Yang, W. b. | bioRxiv Science

bioRxiv2025

Celastrol sensitizes bicalutamide to enhance immunogenic Cell death in the treatment of castration-resistant prostate

BackgroundProstate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. MethodsIn this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro. ResultsOur findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. ConclusionOur study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding informationThe author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003).

cancer biology↗

bioRxiv2020

Allergen specific Treg upregulated by lung-stage schistosome infection alleviates allergic airway inflammation via inhibiting IgE secretion

Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. Moreover, most previous studies focused on understanding the preventive effect of schistosome infection on asthma (infection before allergen sensitization), while its therapeutic effects (infection after allergen sensitization) were rarely investigated. In this study, we investigated the therapeutic effects of schistosome infection on AAI using a mouse model of OVA induced asthma. To explore how the timing of schistosome infection influences its therapeutic effect, the mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day before OVA induced asthma attack (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage schistosome infection could relieve OVA induced asthma in a mouse model. The therapeutic effect was mediated by the upregulated OVA specific Treg which suppressed IgE production and Th2 cytokine secretion. Our results may facilitate the discovery of a new therapy for AAI. Author SummaryAsthma is an increasingly common disease especially in industrialized countries, which is still lack of an optimal therapy. The protective effect of schistosome infection against allergic asthma has been shown in previous studies, which represents a promising candidate immune intervention approach. However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. In this study, we demonstrate that lung-stage schistosome infection could upregulate the frequency of allergen specific Treg, which significantly alleviated OVA induced allergic airway inflammation via inhibiting the production of IgE and Th2 cytokines. Our results proved the therapeutic effect of schistosome infection on allergic asthma. Moreover, we highlighted that lung-stage infection is essential for inducing allergen specific regulatory T cells in lung, which is the key mediator of the observed therapeutic effect. These findings shed new light on exploiting helminths or their derivatives to treat asthma and other allergic diseases.

immunology↗