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Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2578-2591页

作者： elisa rioja-blanco Irene Arroyo-Solera Patriciaálamo Isolda Casanova Alberto Gallardo Ugutz Unzueta Naroa Serna Laura Sánchez-García Miquel Quer Antonio Villaverde Esther Vázquez Ramon Mangues Lorena Alba-Castellón Xavier León Institut d'InvestigacióBiomèdica Sant Pau(IIB-Sant Pau) Barcelona 08041Spain Institut de Recerca contra la Leucèmia Josep Carreras Barcelona 08025Spain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)Madrid 28029Spain Department of Pathology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193Spain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193Spain Department of Otorhinolaryngology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain

Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNSCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNSCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients.

关键词： Targeted drug delivery Protein nanoparticles CXCR4 receptor HNSCC Cell targeting Recombinant proteins Nanotoxins Cancer therapy

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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria blanco Martinez Suelen Adriani Marques PhD Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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End-life Prediction of Commercial PLA Used for Food Packaging through Short Term TGA Experiments: Real Chance or Low Reliability?

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Chinese Journal of Polymer Science 2014年第6期32卷 681-689页

作者： Ignazio blanco Department of Industrial Engineering University of Catania

A long-term （about nine months） isothermal degradation experiment of two different commercial polylactide （PLA） samples used for food packaging was carried out at a relatively low temperature （423 K）. Thermooxidative degradations of the same polymers were carried out in a thermogravimetric （TG） analyser, at higher temperatures （453 K 〈 T 〈 523 K）, under isothermal heating conditions. The obtained set of experimental TG data was used to determine the apparent activation energy （Ea） of degradation through two isothermal kinetic methods. The results from long-term experiment evidenced considerable mass loss for both PLA samples in the investigated period, but the experimental data were not in agreement with those from the short-term degradations at higher temperatures, thus suggesting a different degradation kinetics, and, then a low reliability of the lifetime predictions for polymers in service or degradation forecasts for the end of their life based on experiments at higher temperatures.

关键词： Lifetime prediction Degradation activation energy Kinetics of polymer degradation Thermogravimetry.

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Multi-family therapy for veteran and refugee families: a Delphi study

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Military Medical Research 2019年第1期6卷 39-44页

作者： elisa van Ee Psychotraumacentrum Zuid Nederland Behavioural Science Institute Radboud University

Background: Research indicates that Posttraumatic stress disorder(PTSD) has an extensive impact on family relationships. Nevertheless, there is a dearth of empirically supported interventions addressing family functioning and PTSD. In the Netherlands, it is considered good clinical practice to offer multi-family therapy(MFT) to veteran and refugee families. MFT for traumatized families aims to address the dysfunctional family patterns that have evolved to address the consequences with ***: The aim of this study is to generate a common framework for the practical impact and active ingredients of MFT in families confronted with trauma. The Delphi method was used to study the expert opinion of 11 therapists in Dutch expert trauma ***: The results indicate that MFT is a promising treatment for families dealing with the consequences of trauma. According to experts, positive outcomes include an increased understanding between family members,particularly visible in the de-escalation of conflicts within the family, and improved parenting. One explanation for the effectiveness of MFT with these target groups is its defining feature of therapy with several ***: The findings support the importance of considering family relationships and the family context in interventions for traumatized individuals.

关键词： PTSD Veteran Refugee Multi-family therapy Parenting Expert opinion

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Over-specialization versus synergy in neuroscience:professionals’integration is more than the sum of its parts

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Neural Regeneration Research 2021年第11期16卷 2232-2233页

作者： elisa Cainelli Luca Vedovelli Department of General Psychology University of PadovaPadovaItaly Unit of Biostatistics Epidemiology and Public HealthDepartment of CardiacThoracicVascular Sciencesand Public HealthUniversity of PadovaPadovaItaly

Health care systems in industrialized countries are built around acute health problems(Etzwiler,1997).This approach is successful when the goal is to improve or overcome pathologies that result in severe health issues or *** the recent tremendous improvement of the treatments of life-threatening conditions,the clinical focus has moved from short term results to the overall expected quality of life and longterm ***,the new objectives imply to consider a multitude of interacting processes and *** fact,a complex interplay of biological systems(nervous,immune,and endocrine)works together in an integrated and synergistic way to deal with a constantly evolving environment,determining our physical,behavioral,and psychological/subjective *** interplay is the mechanism that allows us to adapt promptly and appropriately to circumstances,the key feature for successful living.

关键词： overcome synergistic determining

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Interspecific differences in plasma carotenoid profiles in nestlings of three sympatric vulture species

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Current Zoology 2023年第6期69卷 658-669页

作者： Guillermo blanco Damaso Hornero-Mendezb Department of Evolutionary Ecology Museo Nacional de Ciencias Naturales(CSIC)Jose Gutierrez Abascal 228006 MadridSpain Departament of Food Phytochemistry Instituto de la Grasa(CSiC)Campus Universidad Pablo de Olavide41013 SevilleSpain

Carotenoids are diet-based micronutrients important in health and coloration *** species with similar diets can differ in the kinds and levels of circulating carotenoids,which suggests specific physiological mechanisms to efficiently utilize these micronutrients,regardless of their *** explored whether diet and parental provisioning of unusual sources of carotenoids(fresh vegetal matter and vertebrate feces)can explain the occurrence and concentrations of carotenoids in the cinereous vulture Aegypius monachus,griffon vulture Gyps fulvus,and Egyptian vulture Neophron percnopterus nestlings,even when these pigments appear to not be deposited in their integumentary system.A greater diversity of wild prey in diet could be behind the profile of higher concentrations of carotenoids in the Egyptian vulture,the species with carotenoid-dependent coloration during adulthood,while differences in diet composition between cinereous and griffon vultures do not translate to different carotenoid *** carotenoid profile appears to not be related to the ingestion of unusual matter rich in these compounds,although the infrequent occurrence of lycopene and unidentified y-carotene-like compounds suggest that these vultures may be exploiting vegetal matter that left no identifiable unconsumed remains in the nest of Egyptian *** consumption of green plant material by griffon vultures does not result in especially high levels of carotenoids when compared to the carotenoids found in cinereous vultures,which do not consume green plant *** feces were not provisioned to Egyptian vulture nestlings,despite the fact they contain carotenoids that adults need for appropriate ***,this study indicates that diet differences alone appear insufficient to explain contrasting *** carotenoid profiles,especially since all types of food consumed are considered to be poor in carotenoids,except vegetable *** suggest that n

关键词： avian scavengers carotenes coloration feeding habits micronutrients xanthophylls

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Gibberellin signaling turns blue

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Molecular Plant 2021年第8期14卷 1226-1228页

作者： Noel blanco-Tourinan David Alabadi Plant Vascular Development Group ETH Zurich8092 ZurichSwitzerland Instituto de Biologia Molecular y Celular de Plantas(CSIC-UPV) 46022 ValenciaSpain

The effect of envir on mental light on plant growth is mediated,at least in part,by the hormones gibberellins(GAs).The current model is that light signaling affects the GA pathway by transcrip-tional regulation of GA metabolism genes and by degradation of the negative regulators DELLA proteins by *** new studies provide evidenee showing that the blue light photoreceptor CRY1 directly regulates GA signaling.

关键词： CRY1 Gibberellin photoreceptor

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How do stream processes affect hazard exposure on alluvial fans? Insights from an experimental study

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Journal of Mountain Science 2020年第4期17卷 753-772页

作者： Bruno MAZZORANA elisa GHIANDONI Lorenzo PICCO Universidad Austral de Chile Faculty of SciencesInstituto de Ciencias de la Tierra5090000 ValdiviaChile Universidad Austral de Chile RINA–Natural and Anthropogenic Risks Research Center5090000 ValdiviaChile Universidad Austral de Chile Laboratory of HydromorphologyFaculty of Forest Sciences and Natural Resources5090000 ValdiviaChile University of Padova Department of LandEnvironmentAgriculture and Forestry35020 LegnaroItaly

Alluvial fans are among the most privileged settlement areas in many mountain regions. These landforms are particularly dynamic being episodically affected by distributary processes generated by extreme flood events. Addressing risk assessment entails determining hazard exposure and unravelling how it might be related to process loading and to process dynamics once the flow becomes unconfined on the surface of alluvial fans. By following a ‘similarity of process concept’, rather than by attempting to scale a real-world prototype, we performed a set of 72 experimental runs on an alluvial fan model. Thereby, we considered two model layouts, one without a guiding channel and featuring a convex shape and the other one with a guiding channel, a bridge, and inclined but planar overland flow areas as to mirror an anthropic environment. Process magnitude and intensity parameters were systematically varied, and the associated biphasic distributary processes video recorded. For each experiment, the exposure was detected by mapping the exposed area in a GIS, thereby discerning between areas exposed to biphasic flows and the associated depositional phenomena or to the liquid flow phase only. Our results reveal that total event volume, sediment availability and stream power in the feeding channel, as well as depositional effects, avulsion, and channelization on the alluvial fan concur to determine the overall exposure. Stream process loading alone, even when rigorously defined in terms of its characterizing parameters, is not sufficient to exhaustively determine exposure. Hence, further developing reliable biphasic simulation models for hazard assessment on settled alluvial fans is pivotal.

关键词： Alluvial fan Hazard Exposure Flood risk Experimental model Process similarity

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Biomarkers for pancreatic cancer:Recent achievements in proteomics and genomics through classical and multivariate statistical methods

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World Journal of Gastroenterology 2014年第37期20卷 13325-13342页

作者： Emilio Marengo elisa Robotti Department of Sciences and Technological Innovation University of Piemonte Orientale

Pancreatic cancer(PC) is one of the most aggressive and lethal neoplastic diseases. A valid alternative to the usual invasive diagnostic tools would certainly be the determination of biomarkers in peripheral fluids to provide less invasive tools for early diagnosis. Nowadays, biomarkers are generally investigated mainly in peripheral blood and tissues through high-throughput omics techniques comparing control vs pathological samples. The results can be evaluated by two main strategies:(1) classical methods in which the identification of significant biomarkers is accomplished by monovariate statistical tests where each biomarker is considered as independent from the others; and(2) multivariate methods, taking into consideration the correlations existing among the biomarkers themselves. This last approach is very powerful since it allows the identification of pools of biomarkers with diagnostic and prognostic performances which are superior to single markers in terms of sensitivity, specificity and robustness. Multivariate techniques are usually applied with variable selection procedures to provide a restricted set of biomarkers with the best predictive ability; however, standard selection methods are usually aimed at the identification of the smallest set of variables with the best predictive ability and exhaustivity is usually neglected. The exhaustive search for biomarkers is instead an important alternative to standard variable selection since it can provide information about the etiology of the pathology by producing a comprehensive set of markers. In this review, the most recent applications of the omics techniques(proteomics, genomics and metabolomics) to the identification of exploratory biomarkers for PC will be presented with particular regard to the statistical methods adopted for their identification. The basic theory related to classical and multivariate methods for identification of biomarkers is presented and then, the most recent applications in this f

关键词： Pancreatic cancer Biomarker identification Multivariate analysis Principal component analysis Ranking principal component analysis

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Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: Mesenchymal stem cells from induced pluripotent stem cells

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World Journal of Stem Cells 2021年第8期13卷 1094-1111页

作者： Victoria Dupuis elisa Oltra Facultédes Sciences et d’Ingénierie Sorbonne UniversitéParis 75252France Department of Pathology Universidad Católica de Valencia San Vicente MártirValencia 46001Spain Centro de Investigación Traslacional San Alberto Magno Universidad Católica de Valencia San Vicente MártirValencia 46001Spain

Mesenchymal stem cells(MSCs)have received significant attention in recent years due to their large potential for cell ***,they secrete a wide variety of immunomodulatory factors of interest for the treatment of immune-related disorders and inflammatory *** can be extracted from multiple tissues of the human ***,several factors may restrict their use for clinical applications:the requirement of invasive procedures for their isolation,their limited numbers,and their heterogeneity according to the tissue of origin or *** addition,MSCs often present early signs of replicative senescence limiting their expansion in vitro,and their therapeutic capacity in *** to the clinical potential of MSCs,a considerable number of methods to differentiate induced pluripotent stem cells(iPSCs)into MSCs have *** represent a new reliable,unlimited source to generate MSCs(MSCs derived from iPSC,iMSCs)from homogeneous and well-characterized cell lines,which would relieve many of the above mentioned technical and biological ***,the use of iPSCs prevents some of the ethical concerns surrounding the use of human embryonic stem *** this review,we analyze the main current protocols used to differentiate human iPSCs into MSCs,which we classify into five different categories:MSC Switch,Embryoid Body Formation,Specific Differentiation,Pathway Inhibitor,and Platelet *** also evaluate common and method-specific culture components and provide a list of positive and negative markers for MSC *** guidance on material requirements to produce iMSCs with these methods and on the phenotypic features of the iMSCs obtained is *** information may help researchers identify protocol options to design and/or refine standardized procedures for large-scale production of iMSCs fitting clinical demands.

关键词： Mesenchymal stem cells Induced pluripotent stem cells Mesenchymal stem cells derived from induced pluripotent stem cells Differentiation methods Culture components Mesenchymal stem cell markers

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