Current Issue : April - June Volume : 2020 Issue Number : 2 Articles : 5 Articles
Background: We have performed this study to evaluate the association between H19 rs217727 polymorphism and\nthe risk of cancer.\nMethods: An odds ratio (OR) with a 95% confidence interval (CI) was applied to determine a potential association.\nResults: A total of 17 caseâ??control publications were selected. This meta-analysis showed that H19 rs217727 has a\nsignificant increased association with cancer risk in allelic, homozygous, heterozygote, dominant and recessive\nmodels (T vs C: OR = 1.16, 95% CI = 1.06â??1.27, I2 = 75.7; TT vs CC: OR = 1.29, 95% CI = 1.06â??1.56, I2 = 71.6; CT vs CC:\nOR = 1.15, 95% CI = 1.01â??1.31, I2 = 75.4; CT + TT vs CC: OR = 1.20, 95% CI = 1.05â??1.36, I2 = 76.5; TT vs CT + CC: OR =\n1.22, 95% CI = 1.02â??1.45, I2 = 70.6;). In the subgroup analysis of smoking status, both smokers and nonsmokers\nshowed an increase in cancer risk in allelic, homozygous, dominant and heterozygote models.\nConclusion: This meta-analysis revealed H19 rs217727 may influence cancer susceptibility....
Background: This study was performed to determine whether there was any association between abnormal DNA\nmethylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS).\nMethods: A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and\n21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal\nresistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients\nand inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human\nnasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA\nmethylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER.\nResults: A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased\nmethylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false\ndiscovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated\nwith olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04;\nr = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum\ntotal IgE levels were not correlated with the methylation ratios at either CpG unit.\nConclusions: Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis;\nhowever these findings need to be confirmed in larger multicentre group studies....
Introduction: Risk stratification of children with ependymomas of the posterior fossa in current therapeutic\nprotocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease\nentity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of\npatients treated according to the German HIT protocols.\nMethods: Tumor samples of 134 patients aged 0.2â??15.9 years treated between 1999 and 2010 according to HIT\nprotocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and\ngenomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier\nmethod with log rank test and multivariate Cox regression analysis.\nResults: Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as\npredictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features\nincluding vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox\nregression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS\nand OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that\nseparates patients with standard, intermediate and high risk, and which outperforms current stratification procedures.\nConclusion: The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification\nmodel for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide\nthe basis for risk-adapted treatment of children with ependymomas of the posterior fossa....
Background: Genetic mutations cause severe human diseases, and suitable animal models to study the regulatory\nmechanisms involved are required. The CRISPR/Cas9 system is a powerful, highly efficient and easily manipulated\ntool for genetic modifications. However, utilization of CRISPR/Cas9 to introduce point mutations and the exclusion\nof off-target effects in mice remain challenging. TP53-R175 is one of the most frequently mutated sites in human\ncancers, and it plays crucial roles in human diseases, including cancers and diabetes.\nResults: Here, we generated TRP53-R172P mutant mice (C57BL/6 J, corresponding to TP53-R175P in humans) using\na single microinjection of the CRISPR/Cas9 system. The optimal parameters comprised gRNA selection, donor\ndesignation (silent mutations within gRNA region), the concentration of CRISPR components and the cellular sites\nof injection. TRP53-R172P conversion was genetically and functionally confirmed. Combination of TA cloning and\nSanger sequencing helped identify the correctly targeted mice as well as the off-target effects in the engineered\nmice, which provide us a strategy to select the on-target mice without off-target effects quickly and efficiently.\nConclusions: A single injection of the this optimized CRISPR/Cas9 system can be applied to introduce particular\nmutations in the genome of mice without off-target effects to model various human diseases....
Background: Blood has proven to be a useful resource for molecular analysis in numerous biomedical studies,\nwith peripheral blood mononuclear cells (PBMCs) and whole blood being the major specimen types. However,\ncomparative analyses between these two major compartments (PBMCs and whole blood) are few and far between.\nIn this study, we compared gene expression profiles of PBMCs and whole blood samples obtained from research\nsubjects with or without mild allergic asthma.\nMethods: Whole blood (PAXgene) and PBMC samples were obtained from 5 mild allergic asthmatics and 5 healthy\ncontrols. RNA from both sample types was measured for expression of 730 immune-related genes using the\nNanoString nCounter platform.\nResults: We identified 64 uniquely expressed transcripts in whole blood that reflected a variety of innate, humoral,\nand adaptive immune processes, and 13 uniquely expressed transcripts in PBMCs which were representative of T-cell\nand monocyte-mediated processes. Furthermore, analysis of mild allergic asthmatics versus non-asthmatics revealed\n47 differentially expressed transcripts in whole blood compared to 1 differentially expressed transcript in PBMCs\n(FDR < 0.25). Finally, through simultaneous measurement of PBMC proteins on the nCounter assay, we identified\nCD28 and OX40 (TNFRSF4), both of which are critical co-stimulatory molecules during T-cell activation, as significantly\nupregulated in asthmatics.\nConclusions: Whole blood RNA preserved in PAXgene tubes is excellent for producing gene expression data with\nminimal variability and good sensitivity, suggesting its utility in multi-centre studies requiring measurement of blood\ngene expression....
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