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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(wT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,wT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT wT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of wT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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Catalyst-and solvent-free,thermal generation of microporous polymer networks

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Science China Chemistry 2017年第8期60卷 1103-1106页

作者： christian widling michael forster venkata m.suresh ullrich scherf Bergische Universitdt wuppertal Macromolecular Chemistry Group （buwmakro） and Institute for Polymer Technology D-42119 Wuppertal Germany

Multifunctional iodoaryl monomers were used for the catalyst- and solvent-free generation of microporous polymer networks of high surface areas up to 732mEg-1. The thermal conversion of the monomers relies on the homolytic cleavage of weak iodine-carbon bonds followed by a C-C coupling of the radicalic intermediates. By using tri- or tetrafunctional monomers and by tuning reaction temperature and time, the optimum reaction conditions allow the formation of the corresponding microporous networks in good yields of 71%-86%. The resulting networks exhibit notable high CO2 and H2 adsorption capacities of up to 8.89 wt% （273K, 1 bar） and up to 1.31 wt% （77K, 1 bar）, respectively.

关键词： microporous polymer networks thermal generation gas uptake

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Mitochondrial apoptosis:facilitator of NK cell-mediated immunotherapy

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3170-3171页

作者： Evelyn ullrich Meike Vogler Ivana von Metzler University Hospital Frankfurt Department for Children and Adolescents MedicineGoethe UniversityFrankfurt am MainGermany Experimental Immunology Goethe UniversityFrankfurt am MainGermany Frankfurt Cancer Institute Goethe UniversityFrankfurt am MainGermany University Cancer Center Frankfurt(UCT) University Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany Institute for Experimental Cancer Research in Pediatrics Goethe UniversityFrankfurtGermany Department of Medicine Hematology and OncologyUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

In a recent study published in Cell,Pan et *** how NK cell-based immunotherapy can be combined with BCL2 Homology Domain(BH)3 mimetics to increase tumor cell killing,thus highlighting a novel strategy for cancer immunotherapy.1Induc-tion of mitochondrial apoptosis is a multi-step procedure,and knowledge about the regulation of apoptosis may pave the way for new treatment approaches in immune-oncology.

关键词： BCL2 apoptosis NK cell

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The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain——an in vitro study of human periodontal ligament fibroblasts

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International Journal of Oral Science 2019年第4期11卷 315-324页

作者： Niklas ullrich Agnes Schroder Jonathan Jantsch Gerrit Spanier Peter Proff Christian Kirschneck University Medical Centre of Regensburg Franz-Josef-Strauβ-Allee 11D-93053 RegensburgGermany Department of Orthodontics University Medical Centre of RegensburgFranz-Josef-Strauβ-Allee 11D-93053 RegensburgGermany Department of Medical Microbiology and Hygiene University Medical Centre of RegensburgFranz-Josef-Strauβ-Allee 11D-93053 RegensburgGermany Department of Cranio-Maxillo-Facial Surgery University Medical Centre of RegensburgFranz-Josef-Strauβ-Allee 11D-93053 RegensburgGermany

During orthodontic tooth movement(OTM)mechanical forces trigger pseudo-inflammatory,osteoclastogenic and remodelling processes in the periodontal ligament(PDL)that are mediated by PDL fibroblasts via the expression of various signalling *** far,it is unknown whether these processes are mainly induced by mechanical cellular deformation(mechanotransduction)or by concomitant hypoxic conditions via the compression of periodontal blood *** primary PDL fibroblasts were randomly seeded in conventional six-well cell culture plates with O2-impermeable polystyrene membranes and in special plates with gas-permeable membranes(Lumox?,Sarstedt),enabling the experimental separation of mechanotransducive and hypoxic effects that occur concomitantly during *** simulate physiological orthodontic compressive forces,PDL fibroblasts were stimulated mechanically at 2 g·cm?2 for 48 h after 24 h of *** quantified the cell viability by MTT assay,gene expression by quantitative real-time polymerase chain reaction(RT-qPCR)and protein expression by western blot/enzyme-linked immunosorbent assays(ELISA).In addition,PDL-fibroblast-mediated osteoclastogenesis(TRAP+cells)was measured in a 72-h coculture with RAw264.7 *** expression of HIF-1α,COX-2,PGE2,VEGF,COL1A2,collagen and ALPL,and the RANKL/OPG ratios at the mRNA/protein levels during PDL-fibroblast-mediated osteoclastogenesis were significantly elevated by mechanical loading irrespective of the oxygen supply,whereas hypoxic conditions had no significant additional *** cellular–molecular mediation of OTM by PDL fibroblasts via the expression of various signalling molecules is expected to be predominantly controlled by the application of force(mechanotransduction),whereas hypoxic effects seem to play only a minor *** the context of OTM,the hypoxic marker HIF-1αdoes not appear to be primarily stabilized by a reduced O2 supply but is rather stabilised mechanically.

关键词： RAw264.7 periodontal mec

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Tetraphenylethylene-BODIPY aggregation-induced emission luminogens for near-infrared polymer light-emitting diodes

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Science China Chemistry 2018年第8期61卷 932-939页

作者： Sebnem Baysec Alessandro Minotto Patrick Klein Simone Poddi Andrea Zampetti Sybille Allard Franco Cacialli ullrich Scherf Macromolecular Chemistry and Institute for Polymer Technology Bergische Universitat Wuppertal Wuppertal 42097 Germany Department of Physics and Astronomy and London Centre for Nanotechnology University College London London WCIE 6BT UK

The aggregation-induced emission(AIE) phenomenon provides a new direction for the development of organic light-emitting devices. Here, we present a new class of emitters based on 4,4-difluoro-4-bora-3 a,4 a-diaza-s-indacene(BODIPY), functionalized at different positions with tetraphenylethylene(TPE), which is one of the most famous AIE luminogens. Thanks to this modification, we were able to tune the photoluminescence of the BODIPY moiety from the green to the near-infrared(NIR)spectral range and achieve PL efficiencies of ~50% in the solid state. Remarkably, we observed an enhancement of the AIE and up to ~100% photoluminescence efficiencies by blending the TPE-substituted BODIPY fluorophores with a poly[(9,9-di-noctylfluorene-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,7-diyl)](F8 BT) matrix. By incorporating these blends in organic lightemitting diodes(OLEDs), we obtained electroluminescence peaked in the range 650–700 nm with up to 1.8% external quantum efficiency and ~2 m w/cm2 radiance, a remarkable result for red/NIR emitting and solution-processed OLEDs.

关键词： BODIPY organic light-emitting diode aggregation-induced emission NIR emission photoluminescence electro luminescence

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No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men

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Asian Journal of Andrology 2013年第6期15卷 795-798,I0009页

作者： J ullrich Schwarzer Heiko Steinfatt Heiko Steinfatt Manfred Schleyer Frank M Kōhn Klaus Fiedler2, Irene von Hertwig Gottfried Krüsmann wolfgang würfel Andrologie Centrum MOnchen MOnchen D-81241 Germany Kinderwunsch Centrum MOnchen MOnchen D-81241 Germany Andrologicum MOnchen MOnchen D-80331 Germany

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction （TESE）. For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. with microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly （P=0.017）. No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

关键词： intracytoplasmic sperm injection male infertility microdissection testicular sperm extraction non-obstructiveazoospermia sperm retrieval

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Revisiting the upper eyelid blepharoplasty advancement flap:adaptation for the repair of full-thickness upper eyelid defects—a case series

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Annals of Eye Science 2022年第4期7卷 77-83页

作者： Yinon Shapira Katja ullrich Raman Malhotra Andre S.Litwin Corneoplastic Unit Queen Victoria Hospital NHS TrustEast GrinsteadWest SussexUK

A blepharoplasty flap has been previously reported as a useful reconstruction approach for anterior lamellar defects lying between the lash line and the eyelid *** herein describe a variation of the blepharoplasty flap and suggest its use as an adjunct in the reconstruction of full-thickness lateral upper eyelid *** description and retrospective interventional case *** reconstruction technique was used by an experienced oculoplastics surgeon(ASL)in 3 adults with malignant lesions involving the lateral upper eyelid margin,resulting in a post-excision 50%full-thickness defect between November 2017 and June *** posterior lamella was reconstructed using an ipsilateral free tarsal graft and an inferiorly hinged transposition periosteal *** anterior lamella reconstruction was then performed using a local advancement flap utilizing the principles of upper blepharoplasty and Burow’s *** full eyelid excursion and full gentle closure were evident at 1–2 weeks follow-up in all three *** case later developed 1–2 mm of gentle closure lagophthalmos and was managed successfully with topical *** all patients,the final eyelid contour and symmetry were adequate,with only minimal scarring,evident already 3 to 4 months *** were no major complications or need for *** technique described herein highlights the utility of the blepharoplasty flap for lateral,full-thickness upper eyelid *** logical variation enables the reconstruction of significant defects using only local tissue,obeying the“like with like”principle,and helps avoid the need for a bridging *** provide preliminary evidence of the potential of a good cosmetic outcome of upper lid appearance and contour,together with a fast recovery of appropriate eyelid function.

关键词： Upper eyelid defect reconstruction blepharoplasty flap tarsal graft periosteal flap case series

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Differential impact of flow and mouth leak on oropharyngeal humidification during high-flow nasal cannula: a neonatal bench study

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world Journal of Pediatrics 2018年第3期14卷 305-309页

作者： Tim Leon ullrich Christoph Czernik Christoph Bührer Gerd Schmalisch Hendrik Stefan Fischer Department of Neonatology CharitéUniversity Medical CenterCharitéplatz 110117 BerlinGermany

Background Heated humidification is paramount during neonatal high-flow nasal cannula (HFNC) therapy. However, there is little knowledge about the influence of flow rate and mouth leak on oropharyngeal humidification and temperature. Methods The effect of the Optiflow HFNC on oropharyngeal gas conditioning was investigated at flow rates of 4, 6 and 8 L min-1 with and without mouth leak in a bench model simulating physiological oropharyngeal air conditions during spontaneous breathing. Temperature and absolute humidity (AH) were measured using a digital thermo-hygrosensor. Results without mouth leak, oropharyngeal temperature and AH increased significantly with increasing flow (P when high flows were applied. However, temperature and AH always remained clinically acceptable.

关键词： Humidity Infant Non-invasive ventilation Temperature

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Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

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world Journal of Gastroenterology 2012年第39期18卷 5542-5550页

作者： Ramsi Siaj Vanessa Sauer Sandra Stppeler Hans-ullrich Spiegel Gabriele Khler Andree Zibert Hartmut HJ Schmidt Klinik und Poliklinik für Transplantationsmedizin Universittsklinikum MünsterD-48149 MünsterGermany Abteilung Chirurgische Forschung Klinik und Poliklinik für Allgemein-und ViszeralchirurgieUniversittsklinikum MünsterD-48149 MünsterGermany Gerhard-Domagk-Institut für Pathologie Universittsklinikum MünsterD-48149 MünsterGermany

AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of wilson＇s disease （wD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. RESULTS： Regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. with regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is imp

关键词： wilson's disease Fulminant hepatitis Acuteliver failure Dietary copper Long-Evans cinnamon rat A TP7B

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……who has climbed a few Everests himself

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山西中医学院学报 2007年第3期8卷 5-8页

作者： Noel Bruce ullrich Financial & Corporate Services Ltd. P.O.Box 212 ChristchurchNew Zealand

Mr Chancellor, Ladies and gentleman, I would like to extend my warmest congratulations to those graduating today. Today is the culmination of a number of years of hard work, sacrifice and dedication and I know how proud your own family members and colleagues will be. You are also now, life time members of the Massey University ***, as we all well know, is a series of challenges - large and small and with its peaks and troughs, along the way. way back in 1975 I had been appointed Chairman of an Organizing Committee to send a New Zealand Himalayan Expedition to climb the formidable north face of a mountain called 'Jannu'. It was probably the biggest expedition from New Zealand to ever climb in the Himalayas. Sir Edmund Hillary was patron of the expedition and the team contained some of the country's most notable climbers, including Graeme Dingle - but it was also to be a very expensive exercise. Not ever having had any experience of mountaineering, I tried to be innovative in our approach towards the organization of such an event, particularly in the area of fund raising. Along the way, I even declined the offer of a weekend ascent of Mount Cook. I have a fear of *** there was some financial contribution from the team members, we commissioned a medallion for the expedition which was sold through all branches of the Bank of New South wales (now westpac), we had a national raffle organised for us, we ran fashion shows as fund raisers (we even got members of the team to appear in dinner suits for the first time ever) and persuaded Television One, for a fee, to send along a crew to cover the expedition for a documentary - it was all a great deal of hard *** to terrible weather and treacherous climbing conditions the team did not reach the summit - a couple of the team had to be flown out with minor frostbite, but we got them back all unscathed, but not at all that keen to return for more. Graeme Dingle also wrote a book'wall of Shadows'which raised

关键词：目标策略建议毕业演讲高校毕业生

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