Antioxidant molecules reduce oxidative stress and protect cells from reactive oxygen species (ROS)-mediated cellular damage and probably the development of cancer. We have investigated the contribution of X-box-binding protein (XBP1), a major endoplasmic reticulum stress-linked transcriptional factor, to cellular resistance to oxidative stress. After exposure to hydrogen peroxide (H 2 O 2 ) or a strong ROS inducer parthenolide, loss of mitochondrial membrane potential (MMP) and subsequent cell death occurred more extensively in XBP1-deficient cells than wild-type mouse embryonic fibroblast cells, whereas two other anticancer agents induced death similarly in both cells. In XBP1-deficient cells, H 2 O 2 exposure induced more extensive ROS generation and prolonged p38 phosphorylation, and expression of several antioxidant molecules including catalase was lower. Knockdown of XBP1 decreased catalase expression, enhanced ROS generation and MMP loss after H 2 O 2 exposure, but extrinsic catalase supply rescued them. Overexpression of XBP1 recovered catalase expression in XBP1-deficient cells and diminished ROS generation after H 2 O 2 exposure. Mutation analysis of the catalase promoter region suggests a pivotal role of CCAAT boxes, NF-Y-binding sites, for the XBP1-mediated enhancing effect. Taken together, these results indicate a protective role of XBP1 against oxidative stress, and its positive regulation of catalase expression may at least in part account for this function.
The aim of this study was to evaluate whether the expression of annexin A1 (ANXA1) is associated with the progression of cervical neoplasia. ANXA1 expression was examined by immunohistochemistry in paraffin-embedded cervical tissue samples (n = 234), comprising 52 samples of normal cervical epithelia, 30 of cervical intraepithelial neoplasia (CIN) I, 27 of CIN II, 32 of CIN III, and 93 of invasive squamous cell carcinoma (ISCC). ANXA1 expression was strong in normal cervical squamous epithelium and significantly reduced with increasing progression of cervical neoplasia. Moreover, a close association was observed between ANXA1 expression and tumour cell differentiation in ISCC. These preliminary results indicate that ANXA1 may be an effective candidate for detecting CIN lesions and for evaluating tumour cell differentiation in squamous cell carcinoma of the cervix.
Non-small cell lung cancer (NSCLC) is a highly lethal malignancy that often becomes resistant to chemotherapy. The effect of silencing the X-linked inhibitor of apoptosis gene (XIAP) on resistance to cisplatin, paclitaxel and gemcitabine was studied in the NSCLC cell lines A549 and H460. Transfection of these cells with small interfering RNA (siRNA) for XIAP blocked overexpression of the gene, suppressed cell proliferation, increased apoptosis and increased the cells' sensitivity to cisplatin and paclitaxel by preventing the binding of XIAP to caspase3 and increasing the activity of this enzyme. There was no significant difference in resistance to gemcitabine between XIAP-silenced cells and non-transfected cells. Changes in chemoresistance were independent of the activity of caspase-9. Silencing XIAP with siRNA can decrease chemoresistance in NSCLC and may have a potential role in the treatment of this disease.
ObjectiveTo contribute evidence relevant to the policy of supplying iodised salt (IS), non-iodised salt (NIS) or both in Chinese cities.DesignSubnational telephone interview survey.SettingChina.ParticipantsTotally, 24 557 telephone numbers were dialled and 4833 citizens accepted the telephone interview. The telephone numbers were randomly selected by random digit dialling and a Mitofsky-Waksberg two-stage sampling method in 17 capital cities and 6 coastal cities from 17 iodine deficiency disorder (IDD)-eliminated provinces (municipalities).ResultsThe 4833 citizens finished the telephone interview. Among them, 3738 (77.3%) citizens chose IS, 481 (10%) citizens chose NIS, and the others chose both IS and NIS. The citizens’ awareness rates of IDD and IDD preventive measures were 68.7% and 62.5%, respectively.ConclusionsIt is not a suitable time to supply IS and NIS simultaneously in the developed cities of China, but a pilot project may be conducted in the cities where IDD has been sustainably eliminated, there is strong awareness of IDD and the population can make informed decisions regarding IS. IDD health education should be further strengthened, especially regarding the potential for IQ damage.
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