Coaxial Synthesis of PEI-Based Nanocarriers of Encapsulated RNA-Therapeutics to Specifically Target Muscle Cells
Artículo Materias > Biomedicina Universidad Europea del Atlántico > Investigación > Artículos y libros Abierto Inglés In this work, we performed a methodological comparative analysis to synthesize polyethyleneimine (PEI) nanoparticles using (i) conventional nanoprecipitation (NP), (ii) electrospraying (ES), and (iii) coaxial electrospraying (CA). The nanoparticles transported antisense oligonucleotides (ASOs), either encapsulated (CA nanocomplexes) or electrostatically bound externally (NP and ES nanocomplexes). After synthesis, the PEI/ASO nanoconjugates were functionalized with a muscle-specific RNA aptamer. Using this combinatorial formulation methodology, we obtained nanocomplexes that were further used as nanocarriers for the delivery of RNA therapeutics (ASO), specifically into muscle cells. In particular, we performed a detailed confocal microscopy-based comparative study to analyze the overall transfection efficiency, the cell-to-cell homogeneity, and the mean fluorescence intensity per cell of micron-sized domains enriched with the nanocomplexes. Furthermore, using high-magnification electron microscopy, we were able to describe, in detail, the ultrastructural basis of the cellular uptake and intracellular trafficking of nanocomplexes by the clathrin-independent endocytic pathway. Our results are a clear demonstration that coaxial electrospraying is a promising methodology for the synthesis of therapeutic nanoparticle-based carriers. Some of the principal features that the nanoparticles synthesized by coaxial electrospraying exhibit are efficient RNA-based drug encapsulation, increased nanoparticle surface availability for aptamer functionalization, a high transfection efficiency, and hyperactivation of the endocytosis and early/late endosome route as the main intracellular uptake mechanism metadata de la Hoz, Raquel; Diban, Nazely; Berciano, María T.; San Emeterio, Carlos; Urtiaga, Ane; Lafarga, Miguel; Rodríguez-Rey, José C. y Tapia Martínez, Olga mail SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, carlos.sanemeterio@alumnos.uneatlantico.es, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, olga.tapia@uneatlantico.es (2022) Coaxial Synthesis of PEI-Based Nanocarriers of Encapsulated RNA-Therapeutics to Specifically Target Muscle Cells. Biomolecules, 12 (8). p. 1012. ISSN 2218-273X
|
Texto
biomolecules-12-01012.pdf Available under License Creative Commons Attribution. Descargar (3MB) | Vista Previa |
Resumen
In this work, we performed a methodological comparative analysis to synthesize polyethyleneimine (PEI) nanoparticles using (i) conventional nanoprecipitation (NP), (ii) electrospraying (ES), and (iii) coaxial electrospraying (CA). The nanoparticles transported antisense oligonucleotides (ASOs), either encapsulated (CA nanocomplexes) or electrostatically bound externally (NP and ES nanocomplexes). After synthesis, the PEI/ASO nanoconjugates were functionalized with a muscle-specific RNA aptamer. Using this combinatorial formulation methodology, we obtained nanocomplexes that were further used as nanocarriers for the delivery of RNA therapeutics (ASO), specifically into muscle cells. In particular, we performed a detailed confocal microscopy-based comparative study to analyze the overall transfection efficiency, the cell-to-cell homogeneity, and the mean fluorescence intensity per cell of micron-sized domains enriched with the nanocomplexes. Furthermore, using high-magnification electron microscopy, we were able to describe, in detail, the ultrastructural basis of the cellular uptake and intracellular trafficking of nanocomplexes by the clathrin-independent endocytic pathway. Our results are a clear demonstration that coaxial electrospraying is a promising methodology for the synthesis of therapeutic nanoparticle-based carriers. Some of the principal features that the nanoparticles synthesized by coaxial electrospraying exhibit are efficient RNA-based drug encapsulation, increased nanoparticle surface availability for aptamer functionalization, a high transfection efficiency, and hyperactivation of the endocytosis and early/late endosome route as the main intracellular uptake mechanism
| Tipo de Documento: | Artículo |
|---|---|
| Palabras Clave: | nanoparticle; coaxial electrospraying; polyethylenimine; RNA-therapeutics; aptamers; muscle-specific therapy; spinal muscular atrophy; Nusinersen |
| Clasificación temática: | Materias > Biomedicina |
| Divisiones: | Universidad Europea del Atlántico > Investigación > Artículos y libros |
| Depositado: | 06 Sep 2022 17:24 |
| Ultima Modificación: | 12 Jul 2023 23:30 |
| URI: | https://repositorio.uneatlantico.es/id/eprint/3482 |
Acciones (logins necesarios)
 |
Ver Objeto |
<a class="ep_document_link" href="/10290/1/Influence%20of%20E-learning%20training%20on%20the%20acquisition%20of%20competences%20in%20basketball%20coaches%20in%20Cantabria.pdf"><img class="ep_doc_icon" alt="[img]" src="/10290/1.hassmallThumbnailVersion/Influence%20of%20E-learning%20training%20on%20the%20acquisition%20of%20competences%20in%20basketball%20coaches%20in%20Cantabria.pdf" border="0"/></a>
en
open
The main aim of this study was to analyse the influence of e-learning training on the acquisition of competences in basketball coaches in Cantabria. The current landscape of basketball coach training shows an increasing demand for innovative training models and emerging pedagogies, including e-learning-based methodologies. The study sample consisted of fifty students from these courses, all above 16 years of age (36 males, 14 females). Among them, 16% resided outside the autonomous community of Cantabria, 10% resided more than 50 km from the city of Santander, 36% between 10 and 50 km, 14% less than 10 km, and 24% resided within Santander city. Data were collected through a Google Forms survey distributed by the Cantabrian Basketball Federation to training course students. Participation was voluntary and anonymous. The survey, consisting of 56 questions, was validated by two sports and health doctors and two senior basketball coaches. The collected data were processed and analysed using Microsoft® Excel version 16.74, and the results were expressed in percentages. The analysis revealed that 24.60% of the students trained through the e-learning methodology considered themselves fully qualified as basketball coaches, contrasting with 10.98% of those trained via traditional face-to-face methodology. The results of the study provide insights into important characteristics that can be adjusted and improved within the investigated educational process. Moreover, the study concludes that e-learning training effectively qualifies basketball coaches in Cantabria.
Josep Alemany Iturriaga mail josep.alemany@uneatlantico.es, Álvaro Velarde-Sotres mail alvaro.velarde@uneatlantico.es, Javier Jorge mail , Kamil Giglio mail ,
Alemany Iturriaga
<a href="/15625/1/s41598-024-74127-8.pdf" class="ep_document_link"><img class="ep_doc_icon" alt="[img]" src="/style/images/fileicons/text.png" border="0"/></a>
en
open
Plant stress reduction research has advanced significantly with the use of Artificial Intelligence (AI) techniques, such as machine learning and deep learning. This is a significant step toward sustainable agriculture. Innovative insights into the physiological responses of plants mostly crops to drought stress have been revealed through the use of complex algorithms like gradient boosting, support vector machines (SVM), recurrent neural network (RNN), and long short-term memory (LSTM), combined with a thorough examination of the TYRKC and RBR-E3 domains in stress-associated signaling proteins across a range of crop species. Modern resources were used in this study, including the UniProt protein database for crop physiochemical properties associated with specific signaling domains and the SMART database for signaling protein domains. These insights were then applied to deep learning and machine learning techniques after careful data processing. The rigorous metric evaluations and ablation analysis that typified the study’s approach highlighted the algorithms’ effectiveness and dependability in recognizing and classifying stress events. Notably, the accuracy of SVM was 82%, while gradient boosting and RNN showed 96%, and 94%, respectively and LSTM obtained an astounding 97% accuracy. The study observed these successes but also highlights the ongoing obstacles to AI adoption in agriculture, emphasizing the need for creative thinking and interdisciplinary cooperation. In addition to its scholarly value, the collected data has significant implications for improving resource efficiency, directing precision agricultural methods, and supporting global food security programs. Notably, the gradient boosting and LSTM algorithm outperformed the others with an exceptional accuracy of 96% and 97%, demonstrating their potential for accurate stress categorization. This work highlights the revolutionary potential of AI to completely disrupt the agricultural industry while simultaneously advancing our understanding of plant stress responses.
Tariq Ali mail , Saif Ur Rehman mail , Shamshair Ali mail , Khalid Mahmood mail , Silvia Aparicio Obregón mail silvia.aparicio@uneatlantico.es, Rubén Calderón Iglesias mail ruben.calderon@uneatlantico.es, Tahir Khurshaid mail , Imran Ashraf mail ,
Ali
en
close
Technological firms invest in R&D looking for innovative solutions but assuming high costs and great (technological) uncertainty regarding final results and returns. Additionally, they face other problems related to R&D management. This empirical study tries to determine which of the factors favour or constrain the decision of these firms to engage in R&D. The analysis uses financial data of 14,619 ICT listed companies of 22 countries from 2003 to 2018. Additionally, macroeconomic data specific for the countries and the sector were used. For the analysis of dynamic panel data, a System-GMM method is used. Among the findings, we highlight that cash flow, contrary to the known theoretical models and empirical evidences, negatively impacts on R&D investment. Debt is neither the right source for R&D funding, as the effect is also negative. This suggests that ICT companies are forced to manage their R&D activities differently, relying more on other funding sources, taking advantage of growth opportunities and benefiting from a favourable macroeconomic environment in terms of growth and increased business sector spending on R&D. These results are similar in both sub-sectors and in all countries, both bank- and market based. The exception is firms with few growth opportunities and little debt.
Inna Alexeeva-Alexeev mail inna.alexeeva@uneatlantico.es, Cristina Mazas Pérez-Oleag mail cristina.mazas@uneatlantico.es,
Alexeeva-Alexeev
<a class="ep_document_link" href="/15198/1/nutrients-16-03859.pdf"><img class="ep_doc_icon" alt="[img]" src="/15198/1.hassmallThumbnailVersion/nutrients-16-03859.pdf" border="0"/></a>
en
open
Carotenoids Intake and Cardiovascular Prevention: A Systematic Review
Background: Cardiovascular diseases (CVDs) encompass a variety of conditions that affect the heart and blood vessels. Carotenoids, a group of fat-soluble organic pigments synthesized by plants, fungi, algae, and some bacteria, may have a beneficial effect in reducing cardiovascular disease (CVD) risk. This study aims to examine and synthesize current research on the relationship between carotenoids and CVDs. Methods: A systematic review was conducted using MEDLINE and the Cochrane Library to identify relevant studies on the efficacy of carotenoid supplementation for CVD prevention. Interventional analytical studies (randomized and non-randomized clinical trials) published in English from January 2011 to February 2024 were included. Results: A total of 38 studies were included in the qualitative analysis. Of these, 17 epidemiological studies assessed the relationship between carotenoids and CVDs, 9 examined the effect of carotenoid supplementation, and 12 evaluated dietary interventions. Conclusions: Elevated serum carotenoid levels are associated with reduced CVD risk factors and inflammatory markers. Increasing the consumption of carotenoid-rich foods appears to be more effective than supplementation, though the specific effects of individual carotenoids on CVD risk remain uncertain.
Sandra Sumalla Cano mail sandra.sumalla@uneatlantico.es, Imanol Eguren García mail imanol.eguren@uneatlantico.es, Álvaro Lasarte García mail , Thomas Prola mail thomas.prola@uneatlantico.es, Raquel Martínez Díaz mail raquel.martinez@uneatlantico.es, Iñaki Elío Pascual mail inaki.elio@uneatlantico.es,
Sumalla Cano
en
close
Uterine leiomyomas are the most common benign, monoclonal, gynaecological tumors in a woman’s uterus, while leiomyosarcoma is a rare but aggressive condition caused by the malignant transformation of the myometrium. To overcome the common obstacles related to the methods usually used to study these pathologies, we aimed to devise three-dimensional models of myometrium, uterine leiomyoma and leiomyosarcoma cell lines, using two different types of biocompatible scaffolds. Specifically, we exploited the agarose gel matrix in common 6-well plates and the alginate matrix using Bioprinting INKREDIBLE + (CELLINK), a pneumatic extruded base equipped with a system with double printheads, and a UV printer LED curing system. Both methods allowed the development of 3D spheroids of all three cell types, that were also suitable for morphological investigations. We showed that all cell types embedded in both agarose and alginate formed spheroids in their growth medium. The spheroids successfully proliferated and self-organized into complex structures, developing a sustainable system that emulated the condition of the tissues through the accumulation of extracellular matrix. These models could be useful for a better understanding of pathophysiology, etiopathogenesis, and testing new methods or molecules from a preventive and therapeutic point of view.
Pamela Pellegrino mail , Stefania Greco mail , Abel Duménigo Gonzàlez mail , Francesca Giampieri mail francesca.giampieri@uneatlantico.es, Stefano Raffaele Giannubilo mail , Giovanni Delli Carpini mail , Franco Capocasa mail , Bruno Mezzetti mail , Maurizio Battino mail maurizio.battino@uneatlantico.es, Andrea Ciavattini mail , Pasquapina Ciarmela mail ,
Pellegrino