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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.López-Estévez Y.Zhang mar.a Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia mar.a J.Vicent Defang Ouyang Dolores Torres mar.a 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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Study of reverse osmosis membranes fouling by inorganic salts and colloidal particles during seawater desalination

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Chinese Journal of Chemical Engineering 2020年第3期28卷 733-742页

作者： Santiago Gutiérrez Ruiz Juan Antonio López-Ramírez Mohammed Hassani Zerrouk Agata Egea-Corbacho Lopera josémar.a quiroga alonso Department of Environmental Technologies Faculty of Marine and Environmental SciencesUniversity of Cadiz11510Puerto RealCadizSpain

Fouling phenomenon is considered among the major reasons that cause significant increase of operating cost of desalination plants equipped with reverse osmosis(RO)*** phenomenon is studied in the present work in the case of RO polyamide aromatic membranes using model seawater containing inorganic salts and colloidal *** solubility conditions of CaCO3 and CaSO4 were applied to study RO performances with and without colloid *** experiments,the membrane permeate fluxes were continuously ***,studies of chemical composition,structure,and morphology of the materials deposited on the membrane surface were conducted using energy dispersive microanalysis(EDS)X-ray diffraction and scanning electronic microscopy(SEM).Results show that in conditions of calcium carbonate oversaturation there is a reduction in the permeate flow of 11.2%due to fouling of the membrane by the precipitation of this *** in the same conditions of calcium sulphate oversaturation the reduction of the flow is 5%,so we can conclude that in conditions of oversaturation of both salts,calcium carbonate produces a greater fouling of the membrane that in its view causes greater decrease in the flow of *** this based on the results of the test with both salts in oversaturated *** in the formation of calcite and gypsum crystals onto the membranes as XRD analyses *** presence of colloidal silica in those conditions intensifies strongly the fouling,leading until to 24.1%of permeate flux decrease.

关键词： Reverse osmosis Desalination Fouling Seawater Scaling

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Stem cell-based approaches: Possible route to hearing restoration?

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World Journal of Stem Cells 2020年第6期12卷 422-437页

作者： mar.a Beatriz Durán-alonso Institute of Biology and Molecular Genetics University of ValladolidValladolid 47003Spain

Disabling hearing loss is the most common sensorineural disability *** affects around 466 million people and its incidence is expected to rise to around 900 million people by 2050,according to World Health Organization *** cases of hearing impairment are due to the degeneration of hair cells(HCs)in the cochlea,mechano-receptors that transduce incoming sound information into electrical signals that are sent to the *** to these cells is mainly caused by exposure to aminoglycoside antibiotics and to some anti-cancer drugs such as cisplatin,loud sounds,age,infections and genetic *** deficits may also result from damage to the spiral ganglion neurons that innervate cochlear *** from what is observed in avian and nonmammalian species,there is no regeneration of missing sensory cell types in the adult mammalian cochlea,what makes hearing loss an irreversible *** review summarizes the research that has been conducted with the aim of developing cell-based strategies that lead to sensory cell replacement in the adult cochlea and,ultimately,to hearing *** main lines of research are discussed,one directed toward the transplantation of exogenous replacement cells into the damaged tissue,and another that aims at reactivating the regenerative potential of putative progenitor cells in the adult inner *** from some of the studies that have been conducted are presented and the advantages and drawbacks of the various approaches discussed.

关键词： Hearing loss Cochlear hair cells Spiral ganglion neurons Cell regeneration Adult stem cells Cell transplantation

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Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

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World Journal of Gastroenterology 2011年第12期17卷 1531-1537页

作者： mar.a Luisa Manzano-alonso Gregorio Castellano-Tortajada Department of Gastroenterology Hospital 12 de OctubreAv Andalucia28041 MadridSpain

Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus(HBV) replication,often accompanied by an increase in serum transaminase levels,and both events occurring in a patient with a previous inactive hepatitis B *** reactivation can occur in situations in which the ratio of HBV replication and immune response is *** can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune *** manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis,which are sometimes serious and result in acute liver failure with risk of death,and usually occur in the periods between cycles or at the end of *** drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen(HBsAg) or anti-HBc,but much less frequently than chemotherapy *** tumor necrosis factorαinhibitors infliximab,etanercept and adalimumab may cause reactivation of hepatitis B,and the overall frequency with infliximab may be similar(50%-66%) to that caused by *** HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs,and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.

关键词： Hepatitis B Immune response Immunosuppression Reactivation

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Dendritic nanoarchitecture imparts ZSM-5 zeolite with enhanced adsorption and catalytic performance in energy applications

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Journal of Energy Chemistry 2023年第5期80卷 77-88,I0003页

作者： mar.a del mar alonso-Doncel Cristina Ochoa-Hernández Gema Gómez-Pozuelo Adriana Oliveira joséGonzález-Aguilar ángel Peral Raúl Sanz David P.Serrano Thermochemical Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Heterogeneous Catalysis Max-Planck-Institut für KohlenforschungKaiser-Wilhem-Platz14540Muheim an der RuhGermay Department of Chemical and Environmental Technology Rey Juan Carlos UniversityC/Tulipan s/nE28933MostolesMadridSpain High Temperature Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Chemical Energy and Mechanical TechnologyRey Juan Carlos UniversityC/Tulipan s/n28933MostolesMadridSpain

The development of zeolites possessing dendritic features represents a great opportunity for the design of novel materials with applications in a large variety of fields and,in particular,in the energy sector to afford its transition towards a low carbon *** the current work,ZSM-5 zeolite showing a dendritic3D nanoarchitecture has been synthesized by the functionalization of protozeolitic nanounits with an amphiphilic organosilane,which provokes the branched aggregative growth of zeolite *** ZSM-5 exhibits outstanding accessibility arising from a highly interconnected network of radially-oriented mesopores(3-10 nm)and large cavities(20-80 nm),which add to the zeolitic micropores,thus showing a well-defined trimodal pore size *** singular features provide dendritic ZSM-5 with sharply enhanced performance in comparison with nano-and hierarchical reference materials when tested in a number of energy related applications,such as VOCs(toluene)adsorption(improved capacity),plastics(low-density polyethylene)catalytic cracking(boosted activity)and hydrogen production by methane catalytic decomposition(higher activity and deactivation resistance).

关键词： Dendritic ZSM-5 VOCs adsorption Plastics cracking Methane decomposition Hydrogen production

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Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

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World Journal of Gastroenterology 2010年第31期16卷 3936-3943页

作者： Nicole Acosta Andrés quiroga Pilar Delgado mar.a Mercedes Bravo Carlos Jaramillo Molecular Diagnostics and Bioinformatics Laboratory Biological Sciences DepartmentLos Andes University Infectious Agents and Cancer Research Group National Cancer Institute(Colombia)

AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPI-YA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using χ2 test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0. RESULTS: After amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor

关键词： Helicobacter pylori CagA-protein polymorphisms Molecular characterization Bioinformatic analysis Pathogenesis Cancer

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Enhanced depth OCT imaging of the lamina cribrosa for 24 hours

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International Journal of Ophthalmology(English edition) 2017年第2期10卷 306-309页

作者： Pedro Naranjo Bonilla Rafael Giménez Gómez David Ríos Jiménez mar.a Luísa Varas Fabra mar.a del Carmen Munoz Villanueva Rocío García Catalán Pilar Font Ugalde mar.a Soledad Poblador Fernández joséLuís Lancho alonso josémar.a Gallardo Galera Department of Ophthalmology Reina Sofia University HospitalCordoba 14004Spain Methodological Support to Research Maimonides Institute for Biomedical ResearchReina Sofia University HospitalCordoba 14004Spain Department of Medicine UCO Maimonides Institute for Biomedical ResearchReina Sofia University HospitalCordoba 14004Spain Department of Morphological Sciences Faculty of MedicineCordoba 14004Spain

The lamina cribrosa thickness（LCT） could be affected by dynamic changes in its *** spectral-domainoptical coherence tomography（SD-OCT）,we have studied the behaviour of the laminar region in 14 young subjects over 24 *** changes in LCT were observed,depending on the time at which the measurement was taken,with the maximum thickness being observed at 7.30 p.m.,and the minimum at 7.30 *** finding could suggests a circadian pattern in the LCT thickness in healthy subjects,which could have implications for the classification,diagnosis and prognosis of both normal and glaucomatous subjects.

关键词： lamina cribrosa laminar region glaucoma optical coherence tomography twenty-four-hours

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Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

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World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia Labrador-Velandia mar.a Luz alonso-alonso Sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio josé Carlos Pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud Carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： Mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

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Impact of diff erent waves of COVID-19 on emergency medical services and out-of-hospital cardiopulmonary arrest in Madrid, Spain

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World Journal of Emergency Medicine 2022年第5期13卷 386-389页

作者： jose-mar.a Navalpotro-Pascual Diana Monge martín Manuel-josé González León Fernando Neria Serrano Carlos alonso Blas Belén Muñoz Isabel Yago Muñecas Cuesta Alfredo Carrillo Moya Juan Les González alonso Mateos Rodríguez Madrid Emergency Medical Services SUMMA 112Madrid 28045Spain School of Medicine Francisco de Vitoria UniversityMadrid 28223Spain(School of MedicineUniversidad Francisco de VitoriaMadrid 28223Spain)

Out-of-hospital cardiac arrest(OHCA)is one of the three leading causes of death in industrialized countries.[1,2]Some studies have described the impact of the first COVID-19 pandemic wave in terms of the number of cases and OHCA survival rates in various regions,[3-5]but few have addressed the relationship between the successive phases and how they affected OHCA.[6,7]The 14-d cumulative incidence peaked at more than 990 cases,with these rates remaining above 200 for an eight-month period between 15 march 2020 and 15 march 2021 in Madrid,Spain.

关键词： cardiac services successive

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Stroke care during the COVID-19 outbreak in Spain: the experience of Spanish stroke units

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Stroke & Vascular Neurology 2021年第2期6卷 267-273页

作者： mar.a alonso de Lecinana mar Castellanos Oscar Ayo-martin Ana Morales the Stroke Group-Spanish Society of Neurology Department of Neurology and Stroke Center Hospital La Paz Institute for Health Research-IdiPAZ.La Paz University Hospital.Universidad Autonoma de MadridMadridSpain Department of Neurology Complexo Hospitalario Universitario A Coruna.Biomedical Research Institute of A CorunaA CorunaSpain Department of Neurology Complejo Hospitalario Universitario de AlbaceteAlbaceteSpain Department of Neurology University Clinic Hospital Virgen de la ArrixacaMurciaSpain 不详

Background and purpose Spain has been heavily affected by *** of resources for managing the outbreak might have caused a disruption in stroke *** study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this *** and methods We obtained data from a structured survey sent to the responsible of stroke units across the *** recorded the number of strokes,stroke code activations,intravenous thrombolysis treatments and mechanical thrombectomies during February and march 2019 and *** also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments,the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human *** compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence *** Fifty-seven(75%)of all stroke units in Spain responded to the *** was an overall reduction in admissions for all stroke types during the outbreak’s peak and in the number of stroke code activations and intravenous thrombolysis treatments,results that were independent of the COVID-19 incidence *** reported a delay in workflow metrics and a reduction of admissions to stroke units,outpatient clinics and rehabilitation *** pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been *** The COVID-19 outbreak has jeopardised all phases of stroke *** a consequence,some patients with stroke did not receive adequate treatment.

关键词： Spanish consequence outbreak

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