Aim: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). Methods: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. Results: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. Conclusion: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.
Liver fibrosis is characterized by an exacerbated accumulation of deposition of the extracellular matrix (ECM), and the activation of hepatic stellate cells (HSC) plays a pivotal role in the development of liver fibrosis. Periostin has been shown to regulate cell adhesion, proliferation, migration and apoptosis; however, the involvement of periostin and its role in transforming growth factor (TGF)-β1-induced HSC activation remains unclear. We used RT-PCR and Western blot to evaluate the expression level of periostin in hepatic fibrosis tissues and HSCs, respectively. Cell proliferation was determined using the Cell Proliferation ELISA BrdU kit, cell cycle was analysed by flow cytometry. The expression of α-smooth muscle actin (α-SMA), collagen I, TGF-β1, p-Smad2 and p-Smad3 were determined by western blot. Our study found that periostin was up-regulated in liver fibrotic tissues and activated HSCs. In addition, siRNA-periostin suppressed TGF-β1-induced HSC proliferation. The HSC transfected with siRNA-periostin significantly inhibited TGF-β1-induced expression levels of α-SMA and collagen I. Furthermore, TGF-β1 stimulated the expression of periostin, and siRNA-periostin attenuated TGF-β1-induced Smad2/3 activation in HSCs. These results suggest that periostin may function as a novel regulator to modulate HSC activation, potentially by promoting the TGF-β1/Smad signalling pathway, and propose a strategy to target periostin for the treatment of liver fibrosis.
Background: Crohn's disease (CD) is a clinically chronic inflammatory bowel disease, which has been shown to be closely related to the brain-gut axis dysfunction. Although traditionally considered to be a limbic region, the insula has also been commonly identified as an abnormal brain region in previous CD-related studies.Methods: Structural magnetic resonance imaging (MRI) and resting-state functional MRI images were acquired from 45 CD patients in remission and 40 healthy controls (HCs). Three neuroimaging analysis methods including voxel-based morphometry (VBM), structural covariance, and functional connectivity (FC) were applied to investigate structural and functional alterations of the insulae between the CD patients and HCs. Pearson correlation was then used to examine the relationships between neuroimaging findings and clinical symptoms.Results: Compared with the HCs, CD patients exhibited decreased gray matter volume (GMV) in the left dorsal anterior insula (dAI) and bilateral posterior insula (PI). Taking these three areas including the left dAI, right PI, and left PI as regions of interest (ROIs), differences were observed in the structural covariance and FC of the ROI with several regions between the two groups. After controlling for psychological factors, the differences of several regions involved in emotional processing in GMV in the left dAI, the FC of the dAI, and the right PI were not significant. The FC of the parahippocampus/hippocampus with dAI and PI were negatively correlated with the CD activity index (CDAI).
Conclusions:We suggest that the insula-centered structural and/or functional changes may be associated with abnormal visceral sensory processing and related emotional responses in CD patients.
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