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.
In this study, the expression of bone morphogenetic protein-7 (BMP7) was investigated in tissue-engineered cartilage constructed using chondrocytes transfected with the BMP7 gene and that constructed using non-transfected chondrocytes after 7, 14, 21 and 28 days. The volume of the BMP7 gene-transfected tissue-engineered cartilage culture after 5 -7 days was 9 × 9 × 2 mm, while that of the non-transfected tissue-engineered cartilage culture was 8 × 8 × 2 mm. Histomorphological analysis showed that both cultures comprised cartilaginous tissue. Both BMP7 mRNA and BMP7 protein were expressed in BMP7 gene-transfected cartilage culture grown in vitro for 7, 14, 21 or 28 days. The chondrocytes in the BMP7 gene-transfected cartilage culture were active, with increased mitochondria, Golgi bodies and rough endoplasmic reticulum compared with non-transfected cartilage. These results provide an ideal foundation for the study of BMP7 gene-transfected tissueengineered cartilage transplantation in the repair of cartilaginous defects.
This study aimed to analyse the protective effects of quercetin on the toxicity of cadmium (Cd) using metabonomics techniques. Sixty male Sprague–Dawley rats were randomly divided into six groups ( n = 10): control group (C), low-dose quercetin-treated group (Q1; 10 mg/kg bw/day), high-dose quercetin-treated group (Q2; 50 mg/kg bw/day), Cd-treated group (D; 4.89 mg/kg bw/day), low-dose quercetin plus Cd-treated group (DQ1) and high-dose quercetin plus Cd-treated group (DQ2). The rats continuously received quercetin and Cd via gavage and drinking water for 12 weeks, respectively. The rat urine samples were collected for metabonomics analysis. Finally, 10 metabolites were identified via the metabonomics profiles of the rat urine samples. Compared with the control group, the intensities of taurine, phosphocreatine, l-carnitine and uric acid were significantly decreased ( p < 0.01) and those of LysoPC (18: 2 (9Z, 12Z)), guanidinosuccinic acid, dopamine, 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman and allantoic acid were significantly increased ( p < 0.01) in the Cd-treated group. However, the intensities of the aforementioned metabolites had restorative changes in the high-dose quercetin plus Cd-treated groups unlike those in Cd-treated group ( p < 0.01 or p < 0.05). Results indicated that quercetin exerts protective effects on Cd-induced toxicity by regulating energy and lipid metabolism, enhancing the antioxidant defence system and protecting liver and kidney function and so on.
Background: As reliable intercellular transporters, exosomes for the diagnosis and function of various disease are fully explored. Also, exosomes extracted from tear film have been used as indictors for various eye disease, even systemic disease due to the easy and non-invasive collection nature with microRNAs variation. However, there still no reports focus the change and function of on exosomes and exosomal microRNAs during diabetes ocular dysfunction.Methods: Paired diabetes and health tear film-derived exosomes were collected by test strips and identified according standard regimens. Different expression microRNAs were profiled by microarray. The function of exosomes to cornea epithelium was detected by cornea wound model in vivo and cell viability and migration assay in vitro. Bioinformatics analysis, including GO and KEGG were conducted to explore the potential biological signaling pathway.Results: We confirmed diabetic tear film derived exosomes contribute to delay cornea wound healing and aggravate diabetic dry eye-like syndrome. Total 12 differential expression microRNAs were confirmed compared with paired controls, may participate in glycosphingolipid biosynthesis; mucin type O-Glycan biosynthesis; Ras signaling pathway; AMPK signaling pathway; bacterial invasion of epithelial cells; ErbB signaling pathway; cGMP-PKG signaling pathwayConclusion: This study provides evidence that diabetic tear film derived exosomes can affect the ocular surface health during diabetes, while healthy exosomes have no similar effects. Thus, the different expression of microRNAs existed in the exosomes from diabetes and healthy volunteer may be the reason of different function.
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