https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 A gut microbiome metabolite paradoxically depresses contractile function while activating mitochondrial respiration https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54316 30 µM TMAO in hearts performing minimal isovolumic work, although this response was reduced by >65%. In contrast, exposure to 10 µM or 100 μM TMAO increased mitochondrial complex I, II and maximal respiratory fluxes while appearing to reduce outer membrane integrity. Expression of phosphorylated AMPKα and total GSK-3β declined. Thus, acute exposure of mouse hearts to TMAO levels reported in advanced CVD significantly inhibits cardiac contractility and induces modest coronary constriction while paradoxically overactivating mitochondrial respiration.]]> Wed 28 Feb 2024 15:01:29 AEDT ]]> Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14146 Wed 14 Aug 2024 09:09:02 AEST ]]> Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15241 + T cells. We found that a limited number of microRNAs exhibited marked up- or downregulation following early-life infection and sensitisation, for many of which the levels of expression were further changed following chronic challenge with the sensitizing antigen. Targets of these microRNAs included genes involved in immune or inflammatory responses (e.g. Gata3, Kitl) and in tissue remodelling (e.g. Igf1, Tgfbr1), as well as genes for various transcription factors and signalling proteins. In pulmonary CD4+ T cells, there was significant demethylation at promoter sites for interleukin-4 and interferon-γ, the latter increasing following chronic challenge. We conclude that, in this model, progression to an asthmatic phenotype is linked to epigenetic regulation of genes associated with inflammation and structural remodelling, and with T-cell commitment to a Th2 immunological response. Epigenetic changes associated with this pattern of gene activation might play a role in the development of childhood asthma.]]> Wed 11 Apr 2018 14:44:33 AEST ]]> Epigenetic changes in childhood asthma (commentary) https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8198 Sat 24 Mar 2018 08:36:19 AEDT ]]>