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IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis

World Journal of Gastroenterology 2017年第3期23卷 447-454页

作者： Sarah Fischer Erzsébet Kovesdi Lili Magyari Veronika Csongei Kinga Hadzsiev béla melegh Péter Hegyi Patrícia Sarlós Division of Gastroenterology 1st Department of Internal MedicineUniversity of Pécs7624 PécsHungary Department of Medical Genetics University of Pécs7624 PécsHungary Szentágothai Research Centre 7624 PécsHungary Institute for Translational Medicine University of Pécs7624 PécsHungary

AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of *** We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association.

关键词： IL23R gene Ulcerative colitis Phenotype Polymorphism Hungarian

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Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

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World Journal of Gastroenterology 2010年第2期16卷 176-183页

作者： Veronika Csngei Luca Járomi EnikSáfrány Csilla Sipeky Lili Magyari bernadett Faragó Judit bene Noémi Polgár Lilla lakner Patrícia Sarlós Márta Varga béla melegh Department of Medical Genetics University of Pécs Department of Medicine and Gastroenterology Markusovszky Hospital 3rd Department of Internal Medicine University of Pécs 3rd Department of Medicine and Gastroenterology Réthy Pál Hospital

AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IbD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were *** and specific genotype combinations of a total of eight variants were *** variants of IbD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;Plammatory bowel disease (IbD)loci indicated that IL23R,ATG16L1,CARD15 and IbD5(IGR2198a_1)contribute independently to disease *** also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk *** almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one *** highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(Plative effect of individual IbD susceptibility loci.

关键词： Gene interaction Interleukin-23 receptor Autophagy-related 16-like 1 IbD5 Caspase recruitment domain-containing protein 15 Crohn’s disease Inflammatory bowel disease

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Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet

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World Journal of Gastroenterology 2005年第42期11卷 6671-6675页

作者： Judit bene Katalin Komlósi beáta Gasztonyi Márk Juhász Zsolt Tulassay béla melegh Department of Medical Genetics and Child Development School of Medicine University of Pécs Hungary MTA PTE Clinical Genetics Research Group of Hungarian Academy of Sciences at the University of Pécs Hungary Department of Medical Genetics and Child Development School of Medicine University of Pécs Hungary 1st Department of Medicine School of Medicine University of Pécs Hungary 2nd Department of Medicine Semmelweis University Budapest Hungary

AIM： To determine the fasting plasma carnitine ester in patients with celiac disease. METHODS： We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet. RESULTS： The level of free camibine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced （4.703± 0.205 vs 10.227 ± 0.368 nmol/mL, P〈0.01）. The level of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%, octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%, miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease patients compared to the control values, respectively （P〈0.01）. CONCLUSION： The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

关键词： Plasma carnitine ester profile Celiac disease

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Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis

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World Journal of Gastroenterology 2006年第1期12卷 110-113页

作者： Judit bene Katalin Komlósi Viktória Havasi Gábor Talián beáta Gasztonyi Krisztina Horváth Gyula Mózsik béla Hunyady béla melegh Mária Figler MTA PTE Clinical Genetics Research Group of Hungarian Academy of Sciences at the University of Pécs PécsHungary Department of Medical Genetics and Child DevelopmentUniversity of PécsPécsHungary Department of Medical Genetics and Child Development University of PécsPécsHungary Department of Medicine School of MedicineUniversity of PécsPécsHungary

AIM： To determine the plasma carnitine ester profile in adult patients with ulcerative culitis （UC） and compared with healthy control subjects. METHOD： Using ESI triple quadrupole tandem mass spectrometry, the carnitine ester profile was measured in 44 patients with UC and 44 age- and sex-matched healthy controls. RESULTS： There was no significant difference in the fasting free carnitine level between the patients with UC and the healthy controls. The fasting propionyl- （0.331 ± 0.019 vs 0.392 ± 0.017 μmol/L）, butyryl- （0.219 ± 0.014 vs 0.265 ± 0.012）, and isovalerylcarniUne （0.111 ± 0.008 vs 0.134 ± 0.008） levels were decreased in the UC patients. by contrast, the level of octanoyl- （0.147 ± 0.009 vs 0.114 ± 0.008）, decanoyl- （0.180 ± 0.012 vs 0.137 ± 0.008）, myristoyl- （0.048 ± 0.003 vs 0.039 ± 0.003）, palmitoyl- （0.128 ± 0.006 vs 0.109 ± 0.004）, palmitoleyl- （0.042±0.003 vs 0.031 ± 0.002） and oleylcarnitine （0.183 ± 0.007 vs 0.163 ± 0.007; P 〈 0.05 in all comparisons） were increased in the patients with UC. CONCLUSION： Our data suggest selective involvement of the carnitine esters in UC patients, probably due to their altered metabolism.

关键词： Carnitine Carnitine ester profile Ulcerativecolitis

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No association of the cytotoxic T-lymphocyte associated gene CTla4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

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World Journal of Gastroenterology 2007年第15期13卷 2205-2208页

作者： Lili Magyari bernadett Faragó Judit bene Katalin Horvatovich Lilla lakner Márta Varga Mária Figler beáta Gasztonyi Gyula Mózsik béla melegh Department of Medical Genetics and Child Development University of Pécs PécsHungary MTA PTE Clinical Genetics Research Group of the Hungarian Academy of Sciences at the University of Pécs Pécs Hungary Markusovszky Hospital Department of Medicine and Gastroenterology SzombathelyHungary Réthy Pál Hospital 3rd Department of Medicine and Gastroenterology BékéscsabaHungary Department of Medicine School of Medicine University of PécsPécsHungary Department of Gastroenterology Zala County Hospital ZalaegerszegHungary

AIM： The goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene （CTla4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）. METHODS： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （SNP）. The genotypes were determined by using PCR/RFLP test. RESULTS： The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION： The results of the current study show that carriage of the ＋49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

关键词： Cytotoxic T-lymphocyte antigen 4 Crohn's disease Ulcerative colitis Inflammatory bowel disease

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Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease

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World Journal of Gastroenterology 2006年第34期12卷 5550-5553页

作者： Judit bene Lili Magyari Gábor Talián Katalin Komlósi beáta Gasztonyi beáta Tari gnes Várkonyi Gyula Mózsik béla melegh MTA PTE Clinical Genetics Research Group of Hungarian Academy of Sciences at the University of Pécs Pécs Hungary Department of Medical Genetics and Child Development University of Pécs Pécs Hungary Department of Medical Genetics and Child Development University of Pécs Pécs Hungary 1~(st) Department of Medicine School of Medicine University of Pécs Pécs Hungary Department of Pediatrics and Child Health Center University of Szeged Szeged Hungary

AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METHODS： A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn＇s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants （Arg702Trp, Gly908Arg and 2007finsC changes） with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specific regions of these genes. RESULTS： At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profile was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls （9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls）. No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION： The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.

关键词： OCTN1 OCTN2 NOD2/CARD15 Crohn's disease

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Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary

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World Journal of Gastroenterology 2005年第48期11卷 7646-7650页

作者： Gyula Mózsik Gy(o|¨)rgy Rumi András D(o|¨)m(o|¨)t(o|¨)r Mária Figler beáta Gasztonyi El(?)d Papp Alajos Pár Gabriella Pár József belágyi Zoltán Matus béla melegh Department of Medicine Department of Human Clinical Nutrition and Dietetics Department of bioanalysis Department of biochemistry and Medical Chemistry Department of Medical Genetics and Child Development

AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver,pancreatic, and colorectal ***: The changes in serum levels of retinoids (vitamin A, α- and β-carotene, α- and β-cryptoxanthin,zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC)and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21including 9 patients suffering from in situ colon cancer)cancer. Fifty-seven healthy subjects (in matched groups)for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were ***: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of α- and β-carotene,α- and β-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI ***: Retinoids (as environmental factors)are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

关键词： Human gastrointestinal cancer Leiden mutation Retinoids Vitamin A Zeaxanthin

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How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1405-1406页

作者： Livia la barbera Paraskevi Krashia Annalisa Nobili Department of Medicine and Surgery UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly Department of Experimental Neurosciences IRCCS Santa Lucia FoundationVia del Fosso di FioranoRomeItaly Department of Science and Technology for Sustainable Development and One Health UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc *** is cha racterized by featured histological alterations including amyloid-beta (Ab) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

关键词： Alzheimer alterations dopamine

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Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João b.Relvas Institute of Research and Innovation in Health(i3S)and Institute for Molecular and Cell biology(IbMC) University of PortoPortoPortugal Department of biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

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Effect of a force-free end on the mechanical property of a biopolymer--A path integral approach

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Chinese Physics b 2016年第8期25卷 468-473页

作者：周子聪 bla Joós Department of Physics Tamkang University Ottawa Carleton Institute for Physics University of Ottawa Campus

We study the effect of a force-free end on the mechanical property of a stretched *** system can be divided into two *** first part consists of the segment counted from the fixed point（i.e.,the origin） to the forced point in the biopolymer,with arclength L_*** second part consists of the segment counted from the forced point to the force-free end with arclength △*** apply the path integral technique to find the relationship between these two *** finite temperature and without any constraint at the end,we show exactly that if we focus on the quantities related to the first part,then we can ignore the second part *** Carlo simulation confirms this *** contrast,the effect for the quantities related to the second part is dependent on what we want to observe.A force-free end has little effect on the relative extension,but it affects seriously the value of the end-to-end distance if △L is comparable to L_f.

关键词： statistical physics path integral biopolymers mechanical property

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