CIMUS-Artigoshttp://hdl.handle.net/10347/97642024-03-29T07:12:59Z2024-03-29T07:12:59ZDevelopment of an epigenetic age predictor for costal cartilage with a simultaneous somatic tissue differentiation systemFreire Aradas, Ana MaríaAmbroa Conde, AdriánCasares de Cal, María ÁngelesGómez Tato, AntonioÁlvarez Dios, José AntonioPhillips, C.Branicki, Wojciechhttp://hdl.handle.net/10347/332262024-03-21T09:21:44Z2023-01-01T00:00:00ZDevelopment of an epigenetic age predictor for costal cartilage with a simultaneous somatic tissue differentiation system
Freire Aradas, Ana María; Ambroa Conde, Adrián; Casares de Cal, María Ángeles; Gómez Tato, Antonio; Álvarez Dios, José Antonio; Phillips, C.; Branicki, Wojciech
Age prediction from DNA has been a topic of interest in recent years due to the promising results obtained when using epigenetic markers. Since DNA methylation gradually changes across the individual’s lifetime, prediction models have been developed accordingly for age estimation. The tissue-dependence for this biomarker usually necessitates the development of tissue-specific age prediction models, in this way, multiple models for age inference have been constructed for the most commonly encountered forensic tissues (blood, oral mucosa, semen). The analysis of skeletal remains has also been attempted and prediction models for bone have now been reported. Recently, the VISAGE Enhanced Tool was developed for the simultaneous DNA methylation analysis of 8 age-correlated loci using targeted high-throughput sequencing. It has been shown that this method is compatible with epigenetic age estimation models for blood, buccal cells, and bone. Since when dealing with decomposed cadavers or postmortem samples, cartilage samples are also an important biological source, an age prediction model for cartilage has been generated in the present study based on methylation data collected using the VISAGE Enhanced Tool. In this way, we have developed a forensic cartilage age prediction model using a training set composed of 109 samples (19–74 age range) based on DNA methylation levels from three CpGs in FHL2, TRIM59 and KLF14, using multivariate quantile regression which provides a mean absolute error (MAE) of ± 4.41 years. An independent testing set composed of 72 samples (19–75 age range) was also analyzed and provided an MAE of ± 4.26 years. In addition, we demonstrate that the 8 VISAGE markers, comprising EDARADD, TRIM59, ELOVL2, MIR29B2CHG, PDE4C, ASPA, FHL2 and KLF14, can be used as tissue prediction markers which provide reliable blood, buccal cells, bone, and cartilage differentiation using a developed multinomial logistic regression model. A training set composed of 392 samples (n = 87 blood, n = 86 buccal cells, n = 110 bone and n = 109 cartilage) was used for building the model (correct classifications: 98.72%, sensitivity: 0.988, specificity: 0.996) and validation was performed using a testing set composed of 192 samples (n = 38 blood, n = 36 buccal cells, n = 46 bone and n = 72 cartilage) showing similar predictive success to the training set (correct classifications: 97.4%, sensitivity: 0.968, specificity: 0.991). By developing both a new cartilage age model and a tissue differentiation model, our study significantly expands the use of the VISAGE Enhanced Tool while increasing the amount of DNA methylation-based information obtained from a single sample and a single forensic laboratory analysis. Both models have been placed in the open-access Snipper forensic classification website.
2023-01-01T00:00:00ZSelf-assembled peptide/polymer hybrid nanoplatform for cancer immunostimulating therapiesKhazaei, SaeedehVarela Calviño, RubénRad Malekshahi, MazdaQuattrini, FedericoJokar, SafuraRezaei, NimaBalalaie, SaeedHaririan, IsmaeilCsaba, Noemi StefaniaGarcía Fuentes, Marcoshttp://hdl.handle.net/10347/330892024-03-21T09:21:44Z2023-01-01T00:00:00ZSelf-assembled peptide/polymer hybrid nanoplatform for cancer immunostimulating therapies
Khazaei, Saeedeh; Varela Calviño, Rubén; Rad Malekshahi, Mazda; Quattrini, Federico; Jokar, Safura; Rezaei, Nima; Balalaie, Saeed; Haririan, Ismaeil; Csaba, Noemi Stefania; García Fuentes, Marcos
Integrating peptide epitopes in self-assembling materials is a successful strategy to obtain nanovaccines with high antigen density and improved efficacy. In this study, self-assembling peptides containing MAGE-A3/PADRE epitopes were designed to generate functional therapeutic nanovaccines. To achieve higher stability, peptide/polymer hybrid nanoparticles were formulated by controlled self-assembly of the engineered peptides. The nanoparticles showed good biocompatibility to both human red blood- and dendritic cells. Incubation of the nanoparticles with immature dendritic cells triggered immune effects that ultimately activated CD8 + cells. The antigen-specific and IgG antibody responses of healthy C57BL/6 mice vaccinated with the nanoparticles were analyzed. The in vivo results indicate a specific response to the nanovaccines, mainly mediated through a cellular pathway. This research indicates that the immunogenicity of peptide epitope vaccines can be effectively enhanced by developing self-assembled peptide-polymer hybrid nanostructures
2023-01-01T00:00:00ZIntegrating bioprinting, cell therapies and drug delivery towards in vivo regeneration of cartilage, bone and osteochondral tissueAbbadessa, AnnaRonca, AlfredoSalerno, Aureliohttp://hdl.handle.net/10347/330292024-03-21T09:21:42Z2023-01-01T00:00:00ZIntegrating bioprinting, cell therapies and drug delivery towards in vivo regeneration of cartilage, bone and osteochondral tissue
Abbadessa, Anna; Ronca, Alfredo; Salerno, Aurelio
The biological and biomechanical functions of cartilage, bone and osteochondral tissue are naturally orchestrated by a complex crosstalk between zonally dependent cells and extracellular matrix components. In fact, this crosstalk involves biomechanical signals and the release of biochemical cues that direct cell fate and regulate tissue morphogenesis and remodelling in vivo. Three-dimensional bioprinting introduced a paradigm shift in tissue engineering and regenerative medicine, since it allows to mimic native tissue anisotropy introducing compositional and architectural gradients. Moreover, the growing synergy between bioprinting and drug delivery may enable to replicate cell/extracellular matrix reciprocity and dynamics by the careful control of the spatial and temporal patterning of bioactive cues. Although significant advances have been made in this direction, unmet challenges and open research questions persist. These include, among others, the optimization of scaffold zonality and architectural features; the preservation of the bioactivity of loaded active molecules, as well as their spatio-temporal release; the in vitro scaffold maturation prior to implantation; the pros and cons of each animal model and the graft-defect mismatch; and the in vivo non-invasive monitoring of new tissue formation. This work critically reviews these aspects and reveals the state of the art of using three-dimensional bioprinting, and its synergy with drug delivery technologies, to pattern the distribution of cells and/or active molecules in cartilage, bone and osteochondral engineered tissues. Most notably, this work focuses on approaches, technologies and biomaterials that are currently under in vivo investigations, as these give important insights on scaffold performance at the implantation site and its interaction/integration with surrounding tissues
2023-01-01T00:00:00ZEdoxaban treatment in a post-infarction experimental modelMartínez-Fernández, JavierAlmengló Buzón, CristinaBabarro, BorjaIglesias Rey, RamónGarcía-Caballero Parada, TomásFernández, Ángel L.Souto Bayarri, José MiguelGonzález Juanatey, José RamónÁlvarez Castro, Ezequielhttp://hdl.handle.net/10347/329862024-03-21T09:21:42Z2024-01-01T00:00:00ZEdoxaban treatment in a post-infarction experimental model
Martínez-Fernández, Javier; Almengló Buzón, Cristina; Babarro, Borja; Iglesias Rey, Ramón; García-Caballero Parada, Tomás; Fernández, Ángel L.; Souto Bayarri, José Miguel; González Juanatey, José Ramón; Álvarez Castro, Ezequiel
Background
The sequelae of myocardial infarction (MI) require specific pharmacological therapy to minimise the post-MI remodelling, which in many cases evolves into cardiovascular complications. The aim of this study was to analyse the effect of edoxaban, an oral anticoagulant, on cardiac recovery in a rat model of permanent coronary artery ligation.
Methods
An experimental method to assess the post-MI remodelling in rats for 4 weeks, based on cardiac magnetic resonance imaging (MRI) and final histological analysis of the hearts was performed. The influence of daily oral treatment with edoxaban (20 mg/kg/day) for 28 days post-MI was analysed in comparison to vehicle.
Results
In our model, edoxaban was shown to be safe and bleeding was observed in 1 of 10 animals. General physical recovery of the treated animals was shown by higher body weight recovery compared with non-treated animals (38.6 ± 2.9 vs. 29.9 ± 3.1 g, respectively, after 28 days). There was not a pronounced effect of edoxaban in post-MI cardiac remodelling, but mitigated fibrosis was observed by the reduced expression of vascular endothelial growth factor and tumour growth factor β1 in the peri-infarct zone.
Conclusions
Our analysis provided the experimental basis to support the feasibility of MRI to study cardiac function and characterise myocardial scarring in a rat model. Overall data suggested the safety of edoxaban in the model, and compared to placebo, it showed a better post-MI recovery, probably by reducing fibrosis of the heart. Further research on mid-term cardiac recovery with edoxaban after MI is justified.
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