https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45207 Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation.]]> Thu 27 Oct 2022 15:07:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38228 Haemophilus influenzae (NTHi) infection drives the development of steroid-resistant allergic airway disease (SRAAD), exacerbates clinical symptoms, worsens quality of life, and accounts for most of the related healthcare burden. The poor understanding of the pathogenesis of SRAAD deters the development of more effective therapeutic strategies. Here, we established a murine model of NTHi infection-induced exacerbation of allergic airway disease. We showed that NTHi infection drove Th 17-mediated pulmonary neutrophilic inflammation, aggravated airway hyper-responsiveness, and upset the balance of MUC5AC and MUC5B expression. Dexamethasone treatment effectively inhibited the features of allergic airway disease but failed to reduce NTHi-induced exacerbation, which was associated with the hyper-phosphorylation of p38 mitogen-activated protein kinase (MAPK). Interestingly, inhibition of p38 using a specific inhibitor (SB203580) only partly suppressed the airway hyper-responsiveness and mucus hyper-secretion but failed to abrogate the infection-induced neutrophilic inflammatory response in SRAAD. However, SB203580 and dexamethasone co-treatment substantially suppressed all the features of NTHi-induced SRAAD. Our findings highlight the importance of p38 MAPK in the pathogenesis of NTHi-induced steroid resistance, and this combined treatment approach may be a novel strategy against steroid-resistant asthma.]]> Mon 16 Aug 2021 16:15:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40000 Fri 01 Jul 2022 14:31:38 AEST ]]>