Purpose. Dioscorea nipponica Makino (DNM) is a traditional herb with multiple medicinal functions. This study is aimed at exploring the therapeutic effects of DNM on asthma and the underlying mechanisms involving RKIP-mediated MAPK signaling pathway. Methods. An ovalbumin-induced asthma model was established in mice, which was further administrated with DNM and/or locostatin (RKIP inhibitor). ELISA was performed to detect the serum titers of OVA-IgE and OVA-IgG1, bronchoalveolar lavage fluid (BALF) levels of inflammation-related biomarkers, and tissue levels of oxidative stress-related biomarkers. The expression of RKIP was measured by quantitative real-time PCR, Western blot, immunohistochemistry, and immunofluorescence. HE staining was used to observe the pathological morphology of lung tissues. The protein expression of MAPK pathway-related proteins was detected by Western blot. Results. Compared with the controls, the model mice exhibited significantly higher serum titers of OVA-IgE and OVA-IgG1, BALF levels of IL-6, IL-8, IL-13, TGF-β1, and MCP-1, tissue levels of MDA and ROS, lower BALF levels of IL-10 and IFN-γ, and tissue level of GSH. DNM relieved the allergic inflammatory response and oxidative stress in the model mice. DNM also recovered the downregulation of RKIP and the pathological injury of lung tissues in asthma mice. In addition, the Raf-1/MEK/MAPK/ERK pathway in the model mice was blocked by DNM. Silencing of RKIP by locostatin weakened the relieving effects of DNM on asthma through activating the Raf-1/MEK/MAPK/ERK pathway. Conclusion. DNM relieves asthma via blocking the Raf-1/MEK/MAPK/ERK pathway that mediated by RKIP upregulation.
Background. In this study, network pharmacological methods were used to analyze the targets of Rhizoma Dioscoreae Nipponicae (RDN) and investigate the potential underlying mechanism of RDN in the treatment of asthma. Methods. Asthma-related targets were obtained from the GeneCards and DisGeNET databases. The bioactive components of RDN were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and the targets of these compounds were predicted using the BATMAN-TCM database. The network of RDN component targets was constructed using Cytoscape. A protein-protein interaction (PPI) network was constructed in Cytoscape to determine the potential targets of RDN for the treatment of asthma. The hub genes of RDN in the treatment of asthma were screened using network topological parameters. Gene ontology (GO) and the KEGG pathways were analyzed. Molecular docking and in vivo experiments were performed to validate the network pharmacology results. Results. A total of four bioactive components and 55 targets were identified. The results of the enrichment analysis suggested that the treatment of asthma with RDN involved signaling pathways, such as those related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, the cell cycle, prostate cancer, transcriptional misregulation in cancer, hepatitis B, thyroid hormone signaling, and PI3K-AKT signaling, as well as other signaling pathways. Molecular docking showed that the active components of RDN could stably bind to the predicted target. In vivo experiments showed that RDN could regulate the expression of target genes and inhibit the activation of the PI3K-AKT signaling pathway. Conclusion. To a certain extent, this study reveals the potential bioactive components and molecular mechanisms of RDN in the treatment of asthma and provides new insights for the development of new drugs for asthma.
BACKGROUND An immediate hypersensitive immune response to Aspergillus fumigatus antigens is one of the main characteristic features of allergic bronchopulmonary aspergillosis (ABPA). As ABPA is an allergic respiratory disease, immunoglobulin E and peripheral-blood eosinophilia have been used as diagnostic indicators. However, eosinophilia in bronchoalveolar lavage fluid (BALF) has not been considered in the diagnostic criteria for ABPA. CASE SUMMARY We present a case of ABPA in which the eosinophil count in peripheral blood was not increased, whereas the eosinophil percentage in BALF reached 60%. After antifungal and hormone therapy, imaging revealed very good resolution of lung infiltration. CONCLUSION The value of the eosinophil count in BALF for the diagnosis of ABPA is worthy of the clinician's attention, especially when the patient’s clinical features lack specificity and the diagnostic parameters are negative.
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