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World Journal of Clinical Cases 2016年第3期4卷 76-80页

作者： Nina Fluschnik Gunnar Lund Peter Moritz Becher Stefan Blankenberg Kai Muellerleile Department of General and Interventional Cardiology University Heart Center Department of Diagnostic and Interventional Radiology University Medical Center Hamburg Eppendorf

This case report illustrates challenging aspects of diagnosis and treatment of isolated sarcoid heart disease(SHD) and the role of cardiovascular magnetic resonance(CMR) imaging. Here, we present a previously healthy 45-year-old man, who was admitted with pericardial effusion and symptoms of acute heart failure. CMR followed by targeted left ventricular endomyocardial biopsy(EMB) revealed the diagnosis of isolated SHD. The combined use of CMR and EMB was crucial in diagnosing SHD. Furthermore, this case report demonstrates the value of CMR for monitoring response to therapy and lesion healing.

关键词： Heart failure Cardiac sarcoidosis Cardiovascular magnetic resonance imaging Endomyocardial biopsy Internal cardiac defibrillator

Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection

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World Journal of Gastroenterology 2007年第33期13卷 4514-4516页

作者： A Zoufaly S Schmiedel AW Lohse J van Lunzen Department of Medicine 1 University Medical Center Hamburg-Eppendorf Hamburg Germany Infectious Diseases Unit University Medical Center Hamburg-Eppendorf Hamburg Germany

Diffuse intestinal Kaposi＇s sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 （HHV8） and the diagnosis had to be changed to diffuse intestinal Kaposi＇s sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi＇s sarcoma should be determined, as distinct treatment is indicated.

关键词： Gastrointestinal stromal tumor Kaposi's sarcoma HIV infection Human herpesvirus 8 c-kit

Effect of process parameters on additive-free electrospinning of regenerated silk fibroin nonwovens

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Bioactive Materials 2020年第2期5卷 241-252页

作者： Alexander Kopp Ralf Smeets Martin Gosau Nadja Kröger Sandra Fuest Marius Köpf Magnus Kruse Judith Krieger Rico Rutkowski Anders Henningsen Simon Burg Fibrothelium GmbH AachenGermany Department of Oral and Maxillofacial Surgery University Medical Center Hamburg-EppendorfHamburgGermany Department of Oral and Maxillofacial Surgery Division of Regenerative Orofacial MedicineUniversity Medical Center Hamburg-EppendorfHamburgGermany Institut Fuer Textiltechnik of RWTH Aachen university AachenGermany Department of Oral and Maxillofacial Surgery German Armed Forces HospitalHamburgGermany Department of Plastic Reconstructive and Aesthetic SurgeryUniversity Hospital of CologneCologneGermany

Silk fibroin is a biomaterial with multiple beneficial properties for use in regenerative medicine and tissue *** dissolving and processing the reconstituted silk fibroin solution by electrospinning,the arrangement and size of fibers can be manifold varied and according fiber diameters reduced to the nanometer *** nonwovens show high porosity as well as potential ***,electrospinning of most biomaterials demands for the application of additives,which enable stable electrospinning by adjusting viscosity,and are intended to evaporate during processing or to be washed out ***,the use of such additives increases costs and has to be taken into account in terms of biological risks when used for biomedical *** this study,we explored the possibilities of additive-free electrospinning of pure fibroin nonwovens and tried to optimize process parameters to enable stable *** used natural silk derived from the mulberry silkworm Bombyx *** degumming,the silk fibroin was dissolved and the viscosity of the spinning solution was controlled by partial evaporation of the initial solving *** way,we were able to completely avoid the use of additives and manufacture nonwovens,which potentially offer higher biocompatibility and reduced *** and relative humidity during electrospinning were systematically varied(25–35°C,25–30%RH).In a second step,the nonwovens optionally underwent methanol treatment to initiate beta-sheet formation in order to increase structural integrity and *** surface analysis on the different nonwovens was performed using scanning electron microscopy and supplemented by additional mechanical *** was evaluated using BrdU-assay,XTT-assay,LDH-assay and live-dead *** findings were,that an increase of temperature and relative humidity led to unequal fiber diameters and defective *** to penetration decr

关键词： Fibroin Additive-free electrospinning Nanofiber Silk Scaffolds

α-Synuclein conformers reveal link to clinical heterogeneity ofα-synucleinopathies

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Translational Neurodegeneration 2023年第1期12卷 691-701页

作者： Matthias Schmitz NiccolòCandelise Sezgi Canaslan Hermann C.Altmeppen Jakob Matschke Markus Glatzel Neelam Younas Saima Zafar Peter Hermann Inga Zerr Department of Neurology National Reference Center for TSEThe German Center for Neurodegenerative Diseases(DZNE)Georg-August-UniversityUniversity Medicine GottingenGoettingenGermany National center for Drug Research and Evaluation Institute Superiore di SanitàRomeItaly Institute of Neuropathology University Medical Center Hamburg-Eppendorf(UKE)HamburgGermany

α-Synucleinopathies,such as Parkinson’s disease(PD),dementia with Lewy bodies(DLB)and multiple system atrophy,are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfoldedα-synuclein(αSyn),referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions(Papp-Lantos bodies).Even though the specific cellular distribution of aggregatedαSyn differs in PD and DLB patients,both groups show a significant pathological overlap,raising the discussion of whether PD and DLB are the same or different *** clinical investigation,we will focus in addition on methodologies,such as protein seeding assays(real-time quaking-induced conversion),to discriminate between different types ofα-*** approach relies on the seeding conversion properties of misfoldedαSyn,supporting the hypothesis that different conformers of misfoldedαSyn may occur in different types ofα-*** the pathological processes influencing the disease progression and phenotype,provoked by differentαSyn conformers,will be important for a personalized medical treatment in future.

关键词： α-synucleinopathies α-synuclein RT-QuIC Protein strains

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

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Cancer Drug Resistance 2019年第3期2卷 399-418页

作者： Heidi Schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06123Italy

Ovarian cancer has a poor outcome because it is usually detected at advanced tumor stages,and the majority of the patients develop disease relapse as a result of chemotherapy *** most lethal gynecological malignancy metastasizes within the peritoneal fluid or ascites to pelvic and distal *** ovarian cancer progression and metastasis,small non-coding RNAs(ncRNAs),including long noncoding RNAs and microRNAs have been recognized as important *** dysregulation modulates gene expression and cellular signal pathways and can be detected in liquid *** this review,we provide an overview on circulating plasma and serum ncRNAs participating in tumor cell migration and invasion,and contributing to recurrence and metastasis of ovarian *** will also discuss the development of potential,novel therapies using ncRNAs as target molecules or tumor markers for ovarian cancer.

关键词： Ovarian cancer recurrence metastasis epithelial-mesemchmal transition non-coding RNAs chemotherapy tumor markers

How to package and SEND mRNA: a novel “humanized” vector system based on endogenous retroviruses

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3367-3368页

作者： Kristoffer Riecken Dawid Głów Boris Fehse Research Dept.Cell&Gene Therapy Dept.of Stem Cell TransplantationUniversity Medical Centre Hamburg-Eppendorf(UKE)Hamburg 20246Germany

A recent publication in Science describes a novel mRNA delivery system termed SEND,entirely consisting of endogenous proteins.1 These virus-like particles(VLPs),able to deliver mRNA of e.g.,Cas9,represent a new class of gene transfer *** development of efficient,specific,and safe vectors for the delivery of nucleic acids and proteins remains one of the biggest challenges in gene therapy,particularly for in vivo *** currently preferred viral vectors have several limitations,including biosafety issues,laborious and expensive manufacture,as well as the impossibility of multiple applications due to the inherent immunogenicity of viral *** contrast,non-viral vectors are much easier to produce on a large scale,but have not yet reached gene transfer rates comparable with viral vectors.

关键词： endogenous system entirely

Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

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Cancer Drug Resistance 2019年第2期2卷 271-296页

作者： Heidi Schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06126Italy

Initially,most ovarian tumors respond to the treatment with platinum components,but frequently recurrence occurs within the following two years in advanced ovarian cancer *** this regard,previous studies have shown changes in the epigenetic patterns in ovarian cancer that are linked with resistance to cis-and carboplatin ***,epigenetic changes mediated by a treatment with cis-or carboplatin could identify such patients who do or do not respond to this ***,an understanding of the impact of platinum on epigenetics in ovarian cancer is important in overcoming platinum *** this review,we delineate epigenetic abnormalities in cis-and carboplatin-resistant ovarian tumors,such as changes in DNA methylation,histone modifications and deregulation of microRNAs,and discuss the potential of epigenetic therapies in combination with platinum.

关键词： Ovarian cancer carboplatin cisplatin resistance DNA methylation histone modifications microRNAs

Structure-activity relationship of cyclic ADP-ribose, an update

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Journal of Chinese Pharmaceutical Sciences 2013年第2期22卷 127-136页

作者： Andreas H. Guse The Calcium Signalling Group Department of Biochemistry and Signal Transduction and Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg-Eppendorf

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.

关键词： Cyclic ADP-ribose Calcium signaling Cyclic ADP-ribose analogue Ryanodine receptor TRPM2 Cellular signal transduction

Predictive value of exosomes and their cargo in drug response/resistance of breast cancer patients

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Cancer Drug Resistance 2020年第1期3卷 63-82页

作者： Heidi Schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06123Italy

Exosomes are small extracellular vesicles engaged in intercellular communication in both healthy and tumor *** released by the primary tumor,they transfer their cargo including nucleic acids,proteins,and lipids to target cells,thus modulating the character and fate of the recipient *** propagating their oncogenic content,exosomes are able to promote tumor progression,angiogenesis,metastases,and drug *** functions as delivery vehicles of biological material make exosomes promising biomarkers for the early prediction of disease progression and drug resistance in breast cancer,as well as for therapeutic targeting of molecules to treat this deadly *** the present review,we accentuate the relevance of exosomes as vehicles of prognostic and predictive markers and target molecules,and describe their potential therapeutic applications as drug cargo *** made an extensive literature research to clarify the association of their cargo,including exosomal DNA and RNA molecules,with the propagation of drug resistance.

关键词： Breast cancer exosomes exosomal DNA mRNA non-coding RNAs microRNAs lncRNAs

Elucidating the pathological mechanisms of neurodegeneration in the lethal serpinopathy FENIB

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Neural Regeneration Research 2022年第8期17卷 1733-1734页

作者： Elena Miranda Giovanna Galliciotti Department of Biology and Biotechnologies‘Charles Darwin’and Pasteur Institute-Cenci Bo-lognetti Foundation Sapienza University of RomeRomeItaly Institute of Neuropathology University Medical Center Hamburg-EppendorfHamburgGermany

The term serpinopathies was introduced to describe a family of diseases caused by point mutations in serine protease inhibitors,or *** inhibit their cognate protease by an irreversible suicide mechanism starting with the attack of the active site serine on the reactive center loop of the inhibitor,followed by formation of a covalent complex between both proteins,insertion of the reactive center loop of the serpin into its own beta-sheet A,and culminating in distortion of the active site of the serine protease and thus irreversible *** inhibitory mechanism,reminiscent of the movement of a mousetrap,requires a structural flexibility that proves to be unfavorable when the folding of the serpin is altered by mutations responsible for conformational rearrangements,allowing an intermolecular domain exchange characterized by the insertion of the C-terminal domain of a molecule into a second one,thus forming a *** of this insertion reaction leads to the formation of serpin polymers that accumulate within the endoplasmic reticulum(ER)of the cell and consequently reduces the secretion of the wild-type serpin(Greene et al.,2016).

关键词： insertion irreversible starting