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Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK nihr southampton biomedical research centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)***-ing of disease pathogenesis remains limited and has prevented the development of effective *** an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully *** human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory *** review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis Epithelial-mesenchymal transition(EMT) Crosstalk

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

Spatial analysis of the osteoarthritis microenvironment: techniques, insights, and applications

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Bone research 2024年第1期12卷 1-19页

作者： Xiwei Fan Antonia Rujia Sun Reuben S.E.Young Isaac O.Afara Brett R.Hamilton Louis Jun Ye Ong Ross Crawford Indira Prasadam centre for biomedical Technologies Queensland University of TechnologyBrisbaneQLDAustralia School of Mechanical Medical&Process EngineeringQueensland University of TechnologyBrisbaneQLDAustralia Central Analytical research facility Queensland University of TechnologyBrisbaneQLDAustralia Molecular Horizons University of WollongongWollongongNSWAustralia Department of Technical Physics University of Eastern FinlandKuopioFinland School of Electrical Engineering and Computer Science Faculty of EngineeringArchitecture and Information TechnologyUniversity of QueenslandBrisbaneQLDAustralia centre for Microscopy and Microanalysis University of QueenslandBrisbaneQLDAustralia The Prince Charles Hospital BrisbaneQLDAustralia

Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose *** presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial ***,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic *** analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint *** issue has led to standardization difficulties and hindered the success of clinical *** insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease *** resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular *** advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial *** fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial ***,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and *** these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease *** review summarizes the rec

关键词： insight Spatial enable

Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

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World Journal of Stem Cells 2024年第4期16卷 334-352页

作者： Jie-Yu Xiang Lin Kang Zi-Ming Li Song-Lu Tseng Li-Quan Wang Tian-Hao Li Zhu-Jun Li Jiu-Zuo Huang Nan-Ze Yu Xiao Long Department of Plastic and Reconstructive Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China biomedical Engineering facility Institute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100021China

Wound repair is a complex challenge for both clinical practitioners and *** approaches for wound repair have several *** cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin ***,the use of stem cells in skin regeneration presents several ***,stem cells and biomaterials have been identified as crucial components of the wound-healing *** therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable *** scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the *** scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound *** article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine ***,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

关键词： Stem-cell-based therapy Biological scaffolds Wound healing Extracellular matrix mimicry Cellular activities enhancement Scaffold characteristics

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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枕大神经阻滞对丛集性头痛的疗效

中国康复 2024年第7期39卷 438-438页

作者：王玫懿(译) Gordon A Wolfson centre for Age-Related Diseases Institute of Psychiatry Psychology & Neuroscience King's College London Torbay and South Devon NHS Foundation Trust University Hospitals Plymouth NHS Trust nihr-Wellcome Trust King’s clinical research facility/SLaM biomedical research centre King's College Hospital

丛集性头痛被描述为患者经历过的最痛苦的情况。枕大神经阻滞是一种短期预防性治疗方法,通常包括向枕下区域注射皮质类固醇和局部麻醉剂。这项分析回顾了这种干预措施对慢性丛集性头痛患者的疗效。文献综述的研究对象包括接受枕骨神经... 详细信息

丛集性头痛被描述为患者经历过的最痛苦的情况。枕大神经阻滞是一种短期预防性治疗方法,通常包括向枕下区域注射皮质类固醇和局部麻醉剂。这项分析回顾了这种干预措施对慢性丛集性头痛患者的疗效。文献综述的研究对象包括接受枕骨神经阻滞治疗的丛集性头痛患者。治疗效果被定义为头痛频率、严重程度和持续时间的变化。

关键词：丛集性头痛皮质类固醇预防性治疗局部麻醉剂神经阻滞治疗枕大神经阻滞干预措施持续时间

“机械灌注+”应用于扩大标准供肝移植--肝尽其用

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Engineering 2024年第1期32卷 29-40页

作者： Zhoucheng Wang Jack Martin Jiongjie Yu Kai Wang Kourosh Saeb-Parsy Xiao Xu Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006China Department of Surgery Cambridge University Hospitals&NHS Foundation TrustCambridge CB22QQ UK Department of Surgery University of Cambridge&NIHR Cambridge Biomedical Research CentreCambridge CB22QQUK Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China

Transplantation represents the most effective treatment for end-stage liver diseases but is limited by the shortage of healthy donor *** criteria donor(ECD)liver grafts are increasingly utilized in clinical practice to mitigate this ***,impaired ischemic tolerance of these grafts jeopardizes organ viability during cold *** perfusion(MP)was designed to improve organ preservation and reduce posttransplant ***,it is increasingly evident that MP alone may not preserve ECD grafts *** emphasis has thus been placed on modified MP strategies,including the use of different perfusates,modified perfusion modalities,and different therapeutic ***,we introduce a novel term,"MP Plus,"denoting these additional strategies that are designed to restore organ function and potentially enable regeneration of ECD *** this review,we summarize the existing and potential modified MP strategies and discuss their advantages in reconditioning different ECD grafts in clinical settings.

关键词： Liver transplantation Extended criteria donor Machine perfusion plus Organ shortage

Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes Jessica Rast Caichen Zhong Renee M Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind Neil M Davies Brian K Lee Cecilia Magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden Medical research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of clinical Neuroscience Karolinska InstitutetStockholmSweden centre for Epidemiology and Community Medicine Region StockholmStockholmSweden K.G Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK nihr biomedical research centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample Mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

Adipose-derived stem cells in diabetic foot care:Bridging clinical trials and practical application

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World Journal of Diabetes 2024年第6期15卷 1162-1177页

作者： Song-Lu Tseng Lin Kang Zhu-Jun Li Li-Quan Wang Zi-Ming Li Tian-Hao Li Jie-Yu Xiang Jiu-Zuo Huang Nan-Ze Yu Xiao Long Department of Plastic and Reconstructive Surgery Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Plastic and Reconstructive Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China biomedical Engineering facility Institute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences BeijingBeijing 100021China

Diabetic foot ulcers(DFUs)pose a critical medical challenge,significantly impairing the quality of life of ***-derived stem cells(ADSCs)have been identified as a promising therapeutic approach for improving wound healing in *** extensive exploration of the mechanical aspects of ADSC therapy against DFU,its clinical applications remain *** this review,we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of *** review begins with a discussion of the classification and clinical management of diabetic foot *** then discusses the current landscape of clinical trials,focusing on their geographic distribution,reported efficacy,safety profiles,treatment timing,administration techniques,and dosing ***,the review discusses the preclinical strategies to enhance ADSC *** review shows that many trials exhibit biases in study design,unclear inclusion criteria,and intervention *** conclusion,this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches,with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

关键词： Adipose-derived stem cells Diabetic foot ulcers Wound healing clinical