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| 1 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 2 | Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease显示文摘AIM:To investigate intestinal alkaline phosphatase(iAP) in the intestinal mucosa of children with inflammatory bowel disease(IBD).METHODS:Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls.In IBD patients,specimens were obtainedboth from inflamed and non-inflamed areas.The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis,respectively.Tissue localization of iAP and Toll-like receptor(TLR) 4 was investigated by immunofluorescent staining.RESULTS:The iAP protein level in the inflamed mucosa of children with Crohn's disease(CD) and ulcerative colitis(UC) was significantly decreased when compared with controls(both P < 0.05).Similarly,we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD(P < 0.05).In addition,the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD(P < 0.05).iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls.iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD.Expression of iAP mRNA in patients with noninflamed mucosa and in controls were similar.Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern.iAP was present in the inflamed and non-inflamed mucosa of patients with CD,UC,and in control biopsy specimens,irrespective of whether it was present in the terminal ileum or in the colon.However,the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied.CONCLUSION:Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD.Based on our results,administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option. | Kriszta Molnár dám Vannay Beáta Szebeni Nóra Fanni Bánki Erna Sziksz ron Cseh Hajnalka Gyrffy Péter László Lakatos Mária Papp András Arató Gábor Veres | 2012 | World Journal of Gastroenterology2012，18，25： | 5 |
| 3 | Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease显示文摘AIM: To evaluate the role of micro RNA(mi R)-146 a,-155 and-122 in the duodenal mucosa of pediatric patients with Crohn's disease(CD) and the effect of transforming growth factor-β(TGF-β) on these mi Rs in duodenal epithelial and fibroblast cells.METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed(CD inflamed: n = 10) and intact(CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children(C: n = 10) were examined. Expression of mi R-146 a,-155 and-122 was determined by realtime polymerase-chain reaction(PCR). The expression of the above mi Rs was investigated in recombinant human TGF-β(1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells(CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS: Expression of mi R-146 a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD(CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, p ≤ 0.01) and to the control group(CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, p ≤ 0.05). The expression of mi R-155 was significantly increased in the inflamed region of the duodenum compared to the control group(CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, p ≤ 0.001). The expression of mi R-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of mi R-155 in small intestinal epithelial cells(TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, p ≤ 0.05) and also the expression of mi R-146a(TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, p ≤ 0.01) and mi R-155(TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, p ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of mi R-122.CONCLUSION: The elevated expression of mi R-146 a and-155 in the inflamed duodenal mucosa of CD patients suggests the role of these mi Rs in the pathomechanism of inflammatory bowel disease. Antiinflammatory TGF-β plays an important role in the regulation of the expression of these mi Rs. | Dániel Szucs Nóra Judit Béres Réka Rokonay Kriszta Boros Katalin Borka Zoltán Kiss András Arató Attila J Szabó ádám Vannay Erna Sziksz Csaba Bereczki Gábor Veres | 2016 | World Journal of Gastroenterology2016，22，26： | 2 |
| 4 | In vitro anti-diabetic activity and chemical characterization of an apolar fraction of Morus alba leaf water extract 显示文摘 | Hunyadi A Veres K Danko B | 2013 | Phytother Res2013，27，6： | 1 |
| 5 | Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease 显示文摘 | SZEBENI B VERES G DEZSOFI A | 2008 | Clin Exp Immunol2008，151，1： | 1 |
| 6 | Regulation of kinase cascades and transcription factors by a poly (ADP-Ribose) polymerase-1 inhibitor,4-hydroxyquinazoline,in lipopolysaccharide-Induced inflammation in mice显示文摘 | Veres B Radnai B Gallyas F | 2004 | Pharmacol Exp Ther2004，310，1： | 1 |
| 7 | Beta-adrenoceptor modulation and heart rate variability-the value of scatter plot measures of compactness显示文摘 | Silke B Hanratty CG Veres SM | 2000 | Cardiovas-Drugs-ther2000，14，4： | 1 |
| 8 | Caspase-mediated cleacage converts llvin from an antiapoptotic to a proapoptotlc factor: implications for drug-resistant melanoma 显示文摘 | BOAZ N YUQOUB A VERED B | 2003 | Cancer Res2003，63，10： | 1 |
| 9 | Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease 显示文摘 | Szebeni B Veres G Dezsofi A | 2007 | Clin Exp lmmunol2007，151，： | 1 |
| 10 | Feasibility of mitral flow assessment by echo-contrast ultrasound, part 1: determination of the properties of echo-contrast agents显示文摘 | Herman B Einav S Vered Z | 2000 | Uhrasound Med Biol2000，26，5： | 1 |
| 11 | Feasibility of mitral flow as-sessment by echo-contrast ultrasound,part II:experimental study on a mechanical model of the left heart显示文摘 | Herman B Einav S Vered Z | 2000 | Ultra-sound Med Biol2000，26，5： | 1 |
| 12 | Increased expression of Toll-like receptor TLR2 and TLR4 in the colonic mucosa显示文摘 | Szebeni B Veres G Dezsofi A eta/ | 2007 | Clin Exp interleukin-17 aggravates dextran sulfate immunol2007，151，1： | 1 |
| 13 | Increased expression of Toll-like receptor(TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease显示文摘 | SZEBENI B VERES G DEZSOFI A | 2008 | Clin Exp Immunol2008，151，： | 1 |
| 14 | Regulation of kinase cascades and transcription factors by a Poly(ADP-Ribose) polymerase-1 inhibitor, 4-Hydroxyquinazoline, in lipopolysaccharide-Induced inflammation in mice 显示文摘 | Veres B Radnai B Gallyas F | 2004 | JPET2004，310，1： | 1 |
| 15 | Feasibility of mitral flow assessment by echo-contrast ultrasound, part Ⅱ: experimental study on a mechanical model of the left heart显示文摘 | Herman B Einav S Vered Z | 2000 | Ultrasound Med Biol2000，26，5： | 1 |
| 16 | Direct effect of Taxol on free radical formation and mitochondfial permeability transition 显示文摘 | Varbiro G Veres B Gallyas F | 2001 | Free Radic Biol Med2001，31，4： | 1 |
| 17 | Universal adaptive control of satellite formation flying显示文摘 | Pongvthithum R Veres S M Gabriel S B Rogers E | 2005 | International Journal of Control2005，78，1： | 1 |
| 18 | Direct effect of Taxol on free radical formation and mitochondrial permeability transition显示文摘 | Varbiro G Veres B Gallyas FJ | 2001 | Free Radic Biol Med2001，31，4： | 1 |
| 19 | Easpase-mediated cleavage converts livin from an antiapoptotic to a proapoptotic factor:implications for drug-resistant melanoma显示文摘 | Boaz N Yaqoub A Vered B | 2003 | Cancer Res2003，63，10： | 1 |
| 20 | Fabrication of metal nanoring array by nanoimprint lithography (NLL) and reactive ion etching 显示文摘 | Cui B Veres T | 2007 | Mieroelectronic Engineering2007，84，5： | 1 |
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