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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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Identification of a Novel miRNA in Melanocytes of Alpaca(Lama Pacos)

Identification of a Novel miRNA in Melanocytes of Alpaca(Lam...

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中国畜牧兽医学会动物解剖及组织胚胎学分会第十八次学术研讨会

作者： Ruiwen Fan Shanshan Yang Zhanquan Shi Kaiyuan Ji Xiaoyun Jia Jianbo Yao george w smith Changsheng Dong College of Animal Science and Technology Shanxi Agricultural University Laboratory of Animal Biotechnology and Genomics Division of Animal and Nutritional SciencesWest Virginia University Laboratory of Mammalian Reproductive Biology and Genomics Departments of Animal Science and PhysiologyMichigan State University

From the previous deep sequencing of alpaca skins,one of novel miRNAs expressed differently in white and black alpaca skin(named alp-miR066).According to the target gene prediction,one of the target genes is soluble guanylate cyclase(sGC).To get the function of alp-miR-066 in alpaca skin,it was over expressed in alpaca melanocytes in *** expression of miRNA-066 was tested by real-time PCR and the results showed it expressed *** the pathway of cAMP in melanocytes,cGMP was increased by ELASA assay,while cAMP was *** expression of sGC,TYR,TYRP1,TYRP2 and MITF protein were tested by western blotting,and the results showed that sGC was increased and TYR,TYRP1 and MITF protein were ***,the number of melanogenic melanocytes was less and the amount of melanins production was 0.7 fold in alp-miR066 transfection group,compared to Negative control(NC) transfection *** those results suggested that alp-miR-066 might regulate melanogenesis on the pathway of cAMP in alpaca melanocytes by targeting sGC.

关键词： alp-miR066 melanocytes cAMP melanin sGC

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Identification of a novel miRNA important for melanogenesis in alpaca(Lama Pacos)

Identification of a novel miRNA important for melanogenesis ...

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提升骆驼产业科技含量，打造骆驼行业知名品牌——第二届（2013）中国骆驼大会

作者： Ruiwen Fan Shanshan Yang Zhanquan Shi Kaiyuan Ji Xiaoyun Jia Jianbo Yao george w smith Changsheng Dong

The mechanism of coat color formation is complex,microRNAs play important roles in the control of melanogenesis and coat color in *** the previous deep sequencing of alpaca skins,one of novel miRNAs expressed differently in white and black alpaca skin(named alp-miR066).According to the target gene prediction,one of the target genes is soluble guanylate cyclase(sGC).To get the function of alp-miR-066 in alpaca skin,it was over expressed in alpaca melanocytes in *** expression of miRNA-066 was tested by real-time PCR and the results showed it expressed *** the pathway of cAMP in melanocytes,cGMP was increased by ELASA assay,while cAMP was decreased. The expression of sGC,TYR,TYRP1,TYRP2 and MITF protein were tested by western blotting,and the results showed that sGC was increased and TYR,TYRP1 and MITF protein were ***,the number of melanogenic melanocytes was less and the amount of melanins production was 0.7 fold in alp-miR066 transfection group,compared to negative control(NC) transfection *** those results suggested that alp-miR-066 might regulate melanogenesis on the pathway of cAMP in alpaca melanocytes by targeting sGC.

关键词： alp-miR066 melanocytes cAMP melanin sGC

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： wenrui Qu Xiangbing wu wei wu Ying wang Yan Sun Lingxiao Deng Melissa walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia george smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Coat Color Determination by miR-137 Mediated Down-regulation of Microphthalmia-Associated Transcription Factor in a Mouse Model

Coat Color Determination by miR-137 Mediated Down-regulation...

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中国畜牧兽医学会动物解剖学及组织胚胎学分会第十七次学术研讨会

作者： CHANGSHENG DONG HAIDONG wANG LINLI XUE YANJUN DONG LEI YANG RUIwEN FAN XIUJU YU XUE TIAN SHUHUI MA george w.smith College of Animal Science and Veterinary Medicine Shanxi Agricultural University College of Information Shanxi Agricultural University Nephrology Division Baylor College of Medicine Laboratory of Mammalian Reproductive Biology and Genomics Departments of Animal Science and Physiology Michigan State University

Coat color is a key economic trait in wool producing *** development and pigmentation are controlled by complex mechanisms in ***,we report the first production of an altered coat color by overexpression of miR-137 in transgenic *** mice overexpressing miR-137 developed a range of coat color changes from dark black to light *** analyses of the transgenic mice showed decreased expression of the major target gene termed MITF and its downstream genes including TYR,TYRPl and *** also showed that melanogenesis altered by miR-137 is a distinct from that affected by UV radiation in transgenic *** study provides the first mouse model for the study of coat color controlled by miRNAs in animals and may have important applications in wool production.

关键词： miR-137 coat color melanogenesis

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Functional and immunological peculiarities of peripheral nerve allografts

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Neural Regeneration Research 2022年第4期17卷 721-727页

作者： Kelly C.S.Roballo Jason P.Gigley Tyler A.smith george D.Bittner Jared S.Bushman School of Pharmacy University of WyomingLaramieWYUSA Department of Molecular Biology University of WyomingLaramieWYUSA Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA

This review addresses the accumulating evidence that live(not decellularized)allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic *** is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon *** the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in *** topics are addressed:The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon *** second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and ***,potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed.

关键词： allograft animal model immunology neuroimmunology peripheral nerve injury regeneration repair tissue regeneration tissue transplantation transplant

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Acetylation as a mechanism that regulates axonal regeneration

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Neural Regeneration Research 2015年第7期10卷 1034-1036页

作者： Shen Lin george M.smith Shriners Hospitals for Pediatric Research Center Department of Neuroscience Temple University

The capacity for adult axons to regenerate after injury is diminished compared with developing *** the case of central nervous system（CNS）axons,injury causes a total failure to *** failure is due to both the intrins... 详细信息

关键词： gene HDAC Acetylation as a mechanism that regulates axonal regeneration

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Neurotrophin treatment to promote regeneration after traumatic CNS injury

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Frontiers in Biology 2013年第5期8卷 486-495页

作者： Lakshmi KELAMANGALATH george M. smith Center for Neural Repair and Rehabilitation Department of Neuroscience & Shriners Hospitals for Pediatric Research Temple UniversitySchool of Medieine Philadelphia PA 19140-4106 USA

Neurotrophins are a family of growth factors that have been found to be central for the development and functional maintenance of the nervous system, participating in neurogenesis, neuronal survival, axonal growth, synaptogenesis and activity-dependent forms of synaptic plasticity. Trauma in the adult nervous system can disrupt the functional circuitry of neurons and result in severe functional deficits. The limitation of intrinsic growth capacity of adult nervous system and the presence of an inhospitable environment are the major hurdles for axonal regeneration of lesioned adult neurons. Neurotrophic factors have been shown to be excellent candidates in mediating neuronal repair and establishing functional circuitry via activating several growth signaling mechanisms including neuron-intrinsic regenerative programs. Here, we will review the effects of various neurotrophins in mediating recovery after injury to the adult spinal cord.

关键词： axonal guidance neurotrophin regeneration functional recovery sprouting

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Reactive astrocyte scar and axon regeneration:suppressor or facilitator?

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Neural Regeneration Research 2016年第7期11卷 1050-1051页

作者： Yosuke Ohtake george M.smith Shuxin Li Shriners Hospitals Pediatric Research Center Department of Anatomy and Cell BiologyDepartment of NeuroscienceLewis Katz School of Medicine at Temple University

Several major factors are known to contribute to CNS axon regenerative failure after injury, including reduced intrinsic growth capacity of developed neurons and extrinsic factors mediating axon outgrowth. For the latter, a non-permissive environment around the lesion and the lack of sufficient neurotrophic support within the adult CNS play important roles （Silver et al., 2015）. In addition to generation of various inhibitory substrates by oligodendrocytes, fibrotic tissues, inflammatory cells and other cell types, reactive astrocytes surrounding lesions are thought to highly suppress regeneration of injured CNS axons （Silver and Miller, 2004; Ohtake and Li, 2014）. A great number of studies suggest that reactive astrocytic scars form one of the major barriers preventing axon regeneration after CNS iniuries, including spinal cord injury （SCI）. However, reactive astrocytes were reported to provide a beneficial role by reducing infiltrating immunoreactive cells into adjacent domains, protecting bordering neural tissue from damage and generating numerous supportive extracellular matrix （ECM） components to promote cell survival and growth （Bush et al., 1999）. Previ- ous data showed that ablation of reactive astrocytes increased inflammation and secondary tissue damage, prevented blood- brain barrier formation and increased local neurite growth. Interestingly, a recent study by Anderson et al （2016） provides evidence that reactive astrocytes around the lesioned spinal cord support axon regeneration after SCI, rather than block regrowth （Anderson et al., 2016）.

关键词： astrocyte regeneration suppressor neurotrophic extrinsic latter intrinsic glial injured sensory

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Criminal justice in America george F. Cole, Christopher E. smith

Criminal justice in America George F. Cole, Christopher E. S...

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2005年

作者： george F. Cole Christopher E. smith

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