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Impact of allyl-isothiocyanate and high sucrose diet on antimicrobial peptide expression and survival in Drosophila melanogaster
(2026) Dähn, Sonja; Zimmermann, Christian; Merschmann, Ronja; Schmutzler, Paul; Wagner, Anika E.
The global rise of antibiotic-resistant bacteria highlights the urgent need for alternative strategies to support host defense against infections. Bioactive plant-derived compounds, such as isothiocyanates, have gained attention due to their antimicrobial and immunomodulatory properties. Allyl-isothiocyanate (AITC), a hydrolysis product of glucosinolates found in Brassica vegetables, has demonstrated antimicrobial activity in vitro and the ability to modulate antimicrobial peptide (AMP) expression in cell culture models. However, its in vivo effects under metabolically challenging dietary conditions remain poorly understood. In this study, we investigated the impact of dietary AITC supplementation on immune responses and survival in Drosophila melanogaster exposed to a high-sucrose diet (HSD), a dietary condition known to impair metabolic health and immune function. Flies were fed a HSD with or without 0.25 mM AITC and subsequently subjected to oral infection with either Leuconostoc pseudomesenteroides or Pectobacterium carotovorum subsp. carotovorum, which preferentially activate the Toll and Imd signaling pathways, respectively. AMP expression was analyzed by qPCR and RNA sequencing, and physiological consequences were assessed by performing lifespan analysis. AITC did not affect the flies’ feed intake or basal AMP expression under non-infected conditions. HSD significantly shortened the lifespan in both sexes, and AITC supplementation was not able to rescue this effect. Following oral infection of the flies, both HSD alone and HSD supplemented with AITC influenced the survival in a sex- and pathogen-specific manner, with AITC frequently exacerbating mortality rather than improving outcomes. While selected AMPs, particularly Attacin D, were modulated in a context-dependent manner, RNA sequencing revealed no consistent transcriptional changes in core Toll or Imd pathway components. Overall, our findings indicate that dietary AITC does not enhance host defense in Drosophila melanogaster under high-sugar conditions and that its effects on immunity and survival are strongly sex-specific. These results highlight the complexity of diet–immune interactions and caution against extrapolating in vitro antimicrobial effects to in vivo host protection.
RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices
(2026) Mahavadi, Poornima; Korfei, Martina; Müller-Ruttloff, Christin; Ruppert, Clemens; Krauss, Ekaterina; Dorfmüller, Peter; Gattenloehner, Stefan; Dimmeler, Stefanie; El Agha, Elie; Bellusci, Saverio; Herold, Susanne; Witte, Biruta; Ziebuhr, John; Guenther, Andreas
Background: While the renin-angiotensin-aldosterone system (RAAS) is critically involved in pathomechanisms related to SARS-CoV-2 infection, the role of ongoing therapy with angiotensin-converting enzyme 1 inhibitors (ACEi) or Angiotensin-II type 1 receptor (AT1R) blockers (ARB) is much less clear. We evaluated the effects of the ACEi enalapril (ENA) and the ARB losartan (LOS) on SARS-CoV-2 infection in human ex vivo-cultured, precision-cut lung slices (PCLS) obtained from normal human lung tissue. Methods: PCLS were pre-treated for 5d with vehicle, LOS or ENA (300 µM), followed by mock infection or infection with SARS-CoV-2 and incubation with vehicle, LOS or ENA for 1d or 2d. Thereafter, PCLS were harvested for analysis of viral replication, inflammatory responses, endoplasmic reticulum (ER) stress and apoptosis pathways. Results: Both LOS and ENA significantly reduced viral replication in PCLS, with ENA being more potent. LOS was more efficient than ENA in reducing the expression of IL1B, CCL2, CXCL2 and TNFA, but not of IL6, whereas ENA preferentially caused a reduction of IL6 and CCL2 in SARS-CoV-2-infected PCLS. Further, ENA, but not LOS, significantly decreased the expression of viral entry factors, ACE2 and transmembrane serine protease 2 (TMPRSS2), in infected PCLS. Importantly, LOS or ENA did not exert cytotoxic effects. Conclusions: RAAS-antagonizing drugs do not seem to exert detrimental effects during SARS-CoV-2 infection. In opposite, in an ex-vivo model of human PCLS, such treatment was found to dampen SARS-CoV-2 infection and consecutive inflammation.
Reversible causes of death and the potential benefit of invasive emergency techniques in paediatric and adolescent trauma : a 12-years retrospective forensic analysis
(2026) Malolepszy, Leila; Heidl, Stephan; Markmann, Melanie; Zajonz, Thomas S.; Schneider, Niko; Koch, Christian; Hartwig, Sven; Sander, Michael; Schneck, Emmanuel
Background: Early deaths among severely injured children are mainly due to exsanguination and severe traumatic brain injury, some of which may be preventable with timely emergency interventions. However, data on potentially reversible causes of death and the role of advanced prehospital procedures in paediatric trauma are scarce. This study aims to assess post-mortem findings to identify cases where advanced emergency interventions could have been applicable in children. Methods: This retrospective, single-centre study analysed forensic files of deceased children and adolescents (age < 18 years) regarding the potential benefit of advanced emergency procedures (e.g. prehospital transfusion, thoracotomy and resuscitative endovascular ballon occlusion of the aorta [REBOA]). Three independent reviewers systematically assessed each case to determine whether a potentially reversible cause of death was present and if advanced emergency interventions might have been applicable. Results: A total of 243 paediatric cases were included. The majority of deaths occurred prehospitally (91.6%). While the cause of death showed a significant association with age group (p = 0.01), severe traumatic brain injury (TBI) was present across all age groups without significant variation. Cardiopulmonary resuscitation was performed in 68.5% of cases, achieving return of spontaneous circulation only in 12.1%. Advanced emergency procedures were deemed feasible in only two cases (0.8%), including thoracotomy (n = 2), REBOA (n = 1), and prehospital transfusion (n = 2). Conclusion: This study reveals age-dependent patterns in paediatric trauma mortality and a very limited but relevant potential for advanced interventions. A rare subset, adolescents without severe TBI, might have benefited. Findings support structured trauma systems, targeted training, and selected use of prehospital transfusion.
Soluble DLL1 as an indicator of acute kidney injury and postoperative delirium following cardiac surgery : a secondary analysis of a prospective study
(2025) Zajonz, Thomas Simon; Edinger, Fabian; Markmann, Melanie; Schreiner, Anna-Lena; Beckert, Frauke; Weigand, Markus A.; Uhle, Florian; Niemann, Bernd; Sander, Michael; Koch, Christian; Schneck, Emmanuel
Background Acute kidney injury (AKI) displays a common complication after cardiac surgery and must be diagnosed as early as possible. Soluble delta-like protein 1 (sDLL1) was originally evaluated as a sepsis biomarker but might also indicate other adverse outcomes. This study aims to investigate sDLL1 levels, examining its potential relationship with AKI and postoperative delirium (POD) after cardiac surgery and its predictive value. Methods This secondary analysis of a prospective observational trial included elective cardiac surgery patients. ELISA was used for the quantification of sDLL1. Statistical analysis involved repeated measures ANOVA and Pearson’s correlation to assess associations between sDLL1 levels, renal, and inflammatory parameters. Receiver operating curves were used for prediction analysis. Results Ninety patients were included in the study. Compared to patients without AKI, those with AKI (6.1%) showed significantly elevated plasma levels of sDLL1 postoperatively (no AKI 6308.49 [5121.27–7955.28], AKI 7,714.77 [7151.06–10,514.73] ng/mL; p = 0.01). Postoperative sDLL1 levels showed only a low predictive value for AKI (AUCROC 0.63, sensitivity 0.91, specificity 0.53). Postoperative sDLL1 measurements were also significantly elevated in patients with POD (23.3%). Further, postoperative sDLL1 plasma levels showed a moderate prediction for the identification of POD (AUCROC 0.72, sensitivity 0.64 specificity 0.73). Conclusion This study demonstrates that sDLL1 provides moderate predictive value for AKI and POD after cardiac surgery and may provide valuable insights into postoperative complications. sDLL1 levels increase independently of CPB type, suggesting a role in the inflammatory response to the cardiopulmonary bypass and surgical stress rather than specific renal injury.
Probing weak chemical interactions of metal surface atoms with CO-terminated AFM tips identifies molecular adsorption sites
(2025) Tschakert, Jalmar; Zhong, Qigang; Sekels, Alexander; Henkel, Pascal; Jung, Jannis; Pohl, K. Linus H.; Wegner, Hermann A.; Mollenhauer, Doreen; Schirmeisen, André; Ebeling, Daniel
Metal surfaces play a key role in on-surface synthesis as they provide a two-dimensional catalytic reaction environment that stimulates activation, diffusion, and coupling of molecular reactants. Fundamental understanding of the interactions between surface atoms and reactants is very limited but would enable controlling on-surface reaction processes for designing functional nanomaterials. Here, we measure chemical interactions between CO-terminated tips and Cu(111), Ag(111), and Au(111) surface atoms in all spatial directions with picometer resolution via low temperature atomic force microscopy. This allows a site-specific quantification of the weak chemical interactions of densely packed metal surface atoms and provides a picture of the potential energy landscape experienced by adsorbed reactants. Accompanying density functional theory calculations and the crystal orbital overlap population method reveal small covalent binding contributions from orbital overlap of the corresponding p- and d-states of the CO tip and the metal surface atoms as the cause for the site-specific interactions. Accessing such small covalent bonding contributions in the background of the dispersion-dominated interaction enables revealing insights into the nature of chemical bond formation with metal surface atoms and a reliable determination of molecular adsorption sites. The latter can serve both as a starting point and as a direct comparison with theoretical studies.