New insights in osteoarthritis diagnosis and treatment: Nano-strategies for an improved disease management

Osteoarthritis (OA) is a common chronic joint pathology that has become a predominant cause of disability worldwide. Even though the origin and evolution of OA rely on different factors that are not yet elucidated nor understood, the development of novel strategies to treat OA has emerged in the last years. Cartilage degradation is the main hallmark of the pathology though alterations in bone and synovial inflammation, among other comorbidities, are also involved during OA progression. From a molecular point of view, a vast amount of signaling pathways are implicated in the progression of the disease, opening up a wide plethora of targets to attenuate or even halt OA. The main purpose of this review is to shed light on the recent strategies published based on nanotechnology for the early diagnosis of the disease as well as the most promising nano-enabling therapeutic approaches validated in preclinical models. To address the clinical issue, the key pathways involved in OA initiation and progression are described as the main potential targets for OA prevention and early treatment. Furthermore, an overview of current therapeutic strategies is depicted. Finally, to solve the drawbacks of current treatments, nanobiomedicine has shown demonstrated benefits when using drug delivery systems compared with the administration of the equivalent doses of the free drugs and the potential of disease-modifying OA drugs when using nanosystems. We anticipate that the development of smart and specific bioresponsive and biocompatible nanosystems will provide a solid and promising basis for effective OA early diagnosis and treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacemen

“El modelo tecnológico de Flipped Classroom para la enseñanza de Inmunología en 2º de Bachillerato”

En el presente trabajo se expone la propuesta didáctica implimentada durante el Practicum II denominada “El modelo tecnológico de Flipped Classroom para la enseñanza de Inmunología en 2º de Bachillerato”. En primer lugar, se analizan dos actividades llevadas a cabo en el máster que han sido de utilidad en el diseño de la propuesta didáctica. A continuación, se analiza dicha propuesta en detalle, consultando bibliografía que fundamente el diseño de la propuesta y de la metodología empleada. Posteriormente se exponen de forma secuencial las actividades que se han implementado justificando el diseño de las mismas, los objetivos que persiguen y la forma de evaluación llevada a cabo. Por último se recoge una evaluación tanto de la propuesta didáctica como de la docencia, analizando las limitaciones y dificultades encontradas con las consiguientes propuestas de mejora. Finalmente, se exponen unas conclusiones finales acerca del trabajo realizado.<br /

ACCIÓN DE SETAS Y HONGOS EN EL TRATAMIENTO DE LA ARTROSIS Y PROTECCIÓN DEL CARTÍLAGO

La artrosis u osteoartritis es una enfermedad degenerativa del cartílago que cursa con unaprogresiva destrucción e inflamación de la articulación produciendo dolor e incapacidad a lospacientes que la padecen. Actualmente no hay tratamientos curativos para dicha afección quelogren revertir la situación a un estado fisiológico, todos los existentes tratan de paliar el dolor delos pacientes de una forma ineficaz y con multitud de efectos adversos. Por esto y debido alincremento de prevalencia de la enfermedad esperado en el futuro con el envejecimiento de lapoblación mundial actual, es necesario que emerjan nuevas posibles terapias con las que paliar laartrosis de forma efectiva. Últimamente, multitud de estudios han comprobado cómo compuestosfenólicos de origen natural tienen un importante efecto antiinflamatorio en el tratamiento de laartrosis y de otras enfermedades degenerativas, siendo por ello una tendencia a tener en cuenta enel panorama actual para el desarrollo de nuevas terapias futuras. Estos compuestos fenólicos sonubicuos en prácticamente todos los alimentos de origen vegetal (frutas y verduras), por lo que enmuchas ocasiones se emplean extractos obtenidos de residuos procedentes de la industriaalimentaria, con la finalidad de lograr una revalorización de estos. En este trabajo se aborda laevaluación del potencial antiinflamatorio de extractos procedentes de Boletus edulis (Ext) conuna composición rica en polifenoles. En un modelo de inflamación mediado por elLipopolisacarido bacteriano (LPS) en células condrogénicas murinas (ATDC-5), se ha visto comoestos Ext tienen un importante potencial antiinflamatorio, reduciendo notoriamente la expresiónde mediadores de la inflamación y de degeneración del cartílago mediante su intervención en laruta del NF-κB.<br /

Anti-Inflammatory and chondroprotective effects induced by phenolic compounds from onion waste extracts in ATDC-5 chondrogenic cell line

Osteoarthritis is a prevalent degenerative condition that is closely related to the destruction and inflammation of cartilage. The high prevalence of this pathology exhorts researchers to search for novel therapeutic approaches. Vegetable–fruit wastes have emerged as a promising origin of anti-inflammatory and antioxidant compounds that, in some cases, may also exert chondroprotective effects. This study aims to decipher the potential of onion waste products in the inhibition of molecular events involved in osteoarthritis. Onion extracts showed a high content of phenolic compounds and antioxidant properties. Cytocompatibility was demonstrated in the chondrogenic cell line ATDC-5, exerting viability percentages higher than 90% and a slight increase in the S phase cycle cell. The induction of inflammation mediated by the lipopolysaccharide and onion extracts’ treatment substantially inhibited molecular markers related to inflammation and cartilage degradation, highlighting the promising application of onion extracts in biomedical approaches. The in silico analyses suggested that the results could be attributed to protocatechuic, ellagic, and vanillic acids’ greater cell membrane permeability. Our work provides distinctive information about the possible application of waste onion extracts as functional components with anti-inflammatory and chondroprotective characteristics in osteoarthritis.his work was supported by the Grants: Proyectos en Salud AES 2021 (PI21/00911; ISCIII), CIBER-BBN, CIBEROBN, Ministerio de Ciencia e Innovación-Fondo Europeo de Desarrollo Regional (PID2019-104915RB-I00), Fondo Social Europeo-Gobierno de Aragón (B16_20R) and SUDOE (Redvalue, SOE1/PI/E0123). This research was also funded by European Union’s H2020 research and innovation program under Marie Sklodowska-Curie grant agreement number 801586. G.M. gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; ISCIII). M.P. acknowledges the support from the Gobierno de Aragón fellowship (CUS/581/2020). O.G. is Staff Personnel (I3SNS Stable Researcher) of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff contract (ISCIII)/SERGAS

Gold nanoparticles capped with a novel titanium(IV)-containing polyoxomolybdate cluster: Selective and enhanced bactericidal effect against Escherichia coli

Bacterial infections are a public health threat of increasing concern in medical care systems; hence, the search for novel strategies to lower the use of antibiotics and their harmful effects becomes imperative. Herein, the antimicrobial performance of four polyoxometalate (POM)-stabilized gold nanoparticles (Au@POM) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as Gram-negative and Gram-positive bacteria models, respectively, is studied. The bactericidal studies performed, both in planktonic and sessile forms, evidence the antimicrobial potential of these hybrid nanostructures with selectivity toward Gram-negative species. In particular, the Au@GeMoTi composite with the novel [Ti2 (HGeMo7 O28 )2 ]10- POM capping ligand exhibits outstanding bactericidal efficiency with a minimum inhibitory concentration of just 3.12 µm for the E. coli strain, thus outperforming the other three Au@POM counterparts. GeMoTi represents the fourth example of a water-soluble TiIV -containing polyoxomolybdate, and among them, the first sandwich-type structure having heteroatoms in high-oxidation state. The evaluation of the bactericidal mechanisms of action points to the cell membrane hyperpolarization, disruption, and subsequent nucleotide leakage and the low cytotoxicity exerted on five different cell lines at antimicrobial doses demonstrates the antibiotic-like character. These studies highlight the successful design and development of a new POM-based nanomaterial able to eradicate Gram-negative bacteria without damaging mammalian cells.The authors thank the following institutions for the financial support to carry out this research: Spanish Ministerio de Ciencia e Innovación, Spanish Agencia Estatal de Investigación, and FEDER “una manera de hacer Europa” (grant numbers PID2020-113987RB-I00, PDC2021-121405-I00, PID2019-106687RJ-I00, and PID2021-127265OB-C21); Gobierno de Navarra (grant number PC091-092 FOREST2+). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III with the assistance of the European Regional Development Fund. M.P. acknowledges the support from Gobierno de Aragón (Orden CUS/581/2020). G.M. gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; Instituto de Salud Carlos III).Peer reviewe

Valorization of onion waste by obtaining extracts rich in phenolic compounds and feasibility of its therapeutic use on colon cancer

In this study, the total phenolic content, the antioxidant and antiproliferative activities of onion waste extracts were characterized. Some phenolic compounds present in the extracts were also identified and quantified by HPLC-DAD. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The onion extract possessed a high amount of phenolic compounds (177 ± 9 mg/g extract) and had an effective antioxidant capacity measured by ABTS, FRAP and DPPH assays. Regarding the antiproliferative activity, the onion extracts produced cell cycle arrest in the S phase with p53 activation, intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation. Likewise, onion waste increased intracellular ROS with possible NF-kB activation causing a proteasome down regulation. In addition, the extracts protected the intestine against oxidative stress induced by H2O2. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to protocatechuic acid. Therefore, this study provides new insights regarding the potential use of these types of extract as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress, such as cancer. In addition, its valorization would contribute to the circular economy.This work was supported by the Grants: CIBEROBN, CB06/03/1012, 2008, Ministerio de Ciencia e Innovación-Fondo Europeo de Desarrollo Regional (PID2019-104915RB-I00), Fondo Social Europeo-Gobierno de Aragón (B16_20R) and SUDOE (Redvalue, SOE1/PI/E0123). This research was also funded by EUROPEAN UNIONS H2020 research and innovation program under Marie Sklodowska-Curie grant agreement number 801586. G.M. gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; Instituto de Salud Carlos III). M.P. acknowledges the support from the Gobierno de Aragón fellowship (CUS/581/2020)