Artículos de revista (CUN)
Permanent URI for this collectionhttps://hdl.handle.net/10171/70263
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7 results
Results
- Suitability of machine learning for atrophy and fibrosis development in neovascular age-related macular degeneration(John Wiley & Sons Ltd, 2023) Fuente-Cedeño, J. (Jesús) de la; Hernandez-Sanchez, M. (María); Llorente-González, S. (Sara); Garcia-Layana, A. (Alfredo); Ochoa, I. (Idoia); Fernandez-Robredo, P. (Patricia); Recalde, S. (Sergio)Purpose: To assess the suitability of machine learning (ML) techniques in predicting the development of fibrosis and atrophy in patients with neovascular age-related macular degeneration (nAMD), receiving anti-VEGF treatment over a 36-month period. Methods: An extensive analysis was conducted on the use of ML to predict fibrosis and atrophy development on nAMD patients at 36months from start of anti-VEGF treatment, using only data from the first 12months. We use data collected according to real-world practice, which includes clinical and genetic factors. Results: The ML analysis consistently identified ETDRS as a relevant factor for predicting the development of atrophy and fibrosis, confirming previous statistical analyses. Also, it was shown that genetic variables did not demonstrate statistical relevance in the prediction. Despite the complexity of predicting macular degeneration, our model was able to obtain a balance accuracy of 63% and an AUC of 0.72 when predicting the development of atrophy or fibrosis at 36months. Conclusion: This study demonstrates the potential of ML techniques in predicting the development of fibrosis and atrophy in nAMD patients receiving longterm anti-VEGF treatment. The findings highlight the importance of clinical factors, particularly ETDRS (early treatment diabetic retinopathy study) visual acuity test, in predicting these outcomes. The lessons learned from this research can guide future ML-based prediction tasks in the field of ophthalmology and contribute to the design of data collection processes.
- Automatic segmentation and quantification of Nigrosome-1 Neuromelanin and Iron in MRI: a candidate biomarker for Parkinson’s disease(Wiley Periodicals LLC, 2023) Martinez, M. (Martín); Castellanos, G. (Gabriel); Ortiz-de-Solorzano, C. (Carlos); Pastor, P. (Pau); Fernández-Seara, M.A. (María A.); Pastor, M.A. (María A.); Álvarez, I. (Ignacio); Ariz, M. (Mikel)Parkinson’s disease (PD) is caused by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). The incidence of PD increases with age and is one of the major causes of disability. PD early diagnosis is still a challenge as it is based on the clinical assessment of the subject discarding other potential causes of parkinsonism, and the patient’s positive response to Levodopa therapy, leading to a misdiagnosis rate of approximately 16%. The substantia nigra (SN), located in the ventral tegmentum of the midbrain, is divided into two main regions: the iron-rich ventral SN pars reticulata (SNr), and the dorsal SNc, where the neuromelanin-containing dopaminergic neurons (NM) are located. NM is believed to have a neuroprotective function against the toxicity of iron-mediated oxidative processes. Specifically, the death of dopaminergic neurons of the SNc causes NM depigmentation, followed by an increase of iron load. Indeed, it has been reported that a relative decrease of SNc NM leads to a relative increase of SNc iron in PD patients, when compared with age-matched healthy controls (HCs).
- Nanofibrous PCL-based human trabecular meshwork for aqueous humor outflow studies(2023) Moreno-Montañes, J. (Javier); Aldazabal, J. (Javier); Extramiana, L. (Leire); Bikuna-Izagirre, M. (María); Paredes-Puente, J. (Jacobo); Carnero, E. (Elena)Primary open-angle glaucoma is characterized by the progressive degeneration of the optic nerve, with the high intraocular pressure (IOP) being one of the main risk factors. The human trabecular meshwork (HTM), specifically the juxtacanalicular tissue (JCT), is responsible for placing resistance to the aqueous humor (AH) outflow and the resulting IOP control. Currently, the lack of a proper in vitro JCT model and the complexity of three-dimensional models impede advances in understanding the relationship between AH outflow and HTM degeneration. Therefore, we design an in vitro JCT model using a polycaprolactone (PCL) nanofibrous scaffold, which supports cells to recapitulate the functional JCT morphology and allow the study of outflow physiology. Mechanical and morphological characterizations of the electrospun membranes were performed, and human trabecular meshwork cells were seeded over the scaffolds. The engineered JCT was characterized by scanning electron microscopy, quantitative real-time polymerase chain reaction, and immunochemistry assays staining HTM cell markers and proteins. A pressure-sensitive perfusion system was constructed and used for the investigation of the outflow facility of the polymeric scaffold treated with dexamethasone (a glucocorticoid) and netarsudil (a novel IOP lowering the rho inhibitor). Cells in the in vitro model exhibited an HTM-like morphology, expression of myocilin, fibronectin, and collagen IV, genetic expression, outflow characteristics, and drug responsiveness. Altogether, the present work develops an in vitro JCT model to better understand HTM cell biology and the relationship between the AH outflow and the HTM and allow further drug screening of pharmacological agents that affect the trabecular outflow facility.
- Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering(2022) Blanco-Prieto, M.J. (María José); Sanmartin-Grijalba, C. (Carmen); Campo, R. (Ruben) del; Aldazabal, J. (Javier); Plano-Amatriain, D. (Daniel); Paredes-Puente, J. (Jacobo); Luquin, M.R. (María Rosario); Garbayo-Atienza, E. (Elisa); Santamaria, E. (Enrique); Torres-Ortega, P.V. (Pablo Vicente)The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule release and better mimicking the complex properties of the brain tissue. Here, we develop and characterize a drug delivery system for brain repair where MSCs and GDNF are included in a nanoparticle-modified supramolecular guest-host HA HG. In this system, the nanoparticles act as both carriers for the GDNF and active physical crosslinkers of the HG. The multifunctional HG is mechanically compatible with brain tissue and easily injectable. It also protects GDNF from degradation and achieves its controlled release over time. The cytocompatibility studies show that the developed biomaterial provides a friendly environment for MSCs and presents good compatibility with PC12 cells. Finally, using RNA-sequencing (RNA-seq), we investigated how the three-dimensional (3D) environment, provided by the nanostructured HG, impacted the encapsulated cells. The transcriptome analysis supports the beneficial effect of including MSCs in the nanoreinforced HG. An enhancement in the anti-inflammatory effect of MSCs was observed, as well as a differentiation of the MSCs toward a neuron-like cell type. In summary, the suitable strength, excellent self healing properties, good biocompatibility, and ability to boost MSC regenerative potential make this nanoreinforced HG a good candidate for drug and cell administration to the brain.
- Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements(Elsevier, 2022) Unamuno, X. (Xabier); Valenti, V. (Víctor); Ezquerro-Ezquerro, S. (Silvia); Elizalde, R. (Reyes); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Mentxaka, A. (Amaia); Becerril, S. (Sara); Frühbeck, G. (Gema); Moncada, R. (Rafael); Silva, C. (Camilo); Llorente-Ortega, M. (Marcos); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia)Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improve- ments. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up- regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with en- hanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better character- ization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.
- Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP–2 and enhanced bone regeneration(MDPI AG, 2019) Ewald, A. (Andrea); Andreu-Arzuaga, I. (Ion); Granero-Moltó, F. (Froilán); Groll, J. (Jürgen); Flandes-Iparraguirre, M. (María); Elizalde, R. (Reyes); Ripalda-Cemboráin, P. (Purificación); Stuckensen, K. (Kai); Lopez, T. (Tania); Pons-de-Villanueva, J. (Juan); Muiños-López, E. (Emma); Nickel, J. (Joachim); Iglesias, E. (Elena); Prosper-Cardoso, F. (Felipe); Lamo-Espinosa, J.M. (J. M.); Abizanda-Sarasa, G. (Gloria); Gbureck, U. (Uwe)In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
- Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice(Wiley, 2021) Calvo, I.A. (Isabel A.); Granero-Moltó, F. (Froilán); Paramo, J.A. (José Antonio); Ripalda-Cemboráin, P. (Purificación); Montiel-Terrón, V. (Verónica); Aldazabal, J. (Javier); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Lopez, T. (Tania); Valdés-Fernández, J. (José); Muiños-López, E. (Emma); Romero-Torrecilla, J.A. (Juan Antonio); Prosper-Cardoso, F. (Felipe); Saez, B. (Borja)The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion