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Endosomal escape of protein nanoparticles engineered through humanized histidine-rich peptides

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Science China Materials 2020年第4期63卷 644-653页

作者： Hector lopez-Laguna Rafael Cubarsi Ugutz Unzueta Ramon Mangues Esther vazquez antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Aut6noma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingenieria Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Departament de Matematiques Universitat Politecnica de Catalunya08034BarcelonaSpain Institut d'Investigacions Biomediques Sant Pau Hospital de la Santa Creu i Sant Pau08025 BarcelonaSpain

Poly-histidine peptides such as H6(HHHHHH)are used in protein biotechnologies as purification tags,protein-assembling agents and endosomal-escape entities.The pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant proteins.However,the clinical applicability of H6-tagged proteins is restricted by the potential immunogenicity of these segments.In this study,we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins,which can specifically bind and be internalized by the target cells through the tumoral marker CXCR4.We were particularly interested in exploring how protein purification,self-assembling and endosomal escape perform in proteins containing the variant histidine-rich tags.Among the tested candidates,the peptide H5 E(HEHEHEHEH)is promising as a good promoter of endosomal escape of the associated fulllength protein upon endosomal internalization.The numerical modelling of cell penetration and endosomal escape of the tested proteins has revealed a negative relationship between the amount of protein internalized into target cells and the efficiency of cytoplasmic release.This fact demonstrates that the His-mediated,proton sponge-based endosomal escape saturates at moderate amounts of internalized protein,a fact that might be critical for the design of protein materials for cytosolic molecular delivery.

关键词： protein materials nanoparticles genetic design endosomal escape poly-histidines

Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-lopez Eduardo Andres-Leon Laura Carmen Terron-Camero Blanca Cano-Gutierrez Jose Manuel Cozar Jose antonio Lorente Fernando vazquez-Alonso Luis Javier Martinez-Gonzalez Maria Jesus Alvarez-Cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC cases.The increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk individuals.However,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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Science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran Olivia Cano-Garrido Naroa Serna Hector lopez-Laguna Laura Sanchez-Garcia Mireia Pesarrodona Alejandro Sanchez-Chardi Ramon Mangues antonio Villaverde Esther vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction.All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

Building an interoperable space for smart agriculture

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Digital Communications and Networks 2023年第1期9卷 183-193页

作者： Ioanna Roussaki Kevin Doolin antonio Skarmeta George Routis Juan antonio lopez-Morales Ethel Claffey Manuel Mora Juan antonio Martinez Institute of Communications and Computer Systems AthensGreece Walton Institute WaterfordIreland Department of Information and Communications Engineering University of MurciaMurciaSpain School of Business Waterford Institute of TechnologyWaterfordIreland R&D Department Odin SolutionsMurciaSpain

The digital transformation in agriculture introduces new challenges in terms of data,knowledge and technology adoption due to critical interoperability issues,and also challenges regarding the identification of the most suitable data sources to be exploited and the information models that must be used.DEMETER(Building an Interoperable,Data-Driven,Innovative and Sustainable European Agri-Food Sector)addresses these challenges by providing an overarching solution that integrates various heterogeneous hardware and software resources(e.g.,devices,networks,platforms)and enables the seamless sharing of data and knowledge throughout the agri-food chain.This paper introduces the main concepts of DEMETER and its reference architecture to address the data sharing and interoperability needs of farmers,which is validated via two rounds of 20 large-scale pilots along the DEMETER lifecycle.This paper elaborates on the two pilots carried out in region of Murcia in Spain,which target the arable crops sector and demonstrate the benefits of the deployed DEMETER reference architecture.

关键词： Smart agriculture Internet of things(IoT) DEMETER Reference architecture Interoperability Agricultural information model(AIM) Pilot validation

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欧洲房地产集团商业计划

欧洲房地产集团商业计划

作者： lopez Iniesta,Marco antonio 上海外国语大学

学位级别：硕士

近年来,中国买家的身影大规模地出现在了国际房地产市场上。这对于房地产业的开发和发展都是一个崭新的机遇。目前,西班牙的经济发展稳定,房地产市场持续升温。越来越多的中国人也开始在西班牙投资。欧洲房地产集团的商业模式给出了一... 详细信息

近年来,中国买家的身影大规模地出现在了国际房地产市场上。这对于房地产业的开发和发展都是一个崭新的机遇。目前,西班牙的经济发展稳定,房地产市场持续升温。越来越多的中国人也开始在西班牙投资。欧洲房地产集团的商业模式给出了一个差异化的增值提议。市场机遇1.消费者问题。美国,加拿大,澳大利亚和英国市场发展迅速且拥有广阔的前景。然而出现了三个让消费者担心的问题:1.)价格与需求。由于需求上升,价格也随之快速升高。这会让近年内有购买意向的买家不堪重负。2.)政府措施。一些国家,类似澳大利亚,提高了外国人购买房产的赋税。3.)定制服务。大多数房产公司都是直接提供本国房屋,也就是说,消费者需要适应当地的建筑风格。2.欧洲房地产集团的解决方案。他们的战略方案解决了前面提及的三个问题。1.)价格和需求。如今西班牙的房地产价格对欧洲以及其他的发达国家极具吸引力,吸引了世界范围内的很多投资者。2.)政府措施。近期,西班牙政府制定了减少税收的计划。2015年的很多法规都下调了个人所得税和企业所得税。3.)定制服务。通过与合作伙伴的战略联盟,房地产公司给顾客提供了多种个性化选择。3.市场规模。预计中国海外房地产投资额在2020年将冲击2200亿美元。2017年中国投资商仅在西班牙的投资预计达到12亿美元。4.竞争。西班牙的房地产行业高度分散。此外,不到0.1%的公司擅长于亚洲市场。5.为什么是现在?1.)经济增长和对中国投资商的倾向性。中国经济的持续增长以及有相当一部分的人都有移居海外的计划;2.)法规。2013年,西班牙政府通过了“黄金签证”的法案,并投资了50万欧元在住宅房地产市场。3.)需求、价格等。西班牙现在是最具吸引力的房地产市场。根据世邦魏理仕所言,西班牙房地产投资在表面上呈增长势头。总之,整份材料涵盖了所有必要的相关研究与分析得出的结论,揭示了任何盈利和被看好的商业,其运作都是很复杂的。此外,欧洲房地产集团是一个潜在的盈利和可持续发展的商业。

关键词：国际房地产行业中国市场可行性分析

Advances in spray products for skin regeneration

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Bioactive Materials 2022年第10期7卷 187-203页

作者： Paula Pleguezuelos-Beltran Patricia Galvez-Martín Daniel Nieto-Garcí Juan antonio Marchal Elena lopez-Ruiz Biopathology and Regenerative Medicine Institute(IBIMER) Centre for Biomedical Research(CIBM)University of GranadaGranadaSpain Department of Human Anatomy and Embryology Faculty of MedicineUniversity of GranadaGranadaSpain BioFab i3D Lab-Biofabrication and 3D(bio)printing Laboratory GranadaSpain Excellence Research Unit“Modeling Nature”(MNat) University of GranadaGranadaSpain Biosanitary Research Institute of Granada(ibs.GRANADA) University Hospitals of Granada-University of GranadaGranadaSpain R&D Human Health Bioib´erica S.A.UBarcelonaSpain Department of Pharmacy and Pharmaceutical Technology Faculty of PharmacyUniversity of GranadaGranadaSpain Complex Tissue Regeneration Department MERLN Institute for Technology Inspired Regenerative MedicineUniversiteitssingel 406229ER Maastrichtthe Netherlands Department of Health Sciences University of Ja´enJa´enSpain

To date,skin wounds are still an issue for healthcare professionals.Although numerous approaches have been developed over the years for skin regeneration,recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes,including 3D bioprinting,electrospinning or spraying,among others.In particular,skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds.Skin sprays present significant advantages compared to conventional treatments for wound healing,such as the facility of application,the possibility to treat large wound areas,or the homogeneous distribution of the sprayed material.In this article,we review the latest advances in this technology,giving a detailed description of investigational and currently commercially available acellular and cellular skin spray products,used for a variety of diseases and applying different experimental materials.Moreover,as skin sprays products are subjected to different classifications,we also explain the regulatory pathways for their commercialization and include the main clinical trials for different skin diseases and their treatment conditions.Finally,we argue and suggest possible future trends for the biotechnology of skin sprays for a better use in clinical dermatology.

关键词： Skin Spray Tissue engineering Fibrin Hydrogel

Prevalence of meeting 24-Hour Movement Guidelines from pre-school to adolescence: A systematic review and meta-analysis including 387,437 participants and 23 countries

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Journal of Sport and Health Science 2022年第4期11卷 427-437页

作者： Miguel Angel Tapia-Serrano Javier Sevil-Serrano Pedro antonio Sanchez-Miguel Jose Francisco lopez-Gil Mark STremblay antonio Garcıa-Hermoso Department of Didactics of Musical Plastic and Body ExpressionFaculty of Teaching TrainingUniversity of ExtremaduraAvenida de la UniversidadS/NCaceres 10071Spain Department of Physical Activity and Sport Faculty of Sport ScienceUniversity of Murcia(UM)San Javier 30720Spain Healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario(CHEO)Research InstituteOttawaON K1H 8L1Canada Navarrabiomed Public University of Navarra(UPNA)Health Research Institute of Navarra(IdiSNA)Navarra Hospital Complex(CHN)Pamplona 310008Spaia

Background:Meeting the 24-Hour Movement Guidelines(physical activity,screen time,and sleep duration) has been associated with positive health indicators.However,there are no previous meta-analyses that have examined the overall adherence to the 24-Hour Movement Guidelines from pre-school to adolescence across the world.Therefore,the main purpose of this systematic review and meta-analysis was to examine the overall(non)adherence to the 24-Hour Movement Guidelines among preschoolers,children,and adolescents worldwide.Methods:Four electronic databases(MEDLINE,Scopus,Web of Science,and Cochrane Database of Systematic Reviews) were searched for quantitative studies published in Spanish and English between January 2016 and May 2021.Studies that were conducted with apparently healthy participants and reported the overall(non)adherence to the 24-Hour Movement Guidelines in preschoolers and/or children and/or adolescents were included.Results:Sixty-three studies comprising 387,437 individuals(51% girls) aged 3-18 years from 23 countries were included.Overall,7.12%(95%confidence interval(95%CI):6.45%-7.78%) of youth met all three 24-Hour Movement Guidelines,and 19.21%(95%CI:16.73%-21.69%)met none of the 3 recommendations.Concerning sex,adherence to all recommendations was significantly lower in girls(3.75%,95%CI:3.23%-4.27%) than in boys(6.89%,95%CI:5.89%-7.89%)(p <0.001).However,there were no sex differences regarding adherence to any of the 3 individual recommendations(girls,15.66%,95%CI:8.40%-22.92%;boys,12.95%,95%CI:6.57%-19.33%).In terms of age group,adherence to the 3 recommendations was 11.26%(95%CI:8.68%-13.84%),10.31%(95%CI:7.49%-13.12%),and 2.68%(95%CI:1.78%-3.58%) in preschoolers,children,and adolescents,respectively.Conversely,8.81%(95%CI:5.97%-11.64%) of preschoolers,15.57%(95%CI:11.60%-19.54%) of children,and 28.59%(95%CI:22.42%-34.75%) of adolescents did not meet any of the recommendations.South America was the region with the lowest adherence(all:2.93%;none:31.72%).Overall adherence to the 24-Hour Movement

关键词： Exercise Lifestyle Movement behaviors Sedentary behaviors Youth

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2013年第1期19卷 17-25页

作者： Elena Garrido Elisa Carrera Rebeca Manzano antonio lopez-Sanroman Inflammatory Bowel Disease Clinic Department of GastroenterologyUniversity Hospital Ramón y Cajal28034 MadridSpain Department of Gastroenterology University Hospital of Guadalajara19002 GuadalajaraSpain Department of Gastroenterology Hospital Sureste28500 MadridSpain

Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

关键词： Cytomegalovirus Inflammatory bowel disease Crohn’s disease Ulcerative colitis Hematoxylin and eosin Immunohistochemical Polymerase chain reaction Ganciclovir Infectious colitis

各向异性金纳米粒子的制备及其在催化中的应用（英文）

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Chinese Journal of Catalysis 2016年第10期37卷 1619-1650页

作者： Peter Priecel Hammed Adekunle Salami Romen Herrera Padilla Ziyi Zhong Jose antonio lopez-Sanchez 利物浦大学化学系可再生能源斯蒂芬森研究所英国利物浦新加坡科技研究局(A*STAR) 化学与工程科学研究所新加坡裕廊岛627833

尽管有关金纳米粒子催化的研究工作很多,但其中大多数都是采用传统的浸渍法将金盐负载到载体上、共沉淀或沉积-沉淀法制得负载的纳米粒子,但这些方法并未吸收最新的纳米技术.最近,金催化剂的研究者开发了在胶态悬浮液中制取金属纳米粒子... 详细信息

尽管有关金纳米粒子催化的研究工作很多,但其中大多数都是采用传统的浸渍法将金盐负载到载体上、共沉淀或沉积-沉淀法制得负载的纳米粒子,但这些方法并未吸收最新的纳米技术.最近,金催化剂的研究者开发了在胶态悬浮液中制取金属纳米粒子,然后进行固载,从而使得单金属和双金属催化剂的催化活性和形貌控制取得较大进展.另一方面,最近十年出现了金纳米粒子合成的高级控制技术,得到了许多各向异性的金纳米粒子,且很容易制得新的形貌,可以控制纳米粒子的表面原子配位数和光学特性(可调的等离子体带),这些都与催化密切相关.这些形貌包括纳米棒、纳米星、纳米花、树枝状纳米结构或多面体纳米粒子等.除了高度关注各向异性金纳米粒子的最新开发的制备方法和性质,本综述也清楚地总结了这些纳米粒子独特的催化性能,以及通过提供更高催化性能的金催化剂、控制暴露的活性位,以及热、电和光催化的鲁棒性和可调性,从而给多相催化领域带来令人惊奇的潜在变革.

关键词：各向异性金属纳米粒子金催化光催化电催化催化氧化胶状金纳米粒子金纳米棒金纳米星溶胶固定