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Cellular senescence in musculoskeletal homeostasis,diseases,and regeneration

Bone Research 2021年第4期9卷 444-455页

作者： Mei Wan Elise F.Gray-Gaillard jennifer h.elisseeff Department of Orthopaedic Surgery The Johns Hopkins University School of MedicineBaltimoreMDUSA Translational Tissue Engineering Center Wilmer Eye Institute and the Department of Biomedical EngineeringThe Johns Hopkins UniversityBaltimoreMDUSA

Emerging insights into cellular senescence highlight the relevance of senescence in musculoskeletal disorders,which represent the leading global cause of *** senescence was initially described by hayflick et *** 1961 as an irreversible nondividing state in in vitro cell culture *** now know that cellular senescence can occur in vivo in response to various stressors as a heterogeneous and tissue-specific cell state with a secretome phenotype acquired after the initial growth *** the past two decades,compelling evidence from preclinical models and human data show an accumulation of senescent cells in many components of the musculoskeletal *** senescence is therefore a defining feature of age-related musculoskeletal disorders,and targeted elimination of these cells has emerged recently as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration of the skeleton and skeletal *** this review,we summarize evidence of the role of senescent cells in the maintenance of bone homeostasis during childhood and their contribution to the pathogenesis of chronic musculoskeletal disorders,including osteoporosis,osteoarthritis,and *** highlight the diversity of the senescent cells in the microenvironment of bone,joint,and skeletal muscle tissue,as well as the mechanisms by which these senescent cells are involved in musculoskeletal *** addition,we discuss how identifying and targeting senescent cells might positively affect pathologic progression and musculoskeletal system regeneration.

关键词： skeletal homeostasis dividing

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Regulating the proinflammatory response to composite biomaterials by targeting immunometabolism

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Bioactive Materials 2024年第10期40卷 64-73页

作者： Chima V.Maduka Ashley V.Makela Anthony Tundo Evran Ural Katlin B.Stivers Maxwell M.Kuhnert Mohammed Alhaj Ehsanul hoque Apu Nureddin Ashammakhi Kurt D.hankenson Ramani Narayan jennifer h.elisseeff Christopher h.Contag Comparative Medicine&Integrative Biology Michigan State UniversityEast LansingMI48824USA Department of Biomedical Engineering College of EngineeringMichigan State UniversityEast LansingMI48824USA Institute for Quantitative health Science&Engineering Michigan State UniversityEast LansingMI48824USA Translational Tissue Engineering Center Johns Hopkins University School of MedicineBaltimoreMD21231USA Department of Chemical Engineering&Materials Science Michigan State UniversityEast LansingMI48824USA Department of Biomedical Sciences College of Dental MedicineLincoln Memorial UniversityKnoxvilleTN37917USA Department of Orthopedic Surgery University of Michigan Medical SchoolAnn ArborMI48109USA Department of Biomedical Engineering Johns Hopkins University School of MedicineBaltimoreMD21231USA Department of Microbiology Genetics&ImmunologyMichigan State UniversityEast LansingMI48864USA BioFrontiers Institute University of ColoradoBoulderCO 80303USA.

Composite biomaterials comprising polylactide(PLA)and hydroxyapatite(hA)are applied in bone,cartilage and dental regenerative medicine,where hA confers osteoconductive ***,after surgical implantation,adverse immune responses to these composites can occur,which have been attributed to size and morphology of hA *** to effectively modulate these adverse immune responses have not been *** degradation products have been shown to alter immune cell metabolism(immunometabolism),which drives the inflammatory ***,to modulate the inflammatory response to composite biomaterials,inhibitors were incorporated into composites comprised of amorphous PLA(aPLA)and hA(aPLA+hA)to regulate glycolytic *** at specific steps in glycolysis reduced proinflammatory(CD86+CD206-)and increased pro-regenerative(CD206+)immune cell populations around implanted aPLA+***,neutrophil and dendritic cell(DC)numbers along with proinflammatory monocyte and macrophage populations were decreased,and Arginase 1 expression among DCs was *** immunometabolism to control the proinflammatory response to biomaterial composites,thereby creating a pro-regenerative microenvironment,is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis,which could lead to improved bone regeneration.

关键词： hydroxyapatite Polylactide Immunometabolism Inflammation Regenerative medicine

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory hBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis h.Pagan Rivera Jorge D.Miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Visual rating and the use of image analysis for assessing canopy density in a pecan provenance collection during leaf fall

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Journal of Forestry Research 2023年第6期34卷 1843-1854页

作者： Cristina Pisani Clive h.Bock jennifer Randall United States Department of Agriculture−Agricultural Research Service (USDA-ARS)Southeastern Fruit and Tree Nut Research Station(SEFTNRS)ByronGA 31008USA Department of Entomology Plant Pathology and Weed ScienceNew Mexico State UniversityLas CrucesNM 88003USA

A collection representing the native range of pecan was planted at the US DA-ARS Southeastern Fruit and Tree Nut Research Station,Byron,*** collection(867 trees)is a valuable genetic resource for characterizing important horticultural *** density during leaf fall is important as the seasonal canopy dynamics provides insights to environmental cues and breeding potential of *** ability of visual raters to estimate canopy density on a subset of the provenance collection(76 trees)as an indicator of leaf shed during autumn along with image analysis values was *** canopy density using the image analysis software was less compared to visual estimates(11.9%vs 18.4%,respectively).At higher canopy densities,the raters overestimated foliage density,but overall agreement between raters and measured values was good(ρc=0.849 to 0.915),and inter-rater reliability was high(R^(2)=0.910 to 0.953).The provenance from Missouri(MOL),the northernmost provenance,had the lowest canopy density in November,and results show that the higher the latitude of the provenance,the lower the canopy *** on regression,the source provenance latitude explained 0.609 of the variation using image analysis,and0.551 to 0.640 when based on the rater estimates of canopy *** assessment of pecan canopy density due to late season leaf fall for comparing pecan genotypes provides accurate and reliable estimates and could be used in future studies of the whole provenance collection.

关键词： Carya illinoinensis Accuracy Reliability Canopy Foliage density Leaf area density Leaf area index

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Optical tissue clearing enables rapid,precise and comprehensive assessment of three-dimensional morphology in experimental nerve regeneration research

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Neural Regeneration Research 2022年第6期17卷 1348-1356页

作者： Simeon C.Daeschler jennifer Zhang Tessa Gordon Gregory h.Borschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Indiana University School of Medicine IndianapolisINUSA

Morphological analyses are key outcome assessments for nerve regeneration studies but are historically limited to tissue *** optical tissue clearing techniques enabling three-dimensional imaging of entire organs at a subcellular resolution have revolutionized morphological studies of the *** extend their applicability to experimental nerve repair studies we adapted these techniques to nerves and their motor and sensory targets in *** solvent-based protocols rendered harvested peripheral nerves and their target organs transparent within 24 hours while preserving tissue architecture and *** optical clearing was compatible with conventional laboratory techniques,including retrograde labeling studies,and computational image segmentation,providing fast and precise cell ***,optically cleared organs enabled three-dimensional morphometry at an unprecedented scale including dermatome-wide innervation studies,tracing of intramuscular nerve branches or mapping of neurovascular *** their wide-ranging applicability,rapid processing times,and low costs,tissue clearing techniques are likely to be a key technology for next-generation nerve repair *** procedures were approved by the hospital for Sick Children’s Laboratory Animal Services Committee(49871/9)on November 9,2019.

关键词： histology image segmentation morphometry nerve regeneration outcome assessment peripheral nerve three-dimensional imaging tissue clearing

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Advanced concepts in knee arthrodesis

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World Journal of Orthopedics 2015年第2期6卷 202-210页

作者： jennifer h Wood Janet D Conway Department of Orthopaedics University of Maryland School of Medicine University of Maryland Medical System International Center for Limb Lengthening Rubin Institute for Advanced OrthopedicsSinai Hospital of Baltimore

The aim is to describe advanced strategies that can beused to diagnose and treat complications after knee arthrodesis and to describe temporary knee arthrodesis to treat infected knee arthroplasty. Potential difficult complications include nonunited knee arthrodesis, limb length discrepancy after knee arthrodesis, and united but infected knee arthrodesis. If a nonunited knee arthrodesis shows evidence of implant loosening or failure, then bone grafting the nonunion site as well as exchange intramedullary nailing and/or supplemental plate fixation are recommended. If symptomatic limb length discrepancy cannot be satisfactorily treated with a shoe lift, then the patient should undergo tibial lengthening over nail with a monolateral fixator or exchange nailing with a femoral internal lengthening device. If a united knee arthrodesis is infected, the nail must be removed. Then the surgeon has the option of replacing it with a long, antibiotic cement-coated nail. The authors also describe temporary knee arthrodesis for infected knee arthroplasty in patients who have the potential to undergo insertion of a new implant. The procedure has two goals: eradication of infection and stabilization of the knee. A temporary knee fusion can be accomplished by inserting both an antibiotic cement-coated knee fusion nail and a static antibiotic cement-coated spacer. These advanced techniques can be helpful when treating difficult complications after knee arthrodesis and treating cases of infected knee arthroplasty.

关键词： Arthroplasty Knee Arthrodesis Nonunion Limb salvage Limb length inequality Infection Osteomyelitis Bone lengthening External fixator

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hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited

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World Journal of Clinical Cases 2016年第3期4卷 71-75页

作者： jennifer Leong Derek Lin Mindie h Nguyen Division of Liver Diseases Department of Medicine Icahn School of Medicine at Mount Sinai Department of Medicine Stanford University Medical Center Division of Gastroenterology and hepato-logy Stanford University Medical Center

Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.

关键词： hepatitis B virus hepatitis B surface antigen Escape mutant hepatitis B immunoglobulin Vaccination

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Esophageal lichen planus:A case report and review of the literature

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World Journal of Gastroenterology 2013年第14期19卷 2278-2281页

作者： jennifer A Nielsen Robert M Law Keith h Fiman Cory A Roberts Division of Research ProPathDallasTX 75247United States Division of Dermatopathology ProPathDallas TX 75247United States Gastroenterology Consultants Southwest LLP Sugar LandTX 77478United States Division of Gastrointestinal Pathology ProPathDallasTX 75247United States

Esophageal involvement by lichen planus(ELP),previously thought to be quite rare,is a disease much more common in women and frequently the initial manifestation of mucocutaneous lichen planus(LP).Considering that the symptoms of ELP do not present in a predictable manner,ELP is perhaps more under-recognized than *** date,four cases of squamous cell carcinoma in association with ELP have been reported,suggesting that timely and accurate diagnosis of ELP is of importance for appropriate *** this case report,a 69-year-old female presented with dysphagia and *** reported a history of oral LP but had no active oral or skin *** examination revealed severe strictures and web-like areas in the *** examination demonstratedextensive denudation of the squamous epithelium,scattered intraepithelial lymphocytes,rare eosinophils and dyskeratotic *** immunofluorescence showed rare cytoid bodies and was used to exclude other primary immunobullous *** using clinical,endoscopic,and histologic data,a broad list of differential diagnoses can be narrowed,and the accurate diagnosis of ELP can be made,which is essential for proper treatment and subsequent follow-up.

关键词： Esophageal lichen planus Esophagus Immunofluorescence Immunobullous disorders Diagnostic accuracy

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Trends in characteristics of neurologists who provide stroke consultations in the USA,2008-2021

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Stroke & Vascular Neurology 2023年第1期8卷 86-88页

作者： Carter h Nakamoto Andrew D Wilcock Lee h Schwamm jennifer J Majersik Kori S Zachrison Ateev Mehrotra Department of health Care Policy Harvard Medical SchoolBostonMassachusettsUSA Department of Family Medicine University of Vermont Larner College of MedicineBurlingtonVermontUSA Department of Neurology Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of UtahSalt Lake CityUtahUSA Department of Emergency Medicine Massachusetts General HospitalBostonMassachusettsUSA Division of General Medicine and Primary Care Beth Israel Deaconess Medical CenterBostonMassachusettsUSA

Introduction Patients with acute ischaemic strokes(AIS),on average,fare better with timely neurologist consultation,and a growing proportion of them receive ***,little is known about trends in the characteristics of neurologists who treat *** We identified AIS and transient ischaemic attack(TIA)episodes with neurologist consults in fee-for service Medicare from January 2008 to September *** each episode,we determined whether the neurologist was a vascular neurologist,was a high-volume provider,whether the patient was transferred between hospitals and the distance between the patient’s home and physician’s *** From 2008 to 2021,the share of AIS/TIA episodes(n=5073294)with neurologist consults increased(52.9%to 61.7%).Among episodes with consults,the fraction conducted by a vascular neurologist(5.2%to 13.7%)or by a high-volume neurologist(13.2%to 14.9%)also *** fraction with the patient’s home and neurologist greater than 100 miles apart(4.8%to 9.6%)or in different states(5.1%to 8.1%)increased,as did the fraction with transfers(4.2%to 8.5%).Discussion Over the study period,the proportion of AIS/TIA episodes with consultations from neurologists with either vascular neurology certifications or high volumes increased substantially.

关键词： acute characteristics consultation

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