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| 1 | CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells显示文摘AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC. | János P Kósa Péter Horváth János Wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos | 2013 | World Journal of Gastroenterology2013，19，17： | 5 |
| 2 | Alleviated mucosal and neuronal damage in a rat model of Crohn's disease显示文摘AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimicked by repeating administrations of TNBS.Tissue samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation.The means of the ulcerated area were measured to evaluate the macroscopic mu-cosal damage.The density of myenteric neurons was determined on whole mounts by Hu C/Hu D immunohistochemistry.Heme oxygenase-1(HO-1)expression was evaluated by molecular biological techniques.RESULTS:TNBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental period.The widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration.After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed area.HO-1 m RNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined.Nevertheless,the HO-1protein up-regulation after the second TNBS treatment proved to be transient.Following the third treatment HO-1 protein expression could not be detected.CONCLUSION:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage.The persistent up-regulation of HO-1 m RNA expression may correlate with this. | Petra Talapka Lajos István Nagy Alexandra Pál Marietta Zita Poles Anikó Berkó Mária Bagyánszki László Géza Puskás éva Fekete Nikolett Bódi | 2014 | World Journal of Gastroenterology2014，20，44： | 3 |
| 3 | Structural and molecular features of intestinal strictures in rats with Crohn's-like disease显示文摘AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease(CD).METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid(TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9(MMP9) and TIMP1 m RNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells(SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The m RNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation. | Petra Talapka Anikó Berkó Lajos István Nagy Lalitha Chandrakumar Mária Bagyánszki László Géza Puskás éva Fekete Nikolett Bódi | 2016 | World Journal of Gastroenterology2016，22，22： | 3 |
| 4 | Enterotoxigenic Escherichia coli, rotavirus, porcine epidemic diarrhoea virus, adenovirus and calici-like virus in porcine postweaning diarrhoea in Hungary 显示文摘 | NAGY B NAGY G MEDER M | 1996 | Acta Vet Hung1996，44，1： | 1 |
| 5 | Molecular analysis of germline t( 3 ;6) and t( 3 ; 12) associated with convention- al renal cell carcinomas indicates their rate - limiting role and supports the three - hit model of carcinogenesis 显示文摘 | Yusenko M V Nagy A Kovacs G | 2010 | Cancer genetics and cytogenetics2010，201，1： | 1 |
| 6 | Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved显示文摘 | Massenkeil G Nagy M Lawang M | 2003 | Bone MarrowTransplant2003，31，5： | 1 |
| 7 | Enterotoxigenic Escherichia coli,rotavirus,porcine epidemic diarrhoea virus,adenovirus and calici-like virus in porcine postweaning diarrhoea in Hungary显示文摘 | Nagy B Nagy G Meder M | 1996 | Acta Vet Hung1996，44，1： | 1 |
| 8 | Treatment of pituitary tumors显示文摘 | Gabriella Iván Nikoletta Szigeti-Csúcs Márk Oláh Cy?rgy M. Nagy Miklós I. Góth | 2005 | Endocrine2005，，1： | 1 |
| 9 | Aluminous cements containing magnesium aluminate spinel from Egyptian dolomite 显示文摘 | NAGY M A EL-HEMALY S A S LAMEY G G | 2001 | Ceram Int2001，27，： | 1 |
| 10 | High organic carbon stock in a karstic soil of the Middle-European Forest Province persists after centuries-long agroforestry management显示文摘 | Yousif Abdel-Rahman Ahmed Viliam Pichler Marián Homolák Erika G?m?ryová Dezs? Nagy Magdaléna Pichlerová Juraj Gregor | 2012 | European Journal of Forest Research2012，，6： | 1 |
| 11 | Prepared- ness and cognitive legitimacy as antecedents of new venture funding显示文摘 | Pollack J M Rutherford M W Nagy B G | 2012 | Entrepreneurship Theory and Prac- tice2012，36，5： | 1 |
| 12 | Enterotoxigenic Escherichia coil, rotavirus, porcine epidemic diarrhoea virus, adenvirus and calici-like vixus in porcine postweaning diarrhoea in Hungary 显示文摘 | Nagy B Nagy G Meder M | 1996 | Acta Vet hung1996，44，1： | 1 |
| 13 | Light-dependent induction of proline biosynthesis by abscisic acid and salt stress is inhibited by brassinosteroid in Arabidopsis显示文摘 | Edit ábrahám Gábor Rigó Gy?ngyi Székely Réka Nagy Csaba Koncz László Szabados | 2003 | Plant Molecular Biology2003，，3： | 1 |
| 14 | Genome sequence and analysis of the tuber crop potato显示文摘 | Xu X Pan S Cheng S Zhang B Mu D Ni P Zhang G Yang S Li R Wang J Orjeda G Guzman F Tones M Lnzano R Ponce O Martinez D De la Cruz G Chakrabarti S K Patil V U Skryabin K G Kuznetsov B B Ravin N V Kolganova T V Beletsky A V Mardanov A V Di Genova A Bolser D M Martin D M Li G Yang Y Kuang H Hu Q Xiong X Bishop G J Sagredo B Mejia N Zagorski W Gromadka R Gawor J Szczesny P Huang S Zhang Z Liang C He J Li Y He Y Xu J Zhang Y Xie B Du Y Qu D Bonierbale M Ghislain M Herrera Mdel R Giuliano G Pietrella M Perrotta G Faeella P O 'Brien K Feingold S E Barreiro L E Massa G A Diambra L Whitty B R Vaillancourt B Lin H Massa A N Geoffroy M Lundback S DellaPenna D Buell C R Sharma S K Marshall D F Waugh R Bryan G J Destefanis M Nagy I Milbourne D Thomson S J Fiefs M Jacobs J M Nielsen K L Sonderkaer M Iovene M Tortes G A Jiang J Veilleux R E Bachem C W de Boer J Bonn T Kloosterman B van Eck H Datema E Hekkert B Goverse A van Ham R C Visser R G | 2011 | Nature2011，475，7355： | 1 |
| 15 | Zironium oxide/sulfate catalyzed nitration of aromatic compounds 显示文摘 | Nagi S M Zubkov E A Shubin V G | 1990 | Izv Akad Nauk SSSr Ser Khim1990，，7： | 1 |
| 16 | Changes in cognitive function in patients with diabetes mellitus显示文摘 | Szémán B Nagy G Varga T | | 0，，09： | 1 |
| 17 | A prototype document image analysis system for technical journals显示文摘 | S Seth M Viswanathan | 1992 | IEEE Computer1992，25，7： | 1 |
| 18 | Structure,distributionand function of wax ester in Acinetobacter calcoaceticus显示文摘 | FIXTER L M NAGI M N MCCORMACK J G | 1986 | Journal of Gen-eral Microbiology1986，132，11： | 1 |
| 19 | Dopamine-derived sal- solinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains 显示文摘 | NAOI M MARUYAMA W NAGY G M | 2004 | Neuro- toxicology2004，25，12： | 1 |
| 20 | Visual receptive field properties of neurons in the caudate nucleus 显示文摘 | Nagy A Eordegh G Norita M | 2003 | Eur J Neurosci2003，18，2： | 1 |
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