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Engineering hyaluronic acid-based nanoassem.lies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana m.lópez-estévez Y.Zhang maría medel Iker Arriaga lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia maría J.Vicent Defang Ouyang Dolores Torres maría José Alonso Center for Research in m.lecular medicine and Chronic Diseases(CimUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Research in Chinese medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain AlBA Synchrotron light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,form.lation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the com.lex form.lation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassem.lies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEm),asymmetrical flow field-flow fractionation(AF4),and sm.ll-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assem.ling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Standardizing mI-TlIF, a Proposal for a Reproducible Technique

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Open Journal of modern Neurosurgery 2024年第2期14卷 91-103页

作者： Iván Ulises Sámano lópez Jesús Alberto Pérez Contreras Emmanuel Cantú Chávez Diana Chávez lizárraga ana Sofía Peña Blesa Thania Karina Gutiérrez Anchondo Á ngeles Pedregal Ciudad de México México

Background: minim.lly invasive transforaminal lumbar interbody fusion (mI TlIF) is a widely known and performed technique, however its versatility among different physicians continues to hinder its replication and results. Therefore, this study aimed to provide a step-by-step surgical guide to perform a safe mI-TlIF, based on the results obtained in patients operated on by a single surgeon over a period of 12 years. Patients and methods: A retrospective, single center, longitudinal, and observational cohort study was conducted with 931 patients who underwent mI TlIF by a single surgeon between 2010 and 2022 using the technique described on this paper, each with a minimum follow-up of 12 months. Criteria included Schizas classification, listhesis according to meyerding classification, number of levels treated, cage size, and com.lications (screw repositioning or cerebrospinal fluid leak). Patient clinical outcomes were assessed using the Oswestry Disability Index (ODI), Visual analog Scale (VAS) for pre- and postoperative radicular pain. Thin slice CT scans were used to assess the progression of the fusion using the Bridwell classification. In the statistical analysis, percentages, median, and interquartile range (IQR) were calculated. Results: Nine hundred and thirty one patients underwent mI TlIF using the technique described, eight hundred and eighty (94.5%) had a single level treated and fifty one (5.5%) had a 2 level procedure (982 levels), an 8mm cage was placed on five hundred and seventeenlevels (52.7%), six hundred and sixty three levels(67.6%) achieved grade I fusion, two hundred and sixty six levels (27.1%) achieved grade II fusion, 52 levels (5.3) achieved grade III fusion and one level (0.1) achieved a grade IV fusion or non-union. Revision surgery was performed on 3 patients (0.3%) for screw repositioning, cerebrospinal fluid leak was present on 2 patients during surgery and treated before closure. VAS scores and ODI were improved at 12 months postop (V

关键词： mITlIF lumbar Interbody Fusion Technique Pain Relief and Disability

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Academic Stress Assessment Using Virtual Reality as an Educational Tool in Spine Surgery

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Open Journal of modern Neurosurgery 2024年第2期14卷 114-123页

作者： Diana Chávez lizárraga Jesús Alberto Pérez Contreras Fernando Alvarado Gómez Evelyn Quintero medina Emmanuel Cantú Chávez Iván Ulises Sámano lópez ana Sofía Peña Blesa Department of Neurosurgery ángeles Pedregal Ciudad de México México Department of Traumatology and Orthopedics Hospital Santa Fe Bogotá Colombia

Introduction: The evaluation of academic stress in medical students and residents is a topic of significant interest, given the considerable challenges they face during their learning process with traditional teaching methods. The use of technologies like virtual reality presents an opportunity to enhance their skills through sim.lations and training. The main objective of this study is to qualitatively assess the stress levels experienced by medical students and residents by integrating virtual reality into their current learning methods, aiming to improve their ability to manage stressors in their practice. material and methods: A questionnaire was conducted with 12 medical students and 12 Traumatology and orthopedics residents. The purpose of the questionnaire was to evaluate the levels of academic stress using the SISCO inventory. The stress levels were calculated by transforming average values into percentages, and the following criteria were assigned: 0 to 33% for m.ld Stress, 34 to 66% for moderate Stress, and 67 to 100% for Deep Stress. Then, a virtual reality class focused on spine surgery was provided. Both medical students and residents were trained using the Non Nocere SharpSurgeon software platform and Oculus Quest 2 virtual reality glasses. At the end of the session, a second questionnaire related to the practice with virtual reality was conducted with the same evaluation criteria and a comparative analysis was carried out. Results: 12 undergraduate students from Hospital Angeles mexico, CDmX and 12 traumatology and orthopedics residents at Hospital Santa Fe, Bogota were evaluated. The students in CDmX reported an average qualitative stress of 28.50% during habitual practices, which decreased to an average of 14.67% after virtual reality practice. Residents in Bogotá experienced an average qualitative stress of 30.50% with their current learning methods but this reduced to an average of 13.92% after using virtual reality. These findings indicate that t

关键词： Virtual Reality Academic Stress learning Strategies Spine Surgery Training

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-lópez Iva Tic David Valle-García marta Ribalta-Vilella luis labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and m.lecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UmR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in m.ltifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAmP8)control mice and SAmP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAmP8 group treated with G9a inhibitor than in the SAmP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AmPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAmP8

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Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

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Neural Regeneration Research 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-Ortega ana m.Espinosa-Oliva Departamento de Nutrición y Bromatología Toxicología y Medicina LegalFacultad de FarmaciaUniversidad de SevillaSevilleSpain Instituto de Biomedicina de Sevilla IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Departamento de Bioquímica y Biología m.lecular Facultad de FarmaciaUniversidad de SevillaSevillaSpain

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of *** to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 *** 2019,global estimates indicated over 8.5 m.llion individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

关键词： protective Alzheimer prevalence

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola mavillard Javier Perez-Florido Francisco m.Ortuño Amador Valladares miren l.Álvarez-Villegas Gema Roldán Rosario Carmona manuel Soriano Santiago Susarte Pilar Fuentes Daniel lópez-lópez ana maría Nuñez-Negrillo Alejandra Carvajal Yolanda morgado Daniel Arteaga Rosa Ufano Pablo mir Juan F.Gam.lla Joaquín Dopazo Carmen Paradas macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Sol-gel derived B_(2)O_(3)-CaO borate bioactive glasses with hemostatic,antibacterial and pro-angiogenic activities

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Regenerative Biomaterials 2024年第1期3卷 108-118页

作者： Kai Zheng Faina Bider mahshid monavari Zhiyan Xu Christina Janko Christoph Alexiou ana m.Beltran Aldo R.Boccaccini Jiangsu Province Engineering Research Center of Stomatological Translational medicine College of StomatologyNanjing Medical UniversityNanjing 210029China Jiangsu Key laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Institute of Biomaterials University of Erlangen-Nuremberg91058 ErlangenGermany Department of Oto-Rhino-laryngology Head and Neck SurgerySection of Experimental Oncology and Nanomedicine(SEON)Else Kroener-Fresenius-Stiftung ProfessorshipUniversitaetsklinikum Erlangen91058 ErlangenGermany Departamento de Ingenier�ıa y Ciencia de los materiales y del Transporte Escuela Politecnica

Sol-gel borate bioactive glasses(BGs)are promising ion-releasing biomaterials for wound healing ***,we report the synthesis of a series of binary B_(2)O_(3)-CaO borate BGs(CaO ranging from 50 to 90m.l%)using a sol-gel-based *** influence of CaO content in B_(2)O_(3)-CaO borate BG on morphology,structure and ion release behavior was investigated in *** dissolution(ion release)and crystallization could be observed in borate BGs when CaO content increased,while the morphology was not significantly altered by increasing CaO *** results evidenced that the ion release behavior of borate BGs could be tailored by tuning the B_(2)O_(3)/CaO m.lar *** also evaluated the in vitro cytotoxicity,hemostatic,antibacterial and angiogenic activities of borate *** was validated for all borate ***,borate BGs exhibited composition-dependent hemostatic,antibacterial and angiogenic ***,higher contents of Ca in borate BGs facilitated hemostatic activity,while higher contents of B_(2)O_(3) were beneficial for pro-angiogenic *** synthesized sol-gel-derived borate BGs are promising materials for developing advanced wound healing dressings,given their fast ion release behavior and favorable hemostatic,antibacterial and angiogenic activities.

关键词： borate glasses sol-gel processing glass composition wound healing

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Synthesis and applications of lanthanoid com.lexes of pentadentate and hexadentate N_(5) and N_(6) macrocycles:A review

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Journal of Rare Earths 2024年第1期42卷 1-15,I0001页

作者： Julio Corredoira-Vázquez Cristina González-Barreira Paula Oreiro-martínez ana m.García-Deibe Jesús Sanmartín-matalobos matilde Fondo Departamento de Química Inorganica Facultade de QuímicaUniversidade de Santiago de CompostelaCampus Vida15782Santiago de CompostelaSpain Phantom-g CICECO-Aveiro Institute of MaterialsDepartment of PhysicsUniversity of Aveiro3810-193AveiroPortugal Institute of materials(imATUS) Universidade de Santiago de Compostela15782Santiago de CompostelaSpain

In this paper,the lanthanoid com.lexes of N_(5) and N_(6) macrocycle ligands,without pendant arms or additional heteroatoms,are *** review covers the period from 2015 to the current date,since in 2014 Schiff base macrocyclic ligands incorporating the pyridine moiety,and their com.lexes,were revised,and in 2015 the chemistry of pentaaza macrocycle ligands with rare earth metals was also *** and phthalocyanine ligands are not included in this review,which primarily focuses on com.lexes with Schiff bases and amines without pendant arms or any additional donor other than *** synthetic methods,structural characterization,based on single X-ray crystal data,and properties of the lanthanoid com.lexes,with special attention to magneto-structural correlations,are presented herein.

关键词： lanthanoid N_(5),N_(6)macrocycle Coordination chemistry Chirality Biological activity m.lecule magnet

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Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of Clinical Cases 2024年第7期12卷 1200-1204页

作者： ana majic Tengg maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko m.ller Iva markota Department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Department for Sport and Exercise medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental medicine Zagreb 10000Croatia Clinical Department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a com.lication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or m.ltifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism lytic bone lesions Giant cell tumor

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A Novel and Functional Artificial Bruch’s membrane made of Poly (ε-Caprolactone)/Gelatin for Retinal Pigment Epithelium Restoration

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Advances in Bioscience and Biotechnology 2024年第8期15卷 443-461页

作者： lópez Edith Silva-Bermudez Phaedra Gonzalez-Salinas Roberto Velasquillo Cristina Torres-Romero Abigail lópez-Colomé ana maría Pérez Armando Gina Prado-Prone Edgar Ramos-martínez Iván Ramos-martínez Quiroz-mercado Hugo Hernández-Zimbrón luis Fernando Instituto de Fisiologa Celular Universidad Nacional Autnoma de Mxico Ciudad de Mxico City Mxico Unidad de Ingeniería de Tejidos Terapia Celular y Medicina Regenerativa Instituto Nacional de Rehabilitación Luis Guiller-mo Ibarra Ibarra Ciudad de México México Departamento de Investigacin Asociacin Para Evitar la Ceguera Ciudad de Mxico Mxico Subdireccin de Investigacin Tecnolgica Instituto Nacional de Rehabilitacin Luis Guillermo Ibarra Ibarra Ciudad de Mxico Mxico Departamento de Biologa Celular y Tisular Facultad de Medicina Universidad Nacional Autnoma de Mxico Ciudad de Mxico Mxico Escuela de Ciencias Universidad Autnoma Benito Jurez de Oaxaca Oaxaca Mxico Departamento de medicina y Zootecnia de Cerdos Facultad de Medicina Veterinaria y Zootecnia Universidad Nacional utnoma de Mxico Mxico laboratorio de Investigacion Interdisciplinaria rea de Optometria Escuela Nacional de Estudios Superiores Unidad Len Universidad Nacional Autnoma de Mxico Len Guanajuato Mxico laboratorio Nacional de ptica de la Visin-Centro de Investigaciones en ptica Len Guanajuato Mxico

Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (Bm) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal im.lantation in patients. methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Polycaprolactone (PCl), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. mTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch’s membrane and ARPE-19 morphology after 25 days of culture were studied with transmission and scanning electron microscopy. To evaluate expression changes in markers of ARPE-19 (RPE65 and ZO-1) qRT-PCR assays were realized. Data from three independent experiments were pooled and expressed as the mean SD. A confidence level of P 0.05 was considered to be statistically significant. Results ARPE-19 cells grew on PCl/Gelatin membranes mainly in PCl/30% gelatin combination, which had not cytotoxic effect. RPE65/cytokeratin-18/ and actin-positive ARPE-19 cells formed a correctly orientated monolayer of polygonal cells with morphological polarity. The apical cell surfaces exhibited abundant protruding microfolds. moreover, zones of polygonal border look as if ARPE-19 cells fused among, suggesting the presence of tight junctions. The expression of RPE65 and ZO-1 was unchanged. Conclusions: PCl/30% Gelatine membranes may imitate the natural Bm to such extent that they support RPE-cells and exhibited RPE-like morphology. The engineering of a human RPE monolayer with these artificial Bm, em.lating the in vivo retina, arouse their potential subretinal im.lantation in patients with wet age-related macular degene

关键词： Artificial Bruch’s membrane Electrospinning ARPE-19 Cells Age-Related macular Degeneration

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