Search

Addressing large bone segmental defects remains a profound challenge in orthopaedic surgery, demanding graft designs that mirror patient-specific defects while ensuring vascularization, osteoconduction, and structural integrity. Conventional approaches fall short in achieving this level of customization and functionality. This work leverages fuse filament fabrication (FFF) to fabricate innovative yttria stabilize zirconia graft designs that combine several strategies to tackle these multifaceted challenges. Graft designs ingeniously incorporate dense and porous structures mimicking the intricate architecture of natural bone for improved structural integrity and different ridges and protrusions to enhance the fixation. Additionally, these grafts undergo infiltration with PCL/PVA/AgNPs composite polymers, enriching biocompatibility, structural integrity, and antibacterial properties, fostering conducive conditions for optimal bone growth. Attaining printable filaments with YSZ powders below 50 nm and loads reaching 50 vol% marks a pioneering advancement in bone graft fabrication via Fused Filament Fabrication (FFF). This enabled high densification and low grain size at reduced sintering temperatures, imperative to achieve high mechanical performance. The biodegradation capacity of biopolymers in PBS and their role in the mechanical behaviour of grafts have been assessed, demonstrating the beneficial potential of the multicomponent graft proposed reaching strength values of 90–105 MPa.

The incidence of fractures and bone defects has been a significant driving force behind research efforts aimed at enhancing the quality of life for patients. However, it is important to acknowledge the inherent complexities of this research field. Where each patient could have different scenarios along with the difficulty of replicate the properties and complex design of the bones. In this study, scaffolds previously manufactured by different 3D printing techniques made of ceramic materials, specifically yttria-stabilised zirconia, which has excellent biocompatibility and mechanical properties, were used. These samples, which exhibit different designs to be employed in specific medical situation, have been characterised according to his morphology and porosity; using the outcomes for select the most promising for subsequent infiltration with appropriate biopolymers in order to improve their in vivo performance. Specifically oriented towards improve the osseointegration capacity by adding nanohydroxyapatite (nHA). The infiltrated samples were evaluated in terms of polymer degradation inside the composite, swelling evaluation, and studies of apatite formation capacity on the surface (bioactivity) assessed through XRD.

The demand for dental implants is increasing, although there is a wide variety of implants currently available in the market, it is necessary to implement improvements in their design and/or the selection of materials used. The development of biomimetic and bioactive Ti scaffolds for bone regeneration is necessary. In this context, this article proposes the design, manufacture and characterization of a porous titanium implant with the aim of eliminating some of the deficiencies found in commercially available titanium implants. Stress-shielding and the lack of osseointegration or bacterial infection are still some limitations to solve. Porous samples were produced using conventional Powder Metallurgy (PM) and the space holder (SH) technique. Ammonium bicarbonate particles were used as spacers in size ranges of 100–200 µm. The porosity and surface characterization were performed by Archimedes’ method and image analysis, while the mechanical behavior was analyzed by micro-mechanical testing. After that, the micromachining protocol of the implant is carried out. Substrates were chemically etched by immersion in fluorhydric acid at different times (15 s; 60 s and 125 s) to achieve a suitable surface roughness with biofunctional balance. Results showed that it is possible to obtain a desired longitudinal gradient. The optimized method described in this work suggests that it is a reasonable candidate for the development of dental implants with a good balance between reduced stress shielding and adequate mechanical strength.

Los ácidos grasos trans son más perjudiciales desde el punto de vista nutricional que los ácidos grasos saturados. Una ingesta excesiva de grasa trans afecta principalmente al sistema cardiovascular, aumentando la incidencia de cáncer y otras patologías. En 2004, Dinamarca y Canadá lideraron la limitación de su contenido en alimentos al 2% sobre grasa total. Otra medida adoptada fue la obligatoriedad de incluir información sobre grasa trans en el etiquetado, propuesta por la Food and Drug Administration (FDA) de EE. UU. a partir de 2006. En 2015, La FDA prohibió uso de aceites parcialmente hidrogenados, principal fuente de los ácidos grasos trans de origen industrial. En 2019, la Comisión Europea finalmente restringió el contenido de grasa trans de origen industrial en alimentos del 2%, sobre grasa total. Aún existen regiones en países del Este Europeo, antiguas repúblicas soviéticas, zonas asiáticas (India y Pakistán) y gran parte de África donde se detectan cifras muy altas y preocupantes de grasa trans en alimentos procesados, debido a la falta de regulaciones efectivas. La Organización Mundial de la Salud (OMS) está implementando el programa REPLACE para eliminar el uso de la grasa trans a nivel mundial. En este trabajo se analizaron margarinas españolas reformuladas (“cero trans”) que presentaban niveles de grasa trans inferiores al 0,5%, sobre grasa total. Se empleó el método de análisis de infrarrojos ATR-FTIR (-2D) de segunda derivada, el cual se demostró ser más rápido, eficaz y sencillo que el método de cromatografía de gases. Antes de las reformulaciones, la carga de grasa trans en margarinas era muy alta en países como Canadá, Estados Unidos o Países Bajos. Se evaluaron también varios productos tradicionalmente ricos en grasa trans (dónuts, galletas, snacks, palomitas de maíz, sopas deshidratadas y alimentos de comida rápida), encontrando que los niveles de grasa trans eran inferiores al 1% sobre la grasa total, excepto en los casos de las palomitas de m, From a nutritional point of view, trans-fatty acids are even more harmful than saturated fatty acids. Excessive intake of trans fat primarily affects the cardiovascular system, increasing the incidence of cancer and other pathologies. In 2004, Denmark and Canada led the way in limiting trans-fat content in food to 2% of total fat. Another measure implemented was the mandatory inclusion of trans fat information on labeling, proposed by the U.S. Food and Drug Administration (FDA) starting in 2006. In 2015, the FDA banned the use of partially hydrogenated oils, the main source of industrially produced trans fatty acids. In 2019, the European Commission finally restricted industrial trans-fat content in food to 2% of total fat. There are still regions in Eastern European countries, former Soviet republics, Asian areas (India and Pakistan), and much of Africa where very high and concerning levels of trans fat in processed foods are reported due to ineffective regulations. The World Health Organization (WHO) is implementing the REPLACE program to eliminate trans fat use globally. In this study, reformulated Spanish margarines ("zero trans") were analyzed, showing trans-fat levels below 0.5% of total fat. The second derivative ATR-FTIR (-2D) infrared analysis method was used, proving to be faster, more effective, and simpler than gas chromatography. Prior to the reformulations, the trans-fat content in margarines was very high in countries like Canada, the United States, or the Netherlands. Various products traditionally high in trans-fat (doughnuts, biscuits, snacks, popcorn, dried soups, and fast food) were also evaluated, revealing that trans-fat levels were below 1% of total fat, except for cases like McDonald's popcorn and French fries, which ranged from 1.1% to 2%. In no instance did they exceed the legal limit of 2%. Out of the 23 samples of edible vegetable oils analyzed (olive, sunflower, corn), only 7 provided information on quality and authenticity indices (acid

Nanomedicine has been long hailed as a game changer for treating several ailments, but its translation from bench to bedside is facing some hurdles. Over the past few decades, there have been a plethora of reports regarding the synthesis of nanomaterials and, in particular, of iron oxide nanoparticles. However, very few reports discuss the role of stirring speed, reproducibility, and scalability. This work attempts to comprehensively revisit the most widely used existing protocols and discuss how the particle size or shape varies when certain parameters are altered and different precursors and solvents are used. It also discusses the probability of reproducing and scaling up the reactions while deciphering the effect of the ramp rate on size and shape. Lastly, it upgrades the existing methods and suggests a modification to produce highly reproducible and scalable nanoparticles of ∼4 nm, which can be further tuned to ∼2 nm by merely modifying the stirring speed.

Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases’ active sites.

La enseñanza sobre la Educación Ambiental y la lucha contra el cambio climático en las aulas de Educación Primaria es una cuestión de máxima actualidad y necesidad. Se presentan estrategias y actividades didácticas que fomentan la participación activa de los estudiantes y promueven la reflexión y la acción en relación con el cambio climático. En consecuencia, el presente Trabajo de Fin de Grado (TFG) se centra en el desarrollo de un enfoque didáctico de la Educación Ambiental para abordar el desafío del cambio climático desde las aulas de Primaria. El objetivo principal es proporcionar a los docentes herramientas y recursos educativos para concienciar y capacitar a los estudiantes en la protección del medio ambiente, The teaching of Environmental Education and the fight against climate change in Primary school classrooms is a highly topical and necessary issue. Teaching strategies and activities are presented that encourage the students' active participation and promote reflection and action in relation to climate change. Accordingly, this Final Degree Project (FDP) focuses on the development of a didactic approach to Environmental Education to address the challenge of climate change in Primary school classrooms. The main objective is to provide teachers with educational tools and resources to raise awareness and empower students to protect the environment.

El trasplante celular es un procedimiento utilizado para regenerar tejidos dañados, basado en acelerar la auto-reparación en lugar de reemplazarlos. Estos tratamientos están basados en la ingeniería tisular in vitro, que consiste en cultivar células madre en un andamio externo para después implantarlo en el tejido dañado. Para llevar a cabo estos procedimientos, es fundamental el uso de biomateriales que garanticen su eficacia y seguridad, así como la biocompatibilidad para evitar una respuesta inmunológica adversa, ya que esta técnica tiene limitaciones notables. Debido a que la diferenciación celular es un proceso clave para el desarrollo y mantenimiento de los organismos, es esencial comprender cómo las células in vivo responden a las señales mecánicas para diseñar estrategias de inyección de células más efectivas. Para la regeneración de tejidos y órganos, se utilizan diferentes tipos de células, incluyendo células somáticas y células madre pluripotentes inducidas (iPSC), junto con andamiajes de biomateriales, para proporcionar un ambiente adecuado para el crecimiento celular. La ingeniería tisular y el uso de biomateriales ofrecen grandes posibilidades de regenerar tejidos y órganos dañados, así como mejorar la calidad de vida de los pacientes. Es por ello, que la elección de estos biomateriales depende de la actividad específica y del tipo de tejido que se esté tratando. Los polímeros sintéticos biodegradables y no biodegradables, junto con los polímeros naturales, son los más comúnmente utilizados como andamios para la medicina regenerativa. La revisión efectuada ha proporcionado una información detallada que ha permitido describir la importancia de la diferenciación celular en el campo de la medicina regenerativa y la ingeniería tisular, así como los distintos biomateriales, aplicaciones y ventajas.

El reposicionamiento de fármacos es un procedimiento que consiste en el uso de medicamentos para tratar enfermedades distintas para las que fueron originalmente diseñados. A pesar de que la idea de reposicionar fármacos no es nueva, sino que lleva existiendo desde hace varias décadas, constituye una estrategia emergente en el campo de la medicina por su gran potencial para mejorar la eficacia y seguridad de los tratamientos frente a diversas enfermedades, entre las que destaca el cáncer. Por otro lado, se trata de moléculas que han sido previamente evaluadas en cuanto a seguridad y eficacia, reduciendo así tiempos y costes en el desarrollo. La revisión bibliográfica que se presenta en este TFG, proporciona información detallada acerca de algunos de los grupos farmacológicos más prescritos en la mayoría de la población por ser los empleados en el tratamiento de enfermedades de alta prevalencia que se han estudiado en el reposicionamiento de fármacos para el tratamiento del cáncer. Entre estos grupos farmacológicos encontramos los fármacos cardiovasculares, en los que se han observado prometedoras propiedades anticancerosas, los fármacos para controlar la síntesis de colesterol, debido a la correlación que existe entre pacientes con biosíntesis aumentada y acumulación de colesterol con el riesgo de desarrollar cáncer, los fármacos que regulan el metabolismo celular ya que pueden servir como tratamiento frente a tumores malignos en los que una de sus principales características es la alteración del metabolismo celular por presencia de oncogenes, los fármacos antidepresivos, antifúngicos, antiinflamatorios y, por último, los fármacos reposicionados para el tratamiento de la enfermedad respiratoria causada por el virus SARS-CoV-2 (COVID-19). En esta emergencia sanitaria, la metodología del reposicionamiento de fármacos ha sido de gran utilidad, por lo que se ha considerado interesante que contara con un apartado específico en este TFG.

Este Trabajo de Fin de Grado tiene la intención de ser un recopilatorio de experiencias científicas para el área de ciencias naturales en el aula escolar de tercer ciclo de Educación Primaria, obedeciendo para ello la legislación centrada en competencias y saberes básicos que rige los sistemas educativos español y andaluz, ambos con fecha de 2022. Para cumplir este objetivo se ha usado una amplia referencia bibliográfica centrada en la importancia de enseñar aspectos de la Naturaleza de la Ciencia en el aula, así como en los aspectos de la misma que se consideran más relevantes a nivel educativo y divulgativo, puesto que es un enfoque bien asentado en la comunidad científica internacional y que permite y, de hecho, favorece una enseñanza centrada en competencias clave. A la hora de implementar los anteriormente mencionados siempre se ha tenido en cuenta la relevancia que ostentan los saberes teóricos científicos, trabajándose sin ser eclipsados por la importancia de los susodichos aspectos, y haciendo especial hincapié en la construcción del conocimiento científico por parte del propio alumnado, y siempre respetando y actuando de acuerdo a los principios de la didáctica de las ciencias naturales

El absentismo estudiantil, la dificultad para mantener la atención en clase y la falta de organización del trabajo diario fuera del aula son tres de los problemas más importantes a los que se enfrenta el profesorado universitario, sobre todo en asignaturas de los primeros cursos, consideradas por el alumnado como difíciles, como es el caso de la asignatura de Química Orgánica I (QOI) del Grado en Farmacia. En este trabajo se propone incentivar la atención de los estudiantes empleando la plataforma wooclap durante las clases teórico-prácticas de la asignatura de QOI y la mejora del trabajo individual de los alumnos fuera del aula mediante la realización de cuestionarios a través de Blackboard Collaborate ultra. Ambas propuestas pretenden mejorar la calidad del aprendizaje y fomentar la elección por parte del alumnado de la evaluación continua, contribuyendo a disminuir la tasa de suspensos y no presentados que caracteriza a la asignatura. Además, se presenta un modelo de evaluación de la utilidad de la propuesta de innovación planteada a través de un cuestionario anónimo, permitiendo la identificación de las principales fortalezas y debilidades del modelo aplicado y pudiéndose llevar a cabo ciclos de mejora., Student absenteeism, the difficulty to maintain attention in class, and poor organization of daily work outside the classroom are three of the most significant problems faced by university professors, especially in subjects of the early years that students consider difficult, such as the course Organic Chemistry I (OCI) in the Pharmacy Degree. This study proposes to enhance student attention by using the Wooclap platform during OCI theoretical-practical classes and improve individual work outside the classroom through quizzes conducted via Blackboard Collaborate Ultra. Both proposals aim to enhance the quality of student learning and encourage students to choose continuous assessment, thus reducing the failure and non-submission rates that characterize the course. Additionally, the usefulness of the proposed innovative approach will be evaluated through an anonymous questionnaire, allowing for the identification of the main strengths and weaknesses of the applied model, and facilitating improvement cycles.

In industries as diverse as automotive, aerospace, medical, energy, construction, electronics, and food, the engineering technology known as 3D printing or additive manufacturing facilitates the fabrication of rapid prototypes and the delivery of customized parts. This article explores recent advancements and emerging trends in 3D printing from a novel multidisciplinary perspective. It also provides a clear overview of the various 3D printing techniques used for producing parts and components in three dimensions. The application of these techniques in bioprinting and an up-to-date comprehensive review of their positive and negative aspects are covered, as well as the variety of materials used, with an emphasis on composites, hybrids, and smart materials. This article also provides an updated overview of 4D bioprinting technology, including biomaterial functions, bioprinting materials, and a targeted approach to various tissue engineering and regenerative medicine (TERM) applications. As a foundation for anticipated developments for TERM applications that could be useful for their successful usage in clinical settings, this article also examines present challenges and obstacles in 4D bioprinting technology. Finally, the article also outlines future regulations that will assist researchers in the manufacture of complex products and in the exploration of potential solutions to technological issues.

A series of enantiopure chiral NH2/SO palladium complexes have been synthesised with high yields by treating the corresponding tert-butylsulfinamide/sulfoxide derivatives with Pd(CH3CN)2Cl2. The enantiopure chiral ligands were prepared by stereoselective addition of tert-butyl or phenyl methylsulfinyl carbanions to different tert-butylsulfinylimines. In all cases, coordination occurs with concomitant desulfinylation. X-ray studies of the Pd complexes showed a higher trans influence of the phenylsulfinyl group in comparison to that of the tert-butylsulfinyl group. Furthermore, we have obtained and characterised two possible palladium amine/sulfonyl complexes, epimers at sulfur, resulting from N-desulfinylation and coordination of palladium with both oxygens of the prochiral sulfonyl group. The catalytic activity and enantioselectivity of the new Pd(ii) complexes of acetylated amine/tert-butyl- and phenylsulfoxides in the carboxylated cyclopropanes arylation reaction has been studied, obtaining the best results with the phenylsulfoxide ligand 25(SC,SS) that produced the final arylated product in a 93 :7 enantiomeric ratio.

A pesar de los enormes esfuerzos tanto económicos como científicos invertidos en la lucha contra el cáncer, éste sigue siendo una de las primeras causas de muerte en el mundo. Según la Organización Mundial de la Salud (OMS), esta enfermedad mata en la actualidad a ocho millones de personas al año aproximadamente. En general, las estrategias clínicas seguidas hoy en día para tratar el cáncer adolecen de limitaciones importantes. La cirugía es altamente invasiva y en muchos casos no consigue eliminar la totalidad de las células tumorales. La quimioterapia y radioterapia convencionales carecen de selectividad, tienen efectos secundarios severos, inducen resistencia a los medicamentos y causan daños en el sistema inmune a largo plazo. En este sentido, la aplicación de la nanotecnología en medicina, ha proporcionado ya resultados prometedores en el desarrollo de sistemas que pueden superar estas limitaciones, actuando tanto para el diagnóstico como para el tratamiento del cáncer. Esta dualidad en un sistema se conoce como capacidad teranóstica. En esta Tesis Doctoral se ha diseñado un prototipo de nanosistema con capacidad teranóstica para su aplicación en la lucha contra el cáncer. Este sistema está constituido por: 1. Nanopartículas magnéticas de óxido de hierro (IONPs) de un tamaño adecuado, sintetizadas utilizando el método de descomposición térmica y caracterizadas utilizando distintas técnicas de análisis (TEM, DLS, TGA, FTIR, ICP). 2. Ligando heterobifuncional que les permite a las IONPs ser solubles en medio acuoso y su posterior bioconjugación. Para su optimización se han modificado tres elementos fundamentales de su estructura: (i) la naturaleza de los grupos funcionales que actúan como elementos de anclajes a las IONPs: derivados de catecoles (ácido cafeico, dihidrocafeico y gálico) y ácido fosfónico; (ii) la longitud del espaciador derivado de polietilenglicol (PEG de peso 200 Da y 1500 Da); y (iii) la naturaleza del grupo funcional terminal del espaciador (a

first_pagesettingsOrder Article Reprints Open AccessArticle Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells by Emilio Guillén-Mancina 1,†,María del Rosario García-Lozano 2,3,†ORCID,Estefanía Burgos-Morón 1ORCID,Sarah Mazzotta 2,4ORCID,Pablo Martínez-Aguado 2,3,5,6,José Manuel Calderón-Montaño 1ORCID,José Manuel Vega-Pérez 2,Miguel López-Lázaro 1ORCID,Fernando Iglesias-Guerra 2,* andMargarita Vega-Holm 2,*ORCID 1 Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 2 Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain 3 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, 41013 Seville, Spain 4 Department of Chemistry, University of Milan, 20133 Milan, Italy 5 Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena, 41009 Seville, Spain 6 Departament of Medicine, School of Medicine, University of Seville, 41012 Seville, Spain * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(23), 17041; https://doi.org/10.3390/ijms242317041 Original submission received: 31 January 2023 / Resubmission received: 3 November 2023 / Revised: 21 November 2023 / Accepted: 28 November 2023 / Published: 1 December 2023 (This article belongs to the Special Issue Novel Molecular Pathways in Oncology) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has b

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.

Adolescence is a period during which body composition changes deeply. Selenium (Se) is an excellent antioxidant trace element related to cell growth and endocrine function. In adolescent rats, low Se supplementation affects adipocyte development differently depending on its form of administration (selenite or Se nanoparticles (SeNPs). Despite this effect being related to oxidative, insulin-signaling and autophagy processes, the whole mechanism is not elucidated. The microbiota–liver–bile salts secretion axis is related to lipid homeostasis and adipose tissue development. Therefore, the colonic microbiota and total bile salts homeostasis were explored in four experimental groups of male adolescent rats: control, low-sodium selenite supplementation, low SeNP supplementation and moderate SeNPs supplementation. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. Supplementation was received orally through water intake; low-Se rats received twice more Se than control animals and moderate-Se rats tenfold more. Supplementation with low doses of Se clearly affected anaerobic colonic microbiota profile and bile salts homeostasis. However, these effects were different depending on the Se administration form. Selenite supplementation primarily affected liver by decreasing farnesoid X receptor hepatic function, leading to the accumulation of hepatic bile salts together to increase in the ratio Firmicutes/Bacteroidetes and glucagon-like peptide-1 (GLP-1) secretion. In contrast, low SeNP levels mainly affected microbiota, moving them towards a more prominent Gram-negative profile in which the relative abundance of Akkermansia and Muribaculaceae was clearly enhanced and the Firmicutes/Bacteroidetes ratio decreased. This bacterial profile is directly related to lower adipose tissue mass. Moreover, low SeNP administration did not modify bile salts pool in serum circulation. In addition, specific gut microbiota was regulated upon administration of low l

Currently, the field of medicine is drastically advancing, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the liberation, absorption, distribution, metabolism, and excretion (LADME) properties of the derived formulations, with a consequent enhancement in the treatment efficacy, a reduction in the secondary effects, and an increase in compliance with the dosage guidelines. Additionally, the use of biocompatible scaffolds is translating into the possibility of regenerating biological tissues. Personalized medicine is also benefiting from the advantages offered by additive manufacturing. However, all these areas have in common the need to develop novel materials or composites that fulfill the requirements of each application. Therefore, the aim of this Special Issue was to identify novel materials/composites that have been developed with specific characteristics for the designed biomedical application.

Chitosan (CTS) is a polysaccharide with a wide variety of applications in the biomedical field, owing to its outstanding disinfectant properties, biocompatibility and biodegradability, but with limited mechanical properties. The proposed strategy to improve CTS-based hydrogel properties in this study is the formation of a semi-interpenetrating polymer network (semi-IPN). In this way, a photo-initiated radical click reaction was proposed to obtain a synthetic polymer, whose components were included in a CTS solution, resulting in the semi-IPN network after UV illumination. Different crosslinking degrees (CD) and CTS/polymer ratios were evaluated through rheological characterization, along with an assessment of both variables based on an experimental model design, obtaining that, for every CTS/polymer ratio, intermediate values of CD (8 %) offered the best rheological properties. In addition, chemical and microstructural characterization were carried out for selected hydrogels, obtaining consistent results according to rheological characterization, as the 1/1 CTS/polymer ratio with CD 8 % hydrogel displayed the most homogeneous pore size and distribution, consequently leading to the best rheological performance.

Despite the increasing progress achieved in the last 20 years in both the fabrication of porous dental implants and the development of new biopolymers for targeting drug therapy, there are important issues such as bone resorption, poor osseointegration, and bacterial infections that remain as critical challenges to avoid clinical failure problems. In this work, we present a novel microtechnology based on polycaprolactone microspheres that can adhere to porous titanium implant models obtained by the spacer holder technique to allow a custom biomechanical and biofunctional balance. For this purpose, a double emulsion solvent evaporation technique was successfully employed for the fabrication of the microparticles properly loaded with the antibacterial therapeutic agent, rose bengal. The resulting microspheres were infiltrated into porous titanium substrate and sintered at 60 °C for 1 h, obtaining a convenient prophylactic network. In fact, the sintered polymeric microparticles were demonstrated to be key to controlling the drug dissolution rate and favoring the early healing process as consequence of a better wettability of the porous titanium substrate to promote calcium phosphate nucleation. Thus, this joint technology proposes a suitable prophylactic tool to prevent both early-stage infection and late-stage osseointegration problems.

El progreso en la investigación de nuevas dianas terapéuticas (NDTs) es, hoy día, un objetivo clave para la industria farmacéutica, encaminada a conseguir dar otro enfoque a la terapia de enfermedades que desgraciadamente no tienen cura o en las que los efectos secundarios, causados por los tratamientos convencionales, poco específicos, son muy agresivos para los pacientes. En este sentido, cabe mencionar al receptor de Neuroquinina 1 (NK-1), que pertenece a la familia de los receptores acoplados a proteínas G (GPCRs), su ligando endógeno, es la sustancia P (SP) y se ha comprobado que guarda relación con la progresión de diferentes procesos fisiopatológicos. Esto es debido a que la SP causa diversos efectos biológicos sobre el sistema nervioso central, cardiovascular, respiratorio, gastrointestinal e inmune, participando en enfermedades sobre estos sistemas cuando sus niveles están en exceso o en desequilibrio. La SP también tiene un destacado papel en la inflamación y en el estímulo nociceptivo, en dolor crónico, neuropático y agudo, sobre todo a través de la médula espinal, está implicada en la regulación del comportamiento afectivo y en la respuesta al estrés y participa en la fisiopatología de enfermedades tales como el cáncer. Por lo tanto, como resultado de la amplia implicación de la SP en distintos procesos fisiopatológicos, los receptores NK-1 son considerados hoy en día una diana terapéutica de gran relevancia. En consecuencia, los antagonistas de los receptores NK-1 son considerados actualmente agentes terapéuticos potenciales para un gran número de patologías tales como la migraña, la artritis reumatoide, el asma, la enfermedad inflamatoria del intestino, la emesis, el cáncer, así como los trastornos del sistema nervioso central tales como la ansiedad, la depresión o la enfermedad de Parkinson.

Los virus no pueden reproducirse por sí mismos fuera del cuerpo de su huésped, son parásitos intracelulares obligados. Tienen la capacidad de generar mutaciones que cambian potencialmente su estructura, haciendo que el fármaco ya no pueda reconocerlos (originando resistencias a los tratamientos convencionales). Si a todo esto se le suma la aparición de nuevos agentes etiológicos, el cambio climático y la facilidad con la que hoy en día se puede viajar e intercambiar materia con otros países, el resultado es una rápida propagación de las enfermedades infecciosas a nivel global. Actualmente, enfermedades infecciosas provocadas por microorganismos como el Virus del Zika o el Virus del Dengue no tienen tratamientos ni vacunas eficaces, además, virus como el de la Hepatitis C o el de la Inmunodeficiencia Humana generan resistencia a los tratamientos convencionales, originando una necesidad urgente de nuevos fármacos antivirales capaces de frenar los contagios y curar la enfermedad. Una estrategia muy empleada actualmente es la búsqueda de fármacos antivirales basada en estructuras privilegiadas, que son bloques de construcción de gran utilidad para la formación de nuevos compuestos activos farmacológicamente. Se ha realizado un trabajo bibliográfico enfocado en la búsqueda de nuevos fármacos antivirales a través de estructuras privilegiadas. Para las búsquedas se han empleado dos herramientas; la base de datos SciFinder y Google Scholar. Las moléculas han sido dibujadas con el programa ChemDraw. En esta memoria se han descrito una serie de núcleos de gran interés en la búsqueda de nuevos fármacos antivirales, así como compuestos que poseen estos bloques de construcción. Se han desarrollado tanto moléculas en estudio como moléculas aprobadas por la FDA, de todas ellas se han aportado los correspondientes datos de actividad. Finalmente, se ha expuesto un ejemplo del desarrollo completo de un fármaco aprobado actualmente para el Virus de la Inmunodeficiencia Humana tipo 1.

In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics. Some alkyl- and silyl-resveratrol derivatives show bactericidal activity against Gram-positive bacteria in the same low micromolar range of traditional antibiotics, with an original mechanism of action that combines membrane permeability activity with ionophore-related activities. No cross-resistance or antagonistic effect was observed with traditional antibiotics. Synergism was observed for some specific general-use antibiotics, such as aminoglycosides and cationic antimicrobial peptide antibiotics. No hemolytic activity was observed at the active concentrations or above, although some low toxicity against an MRC-5 cell line was noted.

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

An increase in the world population and its life expectancy, as well as the ongoing concern about our physical appearance, have elevated the relevance of dental implantology in recent decades. Engineering strategies to improve the survival rate of dental implants have been widely investigated, focusing on implant material composition, geometry (usually guided to reduce stiffness), and interface surrounding tissues. Although efforts to develop different implant surface modifications are being applied in commercial dental prostheses today, the inclusion of surface coatings has gained special interest, as they can be tailored to efficiently enhance osseointegration, as well as to reduce bacterial-related infection, minimizing peri-implantitis appearance and its associated risks. The use of biomaterials to replace teeth has highlighted the need for the development of reliable analytical methods to assess the therapeutic benefits of implants. This literature review considers the state-of-the-art strategies for surface modification or coating and analytical methodologies for increasing the survival rate for teeth restoration.

Biofortification has been widely used to increase mineral nutrients in staple foods, such as wheat (Triticum aestivum). In this study, a new approach has been used by analyzing the effect of inoculation with a plant growth-promoting rhizobacterium (PGPR), namely, Bacillus aryabhattai RSO25 and the addition of 1% (v/v) of organometallic Fe-containing polymeric nanoparticles (FeNPs) alone and in combination. Previously, the minimal inhibitory concentration of FeNPs for the bacterium was determined in order not to inhibit bacterial growth. All treatments had minor effects on seed germination and plant survival. Considering the physiology of plants, several photosynthetic parameters were significantly improved in individual treatments with FeNPs or the bacterium, particularly the efficiency of the photosystem II and the electron transport rate, which is indicative of a better photosynthetic performance. However, at the end of the experiment, a significant effect on final plant growth was not observed in shoots or in roots. When using FeNPs alone, earlier spike outgrow was observed and the final number of spikes increased by 20%. Concerning biofortification, FeNPs increased the concentration of Fe in spikes by 35%. In fact, the total amount of Fe per plant base rose to 215% with regard to the control. Besides, several side effects, such as increased Ca and decreased Na and Zn in spikes, were observed. Furthermore, the treatment with only bacteria decreased Na and Fe accumulation in grains, indicating its inconvenience. On its side, the combined treatment led to intermediate Fe accumulation in spikes, since an antagonist effect between RSO25 and FeNPs was observed. For this reason, the combined treatment was discouraged. In conclusion, of the three treatments tested, FeNPs alone is recommended for achieving efficient Fe biofortification in wheat.

En la actualidad el hambre y los malos hábitos alimenticios son un problema reconocido por la organización mundial de la salud (OMS). A pesar de todos los esfuerzos propuestos para solventar este problema, la OMS ha admitido que no se alcanzará el objetivo de hambre cero para 2030. Por todo esto y para aportar soluciones imaginativas a este problema, nos propusimos emplear nanopartículas poliméricas cargadas con zinc, junto con la bacteria Pantoea agglomerans, promotora de crecimiento de plantas (PGPR), para mejorar el valor nutricional de plantas como el trigo (Triticum aestivum), mediante bioforitficación. Las plantas de trigo fueron tratadas, tras su previa germinación, y se recogieron medidas de concentración de metales usando técnicas analíticas. Los resultados mostraron que los parámetros físicos y fisiológicos no se vieron afectados y se produjo una acumulación notoria del Zn en la parte aérea.

The use of porous titanium samples fabricated by space-holder powder metallurgy with bioactive coatings has already been reported to prevent resorption of the bone surrounding the implant and improve osseointegration, respectively. However, the presence of pores as well as the poor adherence and the brittle behavior inherent to glassy coatings affect the service behavior of implants fabricated from these samples. Therefore, they need to be optimized. In this work, 50 vol.% of porosity titanium substrates were manufactured with different pore range size (100–200 and 355–500 µm) spacer particles and coated with a bilayer of bioactive glasses (45S5/1393). The effect of the pores on the tribomechanical properties and infiltration of the bioactive glass 1393 along with the bioactivity of the bioactive glass 45S5 were evaluated by instrumented micro-indentation and scratch tests and the formation of hydroxyapatite in simulated body fluid. The results obtained were very promising as potential implants for the replacement of small tumors in cortical bone tissues, mainly due to the smaller pores that present an improved biomechanical and biofunctional balance.

Complexes {Ag[NHCMes,R]}n (R = H, 2a; Me, 2b and 2b’; iPr, 2c; iBu, 2d), were prepared by treatment of imidazolium precursor compounds [ImMes,R] (2-(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1a, (S)-2-alkyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1b–d, and (R)-2-methyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1b’, with Ag2O under appropriate conditions. They were characterised by analytical, spectroscopic (IR, 1H, and 13C NMR and polarimetry), and X-ray methods (2a). In the solid state, 2a is a one-dimensional coordination polymer, in which the silver(I) cation is bonded to the carbene ligand and to the carboxylate group of a symmetry-related Ag[NHCMes,H] moiety. The coordination environment of the silver centre is well described by the DFT study of the dimeric model {Ag[NHCMes,H]}2. The antimicrobial properties of these complexes were evaluated versus Gram-negative bacteria E. coli and P. aeruginosa. From the observed MIC and MBC values (minimal inhibitory concentration and minimal bactericidal concentration, respectively), complex 2b’ showed the best antimicrobial properties (eutomer), which were significantly better than those of its enantiomeric derivative 2b (distomer). Additionally, analysis of MIC and MBC values of 2a–d reveal a clear structure–antimicrobial effect relationship. Antimicrobial activity decreases when the steric properties of the R alkyl group in {Ag[NHCMes,R]}n increase

The preparation of new and functional nanostructures has received more attention in the scientific community in the past decade due to their wide application versatility. Among these nanostructures, micelles appear to be one of the most interesting supramolecular organizations for biomedical applications because of their ease of synthesis and reproducibility and their biocompatibility since they present an organization similar to the cell membrane. In this work, we developed micellar nanocarrier systems from surfactant molecules derived from oleic acid and tetraethylene glycol that were able to encapsulate and in vitro release the drug dexamethasone. In addition, the designed micelle precursors were able to functionalize metallic NPs, such as gold NPs and iron oxide NPs, resulting in monodispersed hybrid nanomaterials with high stability in aqueous media. Therefore, a new triazole-derived micelle precursor was developed as a versatile encapsulation system, opening the way for the preparation of new micellar nanocarrier platforms for drug delivery, magnetic resonance imaging, or computed tomography contrast agents for therapeutic and diagnostic applications.

Articular cartilage (AC) has a low ability for endogenous repair, and current treatments are not completely efficient in generating strong and healthy repair tissue. As a result, there is a great deal of interest in cartilage repair and recovery of joint function due to the aging population and the increasing frequency of cartilage degradation and osteoarthritis. Thus, the search for better and more efficient strategies to regenerate articular cartilage to repair the joints in patients with osteoarthritis is a critical motivation. Biomaterials, which are made of natural or synthetic polymers, or a mixture of the two, serve as a scaffold for tissue regeneration. Cartilage tissue engineering (TE) seeks to develop a treatment that can effectively repair damaged AC caused by trauma or disease. In cartilage TE, scaffolds that provide a 3D environment like native articular cartilage for cells to proliferate, attach, and hence ensure tissue regeneration success are needed. For optimal cell activities, which is associated with proper cartilage regeneration, these scaffolds must meet all necessary criteria, including adequate architectural, physicochemical, and biological properties. This study briefly explores the evolution of scaffolds constructed of synthetic polymers and hybrid materials for cartilage tissue engineering. Initially, general information on AC is presented, as well as a review of medical approaches to treating cartilage injuries or disease. Following that, the requirements for scaffolds in tissue regeneration, specific materials, and techniques for producing them are briefly discussed.

The spread of antibiotic resistance among human and animal pathogens is one of the more significant public health concerns. Moreover, the restrictions on the use of particular antibiotics can limit the options for the treatment of infections in veterinary clinical practice. In this context, searching for alternative antimicrobial substances is crucial nowadays. In this study, 4,4′-dihydroxy-azobenzene (DHAB) was tested for its potential in vitro as an antimicrobial agent against two relevant human and animal pathogens, namely Staphylococcus aureus and Staphylococcus pseudintermedius. The values of minimal inhibitory concentration (MIC) were 64 and 32 mg/L respectively, and they comparable to other azo compounds of probed antimicrobial activity. In addition, the minimal bactericidal concentrations (MCB) were 256 and 64 mg/L. The mechanism by which DHAB produces toxicity in staphylococci has been investigated. DHAB caused membrane damage as revealed by the increase in thiobarbituric acid reactive substances (TBARS) such as malondialdehyde. Furthermore, differential induction of the enzymes peroxidases and superoxide dismutase in S. aureus and S. pseudintermedius suggested their prevalent role in ROS-scavenging due to the oxidative burst induced by this compound in either species. In addition, this substance was able to inhibit the formation of biofilms by both bacteria as observed by colorimetric tests and scanning electron microscopy. In order to assess the relevance of DHAB against clinical strains of MRSA, 10 clinical isolates resistant to either methicillin or daptomycin were assayed; 80% of them gave values of CMI and CMB similar to those of the control S. aureus strain. Finally, cutaneous plasters containing a composite formed by an agar base supplemented with DHAB were designed. These plasters were able to inhibit in vitro the growth of S. aureus and S. pseudintermedius, particularly the later, and this suggests that this substance could be a promising candidat

The antiproliferative effects played by benzothiazoles in different cancers have aroused the interest for these molecules as promising antitumor agents. In this work, a library of phenylacetamide derivatives containing the benzothiazole nucleus was synthesized and compounds were tested for their antiproliferative activity in paraganglioma and pancreatic cancer cell lines. The novel synthesized compounds induced a marked viability reduction at low micromolar concentrations both in paraganglioma and pancreatic cancer cells. Derivative 4l showed a greater antiproliferative effect and higher selectivity index against cancer cells, as compared to other compounds. Notably, combinations of derivative 4l with gemcitabine at low concentrations induced enhanced and synergistic effects on pancreatic cancer cell viability, thus supporting the relevance of compound 4l in the perspective of clinical translation. A target prediction analysis was also carried out on 4l by using multiple computational tools, identifying cannabinoid receptors and sentrin-specific proteases as putative targets contributing to the observed antiproliferative activity.