Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis.

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

Electrochemical and Optical Biosensing Strategies for DNA Methylation Analysis.

DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding to the fifth carbon atom of cytosine while the base sequence of DNA remains unchanged. DNA methylation has significant influences on maintaining cell functions, genetic imprinting, embryonic development and tumorigenesis procedures and hence the analysis of DNA methylation is of great medical significance. With the development of analytical techniques and further research on DNA methylation, numerous DNA methylation detection strategies based on biosensing technology have been developed to fulfill various study requirements. This article reviewed the development of electrochemistry and optical biosensing analysis of DNA methylation in recent years; in addition, we also reviewed some recent advances in the detection of DNA methylation using new techniques, such as nanopore biosensors, and highlighted the key technical and biological challenges involved in these methods. We hope this paper will provide useful information for the selection and establishment of analysis of DNA methylation.

An electrochemical DNA biosensor analytic technique for identifying DNA methylation specific sites and quantify DNA methylation level.

We herein developed a novel electrochemical biosensor to detect DNA methylation level, and to quantitatively analyze multiple methylated sites. Graphene oxide was modified with anti-5-methylcytosine antibody to specifically bind CpG methylation sites, and horseradish peroxidase (HRP)-labeled IgG secondary antibody was bound to the former antibody. In buffer containing H2O2 and hydroquinone, HRP-IgG catalyzed the oxidation of hydroquinone into benzoquinone over H2O2, thereby generating electrochemical reduction signals. The number of 5-methylcytosine was directly proportional to current signal, thereby allowing accurate quantification of methylation level. We also analyzed monomethylated target sequences with different sites. After different methylated sites were captured by the probe, the steric hindrance differences between -CH3 hydrophobic sphere and the electrode surface were induced. The peak current decreased with reducing distance from the electrode surface, so DNA methylation sites were identified by measuring corresponding peak current responses. With a low detection limit (1 fM), this DNA biosensor was suitable for ultrasensitive DNA methylation detection. The linear detection range was 10-15 M to 10-8 M. Meanwhile, this method had high specificity, stability and repeatability, thus being widely applicable to the clinical detection of DNA methylation.

Electrochemical Biosensor for DNA Methylation Detection through Hybridization Chain-Amplified Reaction Coupled with a Tetrahedral DNA Nanostructure.

DNA methylation is a key factor in the pathogenesis of gene expression diseases or malignancies. Thus, it has become a significant biomarker for the diagnosis and prognosis of these diseases. In this paper, we designed an ultrasensitive and specific electrochemical biosensor for DNA methylation detection. The platform consisted of stem-loop-tetrahedron composite DNA probes anchoring at a Au nanoparticle-coated gold electrode, a restriction enzyme digestion of HpaII, and signal amplification procedures including electrodeposition of Au nanoparticles, hybridization chain reaction, and horseradish peroxidase enzymatic catalysis. Under optimal conditions, the design showed a broad dynamic range from 1 aM to 1 pM and a detection limit of about 0.93 aM. The approach also showed ideal specificity, repeatability, and stability. The recovery test demonstrated that the design is a promising platform for DNA methylation detection under clinical circumstances and could meet the need for cancer diagnosis.

A fumed alumina induced gel-like electrolyte for great performance improvement of lithium-sulfur batteries.

The practical application of high energy lithium-sulfur batteries is still limited by unstable lithium anodes and the shuttle effect of polysulfides. Herein, a gel-like electrolyte induced by fumed alumina is proposed for dendrite-free Li deposition, lower over-potential and better cycle stability. Li-S@pPAN cells with the proposed electrolyte exhibit outstanding cycle stability and rate performance with capacity retentions of 95.1% after 300 cycles and 76.5% at 10C against 1C, respectively.

Water-Deactivated Polyelectrolyte Hydrogel Electrolytes for Flexible High-Voltage Supercapacitors.

With the boom of flexible electronic products and wearable devices, flexible energy storage devices, for example, supercapacitors with high performance, are attracting increasing interest. A flexible water-deactivated polyelectrolyte hydrogel electrolyte with good mechanical properties and high ionic conductivity was prepared by using an anionic polymer, carboxy methyl cellulose, and a cationic monomer, methacrylamidopropyltrimethyl ammonium chloride. It was then applied in a supercapacitor with flexible activated carbon electrodes. This flexible supercapacitor possesses a high operating voltage of 2.1 V owing to the low electrochemical activity for water within the hydrogel as a result of the 'molecular cages' effect and hydrophilic interactions between functional groups and surrounding water molecules. Furthermore, this supercapacitor exhibits good flexibility and tailorability. As the first example of water-deactivated polyelectrolyte hydrogel electrolytes in applications involving flexible high-voltage supercapacitors, this work provides a platform for the design of energy storage devices with high energy density for flexible and wearable electronic devices.

Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.

OBJECTIVE: Leucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5) is a candidate marker for colorectal cancer stem cells (CSC). In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features. METHODS: The methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods. RESULTS: The lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169) were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05), as well as better prognosis (p = 0.001) in patients with colorectal cancer. CONCLUSIONS: Our data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.

Hydrophilic mesoporous carbon nanoparticles as carriers for sustained release of hydrophobic anti-cancer drugs.

The uniform mesoporous carbon nanoparticles (MCNs) with size below 200 nm and good water dispersibility were successfully synthesized via a combined hydrothermal synthesis and hard templating. The prepared MCNs served as effective carriers for camptothecin which efficiently inhibited the growth of MCF-7 cancer cells after its sustained release therein.

[Study on the relationship between metabolic syndrome and chronic kidney disease in 1027 patients of Han and Uyguer people].

OBJECTIVE: To investigate the relationship between metabolic syndrome and the chronic kidney disease in both Han and Uyguer populations. METHODS: 1027 cases were enrolled during 2006-3 to 2007-1 from the First Affiliated Hospital, Xinjiang University. According to the identification of chronic kidney disease (CKD) and minor renal dysfunction, these patients were divided into different groups. The correlation between the components of metabolic syndrome and CKD was examined. T test, Chi-square test and logistic regression were used. RESULTS: (1) CKD and mild CKD prevalence were 37.4% and 24.0% in all the cases. (2) The level of age, low-density lipoprotein cholesterol, trigly-caride, high-density lipoprotein cholesterol, uric acid in Han people were higher than those among Uyguer people while body mass index, systolic blood pressure and diastolic blood pressure were lower than those Uyguer people. (3) There were no significant differences found between Han and Uyguer people in different metabolic components. (4) In the group which had only one metabolic component disjunction, the diabetic group accounted for big proportion while in those patients with two or more metabolic component disfunction, hypertension and obesity were significantly high in Han people but diabetes plus obesity were seen in Uyguer people. (5) Diabetes, obesity, metabolic components, uric acid were independent factors associated with CKD and mild CKD. CONCLUSION: There were close connection between metabolic syndrome and CKD found in Xinjiang area.