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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves Stefan Przyborski Department of biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès Sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud University Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud University Medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development Department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland Department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of Molecular and Cellular biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

Enhanced Lead Uptake by an Association of Plant and Earthworm Bioaugmented with Bacteria

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Pedosphere 2018年第2期28卷 311-322页

作者： anamika das jabez w.osborne Department of biosciences Vellore Institute of Technology Vellore 632014 (India)

Lead(Pb) is recorded as the second most hazardous pollutant of the *** cases of Pb bioremediation has been reported using single biosystem,but very few reports are available in biological approaches using multi-biosystems to achieve an enhanced bioremoval of *** present study evaluated the capacity of a unique association of Pennisetum purpureum,a hyperaccumulator plant,and Lumbricus terrestris(earthworm)bioaugmented with a Pb-resistant bacterium,obtained from an industrially contaminated site and identified as isolate VITMVCJ1 Klebsiella variicola,to bioremediate *** Pb-resistant gene was amplified in the bacterial isolate *** study was conducted for 60 *** verified that the bioaugmentation process enhanced1)root and shoot length of the plants,2)chlorophyll content of the plants,and 3)biofilm-producing ability of the microbes from the rhizosphere region of the *** total phenolic and flavonoid contents were found to be lower in the plants in the bioaugmented *** study also observed a reduction in the toxic effects of Pb on earthworm and *** earthworm was used to assess the Pb-induced stress syndrome after exposure to sublethal concentrations of Pb in the soil.A reduction in the content of malondialdehyde,a potential biomarker,on exposure to Pb demonstrated the role of the inoculum to alleviate heavy metal-induced stress in *** three symbionts accumulated Pb;Pb was accumulated mainly in the root of the plant,and poorly in the shoot of the plant and body mass of the *** bioaugmentation system exhibited stable and excellent uptake of Pb from the contaminated *** results of the present study suggest the positive effect of the synergistic association of the plant and earthworm with appropriate microbes for the bioremoval of Pb.

关键词： bioaugmentation bioremediation heavy metal hyperaccumulator Klebsiella variicola Lumbricus terrestris malondi-aldehyde Pennisetum purpureum

Antibiotic susceptibility profiling and virulence potential of Campylobacter jejuni isolates from different sources in Pakistan

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Asian Pacific Journal of Tropical Medicine 2015年第3期8卷 197-202页

作者： Fariha Masood Siddiqui Muhammad Akram Nighat Nourccn Zobia Noreen Habib Bokhari Department of biosciences.COMSATS institute of Information Technology

Objective:To determine antibiotic resistance patterns and virulence potential of Campylobacter jejuni(***) isolates from clinical human diarrheal infections,cattle and healthy ***:Antibiotic sensitivity patterns of *** isolates were determined by Kirby Bauer Disc Diffusion *** isolates were then subjected to virulence profiling for the detection of map A(membrane-associated protein).cadF(fibronectin binding protein).wlaN(beta-1.3-galaclosyltransferase) and neu AB(sialic acid biosynthesis gene).Further *** isolates were grouped by random amplification of polymorphic DNA(RAPD) ***:A total of436 samples from poultry(n=88).cattle(n=216) and humans(n=132) from different locations were *** revealed percentage of *** isolates were 35.2%(31/88).25.0%(54/216) and 11.3%(15/132) among poultry,cattle and clinical human samples *** susceptibility results showed that similar resistance patterns to cephalothin was ie.87.0%,87.1%and 89%among humans,poultry and cattle respectively,followed by sulfamethoxazolc+trimcthoprim 40.0%,38.7%and 31.0%in humans,poultry and cattle and Ampicillin 40%,32%and 20%in humans,poultry and cattle ***-lactamase activity was detected in 40.00%humans.20.37%cattle and 32.25%in poultry *** *** and mapA were present in all poultry,cattle and human C jejuni *** was not detected in any isolate and neu AB was found in 9/31(36%) poultry *** profiling results suggested high diversity of *** ***:Detection of multidrug resistant *** strains from poultry and cattle is alarming as they can be potential hazard to ***,predominant association of virulence factors,cadF and map A(100%each) in *** isolates from all sources and neuAB(36%) with poultry isolates suggest the potential source of transmission of diverse types of *** to humans.

关键词： Campylobacter jejuni Antibiotic susceptibility Virulence genes PCR RAPD

The Epigenome as a therapeutic target for Parkinson's disease

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Neural Regeneration Research 2016年第11期11卷 1735-1738页

作者： Shane V.Hegarty Aideen M.Sullivan Gerard W.O'Keeffe Department of Anatomy and Neuroscience Biosciences InstituteUniversity College Cork

Parkinson＇s disease （PD） is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This ar- ticle first discusses the present evidence implicating global, and dopaminergic neuron-specific, akerations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase （HAT） and histone deacetylase （HDAC） enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.

关键词： Parkinson's disease epigenetics methylation acetylation histone acetyltransferase histonedeacetyIase small molecules