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

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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

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

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Journal of Sport and Health Science 2024年第4期13卷 548-558,F0003页

作者： Hugo de Luca Correa Lysleine Alves Deus Dahan da Cunha Nascimento Nicholas Rolnick Rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araujo Carmen Tzanno-martins fernanda Silveira Tavares Luiz Sinesio Silva Neto Claudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitoria Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate Program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil Graduate Program of Genomic Sciences and Biotechnology Brasılia 71966-700Brazil

Background:Hemodialysis(HD) per se is a risk factor for *** the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training *** aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this ***:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of 70 years old),and HD ***,RE+BFR significantly increases D-dimer after 4 *** with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

关键词： Blood-flow restriction Chronic kidney disease Coagulation Hemodialysis Vascular occlusion exercises

Response to Commentary by Dr. Matthew J. Clarkson on

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Journal of Sport and Health Science 2024年第5期13卷 670-671页

作者： Hugo de Luca Corrêa Lysleine Alves Deus Dahan da Cunha Nascimento Nicholas Rolnick Rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araújo Carmen Tzanno-martins fernanda Silveira Tavares Luiz Sinésio Silva Neto Cláudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitória Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate Program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil g Graduate Program of Genomic Sciences and Biotechnology Brasılia 71966-700Brazil

Dear editor:We sincerely thank Matthew *** for his insightful commentary1 on our recent publication in the Journal of Sport and Health Science.2 Clarkson's pioneering work in the development and application of blood flow restriction (BFR) exercise protocols has undeniably laid the groundwork for subsequent investigations in this field,including our own.(3-6)His commentary not only highlights the relevance and timeliness of our study but also offers valuable perspectives on refining safety considerations for intradialytic BFR exercise among hemodialysis patients.

关键词： patients application flow

Absence of galectin-3 attenuates neuroinflammation improving functional recovery after spinal cord injury

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Neural Regeneration Research 2016年第1期11卷 92-93页

作者： Caio Andrade Prins fernanda martins Almeida Ana Maria Blanco Martinez Laboratorio de Neurodegeneracao e Reparo-Departamento de Patologia-Faculdade de Medicina-HUCFF-UFRJ-Rio de Janeiro-RJ Brazil Instituto de Ciencia Biomedicas UFRJRio de JaneiroRJBrazil

After spinal cord injury （SCI）, a cascade of events begins. At first, there is physical damage with disruption of the blood-brain barrier （BBB） and the integrity of the nervous tissue. The disruption of central ner- vous system （CNS） BBB alters the endothelial permeability, the protein and chemokines expression and the propensity to release in situ inflam- matory cytokines, overcoming anti-inflammatory signals, facilitating the attraction and entry of immune system cells into the injured spinal cord parenchyma （Gaudet et al., 2011）. As a result, there is a neuroin- flammatory response with changes in blood flow, edema, cell infiltra- tion, apoptosis and release of axonal growth inhibitory factors. Nerve function loss occurs when the nerve impulse propagation is interrupted and do not reach its target. This disorder encompasses neuron and glia apoptosis, accompanied by Wallerian degeneration of disconnected axons, and CNS cells exposure to a hostile microenvironment that hampers axon regeneration （Mautes et al., 2000; Harkey et al., 2003）.

关键词： galectin disruption permeability facilitating attraction cascade macrophages cytokines morphologic exposure

Inosine: a novel treatment for sciatic nerve injury

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Neural Regeneration Research 2021年第1期16卷 127-128页

作者： Fellipe Soares dos Santos Cardoso Ana Maria Blanco Martinez fernanda martins de Almeida Laboratório de Neurodegeneração e Reparo–Departamento de Anatomia Patológica–Hospital Universitário Clementino Fraga Filho HUCFF/Universidade Federal do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas–ICB/Universidade Federal do Rio de Janeiro Rio de JaneiroBrazil

Trauma to the peripheral nervous system often results in loss of motor and sensory functions of the affected area of the body,leading to a series of functional impairments(Allodi et al.,2012).Injuries to peripheral nerves initiate a series of complex events,known as Wallerian degeneration,which allows the injured axons to regenerate and reinnervate their targets(Allodi et al.,2012).Damage to a nerve induces multiple alterations,which include:axonal degeneration,breakdown of myelin sheath,Schwann cells(SC)proliferation and conversion to a repair phenotype which express cytokines and chemokines that allow the infiltration and activation of macrophages(Mietto et al.,2015;Jessen and Mirsky,2016).

关键词： al. degeneration alterations

Endoscopic ultrasound-guided celiac plexus neurolysis using a reverse phase polymer

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World Journal of Gastroenterology 2010年第6期16卷 728-731页

作者： Keith L Obstein fernanda P martins Gloria Fernández-Esparrach Christopher C Thompson Gastroenterology Division Brigham and Women's Hospital Federal University of So Paulo Department of Gastroenterology Endoscopy UnitHospital Clinic(Spain)

AIM:To assess the feasibility of endoscopic ultrasound(EUS)guided celiac plexus neurolysis(CPN) using a poloxamer. METHODS:In this prospective evaluation,six Yorkshire pigs underwent EUS-guided *** received an injection of 10 mL of 0.25%Lidocaine plus methylene blue(group 1) and three received an injection of 10 mL of 0.25%Lidocaine plus blue colored poloxamer(PS137-25)(group 2) .Necropsy was performed immediately after the animals were *** abdominal and pelvic cavities were examined for the presence of methylene blue and the blue colored ***:EUS-guided CPN was successfully performed in all 6 pigs without immediate *** blue was identified throughout the peritoneal and retroperitoneal cavity in group *** blue colored poloxamer was found in the retroperitoneal cavity immediately adjacent to the aorta,in the exact location of the celiac plexus in group ***:EUS-guided CPN using a reverse phase polymer in a non-survival porcine model was technically *** presence of a poloxamer gel at the site of the celiac plexus at necropsy indicates a precise delivery of the neurolytic agent.

关键词： Celiac plexus neurolysis Celiac plexus blockade Endoscopic ultrasound Polymer

Thermal and photoperiodic requirements of the seedling stage of three tropical forest species

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Journal of Forestry Research 2023年第1期34卷 209-220页

作者： Fabrina Bolzan martins Mábele de Cássia Ferreira Flávia fernanda Azevedo Fagundes Gabriel Wilson Lorena Florêncio Natural Resource Institute Federal University of ItajubáItajubáMinas Gerais 37500-903Brazil

Air temperature and photoperiod play an important role in the seedling development for tropical forest *** variables are sensitive to climate,and so evaluating thermal and photoperiodic effects on seedling development is fundamental,especially for climate change *** to quantify thermal time and the energy required for plants to reach a development stage include air temperature and cardinal *** photoperiod will also affect physiological reactions of a plant and thus its *** we evaluated the six thermal time methods widely used to compute thermal requirement,and identified the influence of the photoperiod from the 2015 and2016 growing seasons and 12 sowing dates in Itajubá,Minas Gerais state,Brazil,on seedling development of three native tropical forest species Psidium guajava L.(Myrtaceae),Citharexylum myrianthum Cham.(Verbenaceae),and Bixa orellana L.(Bixaceae).The method used to quantify thermal time influenced the analytical results of seedling development;the one that considered three cardinal temperatures and compared them with the mean air temperature(Method5)performed better in computing thermal *** influence of photoperiod on seedling development was inconclusive for the three species,but all three developed better in mild temperatures(between 13.3℃and 26.9℃)with a photoperiod shorter than 13 h.

关键词： Phyllochron Thermal time Day length Seedling stage Phenology

Neural regeneration research model to be explored:SH-SY5Y human neuroblastoma cells

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Neural Regeneration Research 2023年第6期18卷 1265-1266页

作者： Lavynia Ferreira Hoffmann Alexandre martins fernanda Majolo Verônica Contini Stefan Laufer Márcia Inês Goetiert Graduate Program in Biotechnology University of Vale do Taquari(Univates)LajeadoRio Grande do SulBrazil Graduate Program in Medical Sciences-PPGCM University of Vale do Taquari-UnivatesLajeado/RSBrazil Institute of Pharmacy Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery-TÜCADDEberhard Karls University TübingenTübingenGermany

In neuroscience research,neuronal models are crucial tools for elucidating the molecular and cellular processes involved in the disorders of the nervous *** easily and reproducibly executable studies,in vitro models,such as the SH-SY5Y cell line culture,help us explore the pathophysiological mechanisms of neurodegenerative diseases;they are also essential for the efficient screening of drugs for treating the diseases of the nervous system(Peng et al.,2021;Strother et al.,2021).

关键词： neuroblastoma diseases

Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

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Neural Regeneration Research 2018年第6期13卷 1046-1053页

作者： Bruna dos Santos Ramalho fernanda martins de Almeida Conrado Mendonca Sales Silmara de Lima Ana Maria Blanco Martinez Laboratorio de Neurodegeneracao e Reparo Departamento de Patologia - Faculdade de Medicina HUCFF Universidade Federal do Rio de Janeiro Rio de laneiro Brazil

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury （SCI） are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells （MSCs） in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups： sham （anesthesia and laminectomy but without compression injury induction）, MSC i.p. （intraperitoneal injection of 8×10^5 MSCs in 500 μL of DMEM at 7 days after SCI）, MSC i.v. （intravenous injection of 8 × 10^5 MSCs in 500μL of DMEM at 7 days after SCI）, DMEM i.p. （intraperitoneal injection of 500μL of DMEM at 7 days after SCI）, DMEM i.v. （intravenous injection of 500 μL of DMEM at 7 days after SCI）. The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors （brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4） in the spinal cord and improved locomotor performance. Our results indicate that injection of MSC

关键词： spinal cord injury mesenchymal stem cells intravenous route intraperitoneal route functional recovery systemic transplantation neural regeneration