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| 1 | Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors显示文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC. | Orsolya Galamb Barbara K Barták Alexandra Kalmár Zsófia B Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz Béla Molnár | 2019 | World Journal of Gastroenterology2019，25，34： | 18 |
| 2 | Changes of the cytokine profile in inflammatory bowel diseases显示文摘Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut homeostasis.An imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases(IBD).Although Crohn's disease(CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis(UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been changed.The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings.None the less there are many common immunological responses in IBD that are mediated by cytokines.Although they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease.Our aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD.The better understanding of their production and functional activity may lead to the development of new therapeutic modalities. | Gyrgyi Mzes Béla Molnár Zsolt Tulassay Ferenc Sipos | 2012 | World Journal of Gastroenterology2012，18，41： | 16 |
| 3 | Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects显示文摘Toll-like receptors (TLRs) recognize specific motifs which are frequently present in bacteria, fungi, prokaryotes and viruses. Amongst TLRs, TLR9 can be activated by such bacterial or viral DNA fragments, immunoglobulin-DNA complexes or synthetic oligonucleotides, which all contain unmethylated cytosineguanine nucleotide sequences (CpGs). Emerging data indicate that TLR9 signaling has a role in, and may influence, colorectal carcinogenesis and colonic inflammation. CpGs are classified into three groups according to their influence on both the antigen-specific humoraland cellular immunity, and the production of type 1 interferons and proinflammatory cytokines. TLR9 activation via CpGs may serve as a new therapeutic target for several cancerous and various inflammatory conditions. Due to its probable anti-cancer effects, the application possibilities of TLR9-signaling modulation may be extremely diverse even in colorectal tumors. In this review we aimed to summarize the current knowledge about TLR-signaling in the pathogenesis and therapy of inflammatory bowel diseases and colorectal cancer. Due to the species-specific differences in TLR9 expression, however, one must be careful in translating the animal model data into the human system, because of the differences between CpG-oligodeoxynucleotide-responsive cells. TLR9 agonist DNA-based immunomodulatory sequences could also represent a promising therapeutic alternative in systemic inflammatory conditions and chronic colonic inflammations as their side effects are not significant. | István Fri Ferenc Sipos Tiana M Germann Alexandra Kalmár Zsolt Tulassay Béla Molnár Gyrgyi Mzes | 2013 | World Journal of Gastroenterology2013，19，26： | 14 |
| 4 | 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 |
| 5 | Regulatory T cells in inflammatory bowel diseases and colorectal cancer显示文摘Regulatory T cells(T regs) are key elements in immunological self-tolerance.The number of T regs may alter in both peripheral blood and in colonic mucosa during pathological circumstances.The local cellular,microbiological and cytokine milieu affect immunophenotype and function of T regs.Forkhead box P3+ T regs function shows altered properties in inflammatory bowel diseases(IBDs).This alteration of T regs function can furthermore be observed between Crohn's disease and ulcerative colitis,which may have both clinical and therapeutical consequences.Chronic mucosal inflammation may also influence T regs function,which together with the intestinal bacterial flora seem to have a supporting role in colitis-associated colorectal carcinogenesis.T regs have a crucial role in the immunoevasion of cancer cells in sporadic colorectal cancer.Furthermore,their number and phenotype correlate closely with the clinical outcome of the disease,even if their contribution to carcinogenesis has previously been controversial.Despite knowledge of the clinical relationship between IBD and colitis-associated colon cancer,and the growing number of immunological aspects encompassing sporadic colorectal carcinogenesis,the molecular and cellular links amongst T regs,regulation of the inflammation,and cancer development are still not well understood.In this paper,we aimed to review the current data surrounding the role of T regs in the pathogenesis of IBD,colitis-associated colon cancer and sporadic colorectal cancer. | Gyrgyi Mzes Béla Molnár Ferenc Sipos | 2012 | World Journal of Gastroenterology2012，18，40： | 7 |
| 6 | Clinical significance of granuloma in Crohn's disease显示文摘AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this studywas to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course.METHODS: Fifty-six patients with newly diagnosed Cdwere included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted.RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD. | Tamás Molnár László Tiszlavicz Csaba Gyulai Ferenc Nagy János Lonovics | 2005 | World Journal of Gastroenterology2005，11，20： | 5 |
| 7 | 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 |
| 8 | Serrated pathway:Alternative route to colorectal cancer显示文摘Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before,a growing body of literature indicates that these polyps can be precursors of colorectal cancer(CRC).Most of these lesions, particularly those in the proximal colon,have so far been under-recognized and missed during colonoscopy,qualifying these lesions to be the main cause of interval cancers.It is estimated that 10%-20%of CRCs evolve through this alternative,serrated pathway, with a distinct genetic and epigenetic profile.Aberrant DNA methylation plays a central role in the development of this CRC subtype.This characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional pathway.In this review we would like to highlight morphological,molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice. | rpád V Patai Béla Molnár Zsolt Tulassay Ferenc Sipos | 2013 | World Journal of Gastroenterology2013，19，5： | 4 |
| 9 | Characteristics of allergic colitis in breast-fed infants in the absence of cow's milk allergy显示文摘AIM: To investigate the characteristics of mucosal le-sions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. METHODS: In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimi-nation diet for cow's milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as con-trols. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with differ-ent nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. RESULTS: Iron deficiency, peripheral eosinophilia andthrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4±3.2 μmol/L vs 13.7±4.7 μmol/L, P<0.001; 0.67±0.49 G/L vs 0.33±0.17 G/L, P<0.001; 474±123 G/L vs 376±89 G/L, P<0.001, respectively). At colonosco-py, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 contin-ued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when com-pared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients ex-hibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessa-tion of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. CONCLUSION: Infant hematochezia, after cow's milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnor-mality. Formula feeding results in shorter time to cessa-tion of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia. | Kriszta Molnár Petra Pintér Hajnalka Gyrffy ron Cseh Katalin Eszter Müller András Arató Gábor Veres | 2013 | World Journal of Gastroenterology2013，19，24： | 3 |
| 10 | The potential application of red mud and soil mixture as additive to the surface layer of a landfill cover system显示文摘Red mud, the by-product of aluminum production, has been regarded as a problematic residue all over the world. Its storage involves risks as evidenced by the Ajka red mud spill,an accident in Hungary where the slurry broke free, flooding the surrounding areas. As an immediate remediation measure more than 5 cm thick red mud layer was removed from the flooded soil surface. The removed red mud and soil mixture(RMSM) was transferred into the reservoirs for storage. In this paper the application of RMSM is evaluated in a field study aiming at re-utilizing waste, decreasing cost of waste disposal and providing a value-added product. The purpose was to investigate the applicability of RMSM as surface layer component of landfill cover systems. The field study was carried out in two steps: in lysimeters and in field plots. The RMSM was mixed at ratios ranging between 0 and 50% w/w with low quality subsoil(LQS) originally used as surface layer of an interim landfill cover. The characteristics of the LQS + RMSM mixtures compared to the subsoil(LQS) and the RMSM were determined by physical–chemical, biological and ecotoxicological methods. The addition of RMSM to the subsoil(LQS) at up to 20% did not result any ecotoxic effect, but it increased the water holding capacity. In addition, the microbial substrate utilization became about triple of subsoil(LQS) after 10 months. According to our results the RMSM mixed into subsoil(LQS) at20% w/w dose may be applied as surface layer of landfill cover systems. | Eva Ujaczki Viktória Feigl Mónika Molnár Emese Vaszita Nikolett Uzinger Attila Erdélyi Katalin Gruiz | 2016 | Journal of Environmental Sciences2016，28，6： | 3 |
| 11 | Visco-plastic self-consistent modelling of a grain boundary misorientation distribution after equal-channel angular pressing in an AZ31 magnesium alloy显示文摘 | A. Ostapovets P. Molnár A. J?ger | 2013 | Journal of Materials Science2013，，5： | 2 |
| 12 | Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy显示文摘AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped. | Klaudia Farkas Péter László Lakatos Mónika Szcs va Pallagi-Kunstár Anita Bálint Ferenc Nagy Zoltán Szepes Noémi Vass Lajos S Kiss Tibor Wittmann Tamás Molnár | 2014 | World Journal of Gastroenterology2014，20，11： | 2 |
| 13 | Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease显示文摘AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients. | Ferenc Nagy Tamás Molnár Zoltán Szepes Klaudia Farkas Tibor Nyári János Lonovics | 2008 | World Journal of Gastroenterology2008，14，27： | 2 |
| 14 | Elevated insulin-like growth factor 1 receptor, hepatocyte growth factor receptor and telomerase protein expression in mild ulcerative colitis显示文摘 | Ferenc Sipos Orsolya Galamb László Herszényi Béla Molnár Norbert Solymosi Tamás Zágoni Lajos Berczi Zsolt Tulassay | 2008 | Scandinavian Journal of Gastroenterology2008，，3： | 2 |
| 15 | Study of humic-like substances in fog and interstitial aerosol by size-exclusion chromatography and capillary electrophoresis显示文摘 | Z Krivácsy Gy Kiss B Varga I Galambos Zs Sárvári A Gelencsér á Molnár S Fuzzi M.C Facchini S Zappoli A Andracchio T Alsberg H.C Hansson L Persson | 2000 | Atmospheric Environment2000，，25： | 1 |
| 16 | An unusual association:anti-Jol and anti-SRP antibodies in the serum of a patient with polymyositis显示文摘 | Vincze M Molnár PA Tumpek J | 2010 | Clin Rheumatol2010，29，： | 1 |
| 17 | Morphological and genetic differences among actinosporean stages of fish-parasitic myxosporeans (Myxozoa): difficulties of species identification显示文摘 | Edit Eszterbauer Szilvia Marton Orsolya Z. Rácz Márta Letenyei Kálmán Molnár | 2006 | Systematic Parasitology2006，，2： | 1 |
| 18 | Social force model for pedestrian dynamics显示文摘 | Helbing D MoLnr P | 1995 | Physical Review E1995，，51： | 1 |
| 19 | ASPP2 Binds Par-3 and Controls the Polarity and Proliferation of Neural Progenitors during CNS Development显示文摘 | Roberta Sottocornola Christophe Royer Virginie Vives Luca Tordella Shan Zhong Yihua Wang Indrika Ratnayaka Mark Shipman Amanda Cheung Carles Gaston-Massuet Patrizia Ferretti Zoltán Molnár Xin Lu | 2010 | Developmental Cell2010，，1： | 1 |
| 20 | Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase显示文摘 | Aparicio J F Moln~ir I Schwecke T | 1996 | Gene1996，169，： | 1 |
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