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Elucidating the Degradation Pathways of Human Insulin in the Solid State

Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan Lorraine m.Bateman Joseph P.O’Shea abina m.crean SSPC the SFI Centre for Pharmaceutical ResearchSchool of PharmacyUniversity College CorkCork T12 YT20Ireland School of Pharmacy University College CorkCork T12 YT20Ireland Analytical and Biological Chemistry Research Facility(ABCRF) University College CorkCork T12 YN60Ireland School of Chemistry University College CorkCork T12 YN60Ireland

While there have been significant advances in the development of peptide oral dosage forms in recent years,highlighted by the clinical and commercial success of approved peptides such as Rybelsus®,there remain several barriers in the way of broad range applicability of this approach to peptide *** such barrier includes the poor physical and chemical stability inherent to their structures,which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution *** insulin as a model peptide,this work sought to contribute to the development of analytical techniques for investigating common insulin degradation *** denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy,reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding,chemical modifications and covalent aggregation of the insulin molecule *** state degraded samples were prepared by heating insulin powder at 60°C and 75%relative humidity for 1,3,5 and 7 d,and the degradation profiles of the samples were evaluated and compared with those observed in *** no unfolding was observed to occur,significant deamidation and covalent aggregation were *** disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Insulin Stability Solid state Deamidation Covalent aggregation Disulfide cleavage Biopharmaceutical analysis

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The Potential of Targeting DNA Repair Deficiency in Acute myeloid Leukemia

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Journal of Cancer Therapy 2017年第8期8卷 691-698页

作者： Clare m. crean Ken I. mills Kienan I. Savage Centre for Cancer Research and Cell Biology (CCRCB) Queen’s University Belfast Belfast UK

Acute myeloid leukemia (AmL) is a clonal heterogeneous disease of the myeloid white blood cells. It is characterised by an accumulation of immature blast cells and a number of chromosomal and genetic mutations have been identified. In both de novo and therapy-related AmL, defective DNA repair mechanisms are responsible for some of these genetic abnormalities. Targeting the DNA repair mechanism has been shown to be successful against certain forms of solid tumors and may represent a novel therapeutic approach for AmL.

关键词： DNA Repair Acute myeloid Leukemia

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Growth and differentiation of human induced pluripotent stem cell(hiPSC)-derived kidney organoids using fully synthetic peptide hydrogels

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Bioactive materials 2023年第3期21卷 142-156页

作者： Niall J.Treacy Shane Clerkin Jessica L.Davis Ciar´an Kennedy Aline F.miller Alberto Saiani Jacek K.Wychowaniec Dermot F.Brougham John crean Diabetes Complications Research Centre University College Dublin(UCD)Conway Institute of Biomolecular and Biomedical Research and BelfieldDublin 4Ireland UCD School of Biomolecular and Biomedical Science BelfieldDublin 4Ireland Department of materials&manchester Institute of Biotechnology(mIB) School of Natural SciencesFaculty of Science and EngineeringThe University of ManchesterUK UCD School of Chemistry University College DublinBelfieldDublin 4Ireland

Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised ***,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid *** within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and ***,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,***-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct *** compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell ***,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression ***-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid *** work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.

关键词： Human kidney organoids Fully synthetic matrices Self-assembling peptide hydrogels Single-cell RNA sequencing

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多层螺旋CT冠状动脉钙化积分的辐射剂量阈值:我们能够做到多低?

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国际医学放射学杂志 2011年第6期 608-609页

作者： T.D. Newton H. mehrez B.J. Wintersperger A. crean E. Nguyen 杨绮华 Department of medical Imaging NCSB-1C562 Toronto General Hospital University of Toronto 585 University Avenue Toronto ON M5G 2N2 Canada

目的评估在冠状动脉钙化积分(CCS)结果准确的前提下的最低辐射剂量阈值。方法对43例有CCS适应证并且按照厂家推荐扫描方案进行检查的病人进行前瞻性研究。利用专用软件生成模拟管电流为20～300mA的8个序列的影像。而后对影像进行随机、... 详细信息

目的评估在冠状动脉钙化积分(CCS)结果准确的前提下的最低辐射剂量阈值。方法对43例有CCS适应证并且按照厂家推荐扫描方案进行检查的病人进行前瞻性研究。利用专用软件生成模拟管电流为20～300mA的8个序列的影像。而后对影像进行随机、盲法分析,找出CCS准确前提

关键词：冠状动脉疾病 CT 辐射剂量钙化心电门控成像技术

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萨德伯里地区的矿山不断降低成本改进安全和提高劳动生产率

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国外金属矿山 1989年第2期14卷 15-19,14页

作者： m.斯克尔斯王漱英加拿大<加拿大采矿杂志>

国际镍公司过去和现在经营的矿山有:利瓦克(Levaek),弗鲁德(Frood),斯托比(Stobie),克雷顿(Creighton),克林希尔(crean Hill),加森(Garson),谢班多旺(Shebandowan),默雷(murr-ay),麦克里迪(mc Creedy)。

关键词：矿山安全成本生产率

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