Mosbacher, Johannes

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Mosbacher
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Johannes
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Johannes Mosbacher

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2023 - 20243

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Gerade angezeigt 1 - 3 von 3
  • Vorschaubild
    Publikation
    Machine learning for precision diagnostics of autoimmunity
    (Nature, 13.11.2024) Kruta, Jan; Carapito, Raphael; Trendelenburg, Marten; Martin, Thierry; Rizzi, Marta; Voll, Reinhard E.; Cavalli, Andrea; Natali, Eriberto; Meier, Patrick; Stawiski, Marc; Mosbacher, Johannes; Mollet, Annette; Santoro, Aurelia; Capri, Miriam; Giampieri, Enrico; Schkommodau, Erik; Miho, Enkelejda
    Early and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Bryophyllum pinnatum inhibits oxytocin and vasopressin signaling in myometrial cells
    (Thieme, 10.04.2024) Zurfluh, Leonie; Duvaud, Lauriane; Inci, Nejla; Potterat, Olivier; Simões-Wüst, Ana Paula; Mosbacher, Johannes
    The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V 1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT‑C3, and cell lines expressing recombinant human OT and V 1A receptors. We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT‑C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V 1A receptor-mediated signals with a similar potency (IC 50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT‑C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT‑C3 cells. In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild
    Publikation
    How technical innovations may help to prevent drug shortages in switzerland
    (Schweizerische Chemische Gesellschaft, 2023) Gygax, Daniel; Eigenmann, Kaspar; Suter, Christian; Hürzeler Müller, Marianne; Mahmoud, Ahmed; Mosbacher, Johannes; Pöllinger, Norbert
    In this work, we investigated the technical feasibility of 'on-demand' production of selected drugs to cover their demand for a time window of 90 days. We focused on two sub-processes 'automated chemical synthesis' and 'formulation in micropellets'  to enable personalized dosing. The production of drugs 'on-demand' is challenging, important, but also attractive. Switzerland could thus gain access to an additional instrument for increasing resilience for supply-critical drugs. The biggest challenge in the case study presented here is the scalability of automated chemical synthesis and the application range of micropellet formulations.
    01A - Beitrag in wissenschaftlicher Zeitschrift