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Engineering hyaluronic acid-based nanoassemblies 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.l.pez-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 molecular 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,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(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 small-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 assembling 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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Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel Jiménez-Herrera ana Contreras Juan D.Navarro-lópez lydia Jiménez-Díaz Neurophysiology&Behavior lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the... 详细信息

关键词： Alzheimer predominant estimates

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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: minimally 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 complications (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 simulations 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 mild 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 molecular 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 multifactorial 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 molecular 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 million 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.Gamella 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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Concentric Centrifugal Figurate Erythema as an Unusual COVID-19 Evanescent Skin manifestation in a Patient With CD3^(+)/CD45^(+)lymphocyte Infiltration:A Case Report

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International Journal of Dermatology and Venereology 2024年第2期7卷 115-118页

作者： lucía Achell Achell-Nava José luis Zaldivar-Fujigaki Rebeca Pérez-Cabeza de Vaca ana maria Espinosa García luis montiel lópez Dermatology Department National Medical Center 20 de NoviembreISSSTEMexico City 03229Mexico Biomedical Research Department National Medical Center 20 de NoviembreISSSTEMexico City 03100Mexico Clinical Pharmacology Division General Hospital of MexicoMexico City 06720Mexico Internal medicine Department National Medical Center 20 de NoviembreISSSTEMexico City 03100Mexico

Introduction:Coronavirus disease 2019(COVID-19)may be associated with various skin *** them,figurate erythema(FE)is rare;only a few clinical reports have been ***,we reported an unusual concentric FE lesions and their immunohistochemical profile in a patient with *** presentation:A 52-year-old woman was diagnosed with *** month later,she developed asymptomatic annular erythematous concentric ring lesions on her inner right *** margin of every ring increased in coloration,and the lesions then completely resolved in 2 weeks.A biopsy revealed vasculitis of small vessels,an increase in the fluorescence intensity of CD3 and CD45,and negativity for COVID-19 ***:The results showed an unusual FE that has a clinical mixed type between erythema annulare centrifugum and erythema gyratum repens;the physiopathological mechanism in the FE due to COVID-19 is unknown;one theory involves rapid viral passage into the cutaneous vascular system that triggers an immune and inflammatory *** the results exhibited a negative COVID-19 RNA in the tissue,the CD3^(+)/CD45^(+)lymphocyte infiltration could explain the clinical pattern as a direct inflammatory response in the small vessel or as a delayed immune ***:Our findings suggest an immunohistochemical small vessel vasculitis pattern with an unusual clinical FE that differs from other types of COVID-19-associated FE or erythema reported previously.

关键词： erythema COVID-19 leukocytoclastic vasculitis skin manifestation CD3 complex CD45 antigen

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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 90mol%)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 molar *** 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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Sudden openings and gradual closures in canopy cover modulate acclimation, survival, and growth of a shade-tolerant rainforest tree species

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JOURNAl OF FORestRY RESEARCH 2024年第1期35卷 1-13页

作者： moretti, ana Paula Olguin, Flavia Yesica Gauna, Juan marcelo Graciano, Corina Univ Nacl la Plata INFIVE CONICET Diagonal 113 495 RA-1900 La Plata Buenos Aires Argentina Consejo Nacl Invest Cient & Tecn Godoy Cruz 2290 RA-C1425FQB Godoy Cruz Buenos Aires Argentina Univ Nacl mis Fac Ciencias Forestales Bertoni 124 km 3 RA-3380 Eldorado Misiones Argentina Univ Nacl la Plata Fac Ciencias Agr & Forestales Calle 60 & 118 RA-1900 La Plata Buenos Aires Argentina

Forest disturbances at gap levels are one of the most important events for the regeneration and establishment of intermediate tree species. Abrupt canopy openings expose plants to high light intensity and high evaporative demands that stress shade-acclimated plants. later, the slow closure of gaps reduces light availability to plants established when the incident irradiation was higher. This work evaluated the morphological and physiological acclimation of Cabralea canjerana (Vell) mart. regeneration to sudden and to gradual changes in canopy cover. A pot experiment was carried out with plants exposed to a sudden opening. A few days after the light shock, plants rapidly increased photosynthetic rates and decreased leaf water potential. After two months, plants activated physiological responses at leaf and whole plant levels to high light and water stresses, e.g., increased stomatal conductance, stomatal index and reduction of leaf: fine roots ratio and chlorophyll. After seven months, hydraulic conductivity of petioles and the whole leaf increased, and growth was much higher than plants that remained under the canopy. In a field experiment in gaps in the rainforest, plants acclimated to all canopy covers. Seven years after planting, growth was maximum in open environments within the gaps, even if the canopy closed during the first 20 months after planting. In conclusion, if this species is planted to enrich the rainforest, positions within gaps with lower canopy cover should be chosen and gap closure will not affect growth. To manage C. canjerana natural regeneration, the opening of gaps and removal of understory will increase survival and growth without the risk that the stress caused by these sudden openings could lead to the death of seedlings. Combining pot and field experiments helps to understand the autecology of trees with particular ecological interest, and to build sound restoration practices.

关键词： Cabralea canjerana Atlantic forest Abiotic stress Regeneration Seedling lIGHT CONDITIONS ATlANTIC FORest REGENERATION WATER GAPS RESPONSES SEEDlINGS SIZE estABlISHmENT RestORATION

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