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Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

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World Journal of Gastroenterology 2005年第29期11卷 4511-4518页

作者： Christian Hafner Stefanie Meyer Ilja Hagen Bernd Becker Alexander Roesch Michael Landthaler thomas vogt Department of Dermatology University Hospital of Regensburg Regensburg D-93042 Germany

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

关键词： Ephrin-B IEC-6 Wound healing Gene expression c-Fos Egr-1/2 COX-2

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

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World Journal of Gastroenterology 2005年第26期11卷 4024-4031页

作者： Christian Hafner Stefanie Meyer thomas Langmann Gerd Schmitz Frauke Bataille Ilja Hagen Bernd Becker Alexander Roesch Gerhard Rogler Michael Landthaler thomas vogt Department of Dermatology University Hospital of Regensburg D-93042 Regensburg Germany Department of Clinical Chemistry University Hospital of Regensburg D-93042 Regensburg Germany Institute of Pathology University Hospital of Regensburg D-93042 Regensburg Germany Department of Internal Medicine University Hospital of Regensburg D-93042 Regensburg Germany

AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

关键词： Ephrin-B2 Crohn's disease IBD IEC-6 Wound healing Epithelial restitution

Tierexperimentelle Untersuchungen zur Effektivitt der kombinierten transarteriellen Chemoembolisation (TACE) und Laserinduzierten Thermotherapie (LITT)

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Current Medical Science 2005年第3期 332-334页

作者：钱骏,倪岚,Maataoui Adel,Oppermann Elsie,vogt thomas Joesf Rntgenabteilung Xiehe Klinik Tongji Medizinische Institut Huazhong Universitt fr Wissenschaft und Technik Zellbiologische Abteilung Tongji Medizinische Institut Huazhong Universitt fr Wissenscha ft und Technik Institut fr Diagnostische und Interventionelle Radiologie Universittsklinikum Frankfurt am Main Institut fr Diagnostische und Interventionelle Radiologie Universittsklinikum Frankfurt am Main Institut fr Diagnostische und Interventionelle Radiologie Universittsklinikum Frankfurt am Main Wuhan 430022 China Wuhan 430030 China 60590 Frankfurt Deutschland 60590 Frankfurt Deutschland 60590 Frankfurt Deutschland

Evaluation der Effektivitt der Kombinationsbehandlung von TACE und LITT im Kleintiermodell. Lebermetastase wurde nach subkapsulrer Injektion von den Tumorzellen (CC531) in den WAG Ratte (n=30) implantiert (Tag 0). An dem 13. Tag danach wurde die Tumorvolumina (V1) magnettomographisch bestimmt. Im Anschlu erfolgte nach Laparatomie die folgende Therapieprotokolle: (A) TACE allein (0,1 mg Mitomycin C + 0,1 ml Lipiodol + 5,0 mg DSM) (n=10); (B) LITT allein (n=10); (C) TACE + LITT (n=10). Zur Effektivittsbeurteilung der unterschiedlichen Therapieprotokolle erfolgte eine erneute magnettomographische Bestimmung der Tumorvolumina (V2). Das durchschnittliche Tumorvolumen der Gruppen A, B und C vor und nach interventioneller Therapie betrug 0,1100 cm3 und 0,5988 cm3, 0,1108 cm3 und 0,6763 cm3 sowie 0,1110 cm3 und 0,3503 cm3. Das errechnete durchschnittliche Verhltnis (V2/V1) betrug 5,42, 6,14 sowie 3,14. Im Vergleich zu Kontrollegruppen A und B konnte für Therapiegruppe C eine signifikant (P<0,01) geringere Tumorvolumenzunahme im Beobachtungszeitraum ermittelt werden. Im Vergleich zu den Kontrollgruppen konnte das Wachstum der induzierten Lebertumoren unter Behandlung mittels TACE + LITT im Tiermodell statistisch signifikant gehemmt werden.

关键词： Lebermetastase Transarterielle Chemoembolisation Laserinduzierte Therapie

Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin thomas Nystrom Institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden Department of Life Sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi Department of Neurosurgery Heidelberg University HospitalHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Power flow forecasts at transmission grid nodes using Graph Neural Networks

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Energy and AI 2023年第4期14卷 189-200页

作者： Dominik Beinert Clara Holzhuter Josephine M.thomas Stephan vogt Fraunhofer Institute for Energy Economics and Energy System Technology IEE Joseph-Beuys-Straße 8Kassel34117Germany Intelligent Embedded Systems Lab University of KasselWilhelmshöher Allee 73Kassel34121Germany

The increasing share of renewable energy in the electricity grid and progressing changes in power consumption have led to fluctuating,and weather-dependent power *** ensure grid stability,grid operators rely on power forecasts which are crucial for grid calculations and *** this paper,a Multi-Task Learning approach is combined with a Graph Neural Network(GNN)to predict vertical power flows at transformers connecting high and extra-high voltage *** proposed method accounts for local differences in power flow characteristics by using an Embedding Multi-Task Learning *** use of a Bayesian embedding to capture the latent node characteristics allows to share the weights across all transformers in the subsequent node-invariant GNN while still allowing the individual behavioral patterns of the transformers to be *** the same time,dependencies between transformers are considered by the GNN architecture which can learn relationships between different transformers and thus take into account that power flows in an electricity network are not independent from each *** effectiveness of the proposed method is demonstrated through evaluation on two real-world data sets provided by two of four German Transmission System Operators,comprising large portions of the operated German transmission *** results show that the proposed Multi-Task Graph Neural Network is a suitable representation learner for electricity networks with a clear advantage provided by the preceding embedding *** is able to capture interconnections between correlated transformers and indeed improves the performance in power flow prediction compared to standard Neural Networks.A sign test shows that the proposed model reduces the test RMSE on both data sets compared to the benchmark models significantly.

关键词： Power flow forecasting Graph Neural Network Graph Convolutional Network Embedding Multi-Task Learning

Beneficial impact of lithium bis(oxalato)borate as electrolyte additive for high-voltage nickel-rich lithium-battery cathodes

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InfoMat 2023年第8期5卷 67-80页

作者： Fanglin Wu Angelo Mullaliu thomas Diemant Dominik Stepien Tatjana NParac-vogt Jae-Kwang Kim Dominic Bresser Guk-Tae Kim Stefano Passerini Helmholtz Institute Ulm(HIU) UlmGermany Karlsruhe Institute of Technology(KIT) KarlsruheGermany Department of Chemistry KU LeuvenLeuvenBelgium Department of Energy Convergence Engineering Cheongju UniversityCheongjuRepublic of Korea Chemistry Department Sapienza University of RomeRomeItaly

High-voltage nickel-rich layered cathodes possess the requisite,such as excellent discharge capacity and high energy density,to realize lithium batteries with higher energy ***,such materials suffer from structural and interfacial instability at high voltages(>4.3 V).To reinforce the stability of these cathode materials at elevated voltages,lithium borate salts are investigated as electrolyte additives to generate a superior cathode-electrolyte ***,the use of lithium bis(oxalato)borate(LiBOB)leads to an enhanced cycling stability with a capacity retention of 81.7%.Importantly,almost no voltage hysteresis is detected after 200 cycles at *** outstanding electrochemical performance is attributed to an enhanced structural and interfacial stability,which is attained by suppressing the generation of micro-cracks and the superficial structural degradation upon *** improved stability stems from the formation of a fortified borate-containing interphase which protects the highly reactive cathode from parasitic reactions with the ***,the decomposition process of LiBOB and the possible adsorption routes to the cathode surface are deduced and elucidated.

关键词： cathode electrolyte interphase electrolyte additive high voltage cathodes LiBOB nickel-rich cathodes

Subwavelength thick ultrahigh-Q terahertz disc microresonators

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Photonics Research 2020年第7期8卷 1183-1188页

作者： Dominik Walter vogt Angus Harvey Jones thomas Alan Haase Rainer Leonhardt Department of Physics The University of AucklandAuckland 1010New Zealand The Dodd-Walls Centre for Photonic and Quantum Technologies Dunedin 9016New Zealand

Artificial structures that exhibit narrow resonance features are key to a myriad of scientific advances and *** particular,exploration of the terahertz(THz)spectrum—the final frontier of the electromagnetic spectrum—would greatly benefit from high-quality resonant *** we present a new paradigm of terahertz silicon disc microresonators with subwavelength *** results utilizing continuouswave THz spectroscopy establish quality factors in excess of 120,000 at 0.6 *** of the disc thickness to a fraction of the wavelength reduces the losses from the silicon substrate and paves the way to unparalleled possibilities for light–matter interaction in the THz frequency range.

关键词： spectrum utilizing frontier