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measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts

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microsystems & Nanoengineering 2022年第5期8卷 149-160页

作者： Samuel H.Kann Erin m.Shaughnessey Jonathan R.Coppeta Hesham Azizgolshani Brett CIsenberg else m.vedula Xin Zhang Joseph L.Charest Draper Scholar 555 Technology SquareCambridgeMA 02139USA Department of mechanical Engineering Boston University110 Cummington MallBostonMA 02215USA Department of Biomedical Engineering Tufts University4 Colby StreetMedfordMA 02155USA Draper 555 Technology SquareCambridgeMA 02139USA Present address:Biogen 225 Binney StreetCambridgeMA 02142USA

measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip(OOC)systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue ***,current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints,require labels or added substrates,and lack real-time ***,we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer *** membrane bilayer device supported a culture of human renal proximal tubule epithelial cells on a porous membrane suspended between two microchannels and exposed to controlled,unidirectional perfusion and physiologically relevant shear stress for several *** the first time,we measured changes in oxygen in a membrane bilayer format and used a finite element analysis model to estimate cell oxygen consumption rates(OCRs),allowing comparison with OCRs from other cell culture ***,we demonstrated label-free detection of metabolic shifts in human renal proximal tubule cells following exposure to FCCP,a drug known for increasing cell oxygen consumption,as well as oligomycin and antimycin A,drugs known for decreasing cell oxygen *** capability to measure cell OCRs and detect metabolic shifts in an array of membrane bilayer devices contained within an industry standard microtiter plate format will be valuable for analyzing flowresponsive and physiologically complex tissues during drug development and disease research.

关键词： metabolism culture OCR

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala mark Dixon Timothy J England Kailash Krishnan Grant mair Keith W muir John Potter Christopher I Price marc Randall Thompson G Robinson Christine Roffe else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna m Wardlaw Nikola Sprigg Philip m Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or mann-Whitney difference(mWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(mWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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In vitro angiogenesis in response to biomaterial properties for bone tissue engineering:a review of the state of the art

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Regenerative Biomaterials 2023年第1期10卷 744-783页

作者： else Ellermann Nima meyer Ruth E.Cameron Serena m.Best Department of materials Science and metallurgy University of CambridgeCambridge CB30FSUK

Bone tissue engineering(BTE)aims to improve the healing of bone fractures using scaffolds that mimic the native extracellular *** successful bone regeneration,scaffolds should promote simultaneous bone tissue formation and blood vessel growth for nutrient and waste ***,a significant challenge in regenerative medicine remains the development of grafts that can be vascularized *** other things,optimization of physicochemical conditions of scaffolds is key to achieving appropriate angiogenesis in the period immediately following *** phosphates and collagen scaffolds are two of the most widely studied biomaterials for BTE,due to their close resemblance to inorganic and organic components of bone,respectively,and their bioactivity,tunable biodegradability and the ability to produce tailored *** various strategies exist to enhance vascularization of these scaffolds in vivo,further in vitro assessment is crucial to understand the relation between physicochemical properties of a biomaterial and its ability to induce *** mono-culture studies can provide evidence regarding cell-material interaction of a single cell type,a co-culture procedure is crucial for assessing the complex mechanisms involved in angiogenesis.A co-culture more closely resembles the natural tissue both physically and biologically by stimulating natural intercellular interactions and mimicking the organization of the in vivo ***,a co-culture is a complex system requiring optimization of various parameters including cell types,cell ratio,culture medium and seeding *** fundamental knowledge of the mechanism behind the bioactivity of biomaterials and understanding the contribution of surface and architectural features to the vascularization of scaffolds,and the biological response in general,can provide an invaluable basis for future optimization *** review gives an overview of the

关键词： angiogenesis collagen scaffolds hydroxyapatite co-culture architectural features physicochemical properties

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Trefoil factors in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第12期20卷 3223-3230页

作者： Luise Aamann else marie Vestergaard Henning Grφnbk Department of Hepatology and Gastroenterology Aarhus University Hospital Department of Clinical Genetics Aarhus University Hospital

Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn’s disease, is characterized by inflammation of the gastrointestinal tract. The trefoil factors 1, 2, and 3 (TFF1-3) are a family of peptides that play important roles in the protection and repair of epithelial surfaces, including the gastrointestinal tract. TFFs may be involved in IBD pathogenesis and are a potential treatment option. In the present review, we describe the TFF family and their potential role in IBD by summarizing the current knowledge of their expression, possible function and pharmacological role in IBD.

关键词： Trefoil factors, Inflammatory bowel disease, Ulcerative colitis, Crohn’ s disease, Inflammation

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Increased susceptibility to Trichuris muris infection and exacerbation of colitis in mdr1a-/-mice

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World Journal of Gastroenterology 2014年第7期20卷 1797-1806页

作者： Ekta K Bhardwaj Kathryn J else michael T Rogan Geoffrey Warhurst School of Environment and Life Sciences University of SalfordSalford M68HDUnited Kingdom Faculty of Life Sciences University of ManchesterManchester M139PTUnited Kingdom Infection Injury and Inflammation Research GroupSalford Royal NHS Foundation TrustSalford M68HDUnited Kingdom

AIm: To investigate the influence of Trichuris muris (T. muris) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, mdr1a-/-.

关键词： Helminth Colitis Inflammatory bowel disease P-glycoprotein mdr1a

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Sol-gel derived B_(2)O_(3)-CaO borate bioactive glasses with hemostatic,antibacterial and pro-angiogenic activities

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Regenerative Biomaterials 2024年第1期3卷 108-118页

作者： Kai Zheng Faina Bider mahshid monavari Zhiyan Xu Christina Janko Christoph Alexiou Ana m.Beltran Aldo R.Boccaccini Jiangsu Province Engineering Research Center of Stomatological Translational medicine College of StomatologyNanjing Medical UniversityNanjing 210029China Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Institute of Biomaterials University of Erlangen-Nuremberg91058 ErlangenGermany Department of Oto-Rhino-Laryngology Head and Neck SurgerySection of Experimental Oncology and Nanomedicine(SEON)Else Kroener-Fresenius-Stiftung ProfessorshipUniversitaetsklinikum Erlangen91058 ErlangenGermany Departamento de Ingenier�ıa y Ciencia de los materiales y del Transporte Escuela Politecnica

Sol-gel borate bioactive glasses(BGs)are promising ion-releasing biomaterials for wound healing ***,we report the synthesis of a series of binary B_(2)O_(3)-CaO borate BGs(CaO ranging from 50 to 90mol%)using a sol-gel-based *** influence of CaO content in B_(2)O_(3)-CaO borate BG on morphology,structure and ion release behavior was investigated in *** dissolution(ion release)and crystallization could be observed in borate BGs when CaO content increased,while the morphology was not significantly altered by increasing CaO *** results evidenced that the ion release behavior of borate BGs could be tailored by tuning the B_(2)O_(3)/CaO molar *** also evaluated the in vitro cytotoxicity,hemostatic,antibacterial and angiogenic activities of borate *** was validated for all borate ***,borate BGs exhibited composition-dependent hemostatic,antibacterial and angiogenic ***,higher contents of Ca in borate BGs facilitated hemostatic activity,while higher contents of B_(2)O_(3) were beneficial for pro-angiogenic *** synthesized sol-gel-derived borate BGs are promising materials for developing advanced wound healing dressings,given their fast ion release behavior and favorable hemostatic,antibacterial and angiogenic activities.

关键词： borate glasses sol-gel processing glass composition wound healing

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Heterogeneity across the murine small and large intestine

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World Journal of Gastroenterology 2014年第41期20卷 15216-15232页

作者： Rowann Bowcutt Ruth Forman maria Glymenaki Simon Richard Carding Kathryn Jane else Sheena margaret Cruickshank Faculty of Life Sciences University of Manchester Department of microbiology New York University Gut Health and Food Safety Research Programme Institute of Food Research and the Norwich Medical SchoolUniversity of East Anglia

The small and large intestine of the gastrointestinal tract(GIT) have evolved to have discrete functions with distinct anatomies and immune cell *** importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the ***,different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic *** large and small intestine,given their anatomical and functional differences,should be seen as two separate immunological ***,this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the *** largely on the murine small and large intestine,this review addresses the literature relating to the immunology and biology of the two sites,drawing comparisons between them and clarifying similarities and *** also highlight the gaps in our understanding and where further research is needed.

关键词： Large intestine Small intestine Epithelial Immune microbial

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Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions

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Genes & Diseases 2024年第5期11卷 40-43页

作者： Konstantin Deutsch Verena Klambt Thomas m.Kitzler Tilman Jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky Jameela A.Kari Farkhanda Hafeez maria Szczepanska Loai A.Eid Hazem S.Awad muna Al-Saffar Neveen A.Soliman Velibor Tasic Camille Nicolas-Frank Kirollos Yousef Luca m.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant m.mane Nancy Rodig Friedhelm Hildebrandt Division of Nephrology Department of PediatricsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatric Gastroenterology Nephrology and Metabolic DiseasesCharite Universitatsmedizin BerlinBerlin 13353Germany Berlin Institute of Health at Charitee Universitatsmedizin Berlin BIH Biomedical Innovation AcademyBIH Charite Clinician Scientist ProgramBerlin 10178Germany Department of Nephrology and Hypertension FriedrichAlexander-Universitat Erlangen-NurnbergErlangen 91054Germany Department of Pediatrics Faculty of Medicine King Abdulaziz UniversityPediatric Nephrology Center of ExcellenceKing Abdulaziz University HospitalJeddah 21589Saudi Arabia Department of Pediatric Nephrology The Children’s Hospital and Institute of Child HealthLahore 54000Pakistan Department of Pediatrics Faculty of Medical Sciences in ZabrzeMedical University of Silesia in KatowiceKatowice 40-752Poland Dubai Hospital and Al-Jalila Children’s Specialty Hospital Kidney Center of ExcellenceDubai 4545United Arab Emirates Department of Genetics and Genomics UAE UniversityAbu Dhabi 15551United Arab Emirates Department of Pediatrics Division of Genetics and GenomicsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatrics Center of Pediatric Nephrology and TransplantationKasr Al Ainy School of MedicineCairo UniversityCairo 11562Egypt Egypt Center for Research and Regenerative medicine(ECRRm) Cairo 11511Egypt medical Faculty Skopje University Children’s HospitalSkopje 1000North Macedonia Department of Genetics Yale University School of MedicineNew HavenCT 06520USA

Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common *** genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic *** are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关键词： degeneration urinary likely

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S1NOCARPUS AND ASSOCIATED ANGIOSPERm FOSSILS IN JEHOL BIOTA

S1NOCARPUS AND ASSOCIATED ANGIOSPERM FOSSILS IN JEHOL BIOTA

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第二届国际古生物学大会

作者： else marie FRIIS Swedish museum of Natural History Box 50007 SE-104 05 Stockholm Sweden

Angiosperm mega-fossils have been reported from the Yixian Formation, the lower part of the Jehol Group which hosts the renowned Jehol Biota. Angiosperms in the Jehol Biota are mainly represented by reproductive organs, while in other Early Cretaceous mega-fossil assemblages they are mostly represented by vegetative structures. Jehol angiosperms include Archaefructus Sun, Dilcher, Zheng et Zhou and Sinocarpus Leng et Friis, as well as other putative angiosperm fossils such as Beipiaoa Dilcher, Sun et Zheng comprising isolated seeds/fruits with sturdy spines, and some unnamed seeds/fruits with long hairs. Leaves with monocot-like gross morphology have been reported, but due to poor preservation their angiosperm affinity has not been

关键词： Sinocarpus Archaefructus reproductive organs dicot angiosperm leaves

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英国

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作者： David·else等

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