https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25846 Wed 21 Aug 2024 11:12:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38782 Wed 13 Mar 2024 13:54:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29666 10 mg/L, or who were taking anti-inflammatory medications or n-3PUFA supplements, 126 participants (age 77.6 ± 7.3 years; females, 46%) were included in the analysis. After multivariate adjustments, O3I was inversely associated with CRP (β = −0.209, p < 0.05) and monocyte cell counts (β = −0.205, p < 0.05), and total n-3PUFA was inversely related to WBC (β = −0.238, p < 0.05), neutrophils (β = −0.212, p < 0.05) and monocytes (β = −0.246, p < 0.05). However no association between fibrinogen and O3I or total n-3PUFA was detected. Conclusions: This study demonstrated a negative association between O3I and biomarkers of inflammation in an older population. The findings support a potential role for n-3PUFA supplementation in the management of inflammatory diseases.]]> Wed 11 Apr 2018 16:52:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19489 Wed 11 Apr 2018 16:22:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22005 haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.]]> Wed 11 Apr 2018 16:14:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16827 Wed 11 Apr 2018 16:01:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22120 Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.]]> Wed 11 Apr 2018 15:36:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28066 Klebsiella pneumoniae infection, cecal ligation and puncture as well as rhinovirus exacerbated asthma models were also assessed using PXS-4728A. Results: Selective VAP-1/SSAO inhibition by PXS-4728A diminished leukocyte rolling and adherence induced by CXCL1/KC. Inhibition of VAP-1/SSAO also dampened the migration of neutrophils to the lungs in response to LPS, Klebsiella pneumoniae lung infection and CLP induced sepsis; whilst still allowing for normal neutrophil defense function, resulting in increased survival. The functional effects of this inhibition were demonstrated in the RV exacerbated asthma model, with a reduction in cellular infiltrate correlating with a reduction in airways hyperractivity. Conclusions and implications: This study demonstrates that the endothelial cell ligand VAP-1/SSAO contributes to the migration of neutrophils during acute lung inflammation, pulmonary infection and airway hyperractivity. These results highlight the potential of inhibiting of VAP-1/SSAO enzymatic function, by PXS-4728A, as a novel therapeutic approach in lung diseases that are characterized by neutrophilic pattern of inflammation.]]> Wed 11 Apr 2018 14:12:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17958 Wed 11 Apr 2018 09:41:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19497 Ex vivo, sepsis-derived interphase neutrophils expressed arginase, metabolised culture L-arginine and suppressed T cell proliferation and CD3 zeta-chain expression. In vivo, in septic shock there was a longitudinal inverse association between interphase neutrophil number and CD3 zeta-chain expression. Depletion or inhibition of interphase neutrophils in vitro restored zeta-chain expression and T cell function. Conclusions: For the first time during an acute human infection, interphase neutrophils that express arginase were found to circulate in sepsis, in proportion to disease severity. These neutrophil-MDSCs impair T cell CD3 zeta-chain expression and T cell function via L-arginine metabolism, and likely contribute to the T cell dysfunction seen in sepsis. Modulation of neutrophil-MDSC or their downstream effects warrant consideration as targets for novel adjunctive therapies in sepsis.]]> Wed 11 Apr 2018 09:14:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30136 Wed 10 Nov 2021 15:14:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36433 + neutrophils as median fluorescence intensity (MFI). Results: Neutrophil surface expression of CD62L was significantly reduced in COPD (median (IQR) MFI: 1156 (904, 1365)) compared with asthma (1865 (1157, 2408)) and healthy controls (2079 (1054, 2960)); p=0.028. COPD neutrophils also demonstrated a significant reduction in CD62L expression with and without fMLF stimulation. Asthma participants had a significantly increased proportion and number of CD62L^bright/CD16^dim neutrophils (median: 5.4% and 0.14 x 10⁹/L, respectively), in comparison with healthy (3.54% and 0.12 x 10⁹/L, respectively); p<0.017. Conclusion: Reduced CD62L expression suggests blood neutrophils have undergone priming in COPD but not in asthma, which may be the result of systemic inflammation. The increased shedding of CD62L receptor by COPD blood neutrophils suggests a high sensitivity for activation]]> Wed 10 Nov 2021 15:05:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31237 Wed 09 Feb 2022 15:56:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53965 Wed 06 Mar 2024 15:17:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24139 Tue 20 Aug 2024 09:26:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53385 Thu 23 Nov 2023 12:55:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26559 Thu 17 Feb 2022 09:28:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48867 Thu 13 Apr 2023 10:07:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46043 + T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8⁺ T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection. Conclusion: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.]]> Thu 10 Nov 2022 14:51:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36436 Sun 03 May 2020 16:19:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7208 Sat 24 Mar 2018 08:39:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8668 Sat 24 Mar 2018 08:38:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14184 1% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11. Results: Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV₁% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV₁% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation. Conclusion: Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.]]> Sat 24 Mar 2018 08:21:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13283 Sat 24 Mar 2018 08:15:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11169 Sat 24 Mar 2018 08:10:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20832 12% change in FEV₁; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. Conclusions: A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.]]> Sat 24 Mar 2018 08:05:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17886 Sat 24 Mar 2018 07:56:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21276 70%) of chest infections in the previous 12 months. There was also an increased prevalence of rhinosinusitis (64%) and increased symptoms of gastroesophageal reflux disease compared to those with eosinophilic asthma. Conclusions: The clinical pattern of neutrophilic asthma is different from paucigranulocytic and eosinophilic asthma with evidence of abnormal upper airways responses. Specific and targeted treatment of these airway problems may assist in the control and management of neutrophilic asthma.]]> Sat 24 Mar 2018 07:54:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32745 Mon 23 Sep 2019 14:10:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44177 Mon 10 Oct 2022 10:20:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49492 Fri 19 May 2023 10:17:09 AEST ]]>