https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46760 Wed 30 Nov 2022 09:30:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45076 ELN gene expression in tumors from CRC patients and adjacent non-tumor colon tissues and healthy controls from two existing microarray datasets. ELN protein was measured in human normal colon cells and colon cancer epithelial cells and tumor development was assessed in colon epithelial cells cultured in medium with or without ELN peptide on plates coated with ELN recombinant protein. Control plates were coated with PBS only. Results: We found ELN gene expression was increased in tumors from CRC patients compared to adjacent non-tumor tissues and healthy controls. ELN protein was increased in cancer cells compared to normal colon epithelial cells. Transforming growth factor beta (TGF-β) was a key cytokine to induce production of ECM proteins, but it did not induce ELN expression in colon cancer cells. Matrix metalloproteinase 9 (MMP9) gene expression was increased, but that of MMP12 (elastase) did not change between CRC patients and control. Tissue inhibitor of metalloproteinases 3 (TIMP3) gene expression was decreased in colon tissues from CRC patients compared to healthy controls. However, MMP9, MMP12 and TIMP3 proteins were increased in colon cancer cells. ELN recombinant protein increased proliferation and wound healing in colon cancer epithelial cells. This had further increased in cancer cells incubated in plates coated with recombinant ELN coated plate and in culture media containing ELN peptide. A potential mechanism was that ELN induced epithelial mesenchymal transition with increased alpha-smooth muscle actin and vimentin proteins but decreased E-cadherin protein. Tumor necrosis factor alpha (TNF) mRNA was also increased in CRC patients compared to controls. ELN recombinant protein induced further increases in TNF protein in mouse bone marrow derived macrophages after lipopolysaccharide stimulation. Conclusions: These data suggest ELN regulates tumor development and the microenvironment in CRC.]]> Wed 26 Oct 2022 12:30:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45088 Wed 26 Oct 2022 12:23:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37230 Wed 19 Jan 2022 15:15:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38204 Wed 18 Aug 2021 09:53:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36824 Wed 17 Nov 2021 16:29:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48369 Fbln1c-deficient (Fbln1c^–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target.]]> Wed 15 Mar 2023 13:12:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47176 Wed 14 Dec 2022 15:55:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47144 in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.]]> Wed 14 Dec 2022 15:27:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41455 Wed 10 Aug 2022 12:11:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41553 Wed 08 May 2024 09:45:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49859 Wed 07 Jun 2023 10:25:30 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47835 Wed 01 Feb 2023 14:10:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49760 Tue 30 May 2023 18:39:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44965 Tue 25 Oct 2022 13:46:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54312 Tue 20 Feb 2024 14:27:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46351 n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.]]> Tue 15 Nov 2022 15:15:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48325 Tue 14 Mar 2023 16:33:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38252 Thu 19 Aug 2021 11:04:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47210 Thu 15 Dec 2022 17:18:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38383 Mon 29 Jan 2024 17:45:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41886 PXS-5120A (12k), a potent, irreversible inhibitor that is >300-fold selective for LOXL2 over LOX. PXS-5120A also shows potent inhibition of LOXL3, an emerging therapeutic target for lung fibrosis. Key to the development of this compound was the utilization of a compound oxidation assay. PXS-5120A was optimized to show negligible substrate activity in vitro for related amine oxidase family members, leading to metabolic stability. PXS-5120A, in a pro-drug form (PXS-5129A, 12o), displayed anti-fibrotic activity in models of liver and lung fibrosis, thus confirming LOXL2 as an important target in diseases where collagen cross-linking is implicated.]]> Mon 15 Aug 2022 15:37:55 AEST ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44177 Mon 10 Oct 2022 10:20:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37427 Fri 31 Mar 2023 15:03:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47212 Fri 16 Dec 2022 10:09:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40156 Fri 15 Jul 2022 09:51:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38952 Haemophilus influenzae (NTHi), using immunofluorescence microscopy. In addition, expression of a known receptor of NTHi, platelet-activating factor receptor (PAFR), and two pro-inflammatory cytokines, interleukin 6 (IL-6) and interleukin-8 (IL-8), were determined using quantitative polymerase chain reaction. We observed a dose-dependent increase in NTHi adhesion to human bronchial epithelial cells following exposure to cow dung but not wood smoke extracts. Pre-treatment with PAFR antagonists, WEB-2086 and its analogue, C17, decreased adherence by NTHi to airway epithelial cells exposed to cow dung smoke. Both cow dung and wood smoke-induced expression of PAFR, as well as of IL-6 and IL-8, which was inhibited by WEB-2086 and C17. In conclusion, biomass smoke from combustion of cow dung and wood-induced expression of PAFR and airway inflammatory markers in human bronchial epithelial cells. Cow dung exposure, but not wood smoke exposure, mediated a measurable increase in NTHi adhesion to airway epithelial cells that was inhibited by PAFR antagonists. This work highlights the potential of PAFR as a therapeutic target for reducing the impact of hazardous biomass smoke exposure on respiratory health.]]> Fri 11 Mar 2022 14:48:35 AEDT ]]>