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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub Program in neuroscience Indiana UniversityBloomingtonINUSA Department of neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(negative control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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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

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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

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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09期 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 Texas Program in neuroscience Indiana University Department of Molecular Biosciences University of Texas

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 n

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老社区的蝶变之路重庆民主村竟然这么好逛

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城市地理 2024年第5期 68-75页

作者：崔红胡家密左小朵(图) cathy(图) 九龙城市更新公司

位于重庆市九龙坡谢家湾街道的民主村,曾被不少市民戏为“城市中的一块伤疤”,破旧的小区、噜杂的环境、阴暗的巷道是贴在它身上多年的标签。作为工业时代遗留下来的记忆,民主村在时代洪流下走上了蜕变之路,并成功逆袭,一跃成为城市更... 详细信息

位于重庆市九龙坡谢家湾街道的民主村,曾被不少市民戏为“城市中的一块伤疤”,破旧的小区、噜杂的环境、阴暗的巷道是贴在它身上多年的标签。作为工业时代遗留下来的记忆,民主村在时代洪流下走上了蜕变之路,并成功逆袭,一跃成为城市更新中的样板村。

关键词：城市更新时代洪流九龙坡街道民主

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Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation

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World Journal of Gastroenterology 2010年第40期16卷 5047-5056页

作者： Ashley M Lakner cathy c Moore Alyssa A Gulledge Laura W Schrum Department of Biology University of North Carolina at Charlotte Digestive and Metabolic Disorders Laboratory Carolinas Medical Center

AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HScs) to transdifferentiation. METHODS: Primary HScs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSc transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRnA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HScs which correlated with decreased mRnA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. cOncLUSIOn: These data demonstrate unique clustered genetic profiles during the daily progression of HSc transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.

关键词： cluster analysis Fibrosis Genetic profile Hepatic stellate cell Interleukin-6

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Improving genomic tools for outcrossing crops

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Molecular Plant 2021年第4期14卷 538-540页

作者： cathy Jubin Stefanie Griebel Timothy Beissinger Division of Plant Breeding Methodology&center for Integrated Breeding Research Department of Crop ScienceUniversity of Gottingen37075

For decades,practical limitations and cost have created a bias in plant genetic studies toward species that tolerate self *** important work by chen et al.(2021)in this issue provides key tools to overcome this bias a... 详细信息

关键词： crops breeding overcome

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nDRG2 gene copy number is not altered in colorectal carcinoma

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World Journal of clinical Oncology 2017年第1期8卷 67-74页

作者： Anders Lorentzen cathy Mitchelmore Eucaryotic cell Biology Department of Science and Environment Roskilde University

AIM To investigate if the down-regulation of n-myc Downstream Regulated Gene 2(nDRG2) expression in colorectal carcinoma(cRc) is due to loss of the nDRG2 allele(s).METHODS The following were investigated in the human colorectal cancer cell lines DLD-1, Lo Vo and SW-480: nDRG2 mRnA expression levels using quantitative reverse transcriptionpolymerase chain reaction(qRT-PcR); interaction of the MYc gene-regulatory protein with the nDRG2 promoter using chromatin immunoprecipitation; and nDRG2 promoter methylation using bisulfite ***, we performed qPcR to analyse the copy numbers of nDRG2 and MYc genes in the above three cell lines, 8 normal colorectal tissue samples and 40 cRc tissue *** As expected, nDRG2 mRnA levels were low in the three colorectal cancer cell lines, compared to normal *** MYc protein interacted with the nDRG2 core promoter in all three cell *** addition, the nDRG2 promoter was heavily methylated in these cell lines, suggesting an epigenetic regulatory *** gene copy numbers of nDRG2 were observed in the three cell *** the colorectal tissues, one normal and three cRc samples showed partial or complete loss of one nDRG2 *** contrast, the MYc gene was amplified in one cell line and in more than 40% of the cRc *** Our study suggests that the reduction in nDRG2 expression observed in cRc is due to transcriptional repression by MYc and promoter methylation, and is not due to allelic loss.

关键词： n-myc downstream-regulated gene 2 colorectal carcinoma MYc Tumor suppressor Allelic loss Gene amplification copy number

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Therapeutic use of melatonin in schizophrenia:A systematic review

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World Journal of Psychiatry 2021年第8期11卷 463-476页

作者： cathy Duan Zoe M Jenkins David castle Department of Psychiatry University of MelbourneParkville 3010VICAustralia Mental Health Service St.Vincent's HospitalMelbourne 3065VICAustralia centre for complex Interventions Centre for Addictions and Mental HealthToronto ON M6J 1H4Canada Department of Psychiatry University of TorontoToronto ON M5SCanada

BAcKGROUnD Sleep dysfunction is a common problem in people with schizophrenia,and side effects of treatment often exacerbate metabolic and cardiovascular risk and may induce extrapyramidal side ***(n-acetyl-5-methoxytryptamine)is an endogenously produced hormone which has demonstrated direct and indirect antioxidant and neuroprotective *** studies have explored the use of exogenous melatonin in improving sleep outcomes in the general population,yet indications for use in schizophrenia are *** To synthesize the evidence from clinical trials investigating prescribed melatonin as an adjunctive therapy in patients with *** A systematic literature review of MEDLInE(Ovid),Embase,PsychInFO,and PubMed on the 27/08/20;and cInAHL and cochrane Library databases,was *** criteria were:a peer-reviewed clinical trial published in English;included a group of patients with schizophrenia;used melatonin as an adjunctive therapy;and reported any outcome of any *** criteria were:neurodegenerative diseases,primary sleep disorders,co-morbid substance use or animal *** Fifteen studies were included in the current review with the following primary outcomes:sleep(n=6),metabolic profile(n=3),tardive dyskinesia(n=3),cognitive function(n=2)and benzodiazepine discontinuation(n=1).cOncLUSIOn Adjunctive melatonin therapy has some positive outcomes for sleep,metabolic profile and tardive dyskinesia in patients with *** beneficial effect of melatonin was observed on outcomes of cognition or benzodiazepine *** studies utilizing larger samples and investigations specifically comparing the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia are required.

关键词： Schizophrenia Melatonin clinical trials Sleep Metabolic syndrome Tardive dyskinesia

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Amine-catalyzed polycyclotrimerization of arylene bipropiolate:A metal-free and regioselective route to hyperbranched polymer

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Science china chemistry 2008年第8期51卷 705-708页

作者： JIM cathy K W LAM Jacky W Y HAEUSSLER Matthias Department of chemistry The Hong Kong University of Science & TechnologyClear Water BayKowloonHong KongChina

This paper presents a new synthetic route to hyperbranched polymer. An arylene bipropiolate monomer,dimethylmethylenebis(1,4-phenylene) bipropiolate,was prepared by a one-step esterification reaction of bisphenol A with propiolic acid. Polycyclotrimrtization of the monomer was effected by reflux in dimethylformamide(DMF),producing a soluble hyperbranched poly(aroxycarbonylphenylene) in a good yield. The polymer was perfectly branched with a degree of branching of 100%.

关键词： cyclotrimerization regioselectivity hyperbranched polymer

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