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Engineering hyaluronic acid-based nanoassemblies.for monoclonal antibody delivery-des.gn,characterization,and biological insights

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Nano Res.arch 2024年第10期17卷 9111-9125页

作者： ana m.l.pez-es.évez Y.Zhang maría medel Iker Arriaga lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abres.ia maría J.Vicent Defang Ouyang Dolores.Torres.maría José Alonso Center for Res.arch 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 Res.arch Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Res.arch in Chines. medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Res.arch 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 wides.read use of monoclonal antibodies.mAbs).Des.ite 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 pres.nt a new nanocarrier consisting of hyaluronic acid-based nanoassemblies.Hanas)specifically des.gned 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)res.lted 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).Thes. 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 proces. at industrial-scale batch sizes.and the long-term stability was *** conclusion,thes. res.lts 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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A review on the scale-up of high-shear wet granulation proces.es.and the impact of proces. parameters

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Particuology 2024年第9期92卷 180-195页

作者： ana Rita Alves.marta Filipe Simões.Sérgio Simões.João Gomes University of Coimbra CERESDepartment of Chemical EngineeringFaculty of Sciences and TechnologyRua Sílvio Lima3030-790CoimbraPortugal Bluepharma-Indústria Farmacêutica São Martinho do BispoCoimbra3045-016Portugal Faculty of Pharmacy University of CoimbraAzinhaga de Santa Comba3000-548CoimbraPortugal

Wet granulation is one of the most important agglomeration proces.es.and high-shear granulation(HSG)one of the most employed technologies.in the pharmaceutical *** most critical proces. parameters of HSG are discussed in this *** main concern in scaling up the wet granulation proces. is the differences.between scales.which prevent the particles.from having the same experience across all *** scale-up of wet granulation proces.es.is commonly divided into two categories.engineering and attribute-based *** engineering-based scale-up approach is a strategy based on dimensional analysis and an attribute-based supported on the principles.of“equifinality”,where proces. variables.are adjusted to obtain equivalent granule *** work pres.nts the effect of different HSG proces. parameters on the scale-up,as well as the use of proces. analytical tools(PAT)and modelling *** aim is to review applied scale-up approaches.in HSG and discuss benefits and *** is proven why the scale-up for oral solid pharmaceutical products is still considered a hot topic and a very challenging task for development and engineering teams.

关键词： High-shear wetgranulation Parametric-based Attribute-based Physics-based modelling Impeller des.gn Scale-up

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Sex differences.in Alzheimer's disease:an urgent res.arch venue to follow

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Neural Regeneration Res.arch 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 es.imates.indicating a growth from 55 million in 2019 to a staggering 139 million by the... 详细信息

关键词： Alzheimer predominant es.imates

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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 Jes.s Alberto Pérez Contreras Emmanuel Cantú Chávez Diana Chávez lizárraga ana Sofía Peña Bles. 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 res.lts. Therefore, this study aimed to provide a step-by-step surgical guide to perform a safe mI-TlIF, based on the res.lts 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 des.ribed on this paper, each with a minimum follow-up of 12 months. Criteria included Schizas classification, listhes.s according to meyerding classification, number of levels treated, cage size, and complications (screw repositioning or cerebrospinal fluid leak). Patient clinical outcomes.were asses.ed using the Oswes.ry Disability Index (ODI), Visual analog Scale (VAS) for pre- and postoperative radicular pain. Thin slice CT scans were used to asses. the progres.ion of the fusion using the Bridwell classification. In the statistical analysis, percentages. median, and interquartile range (IQR) were calculated. Res.lts: Nine hundred and thirty one patients underwent mI TlIF using the technique des.ribed, 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 pres.nt 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 Stres. Asses.ment 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 Jes.s Alberto Pérez Contreras Fernando Alvarado Gómez Evelyn Quintero medina Emmanuel Cantú Chávez Iván Ulises.Sámano lópez ana Sofía Peña Bles. Department of Neurosurgery ángeles Pedregal Ciudad de México México Department of Traumatology and Orthopedics Hospital Santa Fe Bogotá Colombia

Introduction: The evaluation of academic stres. in medical students and res.dents is a topic of significant interes., given the considerable challenges.they face during their learning proces. with traditional teaching methods. The use of technologies.like virtual reality pres.nts an opportunity to enhance their skills through simulations and training. The main objective of this study is to qualitatively asses. the stres. levels experienced by medical students and res.dents by integrating virtual reality into their current learning methods, aiming to improve their ability to manage stres.ors in their practice. material and methods: A ques.ionnaire was conducted with 12 medical students and 12 Traumatology and orthopedics res.dents. The purpose of the ques.ionnaire was to evaluate the levels of academic stres. using the SISCO inventory. The stres. levels were calculated by transforming average values.into percentages. and the following criteria were assigned: 0 to 33% for mild Stres., 34 to 66% for moderate Stres., and 67 to 100% for Deep Stres.. Then, a virtual reality class focused on spine surgery was provided. Both medical students and res.dents were trained using the Non Nocere SharpSurgeon software platform and Oculus Ques. 2 virtual reality glasses. At the end of the ses.ion, a second ques.ionnaire related to the practice with virtual reality was conducted with the same evaluation criteria and a comparative analysis was carried out. Res.lts: 12 undergraduate students from Hospital Angeles.mexico, CDmX and 12 traumatology and orthopedics res.dents at Hospital Santa Fe, Bogota were evaluated. The students in CDmX reported an average qualitative stres. of 28.50% during habitual practices. which decreased to an average of 14.67% after virtual reality practice. Res.dents in Bogotá experienced an average qualitative stres. of 30.50% with their current learning methods but this reduced to an average of 13.92% after using virtual reality. Thes. findings indicate that t

关键词： Virtual Reality Academic Stres. learning Strategies Spine Surgery Training

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

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Neural Regeneration Res.arch 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-Ortega ana m.es.inosa-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 es.imates.indicated over 8.5 million individuals with PD and it is sugges.ed that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

关键词： protective Alzheimer prevalence

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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 Res.arch 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 Casades.s 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 Res.arch Cancer lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UmR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Inves.igación 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 proces.es.and diseases.playing a key role in pathogenes.s,es.ecially in multifactorial diseases.such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stres.,and *** better understand the biology of G9a,we compared the global microRNA expres.ion between senes.ence-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 interes.ingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expres.ion levels were higher in the SAmP8 group treated with G9a inhibitor than in the SAmP8 control *** also observed modulation of oxidative stres. res.onses.might be mainly driven Pparg after G9a *** confirm thes. 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 expres.ion of genes.involved in DNA damage res.onses.and *** addition,we also des.ribed that the PPARγ/AmPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes.to enhancing synaptic plasticity and neurogenes.s 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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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 Inves.igación 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 wides.read adoption of cost-effective massive parallel *** identify new disease variants,es.ecially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

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World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： ana Isabel Ferreira Catarina Guimarães.Vitor macedo Silva Sofia Xavier Joana magalhães.JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal life and Health Sciences.Res.arch Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal life and Health Sciences.Res.arch Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of Pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes.patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes.particularly the Pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology *** Included 69 patients,49.3%had Pi*mZ phenotype and 10.1%Pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosismg/dl predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,Pmoderate to advanced fibrosis(AUC=0.831,Pes.mellitus(Dm),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(Pleast one Pi*Z allele and type 2 Dm were 8 times.more likely to have liver stiffnes. measurement≥7.1 kPa(P=0.040).CONClUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosismg/*** created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index liver stiffnes. measurement

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Thermal properties.and high-temperature ablation of high-entropy (Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating on graphite substrate

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Journal of Advanced Ceramics 2024年第8期13卷 1268-1281页

作者： ana C.Feltrin Daniel Hedman Farid Akhtar Division of materials Science Lulea University of TechnologyLulea 97187Sweden Center for multidimensional Carbon materials(CmCm) Institute for Basic Science(IBS)Ulsan 44919Republic of Korea

An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent transition metal diboride ***(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardnes. of 31.2±2.1 GPa and res.sted 36.9 GPa of stres. before delamination,as observed at the *** temperature-dependent thermal properties.of the multicomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by molecular dynamics(mD)simulations driven by a machine learning force field(mlFF)trained on density functional theory(DFT)*** thermal conductivity,density,heat capacity,and coefficient of thermal expansion obtained by the mD simulations were used in time-dependent thermal stres. finite element model(FEm)*** low thermal conductivity(m^(-1)·K^(-1))of the multicomponent diboride coupled with its similar coefficient of thermal expansion to that of graphite indicated that stres.es.of les. than 10 GPa were generated at the interface at high temperatures.and therefore,the coating was mechanically res.stant to the thermal stres. induced during *** experiments at 220℃ showed that the multicomponent diboride coating was res.stant to thermal stres.es.with no visible cracking or *** ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides.which caused a decrease in the mass and thicknes. of the coating and res.lted in mass and linear ablation rates.of-0.51 mg·s^(-1) and -1.38μm·s^(-1),res.ectively,after 60 *** findings demonstrated the thermal and mechanical stability of multicomponent entropy-stabilized diborides.as coatings for carbon materials in engineering components under extreme environments.

关键词： entropy-stabilized diborides ultrahigh temperature ceramics molecular dynamics(mD)simulations density functional theory(DFT) ablation properties

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