Background Ceylon cinnamon has been shown to possess anti‐inflammatory properties in many diseases including allergic inflammation. Objective The aim of this study was to analyse in more detail the effects of cinnamon extract (CE) and its major compounds p‐cymene and trans‐cinnamaldehyde (CA) on allergen‐specific immune responses in vitro and in vivo. Methods Therefore, monocyte‐derived mature dendritic cells (DC) from grass or birch pollen allergic donors were pulsed with the respective allergen in the presence or absence of CE, p‐cymene, CA or the solvent ethanol and co‐cultured with autologous CD4+ T cells. Furthermore, basophil activation test was performed with or without CE or ethanol treatment. For the in vivo experiments, BALB/c mice were immunized with ovalbumin (OVA) and orally treated with CE or ethanol. Results Addition of CE, p‐cymene or CA, but not ethanol significantly inhibited DC maturation and subsequent allergen‐specific T cell proliferation as well as Th1 and Th2 cytokine production. Sulphidoleukotriene release and CD63 expression by basophils were also significantly diminished after addition of CE. In vivo, treatment of OVA‐sensitized mice with CE led to a significant shift from OVA‐specific IgE towards IgG2a production and to a strong inhibition of OVA‐specific proliferation. Moreover, airway inflammation as well as anaphylaxis after intranasal or systemic allergen challenge was significantly reduced in CE‐treated mice. Furthermore, topical application of CE prevented calcipotriol‐induced atopic dermatitis‐like inflammation in these mice. Conclusions and Clinical Relevance Taken together, our data indicate that the anti‐inflammatory effect of cinnamon might be exploited for treatment of allergic inflammation, which needs to be further investigated.
Background: Chemotherapy options in advanced urothelial carcinoma (UC) remain limited. Here we evaluated the peptide‐based alkylating agent melphalan‐flufenamide (mel‐flufen) for UC. Methods: UC cell lines J82, RT4, TCCsup and 5637 were treated with mel‐flufen, alone or combined with cisplatin, gemcitabine, dasatinib or bestatin. Cell viability (MTT assay), intracellular drug accumulation (liquid chromatography) apoptosis induction (apoptotic cell nuclei morphology, western blot analysis of PARP‐1/caspase‐9 cleavage and Bak/Bax activation) were evaluated. Kinome alterations were characterized by PathScan array and phospho‐Src validated by western blotting. Aminopeptidase N (ANPEP) expression was evaluated in UC clinical specimens in relation to patient outcome. Results: In J82, RT4, TCCsup and 5637 UC cells, mel‐flufen amplified the intracellular loading of melphalan in part via aminopeptidase N (ANPEP), resulting in increased cytotoxicity compared to melphalan alone. Mel‐flufen induced apoptosis seen as activation of Bak/Bax, cleavage of caspase‐9/PARP‐1 and induction of apoptotic cell nuclei morphology. Combining mel‐flufen with cisplatin or gemcitabine in J82 cells resulted in additive cytotoxic effects and for gemcitabine also increased apoptosis induction. Profiling of mel‐flufen‐induced kinome alterations in J82 cells revealed that mel‐flufen alone did not inhibit Src phosphorylation. Accordingly, the Src inhibitor dasatinib sensitized for mel‐flufen cytotoxicity. Immunohistochemical analysis of the putative mel‐flufen biomarker ANPEP demonstrated prominent expression levels in tumours from 82 of 83 cystectomy patients. Significantly longer median overall survival was found in patients with high ANPEP expression (P = 0.02). Conclusion: Mel‐flufen alone or in combination with cisplatin, gemcitabine or Src inhibition holds promise as a novel treatment for UC.
Introduction: Phase-contrast imaging (PCI) is a novel technology that can visualise variations in X-ray refraction (phase contrast) in addition to differences in X-ray attenuation (absorption contrast). Compared to radiography using conventional methods (i.e. absorption-based imaging), PCI techniques can potentially produce images with higher contrast-to-noise ratio and superior spatial resolution at the same or lower radiation doses. This has led PCI to be explored for implementation in medical imaging. While interest in this research field is increasing, the whole body of PCI research in medical imaging has been under-investigated. This paper provides an overview of PCI literature and then focusses on evaluating its development within the scope of medical imaging. Methods: Bibliographic data between 1995 and 2018 were used to visualise collaboration networks between countries, institutions and authors. Social network analysis techniques were implemented to measure these networks in terms of centrality and cohesion. These techniques also assisted in the exploration of underlying research paradigms of clinical X-ray PCI investigations. Results: Forty-one countries, 592 institutions and 2073 authors contributed 796 investigations towards clinical PCI research. The most influential contributors and network collaboration characteristics were identified. Italy was the most influential country, with the European Synchrotron Radiation Facility being the most influential institution. At an author level, F. Pfeiffer was found to be the most influential researcher. Among various PCI techniques, grating interferometry was the most investigated, while computed tomography was the most frequently examined modality. Conclusions: By gaining an understanding of collaborations and trends within clinical X-ray PCI research, the links between existing collaborators were identified, which can aid future collaborations between emerging and established collaborators. Moreover, exploring the paradigm of past investigations can shape future researchwell-researched PCI techniques may be studied to bring X-ray PCI closer to clinical implementation, or the potential of seldom-investigated techniques may be explored.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.