https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43455 p < 0.001); whilst those with an unhealthy diet and no MVM or fish oil consumption were associated with a higher risk of obesity (p < 0.05). Compared to participants with a long-term healthy diet and no calcium consumption, the combination of a long-term healthy diet and calcium consumption was linked to a lower risk of CVD (IRR = 0.87, 95% CI: 0.78; 0.96). In conclusion, a long-term healthy diet combined with MVM or fish oil was associated with a lower incidence of CVD. Participants who maintained a healthy diet and used calcium supplements were associated with a lower incidence of obesity. However, these associations were not found among those with an unhealthy diet, despite taking similar supplements.]]> Wed 28 Sep 2022 14:35:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50220 Wed 28 Feb 2024 15:47:57 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49965 Wed 21 Jun 2023 11:57:33 AEST ]]> https://nova.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://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:49614 Wed 14 Jun 2023 16:04:06 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23281 Wed 11 Apr 2018 16:20:11 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:42686 Wed 08 May 2024 12:01:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33081 -/-) mice, one with a targeted deletion and another mutant expressing an major histocompatibility complex (MHC) transgene. To determine the importance of RelB in DCs, RelB-sufficient DCs (RelB^-/- or RelB^-/-) were adoptively transferred into RelB^-/- mice. Both strains had increased pulmonary inflammation compared to their respective wild-type (RelB^-/-) and heterozygous (RelB^-/-) controls. RelB^-/- mice also had increased inflammatory cell influx into the airways, levels of chemokines (CCL2/3/4/5/11/17, CXCL9/10/13) and Th2-associated cytokines (IL-4/5) in lung tissues, serum IgE and airway remodelling (mucus secreting cell numbers (MSCs), collagen deposition and epithelial thickening). Transfer of RelB^-/- CD11c⁺ DCs to RelB^-/- mice decreased pulmonary inflammation, with reduced lung chemokine and Th2-associated cytokine (IL-4/5/13/25/33, thymic stromal lymphopoietin) levels, serum IgE, numbers of type 2 innate lymphoid cells, myeloid DCs, γδ T cells and lung Vß13⁺ T cells, MSCs, airway collagen deposition and epithelial thickening.These data indicate that RelB deficiency may be a key pathway underlying AAI and that DC-encoded RelB is sufficient to restore control.]]> Wed 02 Mar 2022 14:25:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53957 Tue 23 Jan 2024 10:53:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48579 Tue 21 Mar 2023 17:43:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43418 Tue 20 Sep 2022 08:26:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43085 Tue 13 Sep 2022 12:19:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33793 –/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild‐type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c^–/– mice with AAD also had reduced numbers of α‐smooth muscle actin‐positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)‐5, IL‐13, IL‐33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL‐5, IL‐33 and TNF levels in lung‐draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3‐positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL‐5 and IL‐13 from co‐cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium‐treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma.]]> Thu 28 Oct 2021 13:02:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55004 Thu 28 Mar 2024 13:31:01 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:45028 Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD. Methods: Here, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36^aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36^+/+) and Zfp36^aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed. Results: After four days of CS exposure, Zfp36^aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36^aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL_(S), and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS‐induced experimental COPD were ameliorated. Conclusion: Collectively, our study provides the first evidence for the therapeutic potential of inducing TTP as a treatment for COPD.]]> Thu 27 Oct 2022 09:28:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50515 Thu 27 Jul 2023 14:34:40 AEST ]]> 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:31553 Sat 24 Mar 2018 08:44:25 AEDT ]]> https://nova.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://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:41982 Fri 19 Apr 2024 11:58:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38589 Fri 12 Nov 2021 15:59:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49107 Fri 05 May 2023 11:32:08 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 ]]>