Epigenetic modulations of immune cells: from normal development to tumor progression.

The dysfunction of immune cell development often impairs immunological homeostasis, thus causing various human diseases. Accumulating evidence shows that the development of different immune cells from hematopoietic stem cells are highly fine-tuned by different epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling and RNA-related regulations. Understanding how epigenetic regulators modulate normal development of immune cells contributes to the identification of new strategies for various diseases. Here, we review recent advances suggesting that epigenetic modulations can orchestrate immune cell development and functions through their impact on critical gene expression. We also discuss the aberrations of epigenetic modulations in immune cells that influence tumor progression, and the fact that underlying mechanisms affect how epigenetic drugs interfere with tumor progression in the clinic.

Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma.

Background: Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods. Methods: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression. Results: A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES. Conlusion: UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.

High grade cervical intraepithelial neoplasia and viral load of high-risk human papillomavirus: significant correlations in patients of 22 years old or younger.

High-risk human papillomavirus (HR-HPV) is recognized as the primary cause for the development of cervical cancers and their precursor lesions. We investigated whether high-grade cervical dysplasia correlates with high viral load of HR-HPV in an age-dependent manner. Cases were retrospectively selected to include patients with a prior cytological diagnosis of ASCUS or higher grade squamous intraepithelial lesions, and a positive Digene Hybrid Capture II (HC-II) HR-HPV testing within 2 months before or after cervical biopsy. The quantitative viral load data was classified as negative, low, moderate and high according to the manufacturer's instruction. Cases were then stratified into 4 age groups: 40 years. Chi-Square analysis and logistic regression were performed where appropriate. A total of 995 patients were identified. Age categories were significantly associated with HPV loads (p=0.046). Moderate to high viral loads of HPV were significantly related to the histological grade of dysplasia (p=0.029). Logistic regression analysis further confirmed the association of HPV with histological grades, even after adjusting for age factor. In particular, high-grade dysplasia (p=0.011) but not low grade dysplasia (p=0.140) was significantly associated with moderate to high HPV loads. Patients of 22 years old or younger were the only group found significantly correlated with high viral loads of HPV (p=0.015). In conclusion, high-grade squamous intraepithelial lesions and patients' age of 22 years old or younger are significantly associated with a moderate to high viral load of HR-HPV.

[Studies on contents of arsenic, selenium, mercury and bismuth in tea samples collected from different regions by atomic fluorescence spectrometry].

After microwave or wet decomposition, the contents of arsenic, selenium, mercury and bismuth in twenty-one Chinese tea samples and five Japanese tea samples were determined by atomic fluorescence spectrometry, and plant standard reference materials were used to verify the accuracy and the precision of the analytical method. Moreover, the contents of these four elements were also determined in different parts of tea sapling sampled from the suburbs of Suzhou, a place famous for its Chinese tea biluochun. It was shown that microwave decomposition is indispensable for getting good results of mercury contents in tea samples by AFS. Compared with those in Japanese tea samples, the contents of arsenic, selenium, mercury and bismuth in Chinese tea samples are significantly high, but the Chinese tea sample produced in Hunan province has the lowest bismuth content. Arsenic, selenium and mercury are mainly present in the bark, the root and the old leaves of tea sapling, nevertheless, the bismuth contents in the root and the bark-deprived trunk are so low that they can not be determined accurately. From this study, a preliminary conclusion can be drawn that tea is not a selenium-accumulating plant and the great majority of selenium in Chinese tea samples originates from the dry and wet deposition of atmospheric aerosols.