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Signal Transduction and Targeted Therapy 2024年第7期9卷 2835-2836页

作者： Imke Atreya markus f.neurath Department of Medicine 1 University Hospital of ErlangenFriedrich-Alexander University Erlangen-NürnbergErlangenGermany Deutsches Zentrum Immuntherapie(DZI) ErlangenGermany

In a recent study published in Nature,York and coworkers identified the immunometabolic regulation of mono-unsaturated fatty acid(MUfA)pools and the subsequent increase in sphingolipid biosynthesis in TLR2-activated macrophages as an important link between impaired IL-10 signaling and the development of intestinal inflammation.1 Thus,targeted interference with the newly identified IL-10/MUfA/sphingolipid axis appears as a promising strategy to restore immunometabolic homeostasis in the intestine of patients with inflammatory bowel diseases(IBD).

关键词： homeostasis impaired intestine

New endoscopic approaches in IBD

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World Journal of Gastroenterology 2011年第1期17卷 63-68页

作者： Helmut Neumann markus f.neurath Jonas Mudter Department of Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany

Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of patients with inflammatory bowel disease(IBD).New,emerging endoscopic imaging techniques visualized a plethora of new mucosal details even at the cellular and subcellular *** review offers an overview about new endoscopic techniques,including chromoendoscopy,magnification endoscopy,spectroscopy,confocal laser endomicroscopy and endocytoscopy in the face of IBD.

关键词： Endoscopy Inflammatory bowel disease Endomicroscopy Endocytoscopy Narrow band imaging fujinon intelligent color enhancement i-Scan Spectroscopy Chromoendoscopy Ulcerative colitis Crohn's disease fluorescence endoscopy

Colon cancer and the immune system:The role of tumor invading T cells

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World Journal of Gastroenterology 2006年第45期12卷 7233-7238页

作者： Maximilian Waldner Carl C Schimanski markus f.neurath I. Department of Medicine University of Mainz Mainz Germany

Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the fas/fasL system in tumor immunology, although the mechanisms and consequences of fasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.

关键词： CD4-positive T-lymphocytes CD8-positive T-lymphocytes Immunology Colonic neoplasms therapy Colorectal neoplasms Humans Lymphocytes Tumor-infiltrating Tumor escape

Cancer risk in IBD: How to diagnose and how to manage DALM and ALM

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World Journal of Gastroenterology 2011年第27期17卷 3184-3191页

作者： Helmut Neumann Michael Vieth Cord Langner markus f.neurath Jonas Mudter Department of Medicine 1 Department of SurgeryUniversity of Erlangen-Nuremberg Ulmenweg 1891054 ErlangenGermany Institute of Pathology Klinikum Bayreuth GmbHPreuschwitzer Str. 10195445 BayreuthGermany Institute of Pathology Medical University of GrazAuenbruggerplatz 25A-8036 Graz Austria

The risk of developing neoplasia leading to colorectal cancer is significantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identify these lesions. The main issue is that colitisassociated neoplasms often occurs in flat mucosa, often being detected on taking random biopsies rather than by identification of these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take four biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted "smart" biopsies. Chromoendoscopy may effectively be performed by experienced endoscopists for routine screening of UC patients. By contrast, endomicroscopy is often only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of neoplasia whereas the interplay between endoscopic experience and interpretation of histological biopsy evaluation allows the physician to make a proper diagnosis and to find the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in flat mucosa of endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable from sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of this review was to summarize endoscopic and histological characteristics of DALM and ALM in the context of therapeutic procedures.

关键词： Inflammatory bowel disease Crohn’s dis- ease Endoscopy Colitis Dysplasia-associated lesion or mass Adenoma-like mass Endomicroscopy Ulcerative colitis Endomicroscopy Confocal laser endomicroscopy Probe-based confocal laser endomicroscopy Integrated confocal laser endomicroscopy Endoscope-based confocal laser endomicroscopy Narrow band imaging Chromoendoscopy Cancer Dysplasia

Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

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World Journal of Gastroenterology 2016年第42期22卷 9300-9313页

作者： Ulrike Billmeier Walburga Dieterich markus f.neurath Raja Atreya Medical Clinic 1 Friedrich-Alexander-Universit?t Erlangen-Nürnberg

Anti-tumor necrosis factor(TNf) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNf, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNf antibodies were shown to differ in their mode-of-action in vivo and in vitro. furthermore, the anti-TNf agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNf in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNf agents in general and analyze comparatively different effects of each antiTNf agent such as TNf neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNf compared to the soluble form for the immunopathogenesis of IBD. furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNf antibodies in chronic intestinal inflammation, by predicting response to therapy.

关键词： Mucosal immunology Lamina propria mononuclear cells Crohn’s disease Ulcerative colitis Transmembrane tumor necrosis factor Apoptosis

Control and vibration analyses of a sandwich doubly curved micro-composite shell with honeycomb,truss,and corrugated cores based on the fourth-order shear deformation theory

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Applied Mathematics and Mechanics(English Edition) 2024年第10期45卷 1773-1790页

作者： f.SHIRDELAN M.MOHAMMADIMEHR f.BARGOZINI Department of Solid Mechanics Faculty of Mechanical EngineeringUniversity of KashanKashan 87317-53153Iran

Curved shells are increasingly utilized in applied engineering due to their shared characteristics with other sandwich structures,flexibility,and attractive ***,the inability of controlling and regulating vibrations and destroying them afterward is a challenge to *** this paper,the curve shell equations and a linear quadratic regulator are adopted for the state feedback design to manage the structure vibrations in state space forms.A five-layer sandwich doubly curved micro-composite shell,comprising two piezoelectric layers for the sensor and actuator,is modeled by the fourth-order shear deformation *** core(honeycomb,truss,and corrugated)is analyzed for the bearing of transverse shear *** results show that the honeycomb core has a greater effect on the *** the parameters related to the core and the weight percentage of graphene increase,the frequency *** uniform distribution of graphene platelets results in the lowest natural frequency while the natural frequency ***,without taking into account the piezoelectric layers,the third-order shear deformation theory(TSDT)and fourth-order shear deformation theory(fOSDT)align ***,when the piezoelectric layers are incorporated,these two theories diverge significantly,with the frequencies in the fOSDT being lower than those in the TSDT.

关键词： vibration and control doubly curved shell micro-composite honeycomb truss corrugate core

Bolstering integrity in environmental data science and machine learning requires understanding socioecological inequity

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frontiers of Environmental Science & Engineering 2024年第5期18卷 171-179页

作者： Joe f.Bozeman III School of Civil and Environmental Engineering Georgia Institute of TechnologyAtlantaGA30332USA School of Public Policy Georgia Institute of TechnologyAtlantaGA30332USA

Socioecological inequity in environmental data science—such as inequities deriving from data-driven approaches and machine learning(ML)—are current issues subject to debate and *** is growing consensus around embedding equity throughout all research and design domains—from inception to administration,while also addressing procedural,distributive,and recognitional ***,practically doing so may seem onerous or daunting to *** current perspective helps to alleviate these types of concerns by providing substantiation for the connection between environmental data science and socioecological inequity,using the Systemic Equity framework,and provides the foundation for a paradigmatic shift toward normalizing the use of equity-centered approaches in environmental data science and ML *** the integrity of environmental data science and ML is just beginning from an equity-centered tool development and rigorous application *** this end,this perspective also provides relevant future directions and challenges by overviewing some meaningful tools and strategies—such as applying the Wells-Du Bois Protocol,employing fairness metrics,and systematically addressing irreproducibility;emerging needs and proposals—such as addressing data-proxy bias and supporting convergence research;and establishes a ten-step path ***,the work that environmental scientists and engineers do ultimately affect the well-being of us all.

关键词： Equity Bias Machine Learning Data Science Justice Systemic Equity

Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives

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World Journal of Gastroenterology 2015年第1期21卷 21-46页

作者： Gian Eugenio Tontini Maurizio Vecchi Luca Pastorelli markus f.neurath Helmut Neumann Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San Donato20097 San Donato MilaneseItaly Department of Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany Department of Biomedical Sciences for Health University of Milan20122 MilanoItaly

Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and ***,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated ***,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification ***,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD *** topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD *** optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal ***,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising *** advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bo

Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim f.Trakhtenberg Department of Neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal *** development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

An unexpected cellular fountain of youth:platelets provide factors rejuvenating brain functions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 16-18页

作者： Harald f.Langer Department of Cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany German Centre for Cardiovascular Research(DZHK) Partner Site Heidelberg/MannheimMannheimGermany European Center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Cardiovascular systems biology Medical Clinic IUniversity Heart Center LübeckLübeckGermany

In a recent manuscript published in Nature,Schroer et *** that platelets and in particular platelet derived Pf-4(CXCL4)are a novel factor,which can rejuvenate the mammalian neuronal system.1 These findings have the potential to trigger an entire new field of research opening new platelet-derived candidate effector molecules for supporting regeneration.

关键词： supporting platelets finding