https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38040 Wed 28 Jul 2021 10:17:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38039 Wed 28 Jul 2021 09:42:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53713 Wed 28 Feb 2024 16:37:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50942 Wed 28 Feb 2024 16:05:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50469 Wed 28 Feb 2024 15:49:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11267 Wed 24 Jul 2013 22:28:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43527 Wed 21 Sep 2022 11:32:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31003 Wed 19 Jan 2022 15:18:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41157 Wed 15 Feb 2023 10:57:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47176 Wed 14 Dec 2022 15:55:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47060 Wed 13 Mar 2024 08:04:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14161 Wed 11 Apr 2018 16:03:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30281 Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-a, IL-33, and CXCL1) in experimental COPD. Fbln1c⌿ mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.]]> Wed 11 Apr 2018 13:33:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30208 Wed 11 Apr 2018 11:33:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42686 Wed 08 May 2024 12:01:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41553 Wed 08 May 2024 09:45:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48779 Wed 05 Apr 2023 14:30:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31006 Wed 02 Mar 2022 14:28:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53453 Tue 28 Nov 2023 10:10:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55703 Tue 18 Jun 2024 12:51:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41995 Tue 16 Aug 2022 16:37:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41168 Tue 15 Aug 2023 14:44:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50999 Tue 15 Aug 2023 11:52:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48325 Tue 14 Mar 2023 16:33:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47003 Tue 13 Dec 2022 10:59:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54156 Tue 06 Feb 2024 12:11:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30656 Thu 28 Oct 2021 13:03:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41158 Thu 28 Jul 2022 09:27:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45342 Thu 27 Oct 2022 15:17:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48427 Thu 25 Jul 2024 15:14:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51390 Thu 23 Nov 2023 14:31:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34597 Thu 13 Jan 2022 10:31:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49088 Thu 04 May 2023 13:43:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33083 Thu 03 Feb 2022 12:19:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33159 in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.]]> Thu 03 Feb 2022 12:18:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55056 Thu 01 Aug 2024 11:56:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14610 Sat 24 Mar 2018 08:20:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11164 Sat 24 Mar 2018 08:08:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29820 Sat 24 Mar 2018 07:40:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22009 Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment. Results: Clarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor a and interleukin 17 responses that induce SSIAAD. Conclusions: Macrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.]]> Sat 24 Mar 2018 07:15:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21997 Sat 24 Mar 2018 07:14:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22105 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46962 Il22^−/−) mice. CS-induced airway remodelling and emphysema-like alveolar enlargement did not occur in Il22^−/− mice. Il22^−/− mice had improved lung function in terms of airway resistance, total lung capacity, inspiratory capacity, forced vital capacity and compliance. These data highlight important roles for IL-22 and its receptors in human COPD and CS-induced experimental COPD.]]> Mon 12 Dec 2022 14:27:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22044 Chlamydia, Haemophilus influenzae and Streptococcus pneumoniae in early life may promote permanent deleterious changes in immunity, lung structure, and function that predispose to, or increase the severity of chronic respiratory diseases in later life. For example, these infections increase immune responses, which drive subsequent asthma pathogenesis. Targeting the pathways involved with specific inhibitors or agonists may prevent these consequences of early-life infection. Vaccination and immunomodulatory therapies that control the infections and their sequelae may also be efficacious.]]> Mon 01 Feb 2016 13:04:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42107 Fri 26 Aug 2022 11:23:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33077 Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results: Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion: We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.]]> Fri 24 Aug 2018 14:41:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33076 Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.]]> Fri 24 Aug 2018 14:40:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54960 Fri 22 Mar 2024 15:34:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53870 Fri 19 Jan 2024 12:39:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Fri 09 Aug 2024 10:45:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33085 -/-) and TLR4-deficient (Tlr4^-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2^-/- mice but was attenuated in Tlr4^-/- mice compared with CS-exposed WT controls. However, Tlr2^-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4^-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.]]> Fri 01 Apr 2022 09:24:33 AEDT ]]>