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

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 m.lnár 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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Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature

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World Journal of Gastroenterology 2013年第28期19卷 4447-4454页

作者： Gyrgyi müzes zsolt Tulassay Ferenc Sipos 2nd Department of Internal medicine Semmelweis University 1088 Budapest Hungary

Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IrGm , NOD2 , XBP1 ) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.

关键词： Crohn’s disease Innate immunity Autophagy genes Autophagy Gut microbiota

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Long-term temporal patterns in flight activities of a migrant diurnal butterfly

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Insect Science 2021年第3期28卷 839-849页

作者： Edit Juhasz Adam Gor Daniella Bali Fanni Kerekgyarto Gergely Katona zsolt Vegvari Department of Evolutionary Zoology and Human Biology University of DebrecenDebrecenHungary Department of Ecology University of Veterinary MedicineBudapestHungary Centre for Ecological research Danube Research InstituteBudapestHungary SDEI Entomology Information Centre Senckenberg Deutsches Entomologisches InstitutMOnchebergGermany

recent studies demonstrated that the Painted Lady(Vanessa cardui),a cosmopolitan diurnal butterfly performs long-range migration between subtropical Africa and north-western Europe,covered by individuals belonging to up to six *** we analyze temporal patterns of complete annual migratory activity of the Painted Lady in Hungary,located in its Central European migratory route,almost completely unstudied *** do so,we used field occurrence data collected between 2000 and 2019 and estimated temporal patterns in migratory activity by fitting kernel density functions on the daily mean number of individuals and observation *** temporal distributions of kernel density estimates were analyzed as a function of time and key climatic predictors of the study *** found that(i)the timing of spring arrivals has been advancing;(ii)the relative intensity of the first and last migratory peaks of the Painted Lady significantly increased during the past decades;and(iii)intensity of the last migratory peak is related to the mean temperature of the previous month,inferring that the migration is shifting to earlier dates and their volume of the migration has substantially intensified,evoking mutually nonexclusive,competing *** study indicates the strengthening migration activities of a southerly distributed,long-distance migrant diurnal butterfly,most probably linked to the northward shift of wintering areas induced by warming trends of the southern parts of ***,the complexity of the likely processes leading to changing migratory strategies calls up for further research in both breeding and wintering areas.

关键词： climatic responsiveness insect migration kernel density estimation Painted Lady

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Comparison of different lymph node staging systems in prognosis of gastric cancer:a bi-institutional study from Hungary

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Chinese Journal of Cancer research 2017年第4期29卷 323-332页

作者： Dezso Toth Adrienn Bfra zsolt Vargal miklos Torok Peter peter Akosy Department of General Surgery Kenezy Gyula Teaching Hospital Debrecen 4031 Hungary Department of General Thoracic and Vascular Surgery Kaposi M6r Teaching Hospital Kaposv~r 7400 Hungary Department of Pathology Ken6zy Gyula Teaching Hospital Debrecen 4031 Hungary Department of Oncology Kan6zy Gyula Teaching Hospital Debrecen 4031 Hungary

Objective： The Union for International Cancer Control （UICC） Node （N） classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes （lns） to be dissected; therefore different staging systems were invented. methods： Between march 2005 and march 2010, 164 patients were evaluated at the Department of General Surgery in the Ken^zy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi m6r Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined lns, the number of harvested negative lns, the metastatic lymph node ratio （mLr） and the log odds of positive lns （LODDS） were determined to measure their 5-year survival rates and to compare them to each other. results： The overall 5year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, mLr and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. NO and N3 vs. NO with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested lns. The mLr gave the best prognostic prediction when adequate （more than or equal to 16） lymphadenectomy was performed. Conclusions： We suggest the application of LODDS system routinely in western patients and the usage of mLr classification in cases with extended lymphadenectomy.

关键词： Gastric cancer lymph node metastasis prognosis staging system survival

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Symmetric carbon tetramers forming spin qubits in hexagonal boron nitride

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npj Computational materials 2023年第1期9卷 407-416页

作者： zsolt Benedek rohit Babar Ádám Ganyecz Tibor Szilvási Örs Legeza Gergely Barcza Viktor Ivády Strongly Correlated Systems Lendület research Group Wigner Research Centre for PhysicsPO Box 49H-1525 BudapestHungary mTA-ELTE Lendület“momentum”NewQubit research Group Pázmány PéterSétány 1/A1117 BudapestHungary Department of Chemical and Biological Engineering The University of AlabamaTuscaloosaAL 35487USA Institute for Advanced Study Technical University of MunichLichtenbergstrasse 2a85748 GarchingGermany Department of Physics of Complex Systems Eötvös Loránd UniversityEgyetem tér 1-3H-1053 BudapestHungary Department of Physics Chemistry and BiologyLinköping UniversitySE-58183 LinköpingSweden

Point defect quantum bits in semiconductors have the potential to revolutionize sensing at atomic ***,vacancy-related defects are at the forefront of high spatial resolution and low-dimensional *** the other hand,it is expected that impurity-related defect structures may give rise to new features that could further advance quantum sensing in low ***,we study the symmetric carbon tetramer clusters in hexagonal boron nitride and propose them as spin qubits for *** utilize periodic-DFT and quantum chemistry approaches to reliably and accurately predict the electronic,optical,and spin properties of the studied *** show that the nitrogen-centered symmetric carbon tetramer gives rise to spin state-dependent optical signals with strain-sensitive intersystem crossing ***,the weak hyperfine coupling of the defect to their spin environments results in a reduced electron spin resonance linewidth that can enhance sensitivity.

关键词： hexagonal boron quantum

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Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release

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

作者： zsolt m.lnár 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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Contribution of TLr signaling to the pathogenesis of colitisassociated cancer in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第36期20卷 12713-12721页

作者： Ferenc Sipos István Fri miklós Constantinovits zsolt Tulassay Gyrgyi mzes 2nd Department of Internal medicine Semmelweis University 1088 Budapest Hungary molecular medicine research Unit Hungarian Academy of Sciences 1088 Budapest Hungary

In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLrs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLrs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLrs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as ”largely antitumorigenic” and ”largely pro-tumorigenic” with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.

关键词： Inflammation Tissue repair Immunoregulation Colitis-associated cancer Toll-like receptor Inflammatory bowel disease Carcinogenesis

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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 m.lnár 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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mortality and Long-Term Outcome of Neonates with Congenital Heart Disease and Acute Perinatal Stroke:A Population-Based Case-Control Study

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Congenital Heart Disease 2022年第4期17卷 447-461页

作者： Eszter Vojcek VAnna Gyarmathy rozsa Graf Anna m.Laszlo Laszlo Ablonczy zsolt Prodan Istvan Seri First Department of Pediatrics Semmelweis UniversityMTA Centre of ExcellenceBudapestHungary Department of Pediatrics Saint John Hospital and North-Buda Unified HospitalsBudapestHungary Epiconsult Biomedical Consulting and medical Communications Agency DoverUSA Department of Epidemiology Johns Hopkins UniversityBaltimoreUSA Department of rehabilitation Saint John Hospital and North-Buda Unified HospitalsBudapestHungary Institute of mathematics and Base Sciences Hungarian University of Agriculture and Life SciencesGödöllőHungary Gottsegen National Cardiovascular Center BudapestHungary Children’s Hospital Los Angeles University of Southern CaliforniaLos AngelesUSA

Objective:Neonates with congenital heart disease(CHD)and perinatal stroke have high mortality and survivors are at risk for poor long-term neurodevelopmental *** aim of this study was to assess the risk factors and outcome of neonates with both CHD and mrI-confirmed perinatal stroke(Study Group)and compare those to the risk factors and outcome of infants matched for CHD without stroke(Control-1)and of infants matched for mrI-confirmed stroke without CHD(Control-2).methods:We conducted a population-based case-control study enrolling 28 term neonates with CHD and mrI-confirmed acute perinatal stroke born between 2007–2017 in the Central-Hungarian *** of the control groups included 56 *** Bayley Scales of Infant Development-II,the Brunet-Lézine test and the Binet Intelligence scales-V were used for neurodevelopmental follow-up at a median age of 61 ***:mortality was highest in the Study Group(25%compared to 5%and 2%,respectively,p=0.001).Adverse neurodevelopmental outcome was prevalent in the Study(53%)and Control-2 Groups(52%,p=0.03).Significantly different parameters among the three groups included Apgar scores,mode of delivery,gestational age at birth,cardiac interventions and twin *** a multivariable regression analysis adjusted for clinically relevant parameters,patients in the Study Group had significantly higher odds for mortality compared to patients in the Control-1 Group(Or:6.595%CI:1.1–39.4).Conclusions:Neonates with perinatal stroke and CHD are at a higher risk for dying compared to neonates with CHD without *** addition,the stroke-associated direct insult to the brain likely plays an important role in the development of neurodevelopmental morbidity in these patients.

关键词： Congenital heart disease perinatal stroke neurodevelopmental outcome mortality

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relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

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World Journal of Clinical Cases 2014年第12期2卷 912-917页

作者： Ibolya File Csilla Trinn zsolt mátyus László Ujhelyi József Balla János mátyus Institute of Internal medicine University of Debrecen Clinical Centre H-4032 Debrecen Hungary Borsod-Abaúj-Zemplén County and University Teaching Hospital 2nd Department of Internal Medicine H-3526 Miskolc Hungary

relapsing polychondritis(rP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of rP with p-ANCA positive AAV. In the first patient rP developed 1.5 years after the onset of AAV. In the others the signs of rP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of rP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

关键词： relapsing polychondritis Anti-neutrophil cytoplasmic antibody Anti-neutrophil cytoplasmic antibody-associated vasculitis rapidly progressive glomerulonephritis Immunosuppressive treatment

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