Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage) and chronically activated (in senescent or pro-apoptotic conditions) p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.
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PMID:Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53. 2579 Jan 37

The aim of this study was to analyze the incidence of caries, in relation to maternal risk behaviors and clinical conditions representing different levels of sickle cell disease severity. A total of 295 children aged 6 to 60 months participated in this cohort conducted from August 2007 to December 2008. They were diagnosed and monitored by the referral service of the state. Interviews were made with families to identify sociodemographic variables, and an oral exam was performed to determine dental caries. The SRQ (Self Report Questionnaire) scale was used to diagnose the presence of common mental disorders, and the CAGE (Cut down, Annoyed, Guilty and Eye opener) was applied to determine abusive use of alcohol. The absolute and relative frequencies of the variables of interest were analyzed by Chi-square and Mann-Whitney, with a 5% significance level. The incidence variables were analyzed according to the logistic regression model, with a confidence interval of 95%. Caries incidence (1.98; SD = 4.68) was higher in the HbSS genotype. There was a statistically significant association between caries incidence and both abusive use of alcohol (32.43%, RR = 1.99; 1.05-3.78; 95%CI) and common mental disorders (8.77% RR = 0.37; 0.15-0.93; 95%CI). There was also an association between caries incidence and maternal risk behavior, indicating that the care network should be expanded to include patients with sickle cell disease.
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PMID:Maternal risk behavior and caries incidence in children with sickle cell disease. 2667 94