https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44648 2NPs) is on the increase, and so the number of studies dedicated to describing this material's biological effects. Previous studies have presented results indicating the controversial impact of TiO₂NPs on cell fate regarding death and survival. We speculate that this may be due to focusing on each of the subject cells as an isolated individual. In this study, we made a difference by looking at the subject cells as an interrelated population. Specifically, we exposed mesenchymal stem cells (MSCs) to TiO₂NPs and observed cell death and stimulation of proliferation among the cell population. Our data shows that the exposure to TiO₂NPs initiated autophagy, which led to an increase in extracellular Wnt protein levels and increased Wnt/GSK3β/β-catenin/cyclin D1 signalling in the cell population. Autophagy inhibitor repressed the effects of TiO₂NPs, which indicates that ß-catenin regulation was dependent on TiO₂NPs-induced autophagy. The inhibition of β-catenin resulted in dysregulation of cyclin D1 protein expression level. In conclusion, following exposure to TiO₂NPs, MSCs undergo autophagy, which induces cell proliferation among the cell population by upregulation of cyclin D1 through the Wnt/GSK3β/β-catenin pathway.]]> Wed 19 Oct 2022 09:00:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26547 in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.]]> Wed 11 Apr 2018 11:05:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46983 Tue 13 Dec 2022 09:07:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30397 Tue 01 May 2018 09:18:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37125 Thu 03 Feb 2022 12:20:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19759 Sat 24 Mar 2018 07:54:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18344 Sat 24 Mar 2018 07:52:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46649 2NP) following environmental exposure. At present, the consequences of TiO₂NP exposure in bone are not well known. The aim of this study was to investigate the effects of TiO₂NP on mesenchymal stem cells (MSCs) and potential underlying mechanisms. Mesenchymal bone marrow-derived cells were cultured and treated with various concentrations of TiO₂NP. Results showed that TiO₂NP incubation produced cytotoxicity as evidenced by reduced cell viability. Using Western blotting TiO₂NP was found to increase autophagy as determined by elevation in ratio of LC3-II from LC3-I without evidence of necrotic cell death as estimated by lactic dehydrogenase (LDH) level. TiO2NP produced a rise in intracellular reactive oxygen species (ROS) levels. The observed alterations in autophagy and oxidant stress were associated with upregulation of protein expression of p38, JNK, and ERK. Data indicate that TiO₂NP-mediated decrease in MSC survival involves a complex series of events associated stimulation of mitogen-activated protein kinase (MAPK) pathway and consequent autophagy and oxidative damage.]]> Mon 28 Nov 2022 17:22:23 AEDT ]]>