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Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release

Journal of Environmental Sciences 2015年第8期27卷 165-170页

作者： zsolt molnár regina Pálf?ldi Anna László Marianna radács Krisztián Sepp Péter Hausinger László Tiszlavicz Zsuzsanna Valkusz Márta Gálfi Institute of Applied Science Department of Environmental Biology and Education Gyula Juhász Faculty of Education University of Szeged Department of Pulmonology Faculty of Medicine University of Szeged Department of Medical Physics and Informatics Faculty of Medicine University of Szeged Endocrine Unit of First Department of Internal Medicine Faculty of Medicine University of Szeged Invasive Cardiology Department Second Department of Internal Medicine and Cardiology Faculty of Medicine University of Szeged Department of Pathology Faculty of Medicine University of Szeged

Many environmental chemicals and pesticides have been found to alter neuroendocrine communication in exposed biological objects. The environmental loads have primary and secondary effects that can alter the homeostatic regulation potential. Since it is difficult to avoid human exposition, a potentially important area of research to develop in vivo and in vitro experimental models. In this context, the primary aim of this study was to demonstrate the effects of chlorobenzenes on adrenocorticotrophic hormone（ACTH） release. In our experimental study, male Wistar rats were exposed to 0.1, 1.0 and 10 μg/b.w.（body weight） kg of 1,2,4-trichlorobenzene and hexachlorobenzene（Cl B） mix via gastric tube for 30, 60 or 90 days. At the endpoints of the experiment blood samples were taken and animals were decapitated. Primary,monolayer adenohypophysis cell cultures were prepared by enzymatic and mechanical digestion. The ACTH hormone content in serum and supernatant media was measured by immuno-chemiluminescence assay. The Mg2＋-dependent ATPase activity was determined by modified method of Martin and Dotty. Significant differences were detected in the hormone release between the control and treated groups. The hormone release was enhanced characteristically in exposed groups depending upon the dose and duration of exposure. The Mg2＋-ATPase activity enhanced after chronic and subtoxic Cl B exposition. Light microscopy revealed that the adenohypophysis seemed to be more abundant. results indicate that Wistar rats exposed to subtoxic Cl B have direct and indirect effects on hypothalamus–hypophysis–adrenal axis.

关键词： Chlorobenzenes Subtoxic Adrenocorticotrophic hormone release Mg2+ -dependent ATPase

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Changes of the cytokine profile in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第41期18卷 5848-5861页

作者： Gyrgyi Mzes Béla molnár zsolt Tulassay Ferenc Sipos 2nd Department of Internal Medicine Semmelweis University1088 BudapestHungary Molecular Medicine research Unit Hungarian Academy of Sciences1051 BudapestHungary

Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut *** 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 *** inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological *** the less there are many common immunological responses in IBD that are mediated by *** 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 *** 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 *** better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

关键词： Ulcerative colitis Crohn's disease Interleu-kin-33 Tumor necrosis factor-like factor Interleukin-8 Interleukin-35 Interleukin-25 Interleukin-4 Tumornecrosis factor ligand superfamily member 14

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Serrated pathway:Alternative route to colorectal cancer

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World Journal of Gastroenterology 2013年第5期19卷 607-615页

作者： rpád V Patai Béla molnár zsolt Tulassay Ferenc Sipos 2~(nd )Department of Internal Medicine Semmelweis University1088 BudapestHungary Molecular Medicine research Group Hungarian Academy of Sciences1051 BudapestHungary

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 *** is estimated that 10%-20%of CrCs evolve through this alternative,serrated pathway, with a distinct genetic and epigenetic *** DNA methylation plays a central role in the development of this CrC *** characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional *** 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.

关键词： Serrated pathway DNA methylation Hyperplastic polyps Serrated adenomas Colorectal cancer Endoscopic surveillance

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Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects

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World Journal of Gastroenterology 2013年第26期19卷 4119-4126页

作者： István Fri Ferenc Sipos Tiana M Germann Alexandra Kalmár zsolt Tulassay Béla molnár Gyrgyi Mzes 2nd Department of Internal Medicine Semmelweis University Faculty of Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

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.

关键词： Toll-like receptor 9 Synthetic oligodeoxy-nucleotide sequences DNA-based immunomodulatory sequences Colorectal cancer Inflammatory bowel diseases

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Diagnostic and prognostic potential of tissue and circulating long non-coding rNAs in colorectal tumors

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World Journal of Gastroenterology 2019年第34期25卷 5026-5048页

作者： Orsolya Galamb Barbara K Barták Alexandra Kalmár Zsófia B Nagy Krisztina A Szigeti zsolt Tulassay Peter Igaz Béla molnár Molecular Medicine research Group Hungarian Academy of SciencesBudapest H-1088Hungary 2nd Department of Internal Medicine Semmelweis UniversityBudapest H-1088Hungary

Long non-coding rNAs(lncrNAs)are members of the non-protein coding rNA family longer than 200 *** 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 *** 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 *** 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 *** review article aims to describe the origin,structure,and functions of lncrNAs and to discuss their contribution to CrC ***,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.

关键词： Long non-coding rNA Colorectal cancer Colorectal adenoma Circulating long non-coding rNAs Exosome Biomarker Diagnostic marker Prognostic marker

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Genetic background of phenotypic variation

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Progress in Natural Science:Materials International 2007年第10期17卷 1119-1126页

作者： zsolt Boldogki Department of Biology Faculty of Medicine University of Szeged Somogyi Bela st. 4 H-6720 Szeged Hungary

A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polymorphism in the overall gene expression profiles of gene networks. In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

关键词： evolution gene network gene regulation genetic variance phenotype variation.

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World Journal of Gastroenterology 2016年第47期22卷 10325-10340页

作者： Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres zsolt Tulassay Béla molnár Molecular Medicine research Group Hungarian Academy of Sciences 2~(nd) Department of Internal Medicine Semmelweis University 1~(st) Department of Paediatrics Semmelweis University

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 *** 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 rmal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFrP1, SYNE1 and hypomethylated CEMIP, SPATA18(P rM 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 rP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P rrelated with significantly increased S

关键词： DNA methylation Aging Colorectal cancer Adenoma Epigenetic drift Epigenetic clock Secreted frizzled related protein 1

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Formability Investigations of High-Strength Dual-Phase Steels

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Acta Metallurgica Sinica(English Letters) 2015年第12期28卷 1471-1481页

作者： Miklós Tisza zsolt Lukács Department of Materials Processing Technology Institute of Materials Science and Technology University of Miskolc

Car manufacturing is always regarded as the key industry behind sheet metal forming, and thus, the requirements of and developments in car manufacturing play a decisive role in the development of sheet metal forming. The automotive industry is faced with contradictory demands and requirements： better performance with lower consumption and less harmful emissions, more safety and comfort; these are extremely difficult to supply simultaneously with conventional materials and conventional manufacturing processes. The fulfillment of these often contradictory requirements is one of the main driving forces in the automotive industry and thus in the material and process developments in sheet metal forming, as well. In recent years, significant developments can be observed in the application of high-strength steels. In this respect, the application of various dual-phase steels is one of the best examples. However, the application of these highstrength steels often leads to formability and manufacturing problems. One formability problem is the springback occurring after sheet metal forming. In the current research, we have dealt mainly with advanced high-strength steels, primarily with dual-phase steels. When applying them, the springback phenomenon is one of the most critical issues. To reduce the tremendous amount of experimental work needed, we also applied numerical simulation using isotropic–kinematic hardening rules. The isotropic–kinematic hardening behavior of a given material in the applied Auto Form numerical package may be characterized with three independent material parameters c, v and K（a detailed explanation of their meaning will be given in the main part of this paper）. However, we found that the material data included in simulation packages for these new high-strength steels are not fully adequate. For the determination of more reliable material parameters and to achieve better simulation results, a new testing device was developed. Numerical simulations were

关键词： Springback Large-strain cyclic deformation High-strength dual-phase steels

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Iterative signal reconstruction of deliberately clipped SMT signals

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Science China(Information Sciences) 2014年第2期57卷 5-17页

作者： KOLLr zsolt GAZDA Juraj HOrVTH Pter VArGA Lajos KOCUr Duan Budapest University of Technology and Economics Technical University of Koice

Staggered MultiTone(SMT)is a modulation technique showing significantly reduced Adjacent Channel Leakage ratio(ACLr)resulting in a more compact Power Spectrum Density(PSD)for the transmitted signal,than the well-known and already widely adopted Orthogonal Frequency Division Multiple Access(OFDMA)***,the unique spectral properties of an SMT signal could be degraded by a non-linear element(e.g.a Power Amplifier(PA))in the *** baseband clipping can be applied to the transmitted signal,reducing the notable high Peak-to-Average Power ratio(PAPr).The objective of this paper is to give a brief introduction to the SMT scheme,with a special emphasis on deliberate clipping efects and their *** paper introduces two receiver-oriented iterative methods aiming at the restoration of the baseband Bit Error rate(BEr)performance of a non-clipped *** methods are evaluated and compared based on numerical *** paper concludes with the selection of a possible candidate for use in systems applying deliberately clipped SMT signals.

关键词： clipping SMT iterative decoding nonlinear distortion PAPr

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Effect of ageing on colonic mucosal regeneration

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World Journal of Gastroenterology 2011年第25期17卷 2981-2986页

作者： Ferenc Sipos Katalin Leiszter zsolt Tulassay 2nd Department of Internal Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the *** the one hand,age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation,which results in epithelial *** the other hand,the altered migration and function of regenerative stem cells,the age-related methylation of mucosal healing-associated genes,together with the alterations of growth factor signaling with age,may be involved in delayed mucosal *** connections of these alterations to the process of ageing are not fully *** understanding and customtailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic ***,we aim to summarize the age-related microscopic and molecular changes of the human colon,as well as their role in altered mucosal healing.

关键词： Colon Mucosal repair Ageing Colorectalcancer Telomere shortening DNA methylation

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