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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil graduate program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil graduate program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： Melissa A.Rudy Trent A.Watkins Division of Neuroimmunology and Glial biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system ***,this stress response drives neuronal apoptosis in non-regenerative *** duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative *** dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve *** this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

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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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From filaments to function: The role of the plant actin cytoskeleton in pathogen perception,signaling and immunity

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Journal of Integrative Plant biology 2016年第4期58卷 299-311页

作者： Katie Porter Brad Day graduate program in Cell and Molecular biology Michigan State University Department of Plant Soil and Microbial Sciences Michigan State University graduate program in Genetics Michigan State University

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.

关键词： Actin cytoskeleton immunity pathogen plant Pseudomonas syringae surveillance

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A pancreatic player in dementia:pathological role for islet amyloid polypeptide accumulation in the brain

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Neural Regeneration Research 2023年第10期18卷 2141-2146页

作者： Angelina S.Bortoletto Ronald J.Parchem Center for Cell and Gene Therapy Stem Cell and Regenerative Medicine CenterDepartment of NeuroscienceDepartment of Molecular and Cellular BiologyTranslational Biology and Molecular Medicine ProgramMedical Scientist Training ProgramBaylor College of MedicineHoustonTXUSA

Type 2 diabetes mellitus patients have a markedly higher risk of developing *** multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes *** amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are *** this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of *** discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced *** are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at ***,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating *** such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.

关键词： Alzheimer’s disease amylin amyloid dementia diabetes human islet amyloid polypeptide islet amyloid polypeptide protofibrils type 2 diabetes mellitus vascular dementia

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Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

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Neural Regeneration Research 2025年第10期20卷 2862-2871页

作者： Prajakta Deshpande Anuradha Venkatakrishnan Chimata Amit Singh Department of biology University of DaytonDaytonOHUSA Premedical program University of DaytonDaytonOHUSA Center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and *** acetylation is a common post-translational modification pivotal to basic cellular *** to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and *** this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in ***,we have focused on N-acetyltransferase 9 and its role in microtubule *** have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative *** have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

关键词： acetyl-coenzyme A Alzheimer’s disease animal models cell death drosophila eye human disease c-Jun N-terminal kinase signaling N-Acetyltransferases N-acetyltransferase 9 neurodegeneration

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Genetic Analyses of Meiotic Recombination in Arabidopsis

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Journal of Integrative Plant biology 2007年第8期49卷 1199-1207页

作者： Asela J.Wijeratne Intercollege graduate program in Plant biology Department of Biology and the Huck Institutes of the Life SciencesThe Pennsylvania State UniversityUniversity ParkPA 16802USA

Meiosis is essential for sexual reproduction and recombination is a critical step required for normal meiosis. Understanding the underlying molecular mechanisms that regulate recombination is important for medical, agricultural and ecological reasons. Readily available molecular and cytological tools make Arabidopsis an excellent system to study meiosis. Here we review recent developments in molecular genetic analyses on meiotic recombination. These include studies on plant homologs of yeast and animal genes, as well as novel genes that were first identified in plants. The characterizations of these genes have demonstrated essential functions from the initiation of recombination by double-strand breaks to repair of such breaks, from the formation of doubie-HoUiday junctions to possible resolution of these junctions, both of which are critical for crossover formation. The recent advances have ushered a new era in plant meiosis, in which the combination of genetics, genomics, and molecular cytology can uncover important gene functions.

关键词： Arabidopsis crossover formation double-Holliday junction resolution double-strand break repair model interference meioticrecombination

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Genome-wide Analysis of Kelch Repeatcontaining F-box Family

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Journal of Integrative Plant biology 2007年第6期49卷 940-952页

作者： Yujin Sun Xiaofan Zhou Hong Ma Department of biology and the Huck Institutes of Life Sciences Intercollege graduate program in Cell and Developmental biology The Pennsylvania State University University Park PA 16802 USA

The ubiquitin-dependent protein degradation pathway plays diverse roles in eukaryotes. Previous studies indicate that both F-box and Kelch motifs are common in a variety of organisms. F-box proteins are subunits of E3 ubiquitin ligase complexes called SCFs （SKP1, Cullinl, F-box protein, and Rbxl）; they have an N-terminal F-box motif that binds to SKP1 （S-phase kinase associated protein）, and often have C-terminal protein-protein interaction domains, which specify the protein substrates for degradation via the ubiquitin pathway. One of the most frequently found protein interaction domains in F-box proteins is the Kelch repeat domain. Although both the F-box and Kelch repeats are ancient motifs, Kelch repeats-containing F-box proteins （KFB） have only been reported for human and Arabidopsis previously. The recent sequencing of the rice genome and other plant genomes provides an opportunity to examine the possible evolution history of KFB. We carried out extensive BLAST searches to identify putative KFBs in selected organisms, and analyzed their relationships phylogenetically. We also carried out the analysis of both gene duplication and gene expression of the KFBs in rice and Arabidopsis. Our study indicates that the origin of KFBs occurs before the divergence of animals and plants, and plant KFBs underwent rapid gene duplications.

关键词： Arabidopsis thaliana F-box motif Kelch repeats Kelch repeats-containing F-box proteins SCF SKP1 like.

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The role of LRRK2 on PKA-NFκB pathway in microglia cells: implications for Parkinson’s disease

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Neural Regeneration Research 2019年第10期14卷 1713-1714页

作者： Isabella Russo biology and Genetic Unit Department of Molecular and Translational Medicine University of Brescia

Leucine-rich repeat kinase 2 (LRRK2), a gene linked to autosomal- dominantly inherited and sporadic Parkinson’s disease (PD) as a risk factor, encodes a large and complex protein with a dual enzymatic activity. LRRK2 contains several domains involved in protein-protein interactions, however, the presence of both a kinase and GTPase domain points to intracellular signaling functions (Marin, 2006). While LRRK2 has been linked to several molecular pathways important for neuronal activity (Martin et al., 2014), the observation that its expression is high in microglia has attracted the attention of different groups to understand whether LRRK2 dysfunctions in these cells may impact neuronal activity as secondary event.

关键词： cells NFκB Parkinson protein GTPase impact gene has

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Regulation of lysosomal ion homeostasis by channels and transporters

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Science China(Life Sciences) 2016年第8期59卷 777-791页

作者： Jian Xiong Michael X.Zhu Department of Integrative biology and Pharmacology Mc Govern Medical School Program of Cell and Regulatory Biology Graduate School of Biomedical Sciences The University of Texas Health Science Center at Houston

Lysosomes are the major organelles that carry out degradation functions. They integrate and digest materials compartmental- ized by endocytosis, phagocytosis or autophagy. In addition to more than 60 hydrolases residing in the lysosomes, there are also ion channels and transporters that mediate the flux or transport of H＋, Ca2＋, Na＋, K＋, and C1- across the lysosomal mem- branes. Defects in ionic exchange can lead to abnormal lysosome morphology, defective vesicle trafficking, impaired autoph- agy, and diseases such as neurodegeneration and lysosomal storage disorders. The latter are characterized by incomplete lyso- somal digestion and accumulation of toxic materials inside enlarged intracellular vacuoles. In addition to degradation, recent studies have revealed the roles of lysosomes in metabolic pathways through kinases such as mechanistic target of rapamycin （mTOR） and transcriptional regulation through calcium signaling molecules such as transcription factor EB （TFEB） and cal- cineurin. Owing to the development of new approaches including genetically encoded fluorescence probes and whole endoly- sosomal patch clamp recording techniques, studies on lysosomal ion channels have made remarkable progress in recent years. In this review, we will focus on the current knowledge of lysosome-resident ion channels and transporters, discuss their roles in maintaining lysosomal function, and evaluate how their dysfunction can result in disease.

关键词： lysosomal storage disease(LSD) ion homeostasis calcium lysosome acidification

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