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Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells

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Nano Research 2016年第11期9卷 3437-3452页

作者： Wolfram C. Poller evelyn Ramberger Philipp Boehm-Sturm Susanne Mueller Konstantin Moller Norbert Lowa Frank Wiekhorst Susanne Wagner Matthias Taupitz eyk Schellenberger Gert Baumann Karl Stangl Verena Stangl Antje Ludwig Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie Charite-Universitatsmedizin Berlin Campus Mitte Chariteplatz 1 10117 Berlin Germany Abteilung fur experimentelle Neurologie Center for Stroke Research Charite-Universitatsmedizin Berlin Chariteplatz 1 10117 Berlin Germany charite Core Facility '7 T experimental MRIs' Charite-Universitatsmedizin Berlin Chariteplatz 1 10117 Berlin Germany Physikalisch-Technische Bundesanstalt Abbestr. 2-12 10587Berlin Germany Institut fur Radiologie Charite-Universitatsmedizin Berlin Campus Mitte Charit@platz 1 10117 Berlin Germany DZHK (German Centre for Cardiovascular Research) partner site Berlin 10115 Berlin Germany berlin Institute of Health (BIH) 10117 Berlin Germany

Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient （LDLR^-/-） mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy （TeM） at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TeM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. experiments with endocytosis inhibitors and small interfering RNA （siRNA） revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.

关键词： atherosclerosis,unstable plaques,magnetic resonanceimaging decreased endothelial barrier function,superparamagnetic ironoxide nanoparticles

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Influence of the body mass index on postoperative outcome and long-term survival after pancreatic resections in patients with underlying malignancy

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 201-210页

作者： Philippa Seika Fritz Klein Uwe Pelzer Johann Pratschke Marcus Bahra Thomas Malinka Department of Surgery Charite Campus Mitte and Charite Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany Department of Hematology/Oncology/Tumorimmunology Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany

Background:While the long-term survival rate among patients with pancreatic and periampullary carcinomas remains low,it can be influenced by various *** purpose of this retrospective study was to investigate the effects of body mass index(BMI)on postoperative complications and patient survival after pancreatic resections for underlying malignancy over a 20-year observation ***:We analyzed 1,384 patients,918 patients with pancreatic ductal adenocarcinoma(PDAC)(66.3%),229 patients with distal cholangiocarcinoma(16.5%),206 ampullary carcinoma patients(14.8%),and 31 duodenal carcinoma patients(2.2%).Patients were classified into four groups(group 130.0)according to their BMI(kg/m2).We analyzed differences in postoperative complications,postoperative length of hospital stays,reoperations,postoperative mortality and survival rate among the ***:Within a mean observation period of 687.7[2–8,500]days,735(53.1%)patients *** were important differences in postoperative complications(group 1,16.2%;group 2,20.3%;group 3,27.2%,group 4,41.6%)with the type of postoperative complications also varying between the *** 1-,5-,10-and 15-year survival rates were 66.4%,25.5%,17.9%,and 12.1%,respectively,with survival rates varying amongst the four ***:Patients with a BMI between 18.5 and 30 show better postoperative outcomes,regarding complications,hospitalization duration,and reoperation rates than underweight or obese ***-term survival depends strongly on postoperative complications while patients with a higher BMI show better long-term survival rates.

关键词： Pancreatic resection body mass index(BMI) outcome long-term survival

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Stigma and its impact on the families of former soldiers of the German Armed Forces: An exploratory study

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Military Medical Research 2019年第2期6卷 143-158页

作者： Katrin Schuy Simone Dors Loni Brants Marie Horzetzky Gerd Willmund Andreas Strohle Peter Zimmermann Heinrich Rau Stefan Siegel Department of Psychiatry and Psychotherapy Campus ChariteMitteCharite-Universitatsmedizin Berlin10117BerlinGermany Psychotraumazentrum Military Hospital10115BerlinGermany

Background: Military families who have a family member with a mental illness see themselves confronted with many demands. Stigmatization is one of these challenges. Stigmatization affects not only the individual who suffers from a mental illness but also other family members via stigma by association and vicarious stigma. Stigma by association occurs when mental illness stigma spills over to individuals associated with an individual with a mental illness. Vicarious stigma describes the suffering of family members when they note the impact of stigma on their relative with mental illness. As a societal phenomenon, stigma plays out in social interactions and might therefore influence the social networks of families. It is also associated with healthcare ***: Narrative interviews were conducted with 15 family members(partners, spouses, parents and children) of former soldiers of the German Armed Forces with a service-induced mental illness. The transcribed interview data were analyzed using a thematic analysis approach, in which codes were formed and emerging themes were systemized. Relationships between stigma, the families’ reactions to it, its effects on their social relationships and its interference with their healthcare utilization were ***: This study provides a detailed description of how relatives of former German soldiers with mental health problems experience stigma by association and vicarious stigma. Their perceptions are shown in a model that describes stigma-related attitudes, reactions to them and their effects on the social relationships of former soldiers’ families. These families felt stigmatized because of the former soldiers’ mental illness(mental illness stigma) and the military context in which it occurred(former soldier stigma). They reacted with nondisclosure, anger, acceptance and self-blame. Stigma was associated with smaller and weaker social networks that were characterized by social exclusion, self-segregation a

关键词： Stigma by association Vicarious stigma Families Mental illness Veteran German Armed Forces

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Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score

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Asian Journal of Andrology 2014年第6期16卷 897-901页

作者： Xin-Hai Hu Henning Cammann Hellmuth-A Meyer Klaus Jung Hong-Biao Lu Natalia Levas Ahmed Magheli Carsten Stephan Jonas Busch Department of Urology Charite - Universitatsmedizin Berlin Berlin Germany Institute of Medical Informatics Charite - Universitatsmedizin Berlin Berlin Germany berlin Institute for Urologic Research Berlin Germany Department of Urology Changzhou No. 2 People's Hospital Changzhou China Stanford University School of Medicine Stanford CA USA.

Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence （BCR）. However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy （LRP） were used to develop an artificial neural network （ANN） to predict BCR and to compare it with a logistic regression （LR） model using clinical and pathologic parameters, prostate-specific antigen （PSA）, margin status （RO/1）, pathological stage （pT）, and Gleason Score （GS）. For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic （ROC） curve （AUC） for the ANN （0.754） and LR models （0.755） calculated immediately following LRP, were larger than that for GS （AUC： 0.715; P= 0.0015 and 0.001）, pT or PSA （AUC： 0.619; Palways 〈0.0001） alone. The GS predicted the BCR better than PSA （P = 0.0001）, but there was no difference between the ANN and LR models （P = 0.39）. Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS ≥7.

关键词： artificial neural network prostate cancer recurrence

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Propriospinal interneurons in the spotlight for anatomical and functional recovery after spinal cord injury

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Neural Regeneration Research 2015年第11期10卷 1737-1738页

作者： Martin Pohland Jana Glumm Institute of Cell Biology and Neurobiology Center for Anatomy Charite-Universitatsmedizin Berlin Department of Neurosurgery HELIOS Klinikum Berlin Buch

Spinal cord injury（SCI）with consecutive paralysis below the lesion level is a severe disorder affecting the patient for the rest of his or her *** far,there is no known fundamental intervention strategy for efficiently helping those patients regain their motor abilities,despite intense research in this ***,effective treatment for those patients is still an open question. A spinal cord injury is accompanied by a prima- ry, severe and irreversible neuronal cell death in the trauma region, fol- lowed by a secondary extensive cell necrosis in the lesion surrounding areas. Nevertheless, recent studies indicate that regeneration after spinal cord injury could be possible if three substantial steps are fulfilled：（1） reduction of the inhibitory environment at the SCI lesion site, （2） iden- tification of a neural substrate to establish new spinal circuits, and （3） support of these circuits to form permanent, functional motor, sensory, or autonomic connections （Dru and Hoh, 2015）.

关键词： Propriospinal interneurons in the spotlight for anatomical and functional recovery after spinal cord injury eGFP GAD DCX

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Synthetic lethality by PARP inhibitors: new mechanism uncovered based on unresolved transcription-replication conflicts

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3163-3164页

作者： Marina Kolesnichenko Claus Scheidereit Department of Hepatology and Gastroenterology Charite-Universitatsmedizin BerlinBerlinGermany Laboratory for Signal Transduction in Tumor Cells Max Delbruck Center for Molecular Medicine in the Helmholtz Association(MDC)BerlinGermany

In a landmark study recently published in Nature,Petropoulous et *** that synthetic lethality of poly(ADP-ribose)polymerase(PARP)inhibitors in cells with defective homologous recombination repair(HR)results predominantly from transcription replication conflicts(TRC)and not,as previously proposed,from PARP trapping on DNA(Fig.1).The article unveils a new mechanism behind synthetic lethality of PARP inhibitors with relevance for cancer therapy.

关键词： PARP mechanism

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Cardiovascular Involvement in Chronic Hepatitis C Virus Infections - Insight from Novel Antiviral Therapies

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Journal of Clinical and Translational Hepatology 2018年第2期6卷 161-167页

作者： Wolfgang Poller Arash Haghikia Mario Kasner Ziya Kaya Udo Bavendiek Heiner Wedemeier Hans-Jorg epple Carsten Skurk Ulf Landmesser Department of Cardiology CC11 Charite Campus Benjamin FranklinCharite-Universitatsmedizin BerlinBerlinGermany German Center for Cardiovascular Research(DZHK)Site berlin BerlinGermany German Center for Cardiovascular Research(DZHK)Site Heidelberg HeidelbergGermany Department of Cardiology University HospitalHeidelbergGermany Department of Cardiology MHHHannoverGermany Department of Gastroenterology MHHHannoverGermany Department of Gastroenterology Infectiology and RheumatologyCC 13Charite Campus Benjamin FranklinCharite-Universitatsmedizin BerlinBerlinGermany

Whereas statistical association of hepatitis C virus(HCV)infection with cardiomyopathy is long known,establishment of a causal relationship has not been achieved so *** with advanced heart failure(HF)are mostly unable to tolerate interferon(IFN)-based treatment,resulting in limited experi-ence regarding the possible pathogenic role of HCV in this patient *** infection often triggers disease in a broad spectrum of extrahepatic organs,with innate immune and autoimmune pathogenic processes *** fact that worldwide more than 70 million patients are chronically infected with HCV illustrates the possible clinical impact arising if cardiomyopathies were induced or aggravated by HCV,resulting in progressive HF or severe arrhythmias.A novel path has been opened to finally resolve the long-standing question of cause-effect relationship between HCV infection and cardiac dysfunction,by the recent development of IFN-free,highly efficient,and well tolerable anti-HCV *** new direct-acting antiviral(DAA)agents are highly virus-specific and lack unspecific side-effects upon cardiac function which have always confounded the interpret-tation of IFN treatment *** actual frequency of un-explained HF in chronic HCV infection will be determined from a planned large-scale *** such patients probably constitute a rather small fraction of all those harboring HCV,they have major clinical *** is not yet known which fraction of these patients will significantly benefit from HCV eradication,but this issue will be addressed now in a prospective study.

关键词： Autoimmunity Cardiovascular immunity Cardiomyopathies Hepatitis C virus Antiviral therapies

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Validation of the enhanced Recovery after Surgery (eRAS) society recommendations for liver surgery: a prospective, observational study

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Hepatobiliary Surgery and Nutrition 2023年第1期12卷 20-36,I0003-I0006页

作者： Moritz Schmelzle Felix Krenzien Paul Dahlke Alina Krombholz Nora Nevermann Linda Feldbrügge Axel Winter Wenzel Schoning Christian Benzing Johann Pratschke Jens Neudecker Department of Surgery Campus Charite Mitte and Campus Virchow-KlinikumCharite-Universitatsmedizincorporate member of Freie Universität BerlinHumboldt-Universitat zu BerlinBerlinGermany berlin Institute of Health(BIH) BerlinGermany

Twenty-three recommendations were summarized by the enhanced Recovery After Surgery(eRAS)society for liver *** aim was to validate the protocol especially with regard to adherence and the impact on ***:Using the eRAS Interactive Audit System(eIAS),eRAS items were evaluated in patients undergoing liver *** a period of 26 months,304 patients were prospectively enrolled in an observational study(DRKS00017229).Of those,51 patients(non-eRAS)were enrolled before and 253 patients(eRAS)after the implementation of the eRAS *** adherence and complications were compared between the two ***:Overall adherence increased from 45.2%in the non-eRAS group to 62.7%in the eRAS group(Ped with significant improvements in the preoperative and postoperative phase(Per than in the outpatient and intraoperative phase(both P>0.05).Overall complications decreased from 41.2%(n=21)in the non-eRAS group to 26.5%(n=67)in the eRAS group(P=0.0423),which was mainly due to the reduction of grade 1-2 complications from 17.6%(n=9)to 7.6%(n=19)(P=0.0322).As for patients undergoing open surgery,implementation of eRAS lead to a reduction of overall complications in patients scheduled for minimally invasive liver surgery(MILS)(P=0.036).Conclusions:Implementation of the eRAS protocol for liver surgery according to the eRAS guidelines of the eRAS Society reduced Clavien-Dindo grade 1-2 complications particularly in patients who underwent *** eRAS guidelines are beneficial for the outcome,while adherence to the various items has not yet been satisfactorily defined.

关键词： enhanced Recovery After Surgery(eRAS) prehabilitation liver surger

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Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2297-2299页

作者： Cameron Mura Saskia Preissner Susanne Nahles Max Heiland Philip e.Bourne Robert Preissner School of Data Science and Deportment of Biomedical engineering University of VirginiaCharlottesvilleVAUSA Department Oral and Maxillofacial Surgery Charite-Universitatsmedizin Berlincorporate member of Freie Universitat BerlinHumboldt-Universitat zu Berlinand Berlin Institute of HealthBerlinGermany Institute of Physiology and Science-IT Charite-Universitatsmedizin Berlincorporate member of Freie Universitat BerlinHumboldt-Universitat zu Berlinand Berlin Institute of HealthBerlinGermany

Dear editor,The COVID-19 pandemic has driven great interest in the therapeutic potential of repurposed drugs with well-established benefits and safety profiles(toxicity,bioavailability,etc.),many of which act via sign... 详细信息

关键词： drugs category COV

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Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity

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Journal of Molecular Cell Biology 2016年第2期8卷 178-181页

作者： Martina Gast Blanche Schroen Antje Voigt Jan Haas Uwe Kuehl Dirk Lassner Carsten Skurk Felicitas escher Xiaomin Wang Adelheid Kratzer Katharina Michalik Anna Papageorgiou Tim Peters Madlen Loebel Sabrina Wilk Nadine Althof Kannanganattu VPrasanth Hugo Katus Benjamin Meder Shinichi Nakagawa Carmen Scheibenbogen Heinz-Peter Schultheiss Ulf Landmesser Stefanie Dimmeler Stephane Heymans Wolfgang Poller Department of Cardiology and Pneumology Campus Benjamin FranklinCharite–Universitatsmedizin BerlinBerlinGermany Center for Heart Failure Research Cardiovascular Research Institute Maastricht(CARIM)Maastricht UniversityMaastrichtNetherlands Institute of Biochemistry Campus Charite MitteCharite–Universitatsmedizin BerlinBerlinGermany Otto-Meyerhof-Centrum University of HeidelbergHeidelbergGermany Medizinische Klinik University of HeidelbergHeidelbergGermany Institute for Cardiac Diagnostics and Therapy(IKDT) BerlinGermany Institute for Cardiovascular Regeneration Goethe University FrankfurtFrankfurtGermany Institute for Medical Immunology Campus Virchow KlinikumCharite–Universitatsmedizin BerlinBerlinGermany berlin Center forRegenerative Therapies(BCRT) Charite–Universitatsmedizin BerlinBerlinGermany Department of CellandDevelopmental Biology University of Illinois at Urbana-ChampaignUrbanaIL 61801USA RNA Biology Laboratory RIKEN Advanced Research InstituteWakoSaitama 351-0198Japan German Center for Cardiovascular Research(DZHK) Site BerlinGermany DZHK Site Rhein-MainGermany

Dear editor,Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding *** is estimated that.30000 long noncoding RNAs(lncRNAs)are expressed in humans,but their functions are largely unknown(Suckau et al.,2009;Rinn and Chang,2012;Poller et al.,2013).Consideration of noncoding genomic elements in pathogenetic studies is warranted and enabled by technological advances allowing comprehensive transcriptome mapping of protein-coding genes as well as small and long ncRNAs.

关键词： MALAT1 immunity

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