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Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon

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World Journal of Gastroenterology 2012年第7期18卷 601-608页

作者： ferenc Sipos Orsolya Galamb Cell Analysis Laboratory 2nd Department of Internal MedicineSemmelweis University1088 BudapestHungary Molecular Medicine Research Unit Hungarian Academy of Sciences1051 BudapestHungary

Epithelial-to-mesenchymal and mesenchymal-to-epi- thelial transitions are well established biological events which have an important role in not just normal tissue and organ development, but in the pathogenesis of diseases. Increasing evidence has established their presence in the human colon during colorectal carcinogenesis and cancer invasion, chronic inflammation-related fibrosis and in the course of mucosal healing. A large body of evidence supports the role for transforming growth factor-13 and its downstream Smad signaling, the phosphatidylinositol 3＇-kinase/Akt/mTOR axis, the Ras-mitogen-activated protein kinase/Snail/Slug and FOXC2 pathway, and Hedgehog signaling and microR- NAs in the development of colorectal cancers via epi- thelial-to-mesenchymal transition. C-met and Frizzled-7, among others, seem to be the principle effectors of mesenchymal-to-epithelial transition, hence have a role not just in mucosal regeneration but in the progression of colonic wall fibrosis. Here we discuss a role for these pathways in the initiation and development of the transition events. A better understanding of their induction and regulation may lead to the identification of pathways and factors that could be potent therapeu- tic targets. The inhibition of epithelial-to-mesenchymal transition using mTOR kinase inhibitors targeting theATP binding pocket and which inhibit both mTORC1 and mTORC2, RNA aptamers or peptide mimetics, such as a Wnt5A-mimetic, may all be useful in both cancer treatment and delaying fibrosis, while the induction of mesenchymal-to-epithelial transition in induced pluripotent stem cells may enhance epithelial healing in the case of severe mucosal damage. The preliminary results of the current studies are promising, but more clinical investigations are needed to develop new and safe therapeutic strategies for diseases of the colon.

关键词： Epithelial-to-mesenchymal transition Mesen-chymal-to-epithelial transition Colorectal cancer Fibrosis Mucosal healing

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

Effect of IBD sera on expression of inducible and endothelial nitric oxide synthase in human umbilical vein endothelial cells

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World Journal of Gastroenterology 2006年第11期12卷 1730-1738页

作者： Károly Palatka Zoltán Serf(o|″)z(o|″) Zoltán Veréb Róbert Bátori Beáta Lontay Zoltán Hargitay Zoltán Nemes Miklós Udvardy ferenc erd(o|″)di István Altorjay Department of Gastroenterology University of Debrecen Nagyerdei k(o|¨)rút 98.Debrecen H-4001Hungary Department of Experimental Zoology BLRI-HAS TihanyHungary Institute of Immunology University of Debrecen Nagyerdei k(o|¨)rút 98.Debrecen H-4001 Hungary Department of Medical Chemistry University of Debrecen Nagyerdei k(o|¨)rút 98.Debrecen H-4001Hungary Department of Pathology Gyula Kenezy Hospital DebrecenBartók Béla út 10.Debrecen H-4026Hungary Institute of Pathology University of Debrecen Nagyerdei k(o|¨)rút 98.Debrecen H-4001Hungary Institute of Internal Medicine University of Debrecen Nagyerdei k(o|¨)rút 98.Debrecen H-4001Hungary

AIM： To study the expression of endothelial and inducible nitric oxide synthases （eNOS and iNOS） and their role in inflammatory bowel disease （IBD）. METHODS： We examined the effect of sera obtained from patients with active Crohn＇s disease （CD） and ulcerative colitis （UC） on the function and viability of human umbilical vein endothelial cells （HUVEC）. HUVECs were cultured for 0-48 h in the presence of a medium containing pooled serum of healthy controls, or serum from patients with active CD or UC. Expression of eNOS and iNOS was visualized by immunofluorescence, and quantified by the densitometry of Western blots. Proliferation activity was assessed by computerized image analyses of Ki-67 immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10^-4 mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin method and by propidium iodide staining, respectively. RESULTS： In HUVEC immediately after exposure to UC, serum eNOS was markedly induced, reaching a peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with CD sera and the eNOS level was minimal at 20 h compared to control （18%±16% vs 23%± 15% P〈0.01）. UC or CD serum caused a significant increase in iNOS compared to control （UC： 300%±21%; CD： 275% ± 27% vs 108% ± 14%, P〈0.01）. Apoptosis/necrosis characteristics did not differ significantly in either experiment. Increased proliferation activity was detected in the presence of CD serum or after treatment with L-NAME. Cultures showed tube-like formations after 24 h treatment with CD serum. CONCLUSION： IBD sera evoked changes in the ratio of eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down-regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased proliferation activity and possibly a reduced antiinflammatory protection of endothelial cells.

关键词： Crohn's disease Human umbilical vein endothelial cells Inflammatory bowel disease Nitric oxide synthase Ulcerative colitis

Isolated lymphoid follicles in colon: Switch points between inflammation and colorectal cancer?

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World Journal of Gastroenterology 2011年第13期17卷 1666-1673页

作者： ferenc Sipos Gyrgyi Müzes 2nd Department of Internal Medicine Semmelweis University

Gut-associated lymphoid tissue is supposed to play a central role in both the organization of colonic repair mechanisms and colorectal carcinogenesis. In inflammatory conditions, the number, diameter and density of isolated lymphoid follicles (ILFs) increases. They are not only involved in immune surveillance, but their presence is also indispensable in normal mucosal regeneration of the colon. In carcinogenesis, ILFs may play a dual role. On the one hand they may support tumor growth and the metastatic process by vascular endothelial growth factor receptor signaling and producing a specific cytokine and cellular milieu, but on the other hand their presence is sometimes associated with a better prognosis. The relation of ILFs to bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts or crypt formation, which are all involved in mucosal repair and carcinogenesis, has not been directly studied. Data about the putative organizer role of ILFs is scattered in scientific literature.

关键词： Isolated lymphoid follicle Colon Mucosal repair Colorectal cancer Epithelial stem cell Myofibroblast Follicular dendritic cell Mesenchymal-epithelial transition Epithelial-mesenchymal transition

Anti-tumor immunity,autophagy and chemotherapy

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World Journal of Gastroenterology 2012年第45期18卷 6537-6540页

作者： Gyrgyi Mzes ferenc Sipos 2nd Department of Internal Medicine Semmelweis University1088 BudapestHungary

Autophagy or self-digestion of cells is activated upon various stressful stimuli and has been found to be a survival and drug resistance pathway in ***,genetic studies support that autophagy can act as a tumor ***,defective autophagy is implicated in tumorigenesis,as *** precise impact of autophagy on malignant transformation has not yet been clarified,but recent data suggest that this complex process is mainly directed by cell types,phases,genetic background and *** of autophagy to anticancer immune responses may indicate a novel aspect in cancer chemotherapy.

关键词： Cancer Autophagy Chemotherapy Antitu-mor immunity Cell death

Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues

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Neural Regeneration Research 2015年第6期10卷 866-869页

作者： éva Korpos ferenc Deák Ibolya Kiss Institute of Physiological Chemistry and Pathobiochemistry University of Muenster Cells-in-Motion Cluster of Excellence University of Muenster Institute of Biochemistry Biological Research CentreHungarian Academy of Sciences Avidin Ltd.

The extracellular matrix （ECM） performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic changes during remodeling concomitant to alterations in the cell-ECM interactions. Here we discuss recent data addressing the critical role of the widely expressed ECM protein, matrilin-2 （Matn2） in the timely onset of differentiation and regeneration processes in myogenic, neural and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it interacts with other ECM proteins and integrins. Matn2 promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing. Matn2 deposition by myoblasts is crucial for the timely induction of the global switch toward terminal myogenic differentiation during muscle regeneration by affecting transforming growth factor beta/bone morphogenetic protein 7/Smad and other signal transduction pathways. Depending on the type of tissue and the pathomechanism, Math2 can also promote or suppress tumor growth.

关键词： Schwann cells neurite outgrowth neuromuscular junction (NM]) multiple sclerosis TGF-β/BMP-7/Smad signaling myogenic differentiation Trf3 tumor suppression

Physiological and pathological role of local and immigrating colonic stem cells

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World Journal of Gastroenterology 2012年第4期18卷 295-301页

作者： ferenc Sipos Gábor Valcz Béla Molnár 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research Unit Hungarian Academy of Sciences

The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstanc- es where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stern cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

关键词： Colon Mesencyhmal stem cells Bone marrow Myofibroblast Fibrosis Colorectal cancer Para-thyroid hormone Transforming growth factor-β

Regulatory T cells in inflammatory bowel diseases and colorectal cancer

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World Journal of Gastroenterology 2012年第40期18卷 5688-5694页

作者： Gyrgyi Mzes Béla Molnár ferenc Sipos 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research Unit Hungarian Academy of Sciences

Regulatory T cells(T regs) are key elements in immunological *** number of T regs may alter in both peripheral blood and in colonic mucosa during pathological *** local cellular,microbiological and cytokine milieu affect immunophenotype and function of T *** 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 *** 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 ***,their number and phenotype correlate closely with the clinical outcome of the disease,even if their contribution to carcinogenesis has previously been *** 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 *** 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.

关键词： Regulatory T cells Forkhead box P3 Inflam-matory bowel diseases Colitis-associated colon cancer Colorectal cancer

不同非酿酒酵母与酿酒酵母混合发酵对脆红李酒品质的影响

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食品与发酵工业 2021年第12期47卷 110-116页

作者：张曼钟涛魏雪阚建全武运 ferenc Hegyi 杜木英西南大学食品科学学院重庆400715 中匈食品科学合作研究中心重庆400715 新疆农业大学食品科学与药学学院新疆乌鲁木齐830052 匈牙利国家农业研究和创新中心食品科学研究所匈牙利布达佩斯H-1022

分别采用热带假丝酵母(Candida tropicalis)、东方伊萨酵母(Issatchenkio orientalis)、美极梅奇酵母(Metschnikowia pulcherrima)、葡萄汁有孢汉逊酵母(Hanseniaspora uvarum)与商业酿酒酵母(Saccharomyces cerevisiae)D254混合发酵脆红李酒,比较其在发酵速率、理化指标、有机酸和挥发性成分的差异,并进行感官评价分析,以期为提升脆红李酒品质提供依据。结果表明,与***单独发酵(10 d)相比,混合发酵延缓了发酵进程(12~13 d)。不同脆红李酒的理化指标均符合国标,混合发酵后酒样中苹果酸、乳酸和乙酸含量显著降低(P1,能够增强酒体果香、花香。感官评价结果也表明Mp-Sc混合发酵的果香味和花香味较为浓郁。综上,Mp-Sc混合发酵更适合应用于脆红李酒酿造,有利于增加香气复杂性,提升品质。

关键词：非酿酒酵母脆红李顶空固相微萃取-气相色谱-质谱法主成分分析香气活度值