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The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm

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Journal of Molecular Cell Biology 2023年第10期15卷 39-53页

作者： Matthias Hamdorf Thomas Imhof Ben Bailey-Elkin Janina Betz Sebastian JTheobald Alexander Simonis Veronica Di Cristanziano Lutz Gieselmann felix Dewald Clara Lehmann Max Augustin Florian Klein Miguel AAlejandre Alcazar Robert Rongisch Mario Fabri Jan Rybniker Heike Goebel Jörg Stetefeld Bent Brachvogel Claus Cursiefen Manuel Koch felix bock Cornea Lab Experimental Ophthalmology Department of OphthalmologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Terasaki Institute for Biomedical Innovation Los AngelesCA 90024USA Center for Biochemistry Faculty of Medicine and University Hospital Cologne50931 CologneGermany Institute for Experimental Dentistry and Oral Musculoskeletal Biology Faculty of Medicine and University Hospital Cologne50931 CologneGermany Department of Microbiology University of ManitobaWinnipeg MB R3B 2E9 ManitobaCanada Department I of Internal Medicine Division of Infectious DiseasesFaculty of Medicine and University Hospital Cologne50937 CologneGermany Center for Molecular Medicine Cologne University of Cologne50931 CologneGermany Institute of Virology Faculty of Medicine and University Hospital Cologne50935 CologneGermany German Center for Infection Research(DZIF) Partner Site Bonn-Cologne50931 CologneGermany Department of Children and Adolescent Medicine Faculty of Medicine and University Hospital Cologne50931 CologneGermany Cologne Excellence Cluster Stress Responses in Aging-associated Diseases 50931 CologneGermany Institute for Lung Health(ILH) Universities of Gießen and Marburg Lung CentreMember of the German Center for Lung Research35392 GießenGermany Dermatology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Institute of Pathology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Department of Pediatrics and Adolescent Medicine Experimental NeonatologyFaculty of Medicine and University Hospital Cologne50931 CologneGermany

The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine *** response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ***,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with *** show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these *** addition,we identified DC-SIGN as a possible interaction partner of ORF8 on *** of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by ***,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.

关键词： COVID-19 SARS-CoV-2 ORF8 cytokine storm dendritic cells

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Central corneal epithelium self-healing after ring-shaped glycerin-cryopreserved lamellar keratoplasty in Terrien marginal degeneration

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 251-252页

作者： Yan-Long Bi felix bock Qi Zhou Claus Cursiefen Department of Ophthalmology Tongji Hospital Affiliated to Tongji University School of Medicine Department of Ophthalmology University Hospital of Cologne

Dear Sir, I am Dr Yan-Long Bi, from the Department of Ophthalmology, Tongji University Affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of total limbal stem cells deficiency after treatment with ring-shaped lamellar keratoplasty secondary to Terrien marginal degeneration. During 3 years

关键词： ring cell Figure Central corneal epithelium self-healing after ring-shaped glycerin-cryopreserved lamellar keratoplasty in Terrien marginal degeneration

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Recurrent interface abscess secondary to Acanthamoeba keratitis treated by deep anterior lamellar keratoplasty

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International Journal of Ophthalmology(English edition) 2012年第6期5卷 774-775页

作者： Yan-Long Bi felix bock Qi Zhou Claus Cursiefen Department of Ophthalmology Tongji Hospital affiliated to Tongji University School of Medicine Department of Ophthalmology University Hospital of Cologne

Dear Sir,I am Dr. Yan-Long Bi, from the Department of Ophthalmology of the Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of recurrent amoebic cor... 详细信息

关键词： deep Figure Recurrent interface abscess secondary to Acanthamoeba keratitis treated by deep anterior lamellar keratoplasty

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Immunological aspects of liver cell transplantation

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World Journal of Transplantation 2016年第1期6卷 42-53页

作者： felix Oldhafer Michael bock Christine S Falk Florian WR Vondran Regenerative Medicine and Experimental Surgery (Re Medi ES) Department of General Visceral and Transplant Surgery Hannover Medical School Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School German Center for Infection Research (DZIF) Partner Site Hannover-Braunschweig Institute of Transplant Immunology Integrated Research and Treatment Centre Transplantation (IFB-Tx) Hannover Medical School

Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation(OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation(LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where longterm graft survival is observed on a regular basis and, hence, the liver has been deemed an immuneprivileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells.

关键词： Liver cell transplantation Cell-based therapy Hepatocyte transplantation Transplant immunology Regenerative medicine

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Molecular phenotypes of human parvovirus B19 in patients with myocarditis

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World Journal of Cardiology 2014年第4期6卷 183-195页

作者： C-Thomas bock Anja Düchting Friederike Utta Eva Brunner Bui Tien Sy Karin Klingel Florian Lang Meinrad Gawaz Stephan B felix Reinhard Kandolf Department of Molecular Pathology University Hospital of Tuebingen Robert Koch Institute Department of Physiology University of Tuebingen Department of Cardiology and Cardiovascular Medicine University Hospital of Tuebingen Clinics for Internal Medicine B Ernst-MoritzArndt-University Department of Molecular Pathology University Hospital of Tuebinge

AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional *** were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology *** tissues were obtained at autopsy from 34 victims of accidents,crime or *** of mononuclear cell infiltrates in EMBs was performed using immunohistological ***-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture *** experiments were conducted using human endothelial cells *** reporter assays were performed to determine B19Vreplication *** analysis and graphical representation were calculated using SPSS and Prism5 ***:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was ***-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B1

关键词： Myocarditis Dilated cardiomyopathy Parvovirus B19 B19V-genotypes B19V co-infection

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