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Nootropics with potential to(re)build neuroarchitecture

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Neural Regeneration Research 2016年第1期11卷 79-80页

作者： Kyoko Koshibu Neuroscience Therapeutic Area UCB Pharma SA

Development of effective treatments for neurodegenerative disorders is a clinical conundrum that has puzzled many *** available drugs target symptomatic relief rather than suppressing,ceasing or repairing the devastat... 详细信息

关键词： devastating damages suppressing approved relief sigma amyloid preliminary mitochondria targeting

Host cell protein quantification workflow using optimized standards combined with data-independent acquisition mass spectrometry

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Journal of pharmaceutical Analysis 2023年第5期13卷 494-502页

作者： Steve Hessmann Cyrille Chery Anne-Sophie Sikora Annick Gervais Christine Carapito BioOrganic Mass Spectrometry Laboratory(LSMBO) IPHC UMR 7178University of StrasbourgCNRSProFI-FR2048Strasbourg67000France Department of Analytical Development Sciences for Biologicals UCB Pharma S.A.Braine l'Alleud1420Belgium

Monitoring of host cell proteins(HCPs)during the manufacturing of monoclonal antibodies(mAb)has become a critical requirement to provide effective and safe drug ***-linked immunosorbent assays are still the gold standard methods for the quantification of protein ***,this technique has several limitations and does,among others,not enable the precise identification of *** this context,mass spectrometry(MS)became an alternative and orthogonal method that delivers qualitative and quantitative information on all identified ***,in order to be routinely implemented in biopharmaceutical companies,liquid chromatography-MS based methods still need to be standardized to provide highest sensitivity and robust and accurate ***,we present a promising MS-based analytical workflow coupling the use of an innovative quantification standard,the HCP Profiler solution,with a spectral library-based data-independent acquisition(DIA)method and strict data validation *** performances of the HCP Profiler solution were compared to more conventional standard protein spikes and the DIA approach was benchmarked against a classical datadependent acquisition on a series of samples produced at various stages of the manufacturing *** we also explored spectral library-free DIA interpretation,the spectral library-based approach still showed highest accuracy and reproducibility(coefficients of variation<10%)with a sensitivity down to the sub-ng/mg mAb ***,this workflow is today mature to be used as a robust and straightforward method to support mAb manufacturing process developments and drug products quality control.

关键词： Host cell proteins Absolute quantification standards Data-independent acquisition

pharmacokinetics,Tolerability,and Bioequivalence of Two Formulations of Rotigotine in Healthy Chinese Subjects

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Pharmacokinetics,Tolerability,and Bioequivalence of Two Form...

SV2B defines a subpopulation of synaptic vesicles

首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： YunLiu Brian Tomlinson Jiyuan Guo Mahnaz Asghamejad Lars Bauer Erwin Surmann Xiaojuan Guo Jan-Peer Elshoff Shanghai Xuhui Central Hospital Prince of Wales Hospital ucb pharma

Purpose:The pharmacokinetics(PK) of rotigotine transdermal patch are well characterized in Caucasian patients with Parkinson's disease(PD) but not in Chinese *** report the PK,safety,and tolerability of rotigotine transdermal patch(2 mg/24 hours and 4 mg/24 hours cold-chain PR2.1.1 formulation) in healthy Chinese subjects(SP0913;NCT01675024).A second separate study(PD0011;NCT02070796)evaluated the relative bioavailability of the cold-chain(PR2.1.1) and room temperature stable(PR2.2.1) formulations of rotigotine in healthy Chinese ***:In Treatment Period 1 of study SP0913,subjects received a single application of rotigotine 2 mg/24 hours on day 1 followed by a washout period(days2-6);Treatment Period 2(days 6-14) involved multiple doses of rotigotine 2 mg/24 hours(days 7-9) followed by multiple doses of rotigotine 4 mg/24 hours(days 10-12),with patches applied for 24 hours *** study PD0011,subjects received a single dose(2 mg/24 hours) of each rotigotine formulation(PR2.2.1 and PR2.1.1) for 24 hours each in a crossover *** samples were collected at scheduled time points to determine plasma concentrations of *** and tolerability were evaluated by adverse events ***:Twenty-four healthy(12 male,12 female) Chinese subjects were enrolled and completed *** mean plasma concentrations of unconjugated and total rotigotine increased to a plateau beginning at～8 hours(multiple dose) to 16 hours(single dose) post-dose;no characteristic Tmax was observed for unconjugated and total *** respective geometric mean Cmax,Cmax,ss,AUC0-tz,AUC0-24,ss values for unconjugated and total rotigotine were similar when rotigotine2 mg/24 hours was applied as a single dose and as a multiple-dose *** the multiple-dose period,geometric mean Cmax,ss and AUC0-24,ss of both unconjugated and total rotigotine were-2-fold higher for rotigotine 4 mg/24 hours than for rotigotine 2 mg/24 ***-seven of 50 male C

关键词： bioequivalence Chinese dopamine agonist pharmacokinetics rotigotine tolerabiity transdermal delivery

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Journal of Molecular Cell Biology 2023年第9期15卷 1-13页

作者： Isabelle Paulussen Hannes Beckert Timothy FMusial Lena J.Gschossmann Julia Wolf Mathieu Schmitt Jérôme Clasadonte Georges Mairet-Coello Christian Wolff Susanne Schoch Dirk Dietrich Synaptic Neuroscience Team Department of NeurosurgeryUniversity Hospital BonnBonn 53127Germany Synaptic Neuroscience Team Department of NeuropathologyUniversity Hospital BonnBonn 53127Germany Microscopy Core Facility Medical FacultyUniversity of BonnBonn 53127Germany ucb pharma Braine l’Alleud 1420Belgium

Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein ***,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron ***2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active *** contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active ***2B and SV2A were found on the membrane in the peri-active zone,suggesting the recycling from both clusters of ***2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency *** data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial *** almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.

关键词： 3D electron microscopy synaptic vesicles synaptic vesicle proteins endocytosis trafficking spatial organization

Micro-porous PLGA/β-TCP/TPU scaffolds prepared by solvent-based 3D printing for bone tissue engineering purposes

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Regenerative Biomaterials 2023年第1期10卷 1538-1551页

作者： Luan P.Hatt Sylvie Wirth Aapo Ristaniemi Daniel J.Ciric Keith Thompson David Eglin Martin J.Stoddart Angela R.Armiento AO Research Institute Davos 7270 Davos PlatzSwitzerland Institute for Biomechanics ETH Zurich8093 ZurichSwitzerland ucb pharma SL13WE SloughUK Mines Saint-Etienne Universitede LyonUniversite´Jean MonnetINSERMU105942023 SainbioseSaint-EtienneFrance Medical Center Faculty of MedicineAlbert-Ludwigs-University of Freiburg79106 FreiburgGermany

The 3D printing process of fused deposition modelling is an attractive fabrication approach to create tissue-engineered bone substitutes to regenerate large mandibular bone defects,but often lacks desired surface porosity for enhanced protein adsorption and cell ***-based printing leads to the spontaneous formation of micropores on the scaffold’s surface upon solvent removal,without the need for further post *** aim is to create and characterize porous scaffolds using a new formulation composed of mechanically stable poly(lactic-co-glycol acid)and osteoconductiveβ-tricalcium phosphate with and without the addition of elastic thermoplastic polyurethane prepared by solvent-based 3D-printing ***-scale regenerative scaffolds can be 3D-printed with adequate fidelity and show porosity at multiple levels analysed via micro-computer tomography,scanning electron microscopy and N_(2) *** mechanical properties compared to a commercially available calcium phosphate ink are demonstrated in compression and screw pull out *** assessments including cell activity assay and live-dead staining prove the scaffold’s *** properties are demonstrated by performing an osteogenic differentiation assay with primary human bone marrow mesenchymal stromal *** propose a versatile fabrication process to create porous 3D-printed scaffolds with adequate mechanical stability and osteoconductivity,both important characteristics for segmental mandibular bone reconstruction.

关键词： solvent-based printing porosity regenerative scaffold osteogenesis mesenchymal stromal cells

fMR在CNS临床药理试验中的应用（英文）

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fMR在CNS临床药理试验中的应用（英文）

Expression and radiolabeling of Cas9 protein

2005年中国神经心理学学术会议

作者：张昊 ucb pharma药品公司

＜正＞fMRI（functional MRI） is gaining attention in pharmaceutical industry for CNS drug development, with focus on cognitive disorder/impairment, motor disorder, incontinence, and pharmacokinetics in early first-in-man clinical trial and later phaseⅢ/Ⅳlarger scale clinical trial. The author summarizes clinical application of fMRI in sense of pharmaco-fMRI, covering sensory, motor/sensory and incontinence, and its perspective

关键词： pharmaco-fMRI CNS drug development Clinical trial

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Nuclear Science and Techniques 2017年第1期28卷 74-79页

作者： Qing-Long Yan Hua-Ting Kong Kai Xia Yu Zhang Ali Aladlbahi Ji-Ye Shi Li-Hua Wang Chun-Hai Fan Yun Zhao Ying Zhu Key Laboratory of Bio-Resources and Eco-Environment Ministry of Education College of Life Sciences Sichuan University Chengdu 610064 China Division of Physical Biology and Bioimaging Center CAS Key Laboratory of Interfacial Physics and TechnologyShanghai Institute of Applied Physics Chinese Academy of Sciences Jiading Campus Shanghai 201800 China Chemistry Department King Saud University Riyadh 11451Saudi Arabia ucb pharma Slough SL1 3WE UK

As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully ***,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled *** optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling *** prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing ***,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.

关键词： Cas9 Radiolabeling 125I labeling yield Stability

Quantum dots protect against MPP＋-induced neurotoxicity in a cell model of Parkinson＇s disease through autophagy induction

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Science China Chemistry 2016年第11期59卷 1486-1491页

作者： Lu Wang Xiaoming Li Yuping Han Ting Wang Yun Zhao Aldalbahi Ali Nahed Nasser El-Sayed Jiye Shi Wenfeng Wang Chunhai Fan Nan Chen Division of Physical Biology and Bioimaging Center Shanghai Synchrotron Radiation FacilityCAS Key Laboratory of Interfacial Physics and TechnologyShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201800China School of Life Science Sichuan UniversityChengdu 610064China Chemistry Department King Saud UniversityRiyadh 11451Saudi Arabia School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China ucb pharma SloughSL1 3WEUK

Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's disease(PD). pharmacological compounds that stimulate autophagy can provide neuroprotection in models of PD. Nanoparticles have emerged as regulators of autophagy and have been tested in adjuvant therapy for diseases. In this present study, we explore the effects of quantum dots(QDs) that can induce autophagy in a cellular model of Parkinson's disease. Cd Te/Cd S/Zn S QDs protect differentiated rat pheochromocytoma PC12 cells from MPP+-induced cell damage, including reduced viability, apoptosis and accumulation of α-Synuclein, a characteristic protein of PD. The protective function of QDs is autophagy-dependent. In addition, we investigate the interaction between quantum dots and autophagic pathways and identify beclin1 as an essential factor for QDs-induced autophagy. Our results reveal new promise of QDs in the theranostic of neurodegenerative diseases.

关键词： quantum dots autophagy Parkinson’s disease α-Synuclein Beclin1

Deciphering active biocompatibility of iron oxide nanoparticles from their intrinsic antagonism

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Nano Research 2018年第5期11卷 2746-2755页

作者： Lu Wang Zejun Wang Xiaoming Li Yi Zhang Min Yin Jiang Li Haiyun Song Jiye Shi Daishun Ling Lihua Wang Nan Chen Chunhai Fan Division of Physical Biology and Bioimaging Center Shanghai Synchrotron Radiation Focility CAS Key Laboratory of Interracial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China School of Life Scienceand Technology Shanghai Tech University Shanghai 201210 China Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China ucb pharma 208 Bath Road Slough SL1 3WE UK College of pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.

关键词： catalase-like activity iron oxide nanoparticles autophagy cytotoxicity reactive oxygen species