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Plants against cancer:towards green Taxol production through pathway discovery and metabolic engineering

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aBIOTECH 2024年第3期5卷 394-402页

作者： philipp Zerbe Department of Plant Biology University of California DavisDavisCA 95616USA

The diversity of plant natural products presents a rich resource for accelerating drug discovery and addressing pressing human health ***,the challenges in accessing and cultivating source species,as well as metabolite structural complexity,and general low abundance present considerable hurdles in developing plant-derived *** in high-throughput sequencing,genome assembly,gene synthesis,analytical technologies,and synthetic biology approaches,now enable us to efficiently identify and engineer enzymes and metabolic pathways for producing natural and new-to-nature therapeutics and drug *** review highlights challenges and progress in plant natural product discovery and engineering by example of recent breakthroughs in identifying the missing enzymes involved in the biosynthesis of the anti-cancer agent Taxol^(®).These enzyme resources offer new avenues for the bio-manufacture and semi-synthesis of an old blockbuster drug.

关键词： Taxol Plant natural products Synthetic biology Pathway discovery Metabolic engineering

Do you want to participate in a clinical study as a healthy control?-Risk or benefit?

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World Journal of Clinical Cases 2017年第12期5卷 437-439页

作者： Hanna Giessen christian A Nebiker Matthias Bruehlmeier Stefan Spreitzer Beat Mueller philipp Schuetz Department of Internal Medicine Kantonsspital Aarau Department of Surgery Kantonsspital Aarau Department of Nuclear Medicine Kan- tonsspital Aarau Department of Pathology Kantonsspital Aarau

A healthy woman volunteered to participate as "healthy control" in a *** increased level of procalcitonin(PCT) was detected and remained elevated on follow-up *** calcitonin levels were elevated as well,thyroid ultrasound was performed which revealed nodes in both thyroid lobes,one of them showing metabolic activity in positron emission tomography-computed tomography *** exclude a malignant thyroid cancer despite the negative findings in a fine needle aspiration the patient underwent thyroidectomy and a medullary thyroid carcinoma(MTC) was detected in the right *** is a rare endocrine tumor with a poor prognosis once having spread,therefore early detection remains a priority for the *** parameter is serum calcitonin,in absence of infection the pro-hormone PCT can be used as a screening parameter as well with high sensitivity.

关键词： Medullary thyroid cancer Procalcitonin Thyroid nodes Endocrinology Public health Healthy control

Calibration-free speckle matrix imaging

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Light(Science & Applications) 2022年第3期11卷 1-3页

作者： philipp del Hougne Univ Rennes CNRSIETR-UMR 616435000RennesFrance

Unknown speckle patterns can be used to image targets embedded in complex scattering media 100 times faster than previous techniques based on carefully calibrated illuminations.

关键词： speckle illumination faster

A new silicon phthalocyanine dye induces pyroptosis in prostate cancer cells during photoimmunotherapy

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Bioactive Materials 2024年第11期41卷 537-552页

作者： Isis Wolf Jonas Storz Susanne Schultze-Seemann philipp REsser Stefan FMartin Susan Lauw Peer Fischer Wolfgang Melchinger Robert Zeiser Oliver Gorka Olaf Groß christian Gratzke Reinhard Brückner philipp Wolf Department of Urology Medical Center–University of Freiburg79106FreiburgGermany Faculty of Medicine University of Freiburg79106FreiburgGermany Faculty of Biology University of Freiburg79104FreiburgGermany Institute for Organic Chemistry University of Freiburg79104FreiburgGermany Allergy Research Group Department of DermatologyMedical Center–University of Freiburg79104FreiburgGermany Core Facility Signalling Factory&Robotics University of Freiburg79104FreiburgGermany BIOSS Centre for Biological Signalling Studies University of Freiburg79104FreiburgGermany Max Planck Institute for Medical Research 69120HeidelbergGermany Institute for Molecular Systems Engineering and Advanced Materials Heidelberg University69120HeidelbergGermany Department of Internal Medicine I Medical Center-University of Freiburg79106FreiburgGermany k Institute of Neuropathology Medical Center-University of Freiburg79106FreiburgGermany CIBSS Centre for Integrative Biological Signalling Studies University of Freiburg79104FreiburgGermany Received 12 Septembe

Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer *** designed and synthesized,in a highly convergent manner,the silicon phthalocyanine dye WB692-CB2,which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to *** the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen(PSMA).The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red *** cells exhibited morphological characteristics associated with *** studies revealed the generation of reactive oxygen species,triggering a cascade of intracellular events involving lipid peroxidation,caspase-1 activation,gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular *** first in vivo experiments,PIT with our antibody dye conjugate led to a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor *** study highlights the future potential of the new phthalocyanine dye WB692-CB2 as PS for the fluorescence-based detection and PIT of cancer,including local prostate tumor lesions,and systemic activation of anti-tumor immune responses by the induction of pyroptosis.

关键词： Silicon phthalocyanine Photoimmunotherapy Cancer Pyroptosis Immunogenic cell death

In vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens of acute cholangitis

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World Journal of Gastroenterology 2008年第20期14卷 3174-3178页

作者： Andreas Weber Wolfgang Huber Klaus Kamereck philipp Winkle Petra Voland hans Weidenbach Roland M Schmid christian Prinz Department of Gastroenterology Klinikum rechts der Isar Technical University Munich Institute of Medical Microbiology Immunology and Hygiene Klinikum rechts der Isar Technical University Munich

AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction （n = 7）, benign biliary stricture （n = 16）, and malignant biliary stricture （n = 42） were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS： Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species （26/63）, Ecoli （13/63） and Klebsiella species （8/63）. A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for *** and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for ***： Enterococcus species, ***/i and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.

关键词： Cholangitis Acute cholangitis Endoscopy Antibiotics Moxifloxacin Piperacillin Sulbactam Biliarystricture Resistance Bacterial pathogens

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk:Results From a German Multicenter Retrospective Cohort Study

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 626-637页

作者： Johannes Gillessen philipp Reuken Peter-Marton Hunyady Matthias christian Reichert Lucian Lothschütz Fabian Finkelmeier Matthias Nowka Gabriel Allo Fabian Kütting Martin Bürger Dirk Nierhoff hans-Michael Steffen Christoph Schramm University Hospital Cologne Department of Gastroenterology and HepatologyCologneGermany University Hospital Jena Department of Internal Medicine IV-GastroenterologyHepatologyInfectious DiseaseJenaGermany University Hospital Frankfurt Department of Internal Medicine 1-Gastroenterology und HepatologyPulmonology und AllergologyEndocrinologyFrankfurtGermany Department of Medicine II Saarland University Medical CenterHomburgGermany Department of Gastroenterology and Hepatology University Hospital of EssenEssenGermany

Background and Aims:Hepatocellular carcinoma(HCC)surveillance in patients at risk is strongly recommended and usually performed by ultrasound(US)semiannually with or without alfa-fetoprotein(AFP)*** pa-rameters except for surveillance intervals have not been strictly *** aimed to evaluate surveillance success and risk factors for surveillance ***:Patients with≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively *** success was defined as HCC detection within Milan ***:Only 47%of 156 patients,median age 63(interquartile range:57-70)years,56%male,and 96%with cirrhosis,received recom-mended surveillance modality and *** fail-ure occurred in 29%and was significantly associated with lower median model for end-stage liver disease(MELD)score odds ratio(OR)1.154,95%confidence interval(CI):1.027-1.297,p=0.025)and HCC localization within right liver lobe(OR:6.083,95%CI:1.303-28.407,p=0.022),but not with AFP≥200μg/*** with surveillance failure had sig-nificantly more intermediate/advanced tumor stages(93%vs.6%,p<0.001),fewer curative treatment options(15%vs.75%,p<0.001)and lower survival at 1 year(54%vs.75%,p=0.041),2 years(32%vs.57%,p=0.019)and 5 years(0%vs.16%,p=0.009).Alcoholic and non-alcoholic fatty liver disease(OR:6.1,95%CI:1.7-21.3,p=0.005)and ascites(OR:3.9,95%CI:1.2-12.6,p=0.021)were in-dependently associated with severe visual limitations on ***:US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related *** MELD score and HCC lo-calization within right liver lobe were significantly associated with surveillance failure.

关键词： Hepatocellular carcinoma Surveillance success Screening Ultra-sound.

Injury patterns of seniors in traffic accidents: A technical and medical analysis

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World Journal of Orthopedics 2012年第9期3卷 151-155页

作者： Stephan Brand Dietmar Otte christian Walter Mueller Maximilian Petri philipp Haas Timo Stuebig christian Krettek Carl Haasper Accident Research Unit Trauma Department Medical School Hannover (MHH) D-30625 Hannover Germany

AIM:To investigate the actual injury situation of seniors in traffic accidents and to evaluate the different injury ***:Injury data,environmental circumstances and crash circumstances of accidents were collected shortly after the accident event at the *** these data,a technical and medical analysis was performed,including Injury Severity Score,Abbreviated Injury Scale and Maximum Abbreviated Injury *** method of data collection is named the German InDepth Accident Study and can be seen as ***:A total of 4430 injured seniors in traffic accidents were *** incidence of sustaining severe injuries to extremities,head and maxillofacial region was significantly higher in the group of elderly people compared to a younger age(P<0.05).The number of accident-related injuries was higher in the group of seniors compared to other ***:Seniors are more likely to be involved in traffic injuries and to sustain serious to severe injuries compared to other groups.

关键词： Traffic accidents Seniors Head injury Injury severity score Abbreviated injury scale

Effect of nanoparticle concentration on zeta-potential measurement results and reproducibility

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Particuology 2010年第3期8卷 279-285页

作者： Ratna Tantra philipp Schulze Paul Quincey National Physical Laboratory Hampton Road Teddington Middlesex TW11 0LW UK Department of Physics University of Bath Bath BA2 7AY UK. National Physical Laboratory Hampton Road Teddington Middlesex TW11 0LW

The effect of nanoparticle concentration on zeta-potential measurement results at dilute concentrations was evaluated. The values of the zeta-potential for four different types of nanoparticles, Ludox （silica）, multi-walled carbon nanotubes （bamboo-shaped and hollow nanotubes） and gold, at various concentrations, were obtained using a laser Doppler electrophoresis instrument. The size of the nanoparticles on dilution was measured using dynamic light scattering （DLS）. The results show that there is a concentration range within which the zeta-potential, and particle size, are not affected by nanoparticle concentration. The lower concentration limit for the system to produce consistent results was dependent on the nature of the sample under study and ranged between 10-2 and 10-4 wt%. Below this concentration, there was an apparent shift in zeta-potential values to less negative values, which was accompanied by an increase in the particle size. The shift in zeta-potential was attributed to an increase in contribution of the signal from extraneous particulate matter. The increase in particle size was attributed to the nature of the homodyne optical configuration of the instrument. The aim of this study was to elucidate the range in nanoparticle concentration that allows for accurate and reliable measurement of the zeta-potential and DLS data.

关键词： Nanoparticles Zeta-potential Dynamic light scattering Reproducibility

Entropy‑Conservative Discontinuous Galerkin Methods for the Shallow Water Equations with Uncertainty

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Communications on Applied Mathematics and Computation 2024年第3期6卷 1978-2010页

作者： Janina Bender philipp Öffner Institute of Mathematics University KasselMonchebergstraße 1934127 KasselGermany Institute of Mathematics Johannes Gutenberg UniversityStaudingerweg 955099 MainzGermany Mathematical Institute Technical University ClausthalErzstraße 138678 Clausthal ZellerfeldGermany

In this paper,we develop an entropy-conservative discontinuous Galerkin(DG)method for the shallow water(SW)equation with random *** of the most popular methods for uncertainty quantifcation is the generalized Polynomial Chaos(gPC)approach which we consider in the following *** apply the stochastic Galerkin(SG)method to the stochastic SW *** the SG approach in the stochastic hyperbolic SW system yields a purely deterministic system that is not necessarily hyperbolic *** lack of the hyperbolicity leads to ill-posedness and stability issues in numerical *** transforming the system using Roe variables,the hyperbolicity can be ensured and an entropy-entropy fux pair is known from a recent investigation by Gerster and Herty(***.27(3):639–671,2020).We use this pair and determine a corresponding entropy fux ***,we construct entropy conservative numerical twopoint fuxes for this augmented *** applying these new numerical fuxes in a nodal DG spectral element method(DGSEM)with fux diferencing ansatz,we obtain a provable entropy conservative(dissipative)*** numerical experiments,we validate our theoretical fndings.

关键词： Shallow water(SW)equations Entropy conservation/dissipation Uncertainty quantification Discontinuous Galerkin(DG) Generalized Polynomial Chaos(gPC)