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- ItemGas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice(Weinheim : Wiley-VCH, 2021) Clemen, Ramona; Freund, Eric; Mrochen, Daniel; Miebach, Lea; Schmidt, Anke; Rauch, Bernhard H.; Lackmann, Jan‐Wilm; Martens, Ulrike; Wende, Kristian; Lalk, Michael; Delcea, Mihaela; Bröker, Barbara M.; Bekeschus, SanderReactive 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. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.
- ItemMedical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion(Weinheim : Wiley-VCH, 2020) Bekeschus, Sander; Clemen, Ramona; Nießner, Felix; Sagwal, Sanjeev Kumar; Freund, Eric; Schmidt, AnkeMedical 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). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune-infiltrates of CD8+ cytotoxic T-cells and dendritic cells. T-cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat-shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.
- ItemUnderstanding Surface Modifications Induced via Argon Plasma Treatment through Secondary Electron Hyperspectral Imaging(Weinheim : Wiley-VCH, 2021) Farr, Nicholas; Thanarak, Jeerawan; Schäfer, Jan; Quade, Antje; Claeyssens, Frederik; Green, Nicola; Rodenburg, CorneliaUnderstanding the effects that sterilization methods have on the surface of a biomaterial is a prerequisite for clinical deployment. Sterilization causes alterations in a material's surface chemistry and surface structures that can result in significant changes to its cellular response. Here we compare surfaces resulting from the application of the industry standard autoclave sterilisation to that of surfaces resulting from the use of low-pressure Argon glow discharge within a novel gas permeable packaging method in order to explore a potential new biomaterial sterilisation method. Material surfaces are assessed by applying secondary electron hyperspectral imaging (SEHI). SEHI is a novel low-voltage scanning electron microscopy based characterization technique that, in addition to capturing topographical images, also provides nanoscale resolution chemical maps by utilizing the energy distribution of emitted secondary electrons. Here, SEHI maps are exploited to assess the lateral distributions of diverse functional groups that are effected by the sterilization treatments. This information combined with a range of conventional surface analysis techniques and a cellular metabolic activity assay reveals persuasive reasons as to why low-pressure argon glow discharge should be considered for further optimization as a potential terminal sterilization method for PGS-M, a functionalized form of poly(glycerol sebacate) (PGS).
- ItemBacterial symbiont subpopulations have different roles in a deep-sea symbiosis(Cambridge : eLife Sciences Publications, 2021) Hinzke, Tjorven; Kleiner, Manuel; Meister, Mareike; Schlüter, Rabea; Hentschker, Christian; Pané-Farré, Jan; Hildebrandt, Petra; Felbeck, Horst; Sievert, Stefan M; Bonn, Florian; Völker, Uwe; Becher, Dörte; Schweder, Thomas; Markert, StephanieThe hydrothermal vent tubeworm Riftia pachyptila hosts a single 16S rRNA phylotype of intracellular sulfur-oxidizing symbionts, which vary considerably in cell morphology and exhibit a remarkable degree of physiological diversity and redundancy, even in the same host. To elucidate whether multiple metabolic routes are employed in the same cells or rather in distinct symbiont subpopulations, we enriched symbionts according to cell size by density gradient centrifugation. Metaproteomic analysis, microscopy, and flow cytometry strongly suggest that Riftia symbiont cells of different sizes represent metabolically dissimilar stages of a physiological differentiation process: While small symbionts actively divide and may establish cellular symbiont-host interaction, large symbionts apparently do not divide, but still replicate DNA, leading to DNA endoreduplication. Moreover, in large symbionts, carbon fixation and biomass production seem to be metabolic priorities. We propose that this division of labor between smaller and larger symbionts benefits the productivity of the symbiosis as a whole.
- ItemRepeated exposure of the oral mucosa over 12 months with cold plasma is not carcinogenic in mice(London : Nature Publishing Group, 2021) Evert, K.; Kocher, T.; Schindler, A.; Müller, M.; Müller, K.; Pink, C.; Holtfreter, B.; Schmidt, A.; Dombrowski, F.; Schubert, A.; von Woedtke, T.; Rupf, S.; Calvisi, D. F.; Bekeschus, S.; Jablonowski, L.Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was compared against UV radiation, carcinogen administration, and untreated conditions over 12 months. Histological analysis of 406 animals revealed that repeated CAP exposure did not foster non-invasive lesions or squamous cell carcinoma (SCCs). Carcinogen administration promoted non-invasive lesions and SCCs. Molecular analysis by a qPCR screening of 144 transcripts revealed distinct inflammatory profiles associated with each treatment regimen. Interestingly, CAP treatment of carcinogen-challenged mucosa did not promote but instead left unchanged or reduced the proportion of non-invasive lesions and SCC formation. In conclusion, repeated CAP exposure of murine oral mucosa was well tolerated, and carcinogenic effects did not occur, motivating CAP applications in patients for dental and implant treatments in the future.
- ItemTumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen(London : Nature Publishing Group, 2021) Miebach, Lea; Freund, Eric; Horn, Stefan; Niessner, Felix; Sagwal, Sanjeev Kumar; von Woedtke, Thomas; Emmert, Steffen; Weltmann, Klaus-Dieter; Clemen, Ramona; Schmidt, Anke; Gerling, Torsten; Bekeschus, SanderRecent 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 (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
- ItemA combination of electrochemistry and mass spectrometry to monitor the interaction of reactive species with supported lipid bilayers([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Ravandeh, M.; Kahlert, H.; Jablonowski, H.; Lackmann, J.-W.; Striesow, J.; Agmo Hernández, V.; Wende, K.Reactive oxygen and nitrogen species (RONS), e.g. generated by cold physical plasma (CPP) or photodynamic therapy, interfere with redox signaling pathways of mammalian cells, inducing downstream consequences spanning from migratory impairment to apoptotic cell death. However, the more austere impact of RONS on cancer cells remains yet to be clarified. In the present study, a combination of electrochemistry and high-resolution mass spectrometry was developed to investigate the resilience of solid-supported lipid bilayers towards plasma-derived reactive species in dependence of their composition. A 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer was undisturbed by 200 µM H2O2 (control) but showed full permeability after CPP treatment and space-occupying oxidation products such as PoxnoPC, PAzePC, and POPC hydroperoxide were found. Electron paramagnetic resonance spectroscopy demonstrated the presence of hydroxyl radicals and superoxide anion/hydroperoxyl radicals during the treatment. In contrast, small amounts of the intramembrane antioxidant coenzyme Q10 protected the bilayer to 50% and LysoPC was the only POPC derivative found, confirming the membrane protective effect of Q10. Such, the lipid membrane composition including the presence of antioxidants determines the impact of pro-oxidant signals. Given the differences in membrane composition of cancer and healthy cells, this supports the application of cold physical plasma for cancer treatment. In addition, the developed model using the combination of electrochemistry and mass spectrometry could be a promising method to study the effect of reactive species or mixes thereof generated by chemical or physical sources.
- ItemRestricted differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice(London : Nature Publishing Group, 2021) Wilm, Thomas P.; Tanton, Helen; Mutter, Fiona; Foisor, Veronica; Middlehurst, Ben; Ward, Kelly; Benameur, Tarek; Hastie, Nicholas; Wilm, BettinaPreviously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal mesothelial cells have a range of differentiative capacities and are the direct progenitors of vascular smooth muscle in the intestine. However, it was not clear whether this was a temporally limited process or continued throughout postnatal life. Here, using a conditional Wt1-based genetic lineage tracing approach, we demonstrate that the postnatal and adult peritoneum covering intestine, mesentery and body wall only maintained itself and failed to contribute to other visceral tissues. Pulse-chase experiments of up to 6 months revealed that Wt1-expressing cells remained confined to the peritoneum and failed to differentiate into cellular components of blood vessels or other tissues underlying the peritoneum. Our data confirmed that the Wt1-lineage system also labelled submesothelial cells. Ablation of Wt1 in adult mice did not result in changes to the intestinal wall architecture. In the heart, we observed that Wt1-expressing cells maintained the epicardium and contributed to coronary vessels in newborn and adult mice. Our results demonstrate that Wt1-expressing cells in the peritoneum have limited differentiation capacities, and that contribution of Wt1-expressing cells to cardiac vasculature is based on organ-specific mechanisms.
- ItemAuthor Correction: A combination of electrochemistry and mass spectrometry to monitor the interaction of reactive species with supported lipid bilayers (Scientific Reports, (2020), 10, 1, (18683), 10.1038/s41598-020-75514-7)(London : Nature Publishing Group, 2021) Ravandeh, M.; Kahlert, H.; Jablonowski, H.; Lackmann, J.-W.; Striesow, J.; Agmo Hernández, V.; Wende, K.Correction to: Scientific Reports https://doi.org/10.1038/s41598-020-75514-7, published online 29 October 2020
- ItemThe association between thyroid function biomarkers and attention deficit hyperactivity disorder([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Albrecht, Diana; Ittermann, Till; Thamm, Michael; Grabe, Hans-Jörgen; Bahls, Martin; Völzke, HenryThe relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81–1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (β 0.08; 95% CI 0.03–0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.