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Extracellular DNA and autoimmune diseases

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Cellular & Molecular Immunology 2018年第8期15卷 746-755页

作者： Hantao Lou Matthew C Pickering Molecular Immunology Imperial College LondonLondon W120NNUK centre for Complement and Inflammation Research Imperial College LondonLondon W120NNUK

Extracellular DNA is secreted from various sources including apoptotic cells,NETotic neutrophils and bacterial *** DNA can stimulate innate immune responses to induce type-I IFN production after being *** process is central in antiviral responses but it also plays important role in the pathogenesis of a range of autoimmune diseases such as systemic lupus *** discuss the recent advances in the understanding of the role of extracellular DNA,released from apoptotic and NETotic cells,in autoimmunity.

关键词： DNA type I IFN autoimmunity

Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation

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World Journal of Gastroenterology 2014年第26期20卷 8471-8481页

作者： Stacey J Coleman Jennifer Watt Prabhu Arumugam Leonardo Solaini Elisabeta Carapuca Mohammed Ghallab Richard P Grose Hemant M Kocher centre for Tumour Biology Barts Cancer Institute - a CR-UK Centre of ExcellenceQueen Mary University of LondonJohn Vane Science CentreCharterhouse SquareLondon EC1M 6BQUnited Kingdom Barts and the london HPB centre The Royal London HospitalBarts Health NHS TrustLondon EC1M 6BQUnited Kingdom

Pancreatic cancer carries a terrible prognosis,as the fourth most common cause of cancer death in the Western *** is clearly a need for new therapies to treat this *** of the reasons no effective treatment has been developed in the past decade may in part,be explained by the diverse influences exerted by the tumour *** tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response ***,appropriate preclinical in vitro models which can bridge simple 2D in vitro cell based assays and complex in vivo models are required to understand the biology of pancreatic *** we discuss the evolution of 3D organotypic models,which recapitulare the morphological and functional features of pancreatic ductal adenocarcinoma(PDAC).Organotypic cultures are a valid high throughput preclinical in vitro model that maybe a useful tool to help establish new therapies for PDAC.A huge advantage of the organotypic model system is that any component of the model can be easily modulated in a short *** allows new therapies that can target the cancer,the stromal compartment or both to be tested in a model that mirrors the in vivo situation.A major challenge for the future is to expand the cellular composition of the organotypic model to further develop a system that mimics the PDAC environment more *** discuss how this challenge is being met to increase our understanding of this terrible disease and develop novel therapies that can improve the prognosis for patients.

关键词： 3D organotypic model Pancreatic cancer Pancreatic stellate cell Stroma Preclinical models

T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： Michelle R Goulart Konstantinos Stasinos Rachel Elizabeth Ann Fincham Francesca R Delvecchio Hemant M Kocher centre for Tumour Biology Barts Cancer Institute-A CRUK centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the london HPB centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom centre for Experimental Medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival *** has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T *** cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant *** tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted ***,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion Tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma

Synaptic dysfunction in Alzheimer's disease:the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention

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Neural Regeneration Research 2018年第4期13卷 616-623页

作者： Jade Marsh Pavlos Alifragis centre for Biomedical Sciences School of Biological SciencesRoyal Holloway University of London

The most prevalent form of dementia in the elderly is Alzheimer＇s disease.A significant contributing factor to the progression of the disease appears to be the progressive accumulation of amyloid-β42（Aβ42）,a small hydrophobic ***,attempts to develop therapies targeting the accumulation of Aβ42 have not been successful to treat or even slow down the *** is possible that this failure is an indication that targeting downstream effects rather than the accumulation of the peptide itself might be a more effective *** accumulation of Aβ42 seems to affect various aspects of physiological cell *** this review,we provide an overview of the evidence that implicates Aβ42 in synaptic dysfunction,with a focus on how it contributes to defects in synaptic vesicle dynamics and neurotransmitter *** discuss data that provide new insights on the Aβ42 induced pathology of Alzheimer＇s disease and a more detailed understanding of its contribution to the synaptic deficiencies that are associated with the early stages of the *** the precise mechanisms that trigger synaptic dysfunction are still under investigation,the available data so far has enabled us to put forward a model that could be used as a guide to generate new therapeutic targets for pharmaceutical intervention.

关键词： Alzheimer's disease amyloid-β 42 synaptic vesicles synaptic dysfunction neurotransmitter release

Cryogel scaffolds: soft and easy to use tools for neural tissue culture

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Neural Regeneration Research 2022年第9期17卷 1981-1983页

作者： Ben Newland Katherine R.Long School of Pharmacy and Pharmaceutical Sciences Cardiff UniversityCardiffUK centre for Developmental Neurobiology Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonMRC Centre for Neurodevelopmental DisordersKing’s College LondonLondonUK

The mammalian central nervous system(CNS)is highly complex,with a vast array of processes and interactions occurring in a dynamic and often transient *** these processes are combined to regulate our behavior remains poorly *** has in turn led to a lack of understanding of how these processes have gone awry in the many disorders of the nervous *** order to address this,researchers need a controlled way to manipulate the nervous system in in vitro and ex vivo cultures,in both a specific area and for a specific period of time to start to pick apart these *** date,this has been technically challenging,especially when modeling focal injury to the CNS or when working with human brain tissue.

关键词： culture neural transient

Lobular capillary hemangioma of the liver

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Hepatobiliary & Pancreatic Diseases International 2009年第3期8卷 323-325页

作者： Faisal Abaalkhail Mathieu Castonguay David K.Driman Jeremy Parfitt Paul Marotta london Health Sciences centre University of Western Ontario

BACKGROUND: Lobular capillary hemangioma (LCH) is a benign vascular tumor that is rare in adults and has never been reported in the liver. This vascular lesion usually presents on the skin or mucous membranes, and predominantly affects children. METHODS: LCH as a large asymptomatic hepatic mass was seen in a 35-year-old female. Imaging and pathologic characteristics of the mass are reviewed, and the relevant literature is also reviewed. RESULTS: A large vascular hepatic lesion was observed in an asymptomatic 35-year-old female. Pathologic examination after surgical resection revealed typical features of LCH. CONCLUSIONS: This is the first case of lobular capillary hemangioma seen as a liver lesion in an adult. Large vascular hepatic lesions pose significant difficulties in discerning benign from potentially malignant conditions. In this report we describe the pitfalls and radiological uncertainties with interpreting vascular lesions of the liver. (Hepatobiliary Pancreat Dis Int 2009; 8: 323-325)

关键词： lobular capillary hemangioma benign

Characterising populations living close to intensive farming and composting facilities in England

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Frontiers of Environmental Science & Engineering 2021年第3期15卷 97-109页

作者： Philippa Douglas Daniela Fecht Deborah Jarvis National Heart and Lung Institute MRC Centre for Environment and HealthImperial College LondonLondonSW36LZUK centre for Radiation Chemical and Environmental HazardsPublic Health EnglandHarwell CampusDidcotOxfordshireOX 11 ORQUK UK Small Area Health Statistics Unit MRC Centre for Environment and HealthSchool of Public HealthImperial College LondonLondonW2 IPGUK

Bioaerosol exposure has been linked to adverse respiratory *** farming and composting facilities are important anthropogenic sources of *** aimed to characterise populations living close to intensive farming and composting *** also infer whether the public are becoming more concerned about anthropogenic bioaerosol emissions,using reports of air pollution related incidents attributed to *** mapped the location of 1,257 intensive farming and 310 composting facilities in England in relation to the resident population and its characteristics(sex and age),area characteristics(deprivation proxy and rural/urban classification)and school locations stratified by pre-defined distance bands from these bioaerosol *** also calculated the average number of air pollution related incidents per year per *** found that more than 16%of the population and 15%of schools are located within 4,828 m of an intensive farming facility or 4,000 m of a composting facility;few people(0.01%)live very close to these sites and tend to be older *** to composting facilities,populations are more likely to be urban and more *** number of incidents were attributed to a small proportion of facilities;population characteristics around these facilities were *** indicate that populations living near composting facilities(particularly>250 to≤4,000 m)are mostly located in ur6an areas(80188%of the population),which supports the need for more community health studies to be *** could also be used to inform risk management strategies at facilities with higher numbers of incidents.

关键词： Composting Intensive farming Bioaerosol Population characteristics Public health

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

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四川生理科学杂志 2024年第7期46卷 1635-1635页

作者： Anissa A Widjaja Cardiovascular and Metabolic Disorders Program Duke–National University of Singapore Medical School Singapore Singapore National Heart Research Institute Singapore National Heart Centre Singapore Singapore Singapore Institute for Big Data and Artificial Intelligence in Medicine School of Science China Pharmaceutical University Nanjing China MRC Laboratory of Medical Sciences London UK Barts Heart centre Barts Health NHS Trust London UK Cardiovascular and Metabolic Sciences Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany DZHK (German centre for Cardiovascular Research) Partner Site Berlin Berlin Germany Charité–Universitätsmedizin Berlin Germany Institute of Clinical Sciences Faculty of Medicine Imperial College London UK Bone Biology and Disease Unit St Vincent’s Institute of Medical Research Melbourne Victoria Australia Department of Medicine St Vincent’s Hospital The University of Melbourne Melbourne Victoria Australia

For healthspan and lifespan,ERK,AMPK and mTORC1 represent critical pathways and inflammation is a centrally important *** we examined whether IL-11,a pro-inflammatory cytokine of the IL-6 family,has a negative effect on age-associated disease and *** mice age,IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular,tissue-and organismal-level ageing *** of Il11 or Il11ra1 protects against metabolic decline,multi-morbidity and frailty in old age.

关键词： inflammation mTORC1 life

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