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PRDI-BFI and RIZ homology domain containing proteins (PRDM) play a key role in cell differentiation and proliferation.Most members of the PRDM gene family are tumor suppressor genes which involved in tumorigenesis and abnormal expression in a variety of tumors.Aberrant DNA methylation often silences these genes,which may occur in the early stage of tumor,Cancer can be reversed by demethylation,which provides a new way for cancer treatment.
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Objective To investigate the relationship among the concentration of plasma interleukin (IL)-10 and plasma IL-13 and the clinical therapeutic effect in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods Thirty-six AECOPD inpatients were enrolled in this study.Blood samples of the subjects were collected as soon as hospitalization, and plasma IL-10 and IL-13concentrations were analyzed by enzyme-linked immunosorbent assay.The clinical manifestations of subjects were quantified by a special designed score standard, and were evaluated at the time points of hospitalization, 48 hours treatment and 96 hours treatment.The therapeutic effect was evaluated by clinical manifestations score combined with pulmonary ventilation functional parameter.Eventually, the correlation among the concentration of IL-10 concentration and IL-13 and the clinical therapeutic effect were analyzed.Results The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-10 concentration after 48 hours treatment were 0.85 and 0.48 respectively,then, 0.64 and 0.52 after 96 hours treatment.The correlation coefficients between clinical manifestations score decrease and pulmonary ventilation function improvement with plasma IL-13 concentration after 48hours treatment were -0.41 and -0.34, after 96 hours treatment , correlation coefficients between clinical manifestations score decrease with plasma IL-13 concentration was -0.36.All of the above correlation coefficients were statistically significant.Conclusion Plasma IL-10 concentration was positively, whereas, IL-13 concentration was negatively correlated with the therapeutic effect in AECOPD patients.
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Objective To investigate the methylation status of 14-3-3σ promoter in nasopharyngeal carcinoma cell lines and the influence of de-methylation treatment on 14-3-3σ expression. Methods Methylation status of 14-3-3σ gene promoter and 14-3-3σ mRNA expression were detected by methylation specific PCR (MSP) and RT-PCR in nasopharyngeal carcinoma cell lines CNE1, CNE2,5-8F,6-10B and immortalized nonneoplastic human nasopharyngeal epithelial cell line, NP69. Four nasopharyngeal carcinoma cell lines were treated with 5-asa-2' -deoxycytidine(5-aza-2dC) in different concentration for 72 h, then 14-3-3σ promoter meth-ylation status and m RNA expression were assessed, and western-blot was performed to detect the expression of 14-3-3σ protein. Results 14-3-3σ promoter methylation was detected by MSP in all of the four nasopharyn-geal carcinoma cell lines untreated by 5-aza-2dC whereas not in the treated ones or the immortalized human na-sopharyngeal epithelial cell line, NP69. Accordingly, 14-3-3σ mRNA expression was significantly discounted in untreated nasopharyngeal carcinoma cell lines as compared with NP69. 5-aza-2dC treatment dose-depend-ently reversed 14-3-3σ promoter methylation status and consequently upregulated the expression of 14-3-3σmRNA and protein in 4 nasopharyngeal carcinoma cell lines. High-differentiated CNE1 was more sensitive to 5-aza-2dC than lowly-differentiated CNE2, 5-8F and 6-10B. Conclusion Promoter methylation directly leads to decreased 14-3-3σ gene expression in nasopharyngeal carcinoma cell lines, and 14-3-3σ promoter de-methylation perhaps indicates a new target for nasopharyngeal carcinoma treatment.
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<p><b>OBJECTIVE</b>To investigate the expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and inducible nitric oxide synthase (iNOS) genes in rats' pulmonary arteries in different phases of hypoxia-induced pulmonary hypertension development.</p><p><b>METHODS</b>Models of chronic hypoxic pulmonary hypertension rat were duplicated by intermittent hypoxia. Mean pulmonary arterial pressure (mPAP) was measured by right-heart catheterization. HIF-1alpha and iNOS messenger ribonucleic acid (mRNA) were detected by in situ hybridization. HIF-1alpha and iNOS protein were measured by immunohistochemical analysis.</p><p><b>RESULTS</b>Expression of HIF-1alpha protein was upregulated in pulmonary arterial tunica intimae of all hypoxic rats. In pulmonary arterial tunica media, the level of HIF-1alpha protein was markedly upregulated at days 3 and 7 of hypoxia (P < 0.01), then tended to restore at 14 days and 21 days. HIF-1alpha mRNA levels in pulmonary arteries of rats began to increase significantly at day 14 of hypoxia (P < 0.01). Expression of iNOS mRNA and protein in pulmonary arteries of rats were upregulated by hypoxia for 3 days (P < 0.01), then reached its peak and maitained the same level while the extension of hypoxia. Linear correlation analysis showed that iNOS protein was associated with both mean pulmonary arterial pressure (r = 0.74, P < 0.01) and hypoxic pulmonary vascular remodeling (r = 0.78, P < 0.01), whereas the inverse was associated with HIF-1alpha protein (r = -0.52, P < 0.01).</p><p><b>CONCLUSIONS</b>HIF-1alpha and iNOS are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rat. HIF-1alpha protein may upregulate the expression of iNOS gene by transcriptional activation; in addition, iNOS protein may inhibit the expression of HIF-1alpha protein.</p>