109 results on '"Javier Ramón-Azcón"'
Search Results
2. Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors
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Marta Fontcuberta-PiSunyer, Ainhoa García-Alamán, Èlia Prades, Noèlia Téllez, Hugo Alves-Figueiredo, Mireia Ramos-Rodríguez, Carlos Enrich, Rebeca Fernandez-Ruiz, Sara Cervantes, Laura Clua, Javier Ramón-Azcón, Christophe Broca, Anne Wojtusciszyn, Nuria Montserrat, Lorenzo Pasquali, Anna Novials, Joan-Marc Servitja, Josep Vidal, Ramon Gomis, and Rosa Gasa
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Biology (General) ,QH301-705.5 - Abstract
Human foreskin fibroblasts are directly reprogrammed into insulin-producing cells using 5 pancreatic transcription factors, without pluripotency induction.
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- 2023
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3. The Tissue Engineering Revolution: From Bench Research to Clinical Reality
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Francesco De Chiara, Ainhoa Ferret-Miñana, Juan M. Fernández-Costa, and Javier Ramón-Azcón
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n/a ,Biology (General) ,QH301-705.5 - Abstract
At its core, tissue engineering involves the use of a scaffold for the formation of new viable tissue for medical purposes [...]
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- 2024
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4. Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy
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Albert Manzano-Muñoz, José Yeste, María A. Ortega, Fernando Martín, Anna López, Jordi Rosell, Sandra Castro, César Serrano, Josep Samitier, Javier Ramón-Azcón, and Joan Montero
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Precision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events (‘priming’) and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We used microfluidic chips to generate a gradient of BIM BH3 peptide, compared it with the standard flow cytometry based DBP, and tested different anticancer treatments. We first examined this new technology’s predictive capacity using gastrointestinal stromal tumor (GIST) cell lines, by comparing imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for cancer patients.
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- 2022
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5. Muscle-on-a-chip devices: a new era for in vitro modelling of muscular dystrophies
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Juan M. Fernández-Costa, Ainoa Tejedera-Vilafranca, Xiomara Fernández-Garibay, and Javier Ramón-Azcón
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Medicine ,Pathology ,RB1-214 - Published
- 2023
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6. High-throughput biointerfaces for direct, label-free, and multiplexed metaplasmonic biosensing
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María J. Ugarte-Orozco, Gerardo A. López-Muñoz, Aurora Antonio-Pérez, Karla M. Esquivel-Ortiz, and Javier Ramón-Azcón
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Nanoplasmonic ,Metaplasmonic ,Biosensing ,Biosensors ,Biointerfaces ,Point-of-Care ,Biotechnology ,TP248.13-248.65 - Abstract
In recent years, metaplasmonic biosensors have emerged as a novel counterpart of well-established plasmonic biosensors based on thin metallic layers. Metaplasmonic biosensors offer high potential for sensor miniaturization, extreme sensitivity biosensing, and high multiplexing capabilities with detection methods free of coupling optical elements. These capabilities make metaplasmonic biosensors highly attractive for Point-of-Care and handled/portable devices or novel On-Chip devices; as a result, it has increased the number of prototypes and potential applications that emerged during the last years. One of the main challenges to achieving fully operative devices is the achievement of high-throughput biointerfaces for sensitive and selective biodetection in complex media. Despite the superior surface sensitivity achieved by metaplasmonic sensors compared to conventional plasmonic sensors based on metallic thin films, the main limitations to achieving high-throughput and multiplexed biosensing usually are associated with the sensitivity and selectivity of the biointerface and, as a consequence, their application to the direct analysis of real complex samples. This graphical review discusses the potential challenges and capabilities of different biofunctionalization strategies, biorecognition elements, and antifouling strategies to achieve scalable and high-throughput metaplasmonic biosensing for Point-of-Care devices and bioengineering applications like Organs-On-Chip.
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- 2023
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7. Scalable, Lithography-Free Plasmonic Metasurfaces by Nano-Patterned/Sculpted Thin Films for Biosensing
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Gerardo A. López-Muñoz, Armando Cortés-Reséndiz, Javier Ramón-Azcón, and Artur Rydosz
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plasmonic ,metasurfaces ,biosensor ,glancing angle deposition ,thermal dewetting ,lithography-free ,Biotechnology ,TP248.13-248.65 - Abstract
Scientific research in plasmonic metasurfaces has been widely widespread in the last years, motivated by the recent advances in the nanofabrication field and the increasing demand for high throughput sensing platforms. The recent advances in electronics, microfluidics, and signal processing have enabled the complete development of highly integrated devices with broad application potential. However, the progress observed from a fabrication point of view has been remarkable, led by the potential benefits metamaterials can offer in plasmonic sensing: sensor miniaturization, multiplexing opportunities, and extreme sensitivity biodetection. Although conventional top-down approaches, i.e., electron-beam lithography, have been extensively employed to develop plasmonic metasurfaces for biosensing, lithography-free bottom-up nanofabrication strategies based on nano-patterned/sculpted thin-films are candidates to surpass the limitations of top-down lithographic techniques with large-scale and high-throughput fabrication processes for 2D and 3D plasmonic metasurfaces over a broad material set. This perspective paper focuses on the challenges and opportunities to achieve lithography-free plasmonic metasurfaces by nano-patterned/sculpted thin films to conduct scalable and high-throughput plasmonic metamaterials for sensitive biosensing platforms.
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- 2022
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8. BlockmiR AONs as Site-Specific Therapeutic MBNL Modulation in Myotonic Dystrophy 2D and 3D Muscle Cells and HSALR Mice
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Sarah J. Overby, Estefanía Cerro-Herreros, Jorge Espinosa-Espinosa, Irene González-Martínez, Nerea Moreno, Juan M. Fernández-Costa, Jordina Balaguer-Trias, Javier Ramón-Azcón, Manuel Pérez-Alonso, Thorleif Møller, Beatriz Llamusí, and Rubén Artero
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Myotonic Dystrophy 1 ,MBNL ,muscleblind ,antisense oligonucleotides ,AON ,miRNA ,Pharmacy and materia medica ,RS1-441 - Abstract
The symptoms of Myotonic Dystrophy Type 1 (DM1) are multi-systemic and life-threatening. The neuromuscular disorder is rooted in a non-coding CTG microsatellite expansion in the DM1 protein kinase (DMPK) gene that, upon transcription, physically sequesters the Muscleblind-like (MBNL) family of splicing regulator proteins. The high-affinity binding occurring between the proteins and the repetitions disallow MBNL proteins from performing their post-transcriptional splicing regulation leading to downstream molecular effects directly related to disease symptoms such as myotonia and muscle weakness. In this study, we build on previously demonstrated evidence showing that the silencing of miRNA-23b and miRNA-218 can increase MBNL1 protein in DM1 cells and mice. Here, we use blockmiR antisense technology in DM1 muscle cells, 3D mouse-derived muscle tissue, and in vivo mice to block the binding sites of these microRNAs in order to increase MBNL translation into protein without binding to microRNAs. The blockmiRs show therapeutic effects with the rescue of mis-splicing, MBNL subcellular localization, and highly specific transcriptomic expression. The blockmiRs are well tolerated in 3D mouse skeletal tissue inducing no immune response. In vivo, a candidate blockmiR also increases Mbnl1/2 protein and rescues grip strength, splicing, and histological phenotypes.
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- 2023
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9. Disposable Polymeric Nanostructured Plasmonic Biosensors for Cell Culture Adhesion Monitoring
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Judith Camaló Vila, Nerea Castro-Aguirre, Gerardo A. López-Muñoz, Ainhoa Ferret-Miñana, Francesco De Chiara, and Javier Ramón-Azcón
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plasmonic nanostructures ,cell confluency ,cell culture ,nanocrystals ,optical biosensor ,Biotechnology ,TP248.13-248.65 - Abstract
Over the last years, optical biosensors based on plasmonic nanomaterials have gained great scientific interest due to their unquestionable advantages compared to other biosensing technologies. They can achieve sensitive, direct, and label-free analysis with exceptional potential for multiplexing and miniaturization. Recently, it has been demonstrated the potential of using optical discs as high throughput nanotemplates for the development of plasmonic biosensors in a cost-effective way. This work is a pilot study focused on the development of an integrated plasmonic biosensor for the monitoring of cell adhesion and growth of human retinal pigmented cell line (ARPE-19) under different media conditions (0 and 2% of FBS). We observed an increase of the plasmonic band displacement under 2% FBS compared to 0% conditions over time (1, 3, and 5 h). These preliminary results show that the proposed plasmonic biosensing approach is a direct, non-destructive, and real-time tool that could be employed in the study of living cells behavior and culture conditions. Furthermore, this setup could assess the viability of the cells and their growth over time with low variability between the technical replicates improving the experimental replicability.
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- 2021
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10. Bioengineered skeletal muscles as new tools for muscular dystrophies preclinical studies
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Juan M. Fernández-Costa, Xiomara Fernández-Garibay, Ferran Velasco-Mallorquí, and Javier Ramón-Azcón
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Biochemistry ,QD415-436 - Abstract
Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.
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- 2021
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11. Fatty Hepatocytes Induce Skeletal Muscle Atrophy In Vitro: A New 3D Platform to Study the Protective Effect of Albumin in Non-Alcoholic Fatty Liver
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Francesco De Chiara, Ainhoa Ferret-Miñana, Juan M. Fernández-Costa, Alice Senni, Rajiv Jalan, and Javier Ramón-Azcón
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crosstalk ,tissue engineering ,ammonia ,3R ,NEFAs ,Biology (General) ,QH301-705.5 - Abstract
The liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass known as sarcopenia. Liver transplantation solves the hepatic-related insufficiencies, but it is unable to revert sarcopenia. Knowing the mechanism(s) by which different organs communicate with each other is crucial to improve the drug development that still relies on the two-dimensional models. However, those models fail to mimic the pathological features of the disease. Here, both liver and skeletal muscle cells were encapsulated in gelatin methacryloyl and carboxymethylcellulose to recreate the disease’s phenotype in vitro. The 3D hepatocytes were challenged with non-esterified fatty acids (NEFAs) inducing features of Non-alcoholic fatty liver (NAFL) such as lipid accumulation, metabolic activity impairment and apoptosis. The 3D skeletal muscle tissues incubated with supernatant from fatty hepatocytes displayed loss of maturation and atrophy. This study demonstrates the connection between the liver and the skeletal muscle in NAFL, narrowing down the players for potential treatments. The tool herein presented was employed as a customizable 3D in vitro platform to assess the protective effect of albumin on both hepatocytes and myotubes.
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- 2022
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12. Microphysiological sensing platform for an in-situ detection of tissue-secreted cytokines
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Alejandro Hernández-Albors, Albert G. Castaño, Xiomara Fernández-Garibay, María Alejandra Ortega, Jordina Balaguer, and Javier Ramón-Azcón
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Microphysiological tissues ,Tissue engineering ,Electrochemical, biosensors ,Magnetic particles ,Skeletal muscle ,Electric stimulation ,Biotechnology ,TP248.13-248.65 - Abstract
Understanding the protein-secretion dynamics from single, specific tissues is critical toward the advancement of disease detection and treatments. However, such secretion dynamics remain difficult to measure in vivo due to the uncontrolled contributions from other tissue populations. Here, we describe an integrated platform designed for the reliable, near real-time measurements of cytokines secreted from an in vitro single-tissue model. In our setup, we grow 3D biomimetic tissues to discretize cytokine source, and we separate them from a magnetic microbead-based biosensing system using a Transwell insert. This design integrates physiochemically controlled biological activity, high-sensitivity protein detection (LOD
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- 2019
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13. In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip
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María A. Ortega, Júlia Rodríguez-Comas, Ozlem Yavas, Ferran Velasco-Mallorquí, Jordina Balaguer-Trias, Victor Parra, Anna Novials, Joan M. Servitja, Romain Quidant, and Javier Ramón-Azcón
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LSPR sensors ,organ-on-a-chip ,in situ insulin monitoring ,Biotechnology ,TP248.13-248.65 - Abstract
Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.
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- 2021
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14. The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research
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Francesco De Chiara, Ainhoa Ferret-Miñana, and Javier Ramón-Azcón
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NAFLD ,extra-hepatic outcome ,organ-on-a-chip ,artificial intelligence ,Biology (General) ,QH301-705.5 - Abstract
Non-alcoholic fatty liver affects about 25% of global adult population. On the long-term, it is associated with extra-hepatic compliances, multiorgan failure, and death. Various invasive and non-invasive methods are employed for its diagnosis such as liver biopsies, CT scan, MRI, and numerous scoring systems. However, the lack of accuracy and reproducibility represents one of the biggest limitations of evaluating the effectiveness of drug candidates in clinical trials. Organ-on-chips (OOC) are emerging as a cost-effective tool to reproduce in vitro the main NAFLD’s pathogenic features for drug screening purposes. Those platforms have reached a high degree of complexity that generate an unprecedented amount of both structured and unstructured data that outpaced our capacity to analyze the results. The addition of artificial intelligence (AI) layer for data analysis and interpretation enables those platforms to reach their full potential. Furthermore, the use of them do not require any ethic and legal regulation. In this review, we discuss the synergy between OOC and AI as one of the most promising ways to unveil potential therapeutic targets as well as the complex mechanism(s) underlying NAFLD.
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- 2021
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15. Direct and Label-Free Monitoring of Albumin in 2D Fatty Liver Disease Model Using Plasmonic Nanogratings
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Gerardo A. Lopez-Muñoz, Maria Alejandra Ortega, Ainhoa Ferret-Miñana, Francesco De Chiara, and Javier Ramón-Azcón
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2D fatty liver in vitro model ,Blu-Ray disc ,plasmonic nanomaterials ,Label-Free Biosensing ,Chemistry ,QD1-999 - Abstract
Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related to a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide, and it is estimated that it is present in up to 25% of the world’s population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthesized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allows direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight into NAFLD’s mechanism and drug action. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical discs. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using a highly-specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈0.26 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the cells’ lipid accumulation. Moreover, we discovered that the hepatocytes increased the amount of albumin secreted on the third day from the lipids challenge. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation is needed to unveil the biological significance of that cell behavior.
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- 2020
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16. Consequences of Lmna Exon 4 Mutations in Myoblast Function
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Déborah Gómez-Domínguez, Carolina Epifano, Fernando de Miguel, Albert García Castaño, Borja Vilaplana-Martí, Alberto Martín, Sandra Amarilla-Quintana, Anne T Bertrand, Gisèle Bonne, Javier Ramón-Azcón, Miguel A Rodríguez-Milla, and Ignacio Pérez de Castro
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LMNA ,laminopathy ,CRISPR ,nuclear envelope ,Cytology ,QH573-671 - Abstract
Laminopathies are causally associated with mutations on the Lamin A/C gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models included different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy, LMNA-associated congenital muscular dystrophy (L-CMD). We characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and levels of p-ERK and p-AKT (phosphorylated Mitogen-Activated Protein Kinase 1/3 and AKT serine/threonine kinase 1). Our results indicated that Lmna exon 4 mutants showed abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC (LInker of Nucleoskeleton and Cytoskeleton) complex were altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies.
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- 2020
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17. Al2O3 Microresonator Based Passive and Active Biosensors.
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Michiel de Goede, Lantian Chang, Meindert Dijkstra, Raquel Obregón, Javier Ramón-Azcón, Elena Martinez, Laura Padilla, Jaume Adan, Francesc Mitjans, and Sonia M. Garcia-Blanco
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- 2018
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18. Immunoaffinity‐Based Microfluidic Platform for Exosomal MicroRNA Isolation from Obese and Lean Mouse Plasma
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Júlia Rodríguez‐Comas, Carlos Castaño, María Alejandra Ortega, Ainoa Tejedera, Míriam Fernandez‐González, Anna Novials, Marcelina Párrizas, and Javier Ramón‐Azcón
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Mechanics of Materials ,General Materials Science ,Industrial and Manufacturing Engineering - Published
- 2023
19. Metallic glass nanofibers in future hydrogel-based scaffolds.
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Ramin Banan-Sadeghian, Samad Ahadian, Shin Yaginuma, Javier Ramón-Azcón, Xiaobin Liang, Ken Nakajima, Hitoshi Shiku, Tomokazu Matsue, Koji S. Nakayama, and Ali Khademhosseini
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- 2014
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20. Immunosensors for Atrazine Detection in Red Wine Samples.
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Enrique Valera, ángel Rodríguez, Javier Ramón-Azcón, Francisco J. Sanchez, and María-Pilar Marco
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- 2009
21. Sensors and Biosensors in Organs-on-a-Chip Platforms
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Gerardo A, Lopez-Muñoz, Sheeza, Mughal, and Javier, Ramón-Azcón
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Organoids ,Tissue Engineering ,Lab-On-A-Chip Devices ,Microfluidics ,Animals ,Biosensing Techniques - Abstract
Biosensors represent a powerful analytical tool for analyzing biomolecular interactions with the potential to achieve real-time quantitative analysis with high accuracy using low sample volumes, minimum sample pretreatment with high potential for the development of in situ and highly integrated monitoring platforms. Considering these advantages, their use in cell-culture systems has increased over the last few years. Between the different technologies for cell culture, organs-on-a-chip (OOCs) represent a novel technology that tries to mimic an organ's functionality by combining tissue engineering/organoid with microfluidics. Although there are still challenges to achieving OOC models with high organ mimicking relevance, these devices can offer effective models for drug treatment development by identifying drug targets, screening toxicity, and determining the potential effects of drugs in living beings. Consequently, in the future, we might replace animal studies by offering more ethical test models. Considering the relevance that different physiological and biochemical parameters have in the correct functionality of cells, sensing and biosensing platforms can offer an effective way for the real-time monitoring of physiological parameters and, in our opinion, more relevant, the secretion of biomarkers such as cytokines, growth factors, and others related with the influence of drugs or other types of stimulus in cell metabolism. Keeping this concept in mind, in this chapter, we focus on describing the potential use of sensors and biosensors in OOC devices to achieve fully integrated platforms that monitor physiological parameters and cell metabolism.
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- 2022
22. Sensors and Biosensors in Organs-on-a-Chip Platforms
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Gerardo A. Lopez-Muñoz, Sheeza Mughal, and Javier Ramón-Azcón
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- 2022
23. Correction to: Sensors and Biosensors in Organs-on-a-Chip Platforms
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Gerardo A. Lopez-Muñoz, Sheeza Mughal, and Javier Ramón-Azcón
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- 2022
24. Islet-on-a-chip for the study of pancreatic β-cell function
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Júlia Rodríguez-Comas and Javier Ramón-Azcón
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β cell function ,geography ,endocrine system ,geography.geographical_feature_category ,Diabetis ,endocrine system diseases ,business.industry ,Pancreatic islets ,Diabetes ,Disease ,Islet ,Chronic disorders ,Transplantation ,medicine.anatomical_structure ,medicine ,Enginyeria biomèdica ,business ,Neuroscience ,Biomedical engineering ,Function (biology) - Abstract
Diabetes mellitus is a significant public health problem worldwide. It encompasses a group of chronic disorders characterized by hyperglycemia, resulting from pancreatic islet dysfunction or as a consequence of insulin-producing β-cell death. Organ-on-a-chip platforms have emerged as technological systems combining cell biology, engineering, and biomaterial technological advances with microfluidics to recapitulate a specific organ’s physiological or pathophysiological environment. These devices offer a novel model for the screening of pharmaceutical agents and to study a particular disease. In the field of diabetes, a variety of microfluidic devices have been introduced to recreate native islet microenvironments and to understand pancreatic β-cell kinetics in vitro. This kind of platforms has been shown fundamental for the study of the islet function and to assess the quality of these islets for subsequent in vivo transplantation. However, islet physiological systems are still limited compared to other organs and tissues, evidencing the difficulty to study this “organ” and the need for further technological advances. In this review, we summarize the current state of islet-on-a-chip platforms that have been developed so far. We recapitulate the most relevant studies involving pancreatic islets and microfluidics, focusing on the molecular and cellular-scale activities that underlie pancreatic β-cell function., This review received financial support from the European Research Council program under grants ERC-StG-DAMOC (714317), the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Program for Centres of Excellence in R&D (SEV-2016-2019) and “Retos de investigación: Proyectos I+D+i” (TEC2017-83716-C2-2-R), the CERCA Programme/Generalitat de Catalunya (2017-SGR-1079), and Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Healthy Ageing).
- Published
- 2021
25. Plasmonic nanocrystals on polycarbonate substrates for direct and label-free biodetection of Interleukin-6 in bioengineered 3D skeletal muscles
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Javier Ramón-Azcón, Gerardo A. López-Muñoz, Juan M. Fernandez-Costa, Eduard Martin-Lasierra, Jordina Balaguer-Trias, and Maria Alejandra Ortega
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interleukin-6 ,Physics ,QC1-999 ,European research ,Striated muscle ,Library science ,label-free biosensing ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,plasmonic nanostructures ,Enginyeria de teixits ,tissue engineering ,Political science ,Múscul estriat ,Christian ministry ,European commission ,Tissue engineering ,Healthy ageing ,skeletal muscle ,Electrical and Electronic Engineering ,Biotechnology ,Label free - Abstract
The development of nanostructured plasmonic biosensors has been widely widespread in the last years, motivated by the potential benefits they can offer in integration, miniaturization, multiplexing opportunities, and enhanced performance label-free biodetection in a wide field of applications. Between them, engineering tissues represent a novel, challenging, and prolific application field for nanostructured plasmonic biosensors considering the previously described benefits and the low levels of secreted biomarkers (?pM–nM) to detect. Here, we present an integrated plasmonic nanocrystals-based biosensor using high throughput nanostructured polycarbonate substrates. Metallic film thickness and incident angle of light for reflectance measurements were optimized to enhance the detection of antibody–antigen biorecognition events using numerical simulations. We achieved an enhancement in biodetection up to 3× as the incident angle of light decreases, which can be related to shorter evanescent decay lengths. We achieved a high reproducibility between channels with a coefficient of variation below 2% in bulk refractive index measurements, demonstrating a high potential for multiplexed sensing. Finally, biosensing potential was demonstrated by the direct and label-free detection of interleukin-6 biomarker in undiluted cell culture media supernatants from bioengineered 3D skeletal muscle tissues stimulated with different concentrations of endotoxins achieving a limit of detection (LOD) of ? 0.03 ng/mL (1.4 pM)., Research funding: This project received financial support from the European Research Council program under grants ERC-StG-DAMOC (714317), the European Commission under FET-open program BLOC project (GA-863037), the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Program for Centres of Excellence in R&D (SEV-2016–2019) and “Retos de investigación: Proyectos I+D+i” (TEC2017-83716-C2-2-R), the CERCA Programme/Generalitat de Catalunya (2014-SGR-1460) and Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Healthy Ageing) to Javier Ramon-Azcon.
- Published
- 2021
26. Direct reprogramming of human fibroblasts into insulin-producing cells by transcription factors
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Rosa Gasa, Anne Wojtusciszyn, Josep Vidal, Sara Cervantes, Laura Clua, Christophe Broca, Javier Ramón-Azcón, Èlia Prades, Rebeca Fernandez-Ruiz, Anna Novials, Carlos Enrich, Hugo Figueiredo, Marta Fontcuberta-PiSunyer, Nuria Montserrat, Ainhoa García-Alamán, Noèlia Téllez, and Ramon Gomis
- Subjects
Cell type ,medicine.anatomical_structure ,Somatic cell ,Chemistry ,Cell ,medicine ,PDX1 ,PAX4 ,Induced pluripotent stem cell ,Reprogramming ,Embryonic stem cell ,Cell biology - Abstract
Direct lineage reprogramming of one somatic cell into another bypassing an intermediate pluripotent state has emerged as an alternative to embryonic or induced pluripotent stem cell differentiation to generate clinically relevant cell types. One cell type of clinical interest is the pancreatic β cell that secretes insulin and whose loss and/or dysfunction leads to diabetes. Generation of functional β-like cells from developmentally related somatic cell types (pancreas, liver, gut) has been achieved via enforced expression of defined sets of transcription factors. However, clinical applicability of these findings is challenging because the starting cell types are not easily obtainable. Skin fibroblasts are accessible and easily manipulated cells that could be a better option, but available studies indicate that their competence to give rise to β cells through similar direct reprogramming approaches is limited. Here, using human skin fibroblasts and a protocol that ensures high and consistent expression of adenovirus-encoded reprogramming factors, we show that the transcription factor cocktail consisting of Pdx1, Ngn3, MafA, Pax4 and Nkx2-2 activates key β cell genes and down-regulates the fibroblast transcriptional program. The converted cells produce insulin and exhibit intracellular calcium responses to glucose and/or membrane depolarization. Furthermore, they secrete insulin in response to glucose in vitro and after transplantation in vivo. These findings demonstrate that transcription factor-mediated direct reprogramming of human fibroblasts is a feasible strategy to generate insulin-producing cells.
- Published
- 2021
27. Organs‐on‐Chips: Trends and Challenges in Advanced Systems Integration
- Author
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Sheeza Mughal, Gerardo A. López‐Muñoz, Juan M. Fernández‐Costa, Armando Cortés‐Reséndiz, Francesco De Chiara, and Javier Ramón‐Azcón
- Subjects
Mechanics of Materials ,Mechanical Engineering - Published
- 2022
28. In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip
- Author
-
Júlia Rodríguez-Comas, Javier Ramón-Azcón, Ozlem Yavas, Ferran Velasco-Mallorquí, Romain Quidant, Victor Parra, Joan-Marc Servitja, Jordina Balaguer-Trias, Anna Novials, and Maria Alejandra Ortega
- Subjects
In situ ,Scaffold ,Computer science ,Interface (computing) ,Clinical Biochemistry ,Biomedical Engineering ,Drug Evaluation, Preclinical ,Insulins ,Nanotechnology ,02 engineering and technology ,Biosensing Techniques ,Organ-on-a-chip ,Article ,Analytical Chemistry ,03 medical and health sciences ,Insulina ,Lab-On-A-Chip Devices ,Drug Discovery ,Insulin Secretion ,medicine ,Insulin ,Animals ,Humans ,Surface plasmon resonance ,Instrumentation ,Engineering (miscellaneous) ,Bionanophotonics ,030304 developmental biology ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,organ-on-a-chip ,Diabetis ,LSPR sensors ,In situ insulin monitoring ,Drug discovery ,Pancreatic islets ,Diabetes ,General Medicine ,Surface Plasmon Resonance ,021001 nanoscience & nanotechnology ,medicine.anatomical_structure ,Biosensors ,Diabetes Mellitus, Type 2 ,Proof of concept ,in situ insulin monitoring ,0210 nano-technology ,TP248.13-248.65 ,Biotechnology - Abstract
Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing., Biosensors, 11 (5), ISSN:2079-6374
- Published
- 2021
29. Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies
- Author
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Ferran Velasco-Mallorquí, Juan M. Fernandez-Costa, Javier Ramón-Azcón, and Xiomara Fernández-Garibay
- Subjects
Distròfia muscular ,Biomedical Engineering ,Medicine (miscellaneous) ,02 engineering and technology ,Biomaterials ,lcsh:Biochemistry ,03 medical and health sciences ,Tissue engineering ,medicine ,Skeletal Muscle Tissue ,Myocyte ,Screening tool ,lcsh:QD415-436 ,Muscular dystrophy ,030304 developmental biology ,0303 health sciences ,business.industry ,Muscle weakness ,Skeletal muscle ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,medicine.anatomical_structure ,Enginyeria de teixits ,Materials biomèdics ,medicine.symptom ,0210 nano-technology ,business ,Neuroscience ,Biomedical materials - Abstract
Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.
- Published
- 2021
30. Cellulose-based scaffolds enhance pseudoislets formation and functionality
- Author
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Júlia Rodríguez-Comas, Ferran Velasco-Mallorquí, and Javier Ramón-Azcón
- Subjects
Scaffold ,food.ingredient ,0206 medical engineering ,Islets of Langerhans Transplantation ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,Biochemistry ,Gelatin ,Biomaterials ,Islets of Langerhans ,food ,Tissue engineering ,medicine ,Animals ,Humans ,Insulin ,Pancreatic islet function ,Viability assay ,Cellulose ,Diabetis ,Tissue Engineering ,Tissue Scaffolds ,Chemistry ,Pancreatic islets ,Diabetes ,General Medicine ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Carboxymethyl cellulose ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Enginyeria de teixits ,Materials biomèdics ,Biophysics ,0210 nano-technology ,Immortalised cell line ,Biomedical materials ,Biotechnology ,medicine.drug - Abstract
In vitro research for the study of type 2 diabetes (T2D) is frequently limited by the availability of a functional model for islets of Langerhans. To overcome the limitations of obtaining pancreatic islets from different sources, such as animal models or human donors, immortalized cell lines as the insulin-producing INS1E β-cells have appeared as a valid alternative to model insulin-related diseases. However, immortalized cell lines are mainly used in flat surfaces or monolayer distributions, not resembling the spheroid-like architecture of the pancreatic islets. To generate islet-like structures, the use of scaffolds appeared as a valid tool to promote cell aggregations. Traditionally-used hydrogel encapsulation methods do not accomplish all the requisites for pancreatic tissue engineering, as its poor nutrient and oxygen diffusion induces cell death. Here, we use cryogelation technology to develop a more resemblance scaffold with the mechanical and physical properties needed to engineer pancreatic tissue. This study shows that carboxymethyl cellulose (CMC) cryogels prompted cells to generate β-cell clusters in comparison to gelatin-based scaffolds, that did not induce this cell organization. Moreover, the high porosity achieved with CMC cryogels allowed us to create specific range pseudoislets. Pseudoislets formed within CMC-scaffolds showed cell viability for up to 7 d and a better response to glucose over conventional monolayer cultures. Overall, our results demonstrate that CMC-scaffolds can be used to control the organization and function of insulin-producing β-cells, representing a suitable technique to generate β-cell clusters to study pancreatic islet function.
- Published
- 2021
31. Bioengineered
- Author
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Xiomara, Fernández-Garibay, María A, Ortega, Estefanía, Cerro-Herreros, Jordi, Comelles, Elena, Martínez, Rubén, Artero, Juan M, Fernández-Costa, and Javier, Ramón-Azcón
- Subjects
Myoblasts ,Muscle Fibers, Skeletal ,Animals ,Humans ,Myotonic Dystrophy ,Cell Differentiation ,Muscle, Skeletal - Abstract
Myotonic dystrophy type 1 (DM1) is the most common hereditary myopathy in the adult population. The disease is characterized by progressive skeletal muscle degeneration that produces severe disability. At present, there is still no effective treatment for DM1 patients, but the breakthroughs in understanding the molecular pathogenic mechanisms in DM1 have allowed the testing of new therapeutic strategies. Animal models and
- Published
- 2020
32. Human Organs-on-a-Chip : Novel Organ-on-a-Chip Techniques in Medicine
- Author
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Javier Ramón-Azcón, Artur Rydosz, Javier Ramón-Azcón, and Artur Rydosz
- Abstract
Human Organs-on-Chip: Novel Organ-on-a-Chip Techniques in Medicine paves the way for novel approaches that push forward in-vitro and in-vivo studies and fills a gap between laboratory and clinical use. These experienced authors share the knowledge they've developed with over a decade of experience and research with organ-on-chips and multi-organ-on-chips. This book collects all of the developments in the field and sheds new light on possibilities to develop human on-chip measurement methods with the utilization of currently available measurement techniques including both invasive and non-invasive tests. Human Organs-on-Chip: Novel Organ-on-a-Chip Techniques in Medicine serves as a starting point for young researchers who are beginning their scientific journeys.Provides an overview of the progress suborgan-on-chips development has made in recent yearsIntroduces the fundamentals needed to understand lab-on-chip ideas with references and in-depth explanationsPresents commercial achievements obtained and future perspectives
- Published
- 2023
33. Bioengineered
- Author
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Juan M, Fernández-Costa, Xiomara, Fernández-Garibay, Ferran, Velasco-Mallorquí, and Javier, Ramón-Azcón
- Subjects
muscular dystrophy ,tissue engineering ,Skeletal muscle ,Review ,Technological advances in 3D tissue and organ models ,drug screening platforms ,biomaterials - Abstract
Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.
- Published
- 2020
34. Consequences of Lmna Exon 4 Mutations in Myoblast Function
- Author
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Gisèle Bonne, Anne Bertrand, Carolina Epifano, Javier Ramón-Azcón, Alberto Martín, Albert G. Castaño, Miguel Ángel Rodríguez-Milla, Déborah Gómez-Domínguez, Fernando de Miguel, Borja Vilaplana-Martí, Sandra Amarilla-Quintana, Ignacio Pérez de Castro, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Instituto de Salud Carlos III [Madrid] (ISC), Universidad Europea de Madrid, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institució Catalana de Recerca i Estudis Avançats (ICREA), and Centre de recherche en Myologie – U974 SU-INSERM
- Subjects
life_sciences_other ,0301 basic medicine ,Laminopathy ,[SDV]Life Sciences [q-bio] ,Mutant ,laminopathy ,medicine.disease_cause ,Muscle Development ,LMNA ,Myoblasts ,Exon ,Mice ,0302 clinical medicine ,Tecnología médica ,lcsh:QH301-705.5 ,Genetics ,Mutation ,integumentary system ,Cell Differentiation ,General Medicine ,nuclear envelope ,Exons ,Lamin Type A ,030220 oncology & carcinogenesis ,CRISPR ,Female ,C2C12 ,Microtubule-Associated Proteins ,Subcellular Fractions ,congenital, hereditary, and neonatal diseases and abnormalities ,Cell Nucleus Shape ,Membrana nuclear ,Nuclear Envelope ,MAP Kinase Signaling System ,Telomere-Binding Proteins ,Biology ,Distrofias musculares ,Article ,Cell Line ,03 medical and health sciences ,medicine ,Animals ,Protein kinase B ,Cell Nucleus ,Biología celular ,Base Sequence ,Membrane Proteins ,medicine.disease ,Genética ,Clone Cells ,030104 developmental biology ,lcsh:Biology (General) ,Lamin ,DNA Damage - Abstract
Laminopathies are causally associated with mutations on the Lamin A/C gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models included different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy, LMNA-associated congenital muscular dystrophy (L-CMD). We characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and levels of p-ERK and p-AKT (phosphorylated Mitogen-Activated Protein Kinase 1/3 and AKT serine/threonine kinase 1). Our results indicated that Lmna exon 4 mutants showed abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC (LInker of Nucleoskeleton and Cytoskeleton) complex were altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies. Ministerio de Ciencia e Innovación (Acción estratégica en Salud intramural PI16III/00017-TPY1348/16). Fundación Andrés Marcio, niños contra la laminopatía (TPY-259/19). 6.600 JCR (2020) Q2, 53/195 Cell Biology 1.220 SJR (2020) Q1, 51/254 Biochemistry, Genetics and Molecular Biology (miscellaneous) No data IDR 2020 UEM
- Published
- 2020
35. New volumetric CNT-doped gelatin–cellulose scaffolds for skeletal muscle tissue engineering
- Author
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Ferran Velasco-Mallorquí, Javier Ramón-Azcón, Luisa Neves, and Juan M. Fernandez-Costa
- Subjects
Scaffold ,food.ingredient ,Materials science ,Bioengineering ,02 engineering and technology ,Carbon nanotube ,010402 general chemistry ,01 natural sciences ,Gelatin ,law.invention ,3D cell culture ,food ,law ,medicine ,General Materials Science ,Tissue engineering ,Myogenesis ,General Engineering ,Skeletal muscle ,General Chemistry ,021001 nanoscience & nanotechnology ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Transplantation ,medicine.anatomical_structure ,Enginyeria de teixits ,Materials biomèdics ,Swelling ,medicine.symptom ,0210 nano-technology ,Biomedical materials ,Biomedical engineering - Abstract
Currently, the fabrication of scaffolds for engineered skeletal muscle tissues is unable to reach the millimeter size. The main drawbacks are the poor nutrient diffusion, lack of an internal structure to align the precursor cells, and poor mechanical and electric properties. Herein, we present a combination of gelatin-carboxymethyl cellulose materials polymerised by a cryogelation process that allowed us to reach scaffold fabrication up to millimeter size and solve the main problems related to the large size muscle tissue constructs. (1) By incorporating carbon nanotubes (CNT), we can improve the electrical properties of the scaffold, thereby enhancing tissue maturation when applying an electric pulse stimulus (EPS). (2) We have fabricated an anisotropic internal three-dimensional microarchitecture with good pore distribution and highly aligned morphology to enhance the cell alignment, cell fusion and myotube formation. With this set up, we were able to generate a fully functional skeletal muscle tissue using a combination of EPS and our doped-biocomposite scaffold and obtain a mature tissue on the millimeter scale. We also characterized the pore distribution, swelling, stiffness and conductivity of the scaffold. Moreover, we proved that the cells were viable and could fuse in three-dimensional (3D) functional myotubes throughout the scaffold. In conclusion, we fabricated a biocompatible and customizable scaffold for 3D cell culture suitable for a wide range of applications such as organ-on-a-chip, drug screening, transplantation and disease modelling.
- Published
- 2020
- Full Text
- View/download PDF
36. Direct and label-free monitoring of albumin in 2D fatty liver disease model using plasmonic nanogratings
- Author
-
Javier Ramón-Azcón, Gerardo A. López-Muñoz, Ainhoa Ferret-Miñana, Maria Alejandra Ortega, and Francesco De Chiara
- Subjects
General Chemical Engineering ,Population ,plasmonic nanomaterials ,02 engineering and technology ,Blu-Ray disc ,Article ,Liver cells ,Liver disorder ,lcsh:Chemistry ,Cèl·lules hepàtiques ,03 medical and health sciences ,medicine ,General Materials Science ,education ,Liver diseases ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Chemistry ,2D fatty liver in vitro model ,Malalties del fetge ,Metabolic disorder ,Fatty liver ,Albumin ,Nanostructured materials ,021001 nanoscience & nanotechnology ,medicine.disease ,3. Good health ,Label-Free Biosensing ,medicine.anatomical_structure ,Biosensors ,Nanomedicine ,Biochemistry ,lcsh:QD1-999 ,Cell culture ,Hepatocyte ,Nanomedicina ,Materials nanoestructurats ,0210 nano-technology ,Fetal bovine serum ,biomaterials - Abstract
Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related to a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide, and it is estimated that it is present in up to 25% of the world&rsquo, s population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthesized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allows direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight into NAFLD&rsquo, s mechanism and drug action. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical discs. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using a highly-specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (&asymp, 0.26 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the cells&rsquo, lipid accumulation. Moreover, we discovered that the hepatocytes increased the amount of albumin secreted on the third day from the lipids challenge. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation is needed to unveil the biological significance of that cell behavior.
- Published
- 2020
37. Topography and Permeability Analyses of Vasculature‐on‐a‐Chip Using Scanning Probe Microscopies (Adv. Healthcare Mater. 21/2021)
- Author
-
Yuji Nashimoto, Noriko Taira, Ryota Fujii, Hitoshi Shiku, Hiroki Ida, Javier Ramón-Azcón, Minori Abe, Yasufumi Takahashi, and Kosuke Ino
- Subjects
Biomaterials ,Materials science ,Permeability (electromagnetism) ,Biomedical Engineering ,Pharmaceutical Science ,Chip ,Biomedical engineering - Published
- 2021
38. Topography and Permeability Analyses of Vasculature‐on‐a‐Chip Using Scanning Probe Microscopies
- Author
-
Hitoshi Shiku, Javier Ramón-Azcón, Ryota Fujii, Kosuke Ino, Hiroki Ida, Yasufumi Takahashi, Minori Abe, Noriko Taira, and Yuji Nashimoto
- Subjects
In situ ,Materials science ,fungi ,Biomedical Engineering ,Endothelial Cells ,Pharmaceutical Science ,Microscopy, Scanning Probe ,Chip ,Cell function ,Permeability ,Biomaterials ,Scanning probe microscopy ,Scanning electrochemical microscopy ,Permeability (electromagnetism) ,Lab-On-A-Chip Devices ,Scanning ion-conductance microscopy ,High spatial resolution ,Humans ,skin and connective tissue diseases ,Biomedical engineering - Abstract
Microphysiological systems (MPS) or organs-on-chips (OoC) can emulate the physiological functions of organs in vitro and are effective tools for determining human drug responses in preclinical studies. However, the analysis of MPS has relied heavily on optical tools, resulting in difficulties in real-time and high spatial resolution imaging of the target cell functions. In this study, the role of scanning probe microscopy (SPM) as an analytical tool for MPS is evaluated. An access hole is made in a typical MPS system with stacked microchannels to insert SPM probes into the system. For the first study, a simple vascular model composed of only endothelial cells is prepared for SPM analysis. Changes in permeability and local chemical flux are quantitatively evaluated during the construction of the vascular system. The morphological changes in the endothelial cells after flow stimulation are imaged at the single-cell level for topographical analysis. Finally, the possibility of adapting the permeability and topographical analysis using SPM for the intestinal vascular system is further evaluated. It is believed that this study will pave the way for an in situ permeability assay and structural analysis of MPS using SPM.
- Published
- 2021
39. Al2O3 microring resonators for the detectin of a cancer biomarker in undiluted urine
- Author
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Laura Padilla, Sonia M. García-Blanco, Javier Ramón-Azcón, Meindert Dijkstra, Elena Martínez, Francesc Mitjans, Raquel Obregón, M. de Goede, and Optical Sciences
- Subjects
Materials science ,02 engineering and technology ,Urine ,01 natural sciences ,010309 optics ,Resonator ,Optics ,0103 physical sciences ,Càncer ,Point of care ,Cancer ,Detection limit ,business.industry ,Biochemical markers ,Proteins ,021001 nanoscience & nanotechnology ,6. Clean water ,Atomic and Molecular Physics, and Optics ,3. Good health ,Human tumor ,Materials biomèdics ,Marcadors bioquímics ,Biomarker (medicine) ,Optoelectronics ,Photonics ,0210 nano-technology ,business ,Biosensor ,Proteïnes ,Biomedical materials - Abstract
Concentrations down to 3 nM of the rhS100A4 protein, associated with human tumor development, have been detected in undiluted urine using an integrated sensor based on microring resonators in the emerging Al2O3 photonic platform. The fabricated microrings were designed for operation in the C-band (λ = 1565 nm) and exhibited a high-quality factor in air of 3.2 × 105. The bulk refractive index sensitivity of the devices was ~100 nm/RIU (for TM polarization) with a limit of detection of ~10−6 RIU. A surface functionalization protocol was developed to allow for the selective binding of the monoclonal antibodies designed to capture the target biomarker to the surface of the Al2O3 microrings. The detection of rhS100A4 proteins at clinically relevant concentrations in urine is a big milestone towards the use of biosensors for the screening and early diagnosis of different cancers. Biosensors based on this microring technology can lead to portable, multiplexed and easy-to-use point of care devices
- Published
- 2019
40. Muscle-on-a-chip with an on-site multiplexed biosensing system for in situ monitoring of secreted IL-6 and TNF-α
- Author
-
Javier Ramón-Azcón, Jordina Balaguer-Trias, Francesco De Chiara, Alejandro Hernández-Albors, Maria Alejandra Ortega, Xiomara Fernández-Garibay, and Albert G. Castaño
- Subjects
In situ ,Cell type ,Cost-Benefit Analysis ,Biomedical Engineering ,Bioengineering ,Biosensing Techniques ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Multiplexing ,Cell Line ,Mice ,Necrosis ,Lab-On-A-Chip Devices ,Animals ,Myocyte ,Interleukin 6 ,Electrodes ,biology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Chemistry ,Biochemical markers ,010401 analytical chemistry ,Tin Compounds ,General Chemistry ,Necrosi ,021001 nanoscience & nanotechnology ,Chip ,In vitro ,0104 chemical sciences ,Marcadors bioquímics ,biology.protein ,Cell culture ,0210 nano-technology ,Biosensor ,Cultiu cel·lular ,Biomedical engineering - Abstract
Despite the increasing number of organs-on-a-chip that have been developed in the past decade, limited efforts have been made to integrate a sensing system for in situ continual measurements of biomarkers from three-dimensional (3D) tissues. Here, we present a custom-made integrated platform for muscle cell stimulation under fluidic conditions connected with a multiplexed high-sensitivity electrochemical sensing system for in situ monitoring. To demonstrate this, we use our system to measure the release levels and release time of interleukin 6 and tumor necrosis factor alpha in vitro by 3D muscle microtissue under electrical and biological stimulations. Our experimental design has enabled us to perform multiple time point measurements using functionalized screen-printed gold electrodes with sensitivity in the ng mL−1 range. This affordable setup is uniquely suited for monitoring factors released by 3D single cell types upon external stimulation for metabolic studies.
- Published
- 2019
- Full Text
- View/download PDF
41. Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle
- Author
-
Estefanía Cerro-Herreros, Ruben Artero, Javier Ramón-Azcón, Juan M. Fernandez-Costa, Elena Martínez, Jordi Comelles, Maria Alejandra Ortega, and Xiomara Fernández-Garibay
- Subjects
musculoskeletal diseases ,Distròfia muscular ,congenital, hereditary, and neonatal diseases and abnormalities ,Cellular differentiation ,0206 medical engineering ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,Biology ,Biochemistry ,Myotonic dystrophy ,Biomaterials ,3D cell culture ,medicine ,Myocyte ,Tissue engineering ,Myopathy ,Myogenesis ,Skeletal muscle ,General Medicine ,Muscular dystrophy ,021001 nanoscience & nanotechnology ,medicine.disease ,020601 biomedical engineering ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Enginyeria de teixits ,Cell culture ,medicine.symptom ,0210 nano-technology ,Biotechnology - Abstract
Myotonic dystrophy type 1 (DM1) is the most common hereditary myopathy in the adult population. The disease is characterized by progressive skeletal muscle degeneration that produces severe disability. At present, there is still no effective treatment for DM1 patients, but the breakthroughs in understanding the molecular pathogenic mechanisms in DM1 have allowed the testing of new therapeutic strategies. Animal models and in vitro two-dimensional cell cultures have been essential for these advances. However, serious concerns exist regarding how faithfully these models reproduce the biological complexity of the disease. Biofabrication tools can be applied to engineer human three-dimensional (3D) culture systems that complement current preclinical research models. Here, we describe the development of the first in vitro 3D model of DM1 human skeletal muscle. Transdifferentiated myoblasts from patient-derived fibroblasts were encapsulated in micromolded gelatin methacryloyl-carboxymethyl cellulose methacrylate hydrogels through photomold patterning on functionalized glass coverslips. These hydrogels present a microstructured topography that promotes myoblasts alignment and differentiation resulting in highly aligned myotubes from both healthy and DM1 cells in a long-lasting cell culture. The DM1 3D microtissues recapitulate the molecular alterations detected in patient biopsies. Importantly, fusion index analyses demonstrate that 3D micropatterning significantly improved DM1 cell differentiation into multinucleated myotubes compared to standard cell cultures. Moreover, the characterization of the 3D cultures of DM1 myotubes detects phenotypes as the reduced thickness of myotubes that can be used for drug testing. Finally, we evaluated the therapeutic effect of antagomiR-23b administration on bioengineered DM1 skeletal muscle microtissues. AntagomiR-23b treatment rescues both molecular DM1 hallmarks and structural phenotype, restoring myotube diameter to healthy control sizes. Overall, these new microtissues represent an improvement over conventional cell culture models and can be used as biomimetic platforms to establish preclinical studies for myotonic dystrophy.
- Published
- 2021
42. The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research
- Author
-
Javier Ramón-Azcón, Francesco De Chiara, and Ainhoa Ferret-Miñana
- Subjects
0301 basic medicine ,Artificial intelligence ,Basic science ,Computer science ,Medicine (miscellaneous) ,Computed tomography ,Review ,Organ-on-a-chip ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,NAFLD ,medicine ,extra-hepatic outcome ,lcsh:QH301-705.5 ,Liver diseases ,organ-on-a-chip ,medicine.diagnostic_test ,business.industry ,Mechanism (biology) ,Malalties del fetge ,Intel·ligència artificial ,Drug testing ,Unstructured data ,artificial intelligence ,Multiorgan failure ,3. Good health ,Clinical trial ,030104 developmental biology ,Clinical research ,lcsh:Biology (General) ,Ensayos clínicos de medicamentos ,030211 gastroenterology & hepatology ,business - Abstract
Non-alcoholic fatty liver affects about 25% of global adult population. On the long-term, it is associated with extra-hepatic compliances, multiorgan failure, and death. Various invasive and non-invasive methods are employed for its diagnosis such as liver biopsies, CT scan, MRI, and numerous scoring systems. However, the lack of accuracy and reproducibility represents one of the biggest limitations of evaluating the effectiveness of drug candidates in clinical trials. Organ-on-chips (OOC) are emerging as a cost-effective tool to reproduce in vitro the main NAFLD’s pathogenic features for drug screening purposes. Those platforms have reached a high degree of complexity that generate an unprecedented amount of both structured and unstructured data that outpaced our capacity to analyze the results. The addition of artificial intelligence (AI) layer for data analysis and interpretation enables those platforms to reach their full potential. Furthermore, the use of them do not require any ethic and legal regulation. In this review, we discuss the synergy between OOC and AI as one of the most promising ways to unveil potential therapeutic targets as well as the complex mechanism(s) underlying NAFLD.
- Published
- 2021
43. Carbon Nanotubes and Graphene-Based Nanomaterials for Stem Cell Differentiation and Tissue Regeneration
- Author
-
Hitoshi Shiku, Murugan Ramalingam, Javier Ramón-Azcón, Tomokazu Matsue, Raquel Obregón, Samad Ahadian, and Georgina To'a Salazar
- Subjects
Materials science ,Graphene ,Cellular differentiation ,Biomedical Engineering ,Bioengineering ,Nanotechnology ,02 engineering and technology ,General Chemistry ,Carbon nanotube ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,law.invention ,Nanomaterials ,law ,General Materials Science ,0210 nano-technology - Published
- 2016
44. Hybrid hydrogel-aligned carbon nanotube scaffolds to enhance cardiac differentiation of embryoid bodies
- Author
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Javier Ramón-Azcón, Hitoshi Shiku, Xiaobin Liang, Ali Khademhosseini, Samad Ahadian, Tomokazu Matsue, Shukuyo Yamada, Ken Nakajima, and Mehdi Estili
- Subjects
0301 basic medicine ,Polymers ,Cellular differentiation ,Biocompatible Materials ,02 engineering and technology ,Embryoid body ,Microscopy, Atomic Force ,Biochemistry ,Gelatin ,law.invention ,Mice ,Tissue engineering ,law ,Tissue Scaffolds ,Stem Cells ,Cell Differentiation ,Heart ,Hydrogels ,General Medicine ,021001 nanoscience & nanotechnology ,Self-healing hydrogels ,Stem cell ,0210 nano-technology ,Biotechnology ,Materials science ,food.ingredient ,DNA, Complementary ,Cell Survival ,Biomedical Engineering ,Nanotechnology ,Carbon nanotube ,Cell Line ,Biomaterials ,03 medical and health sciences ,food ,Troponin T ,Animals ,Regeneration ,Molecular Biology ,Electrodes ,Embryoid Bodies ,Tissue Engineering ,Nanotubes, Carbon ,technology, industry, and agriculture ,Dielectrophoresis ,030104 developmental biology ,Anisotropy ,Stress, Mechanical ,Biomedical engineering - Abstract
Carbon nanotubes (CNTs) were aligned in gelatin methacryloyl (GelMA) hydrogels using dielectrophoresis approach. Mouse embryoid bodies (EBs) were cultured in the microwells fabricated on the aligned CNT-hydrogel scaffolds. The GelMA-dielectrophoretically aligned CNT hydrogels enhanced the cardiac differentiation of the EBs compared with the pure GelMA and GelMA-random CNT hydrogels. This result was confirmed by Troponin-T immunostaining, the expression of cardiac genes (i.e., Tnnt2, Nkx2-5, and Actc1), and beating analysis of the EBs. The effect on EB properties was significantly enhanced by applying an electrical pulse stimulation (frequency, 1 Hz; voltage, 3 V; duration, 10 ms) to the EBs for two continuous days. Taken together, the fabricated hybrid hydrogel-aligned CNT scaffolds with tunable mechanical and electrical characteristics offer an efficient and controllable platform for electrically induced differentiation and stimulation of stem cells for potential tissue regeneration and cell therapy applications. Statement of significance Dielectrophoresis approach was used to rapidly align carbon nanotubes (CNTs) in gelatin methacryloyl (GelMA) hydrogels resulting in hybrid GelMA-CNT hydrogels with tunable and anisotropic electrical and mechanical properties. The GelMA-aligned CNT hydrogels may be used to apply accurate and controllable electrical pulses to cell and tissue constructs and thereby regulating their behavior and function. In this work, it was demonstrated that the GelMA hydrogels containing the aligned CNTs had superior performance in cardiac differentiation of stem cells upon applying electrical stimulation in contrast with control gels. Due to broad use of electrical stimulation in tissue engineering and stem cell differentiation, it is envisioned that the GelMA-aligned CNT hydrogels would find wide applications in tissue regeneration and stem cell therapy.
- Published
- 2015
45. High Protein Diet and Metabolic Plasticity in Non-Alcoholic Fatty Liver Disease: Myths and Truths
- Author
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Javier Ramón Azcón, Cynthia Ureta Checcllo, and Francesco De Chiara
- Subjects
0301 basic medicine ,medicine.medical_treatment ,physical activity ,Physiology ,High-protein diet ,Review ,Disease ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,NAFLD ,Dietary Carbohydrates ,medicine ,high protein diet ,Humans ,Obesity ,Exercise ,Liver diseases ,Nutrition and Dietetics ,Malalties del fetge ,Insulin ,Fatty liver ,NASH ,Metabolism ,Physical fitness ,medicine.disease ,Dietary Fats ,Diet ,3. Good health ,Metabolic pathway ,030104 developmental biology ,Liver ,Diet, High-Protein ,030211 gastroenterology & hepatology ,Dietary Proteins ,Insulin Resistance ,Steatosis ,low carbohydrates ,Condició física ,Food Science - Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation within the liver affecting 1 in 4 people worldwide. As the new silent killer of the twenty-first century, NAFLD impacts on both the request and the availability of new liver donors. The liver is the first line of defense against endogenous and exogenous metabolites and toxins. It also retains the ability to switch between different metabolic pathways according to food type and availability. This ability becomes a disadvantage in obesogenic societies where most people choose a diet based on fats and carbohydrates while ignoring vitamins and fiber. The chronic exposure to fats and carbohydrates induces dramatic changes in the liver zonation and triggers the development of insulin resistance. Common believes on NAFLD and different diets are based either on epidemiological studies, or meta-analysis, which are not controlled evidences; in most of the cases, they are biased on test-subject type and their lifestyles. The highest success in reverting NAFLD can be attributed to diets based on high protein instead of carbohydrates. In this review, we discuss the impact of NAFLD on body metabolic plasticity. We also present a detailed analysis of the most recent studies that evaluate high-protein diets in NAFLD with a special focus on the liver and the skeletal muscle protein metabolisms.
- Published
- 2019
46. Al2O3 Microresonator Based Passive and Active Biosensors
- Author
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Laura Padilla, Javier Ramón-Azcón, Francesc Mitjans, Sonia M. García-Blanco, Raquel Obregón, Jaume Adan, Michiel de Goede, Lantian Chang, Elena Martínez, and Meindert Dijkstra
- Subjects
Ytterbium ,Detection limit ,Materials science ,Sensing applications ,business.industry ,chemistry.chemical_element ,02 engineering and technology ,Laser ,law.invention ,Resonator ,020210 optoelectronics & photonics ,chemistry ,law ,0202 electrical engineering, electronic engineering, information engineering ,Optoelectronics ,business ,Biosensor ,Sensitivity (electronics) ,Refractive index - Abstract
Al 2 O 3 microresonators were realized for sensing applications of both passive and active devices. Passive microring resonators exhibited quality factors up to 3.2×105 in air. A bulk refractive index sensitivity of ~100 nm/RIU was demonstrated together with a limit of detection of ~10−6 RIU. Functionalizing their surface allowed for the label-free detection of the biomarker rhS100A4 from urine with a limit of detection of 3 nM. Furthermore, single-mode Al 2 O 3 :Yb3+ microdisk lasers were realized that could operate in an aqueous environment. Upon varying the bulk refractive index their lasing wavelength could be tuned with a sensitivity of ~20 nm/RIU and a LOD of ~3×10−6 RIU.
- Published
- 2018
47. Al2O3 microresonators for passive and active sensing applications
- Author
-
Javier Ramón-Azcón, Jaume Adan, Lantian Chang, Laura Padilla, Raquel Obregón, Sonia M. García-Blanco, Francesc Mitjans, Elena Martínez, Michiel de Goede, Meindert Dijkstra, and Optical Sciences
- Subjects
Optical pumping ,Materials science ,Refractive index ,01 natural sciences ,Waveguide (optics) ,law.invention ,010309 optics ,03 medical and health sciences ,Resonator ,0302 clinical medicine ,law ,0103 physical sciences ,Microdisk lasers ,Diode pumped lasers ,030203 arthritis & rheumatology ,Detection limit ,business.industry ,Distributed feedback lasers ,Single-mode optical fiber ,Laser ,6. Clean water ,Sensor performance ,Optoelectronics ,business ,Lasing threshold - Abstract
The Al2O3 waveguide technology was explored for sensing applications. Passive microring resonators with a quality factor in air of 3.2×105 were developed with a bulk refractive index sensitivity of ~100 nm/RIU and limit of detection of ~10-6 RIU. These were functionalized to detect the biomarker rhS100A4 from urine down to concentrations of 3 nM. Furthermore, Al2O3:Yb3+ microdisk lasers were realized that exhibited single mode lasing operation in water. Their lasing wavelength was tuned by varying the bulk refractive index and a bulk refractive index sensitivity of ~20 nm/RIU with a LOD of ~3×10-6 was achieved.
- Published
- 2018
48. Carbon-Based Nanobiomaterials
- Author
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Farhad Batmanghelich, Javier Ramón-Azcón, Murugan Ramalingam, Deepti Rana, Ramin Banan Sadeghian, Samad Ahadian, and Raquel Obregón
- Subjects
Materials science ,Graphene ,chemistry.chemical_element ,Nanotechnology ,02 engineering and technology ,Carbon nanotube ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,law.invention ,Tissue engineering ,chemistry ,law ,0210 nano-technology ,Carbon ,Biosensor - Published
- 2017
49. Hydrogels containing metallic glass sub-micron wires for regulating skeletal muscle cell behaviour
- Author
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Yuji Nashimoto, Hojae Bae, Koji S. Nakayama, Ali Khademhosseini, Hitoshi Shiku, Javier Ramón-Azcón, Samad Ahadian, Ramin Banan Sadeghian, Xiaobin Liang, Tomokazu Matsue, Ken Nakajima, and Shin Yaginuma
- Subjects
Materials science ,food.ingredient ,Biomedical Engineering ,Biocompatible Materials ,Nanotechnology ,Conductivity ,Gelatin ,Myoblasts ,food ,Tissue engineering ,Electrical resistivity and conductivity ,General Materials Science ,Muscle, Skeletal ,Amorphous metal ,Tissue Engineering ,Tissue Scaffolds ,Nanotubes, Carbon ,Electric Conductivity ,Hydrogels ,Adhesion ,Chemical engineering ,Self-healing hydrogels ,Methacrylates ,Glass ,Biosensor ,Palladium - Abstract
Hydrogels with tunable electrical and mechanical properties have a wide range of biological applications in tissue engineering, biosensing, and biorobotics. In this work, palladium-based metallic glass sub-micron wires (PdMGSMWs) were employed to enhance the conductivity and mechanical strength of gelatin methacryloyl (GelMA) gels. The values of electrical resistivity and stiffness of hybrid GelMA-PdMGSMW hydrogels were varied by the concentration of the sub-micron wires in the gels. Compared with pristine GelMA gels, hybrid GelMA-PdMGSMW gels were more efficient in regulating adhesion and spreading of C2C12 myoblasts. Formation, contractility, and metabolic activity of C2C12 myotubes in GelMA hydrogels also increased upon inclusion of the PdMGSMWs and applying electrical stimulation. The latter phenomenon is likely because of the electrical conductivity of hybrid GelMA gels.
- Published
- 2015
50. Facile and green production of aqueous graphene dispersions for biomedical applications
- Author
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Tomokazu Matsue, Hojae Bae, Velappa Jayaraman Surya, Yoshio Sakka, Javier Ramón-Azcón, Murugan Ramalingam, Ali Khademhosseini, Mehdi Estili, Hitoshi Shiku, Yoshiyuki Kawazoe, Samad Ahadian, Ken Nakajima, and Xiaobin Liang
- Subjects
Materials science ,Sonication ,Biomedical Technology ,Nanotechnology ,Microscopy, Atomic Force ,Spectrum Analysis, Raman ,Cell Line ,law.invention ,Mice ,symbols.namesake ,Microscopy, Electron, Transmission ,X-ray photoelectron spectroscopy ,law ,Ab initio quantum chemistry methods ,Elastic Modulus ,Animals ,General Materials Science ,Graphite ,Amino Acids ,Particle Size ,Spectroscopy ,Aqueous solution ,Graphene ,technology, industry, and agriculture ,Water ,Green Chemistry Technology ,Serum Albumin, Bovine ,Microscopy, Electron, Scanning ,symbols ,Cattle ,Raman spectroscopy - Abstract
We proposed a facile, low cost, and green approach to produce stable aqueous graphene dispersions from graphite by sonication in aqueous bovine serum albumin (BSA) solution for biomedical applications. The production of high-quality graphene was confirmed using microscopy images, Raman spectroscopy, UV-vis spectroscopy, and XPS. In addition, ab initio calculations revealed molecular interactions between graphene and BSA. The processability of aqueous graphene dispersions was demonstrated by fabricating conductive and mechanically robust hydrogel-graphene materials.
- Published
- 2015
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