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Mechanism-driven strategies for prevention of rheumatoid arthritis

Rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： v.michael holers Kristine A.Kuhn M.Kristen Demoruelle Jill M.Norris Gary S.Firestein Eddie A.James William H.Robinson Jane H.Buckner Kevin D.Deane Division of Rheumatology University of Colorado School of MedicineAuroraColoradoUSA Department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA Division of Rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research Institute SeattleWashingtonUSA Division of Immunology and Rheumatology Stanford UniversityStanfordCaliforniaUSA Department of Medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

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超顺磁铁纳米材料与血清蛋白结合模式

超顺磁铁纳米材料与血清蛋白结合模式

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作者：陈芳芳王冠奎 James I.Griffin Barbara Brenneman Nirmal K.Banda v.michael holers Donald S.Backos 吴林平 Seyed Moein Monghimi Dmitri Simberg 吉林大学

成果内容研究属于纳米医学转化领域成果,应用医学免疫学及化学、材料学的技术揭示纳米材料与补体、免疫细胞等固有免疫应答系统相互作用的结果及客观规律。纳米材料造影剂和药物载体静脉注射后吸附血液蛋白质形成蛋白冠,蛋白冠的组成取...

成果内容研究属于纳米医学转化领域成果,应用医学免疫学及化学、材料学的技术揭示纳米材料与补体、免疫细胞等固有免疫应答系统相互作用的结果及客观规律。纳米材料造影剂和药物载体静脉注射后吸附血液蛋白质形成蛋白冠,蛋白冠的组成取决于纳米材料固有的物理化学性质,其在纳米材料药代动力学和生物学性能中发挥调节作用,对其靶向、免疫识别和毒性均有影响。本研究尝试通过工程学超顺磁氧化

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Use of an immunocapture device to detect cytokine release in discrete brain regions

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Neural Regeneration Research 2024年第4期19卷 703-704页

作者： Matthew G.Frank michael v.Baratta Department of Integrative Physiology University of Colorado BoulderBoulderCOUSA(Frank MG)Department of Psychology and NeuroscienceUniversity of Colorado BoulderBoulderCOUSA(Baratta MV)

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

关键词： system release innate

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Geometric Programming for Nonlinear Satellite Buffer Networks With Time Delays under L_(1)-Gain Performance

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 554-556页

作者： Yukang Cui Yihui Huang michael v.Basin Zongze Wu College of Mechatronics and Control Engineering Shenzhen UniversityShenzhen 518060China Shenzhen University Shenzhen 518060China Peng Cheng Laboratory Shenzhen 518060China Robotics Institute Ningbo University of TechnologyNingbo 315211China Autonomous University of Nuevo Leon Nuevo Leon 66455Mexico

Dear Editor,This letter concerns the parameter tuning problem for nonlinear satellite buffer networks with communication delays, aiming to optimize their stability properties under L_(1)-gain. We first model the satellite buffer networks by a nonlinear time-delay positive system and propose a novel characterization under which the nonlinear system is asymptotically stable with a prescribed L_(1)-induced performance.

关键词： nonlinear system prescribed

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Ion-conducting Membranes Based on Bacterial Cellulose Nanofibers Modified by Poly(sodium acrylate-co-2-acrylamido-2-methylpropanesulfonic acid)

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Chinese Journal of Polymer Science 2024年第3期42卷 333-343,I0007页

作者： Elizaveta v.Batishcheva Nikolay N.Smirnov Natalya v.Bobrova Maria P.Sokolova michael A.Smirnov Institute of Macromolecular Compounds Russian Academy of SciencesBolshoy pr.31Saint Petersburg 199004Russia

Green method for preparation of ion-conducting membranes(ICM) based on bacterial cellulose nanofibers(CNF) modified by a copolymer of sodium acrylate and 2-acrylamido-2-methylpropanesulfonic acid was elaborated. FTIR and NMR data confirmed grafting of polyacrylate onto cellulose surface. Formation of porous structure of the ICM was controlled by SEM and AFM. The maximal ionic conductivity of the membranes reaches 1.5 and 3.1 mS·cm^(-1)(60 ℃ and 98% relative humidity) when they are saturated with water or H_2SO_4(1 mol·L^(-1)) electrolyte,respectively. Prepared ICM was tested as a separator in a symmetrical supercapacitor with electrodes based on polyaniline hydrogel. The assembled cell demonstrate ability to operate at high current density up to 100 A·g^(-1) maintaining specific capacitance 165 F·g^(-1). Maximal specific capacitance of 289 F·g^(-1) was achieved at current density 1 A·g^(-1). Retaining of 90% of initial capacitance after 10000 of charge-discharge cycles proves high electrochemical stability of prepared ICM.

关键词： Bacterial cellulose Ion conductivity Porous membrane Supercapacitor

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An examination of thematic research,development,and trends in remote sensing applied to conservation agriculture

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International Soil and Water Conservation Research 2024年第1期12卷 77-95页

作者： Zobaer Ahmed Aaron Shew Lawton Nalley michael Popp v.Steven Green Kristofor Brye Center for Advanced Spatial Technologies University of ArkansasFayettevilleARUSA Environmental Dynamics Program University of ArkansasFayettevilleARUSA Department of Agricultural Economics and Agribusiness University of ArkansasFayettevilleARUSA College of Agriculture Arkansas State UniversityJonesboroARUSA University of Arkansas System Division of Agriculture Little RockARUSA Department of Crop Soiland Environmental SciencesUniversity of ArkansasFayettevilleARUSA

Conservation agriculture seeks to reduce environmental degradation through sustainable management of agricultural land.Since the 1990s,agricultural research has been conducted using remote sensing technologies;however,few previous reviews have been conducted focused on different conservation management practices.Most of the previous literature has focused on the application of remote sensing in agriculture without focusing exclusively on conservation practices,with some only providing a narrative review,others using biophysical remote sensing for quantitative estimates of the bio-geo-chemical-physical properties of soils and crops,and few others focused on single agricultural management practices.This paper used the preferred reporting items for systematic review(PRISMA)methodology to examine the last 30 years of thematic research,development,and trends associated with remote sensing technologies and methods applied to conservation agriculture research at various spatial and temporal scales.A set of predefined key concepts and keywords were applied in three databases:Scopus,Web of Science,and Google Scholar.A total of 188 articles were compiled for initial examination,where 68 articles were selected for final analysis and grouped into cover crops,crop residue,crop rotation,mulching,and tillage practices.Publications on conservation agriculture research using remote sensing have been increasing since 1991 and peaked at 10 publications in 2020.Among the 68 articles,94%used a pixel-based,while only 6%used an object-based classification method.Prior to 2005,tillage practices were abundantly studied,then crop residue was a focused theme between 2004 and 2012.From 2012 to 2020,the focus shifted again to cover crops.Ten spectral indices were used in 76%of the 68 studies.This examination offered a summary of the new potential and identifies crucial future research needs and directions that could improve the contribution of remote sensing to the provision of long-term operational services for various conservation agricult

关键词： Remote sensing Conservation agriculture Classification algorithm Spatial resolution Satellite Spectral indices PRISMA

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Diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder michael Roden Nicolas venteclef Institute for Clinical Diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German Center for Diabetes Research(DZD) Partner Düsseldorf85764München-NeuherbergGermany Department of Endocrinology and Diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants Malades(INEM) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

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Large-scale genome-wide SNP analysis reveals the rugged(and ragged)landscape of global ancestry,phylogeny,and demographic history in chicken breeds

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 324-340页

作者： Natalia v.DEMENTIEvA Yuri S.SHCHERBAKOv Olga I.STANISHEvSKAYA Anatoly B.vAKHRAMEEv Tatiana A.LARKINA Artem P.DYSIN Olga A.NIKOLAEvA Anna E.RYABOvA Anastasiia I.AZOvTSEvA Olga v.MITROFANOvA Grigoriy K.PEGLIvANYAN Natalia R.REINBACH Darren K.GRIFFIN michael N.ROMANOv Russian Research Institute of Farm Animal Genetics and Breeding-Branch of the L.K.Ernst Federal Research Centre for Animal Husbandry.Pushkin St.Petersburg196601Russia School of Biosciences University of KentCanterburyCT27NJUK L.K.Ernst Federal Research Center for Animal Husbandry DubrovitsyPodolskMoscow Oblast142132Russia

The worldwide chicken gene pool encompasses a remarkable,but shrinking,number of divergently selected breeds of diverse origin.This study was a large-scale genome-wide analysis of the landscape of the complex molecular architecture,genetic variability,and detailed structure among 49 populations.These populations represent a significant sample of the world's chicken breeds from Europe(Russia,Czech Republic,France,Spain,UK,etc.),Asia(China),North America(USA),and Oceania(Australia).Based on the results of breed genotyping using the Illumina 60K single nucleotide polymorphism(SNP)chip,a bioinformatic analysis was carried out.This included the calculation of heterozygosity/homozygosity statistics,inbreeding coefficients,and effective population size.It also included assessment of linkage disequilibrium and construction of phylogenetic trees.Using multidimensional scaling,principal component analysis,and ADMIXTURE-assisted global ancestry analysis,we explored the genetic structure of populations and subpopulations in each breed.An overall 49-population phylogeny analysis was also performed,and a refined evolutionary model of chicken breed formation was proposed,which included egg,meat,dual-purpose types,and ambiguous breeds.Such a large-scale survey of genetic resources in poultry farming using modern genomic methods is of great interest both from the viewpoint of a general understanding of the genetics of the domestic chicken and for the further development of genomic technologies and approaches in poultry breeding.In general,whole genome SNP genotyping of promising chicken breeds from the worldwide gene pool will promote the further development of modern genomic science as applied to poultry.

关键词： Chicken genome diversity Single nucleotide polymorphism(SNP)analysis Gene pool Global ancestry Phylogeny Demographic history

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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 activation.Mechanistically,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling.In 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 phosphorylation.Conversely,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity.The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression.We 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 explants.Similar 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 animals.Consistently,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by Syntenin-1.In 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

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor vivian Szymczuk Brendan Boyce Daniel Martin vardit Kram Rebeca Galisteo Kamran Melikov Leonid v.Chernomordik michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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