Identification of biomarkers for the diagnosis and treatment of primary colorectal cancer based on microarray technology.

BACKGROUND: Primary colorectal cancer (PCRC) is one of the most common malignant tumors in clinic, and is characterized by high heterogeneity occurring between tumors and intracellularly. Therefore, this study aimed to explore potential gene targets for the diagnosis and treatment of PCRC via bioinformatic technology. METHODS: Gene Expression Omnibus (GEO) was used to download the data used in this study. Differently expressed genes (DEGs) were identified with GEO2R, and the gene set enrichment analysis (GSEA) was implemented for enrichment analysis. Then, the researchers constructed a protein-protein interaction (PPI) network, a significant module, and a hub genes network. RESULTS: The GSE81558 dataset was downloaded, and a total of 97 DEGs were found. There were 23 up-regulated DEGs and 74 down-regulated DEGs in the PCRC samples, compared with the control group. The PPI network included a total of 42 nodes and 63 edges. One module network consisted of 11 nodes and 25 edges. Another module network consisted of 4 nodes and 6 edges. The hub genes network was created by cytoHubba using GCG, GUCA2B, CLCA4, ZG16, TMIGD1, GUCA2A, CHGA, PYY, SST, and MS4A12. CONCLUSIONS: Ten hub genes were found from the genomic samples of patients with PCRC and normal controls by bioinformatics analysis. The hub genes might provide novel ideas and evidence for the diagnosis and targeted therapy of PCRC.

DNA methylation analysis of murine hematopoietic side population cells during aging.

Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematopoiesis as a model system. Hematopoietic stem cells (HSCs) were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged and old mice and subjected to comprehensive, global methylome (MeDIP-seq) analysis. With age, we observed a global loss of DNA methylation of approximately 5%, but an increase in methylation at some CpG islands. Just over 100 significant (FDR<0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. Interestingly, the polycomb repressive complex -2 (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. This occurred concurrently with an increase in gene expression with age. To explore this relationship further, we cultured isolated SP-HSC in the presence of 5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter methylation and gene expression. We report that DNA methylation patterns are well preserved during hematopoietic stem cell aging, confirm that PCRC2 targets are increasingly methylated with age, and suggest that SDPR expression changes with age in HSCs may be regulated via age-based alterations in DNA methylation.

Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs.

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 microg/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K(+) (56 mM), DMPP (100 microM) and McN-A-343 (100 microM). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 microg/ml), the CA secretory responses to veratridine (a selective Na(+) channel activator (10 microM), Bay-K-8644 (a L-type dihydropyridine Ca(2+) channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca(2+) -ATPase inhibitor, 10 microM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microg/ml) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K(+), DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 microg/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca(2+) release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.

Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 microgram/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 micrometer) and McN-A-343 (100 micrometer). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 microgram/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 micrometer), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 micrometer) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microgram/ml) and L-NAME (an inhibitor of NO synthase, 30 micrometer), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 microgram/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.