeutics Used for High-Risk Neuroblastoma Therapy Improve the Efficacy of Anti-GD2 Antibody Dinutuximab Beta in Preclinical Spheroid Models(Basel : MDPI, 2023) Troschke-Meurer, Sascha; Zumpe, Maxi; Meißner, Lena; Siebert, Nikolai; Grabarczyk, Piotr; Forkel, Hannes; Maletzki, Claudia; Bekeschus, Sander; Lode, Holger N.Anti-disialoganglioside GD2 antibody ch14.18/CHO (dinutuximab beta, DB) improved the outcome of patients with high-risk neuroblastoma (HR-NB) in the maintenance phase. We investigated chemotherapeutic compounds used in newly diagnosed patients in combination with DB. Vincristine, etoposide, carboplatin, cisplatin, and cyclophosphamide, as well as DB, were used at concentrations achieved in pediatric clinical trials. The effects on stress ligand and checkpoint expression by neuroblastoma cells and on activation receptors of NK cells were determined by using flow cytometry. NK-cell activity was measured with a CD107a/IFN-γ assay. Long-term cytotoxicity was analyzed in three spheroid models derived from GD2-positive neuroblastoma cell lines (LAN-1, CHLA 20, and CHLA 136) expressing a fluorescent near-infrared protein. Chemotherapeutics combined with DB in the presence of immune cells improved cytotoxic efficacy up to 17-fold compared to in the controls, and the effect was GD2-specific. The activating stress and inhibitory checkpoint ligands on neuroblastoma cells were upregulated by the chemotherapeutics up to 9- and 5-fold, respectively, and activation receptors on NK cells were not affected. The CD107a/IFN-γ assay revealed no additional activation of NK cells by the chemotherapeutics. The synergistic effect of DB with chemotherapeutics seems primarily attributed to the combined toxicity of antibody-dependent cellular cytotoxicity and chemotherapy, which supports further clinical evaluation in frontline induction therapy.
- ItemFlux Growth and Characterization of Bulk InVO4 Crystals(Basel : MDPI, 2023) Voloshyna, Olesia; Gorbunov, Mikhail V.; Mikhailova, Daria; Maljuk, Andrey; Seiro, Silvia; Büchner, BerndThe flux growth of InVO4 bulk single crystals has been explored for the first time. The reported eutectic composition at a ratio of V2O5:InVO4 = 1:1 could not be used as a self-flux since no sign of melting was observed up to 1100 °C. Crystals of InVO4 of typical size 0.5 × 1 × 7 mm3 were obtained using copper pyrovanadate (Cu2V2O7) as a flux, using Pt crucibles. X-ray powder diffraction confirmed the orthorhombic Cmcm structure. Rests of the flux material were observed on the sample surface, with occasional traces of Pt indicating some level of reaction with the crucible. X-ray absorption spectroscopy showed that oxidation states of indium and vanadium ions are +3 and +5, respectively. The size and high quality of the obtained InVO4 crystals makes them excellent candidates for further study of their physical properties.
- ItemModulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma(Basel : MDPI, 2023) Förster, Sarah; Niu, Yuequn; Eggers, Benedikt; Nokhbehsaim, Marjan; Kramer, Franz-Josef; Bekeschus, Sander; Mustea, Alexander; Stope, Matthias B.Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.
- ItemChemotherapeutics Used for High-Risk Neuroblastoma Therapy Improve the Efficacy of Anti-GD2 Antibody Dinutuximab Beta in Preclinical Spheroid Models(Basel : MDPI, 2023) Troschke-Meurer, Sascha; Zumpe, Maxi; Meißner, Lena; Siebert, Nikolai; Grabarczyk, Piotr; Forkel, Hannes; Maletzki, Claudia; Bekeschus, Sander; Lode, Holger N.Anti-disialoganglioside GD2 antibody ch14.18/CHO (dinutuximab beta, DB) improved the outcome of patients with high-risk neuroblastoma (HR-NB) in the maintenance phase. We investigated chemotherapeutic compounds used in newly diagnosed patients in combination with DB. Vincristine, etoposide, carboplatin, cisplatin, and cyclophosphamide, as well as DB, were used at concentrations achieved in pediatric clinical trials. The effects on stress ligand and checkpoint expression by neuroblastoma cells and on activation receptors of NK cells were determined by using flow cytometry. NK-cell activity was measured with a CD107a/IFN-γ assay. Long-term cytotoxicity was analyzed in three spheroid models derived from GD2-positive neuroblastoma cell lines (LAN-1, CHLA 20, and CHLA 136) expressing a fluorescent near-infrared protein. Chemotherapeutics combined with DB in the presence of immune cells improved cytotoxic efficacy up to 17-fold compared to in the controls, and the effect was GD2-specific. The activating stress and inhibitory checkpoint ligands on neuroblastoma cells were upregulated by the chemotherapeutics up to 9- and 5-fold, respectively, and activation receptors on NK cells were not affected. The CD107a/IFN-γ assay revealed no additional activation of NK cells by the chemotherapeutics. The synergistic effect of DB with chemotherapeutics seems primarily attributed to the combined toxicity of antibody-dependent cellular cytotoxicity and chemotherapy, which supports further clinical evaluation in frontline induction therapy.
- ItemGas Flow Shaping via Novel Modular Nozzle System (MoNoS) Augments kINPen-Mediated Toxicity and Immunogenicity in Tumor Organoids(Basel : MDPI, 2023) Berner, Julia; Miebach, Lea; Herold, Luise; Höft, Hans; Gerling, Torsten; Mattern, Philipp; Bekeschus, SanderMedical gas plasma is an experimental technology for anticancer therapy. Here, partial gas ionization yielded reactive oxygen and nitrogen species, placing the technique at the heart of applied redox biomedicine. Especially with the gas plasma jet kINPen, anti-tumor efficacy was demonstrated. This study aimed to examine the potential of using passive flow shaping to enhance the medical benefits of atmospheric plasma jets (APPJ). We used an in-house developed, proprietary Modular Nozzle System (MoNoS; patent-pending) to modify the flow properties of a kINPen. MoNoS increased the nominal plasma jet-derived reactive species deposition area and stabilized the air-plasma ratio within the active plasma zone while shielding it from external flow disturbances or gas impurities. At modest flow rates, dynamic pressure reduction (DPR) adapters did not augment reactive species deposition in liquids or tumor cell killing. However, MoNoS operated at kINPen standard argon fluxes significantly improved cancer organoid growth reduction and increased tumor immunogenicity, as seen by elevated calreticulin and heat-shock protein expression, along with a significantly spurred cytokine secretion profile. Moreover, the safe application of MoNoS gas plasma jet adapters was confirmed by their similar-to-superior safety profiles assessed in the hen’s egg chorioallantoic membrane (HET-CAM) coagulation and scar formation irritation assay.
- ItemAmorphous Silicon Thin-Film Solar Cells on Fabrics as Large-Scale Detectors for Textile Personal Protective Equipment in Active Laser Safety â€(Basel : MDPI, 2023) Gawlik, Annett; Brückner, Uwe; Schmidl, Gabriele; Wagner, Volker; Paa, Wolfgang; Plentz, JonathanLaser safety is starting to play an increasingly important role, especially when the laser is used as a tool. Passive laser safety systems quickly reach their limits and, in some cases, provide inadequate protection. To counteract this, various active systems have been developed. Flexible and especially textile-protective materials pose a special challenge. The market still lacks personal protective equipment (PPE) for active laser safety. Covering these materials with solar cells as large-area optical detectors offers a promising possibility. In this work, an active laser protection fabric with amorphous silicon solar cells is presented as a large-scale sensor for continuous wave and pulsed lasers (down to ns). First, the fabric and the solar cells were examined separately for irradiation behavior and damage. Laser irradiation was performed at wavelengths of 245, 355, 532, and 808 nm. The solar cell sensors were then applied directly to the laser protection fabric. The damage and destruction behavior of the active laser protection system was investigated. The results show that the basic safety function of the solar cell is still preserved when the locally damaged or destroyed area is irradiated again. A simple automatic shutdown system was used to demonstrate active laser protection within 50 ms.
- ItemMo3Ni2N Nanoparticle Generation by Spark Discharge(Basel : MDPI, 2023) Elmroth Nordlander, Jonas; Bermeo, Marie; Ternero, Pau; Wahlqvist, David; Schmeida, Toni; Blomberg, Sara; Messing, Maria E.; Ek, Martin; Hübner, Julia-MariaSpark ablation is an advantageous method for the generation of metallic nanoparticles with defined particle sizes and compositions. The reaction of the metal particles with the carrier gas during the synthesis and, therefore, the incorporation of those light elements into structural voids or even compound formation was confirmed for hydrides and oxides but has only been suspected to occur for nitrides. In this study, dispersed nanoparticles of Mo3Ni2N and Mo with Janus morphology, and defined particle sizes were obtained by spark discharge generation as a result of carrier gas ionization and characterized using transmission electron microscopy and powder X-ray diffraction. Metal nitrides possess beneficial catalytic and thermoelectric properties, as well as high hardness and wear resistance. Therefore, this method offers the possibility of controlled synthesis of materials which are interesting for numerous applications.
- ItemInfluence of Lattice Mismatch on Structural and Functional Properties of Epitaxial Ba0.7Sr0.3TiO3 Thin Films(Basel : MDPI, 2023) Wawra, Jonas; Nielsch, Kornelius; Hühne, RubenSubstrate-induced strains can significantly influence the structural properties of epitaxial thin films. In ferroelectrics, this might lead to significant changes in the functional properties due to the strong electromechanical coupling in those materials. To study this in more detail, epitaxial Ba0.7Sr0.3TiO3 films, which have a perovskite structure and a structural phase transition close to room temperature, were grown with different thicknesses on REScO3 (RE–rare earth element) substrates having a smaller lattice mismatch compared to SrTiO3. A fully strained SrRuO3 bottom electrode and Pt top contacts were used to achieve a capacitor-like architecture. Different X-ray diffraction techniques were applied to study the microstructure of the films. Epitaxial films with a higher crystalline quality were obtained on scandates in comparison to SrTiO3, whereas the strain state of the functional layer was strongly dependent on the chosen substrate and the thickness. Differences in permittivity and a non-linear polarization behavior were observed at higher temperatures, suggesting that ferroelectricity is supressed under tensile strain conditions in contrast to compressive strain for our measurement configuration, while a similar reentrant relaxor-like behavior was found in all studied layers below 0°C.