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Thyme oil (THO) possesses excellent antibacterial and antioxidant properties which are suitable for skin inflammatory disorders such as acne vulgaris. However, THO is insoluble in water and its components are highly volatile. Therefore, these drawbacks may be overcome by its encapsulation in biodegradable PLGA nanoparticles (THO-NPs) that had been functionalized using several strategies. Moreover, cell viability was studied in HaCat cells, confirming their safety. In order to assess therapeutic efficacy against acne, bacterial reduction capacity and antioxidant properties were assessed. Moreover, the anti-inflammatory and wound-healing abilities of THO-NPs were also confirmed. Additionally, ex vivo antioxidant assessment was carried out using pig skin, demonstrating the suitable antioxidant properties of THO-NPs. Moreover, THO and THO-NPs were dispersed in a gelling system, and stability, rheological properties, and extensibility were assessed. Finally, the biomechanical properties of THO-hydrogel and THO-NP-hydrogel were studied in human volunteers, confirming the suitable activity for the treatment of acne. As a conclusion, THO has been encapsulated into PLGA NPs, and in vitro, ex vivo, and in vivo assessments had been carried out, demonstrating excellent properties for the treatment of inflammatory skin disorders.

Abstract Background Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed. Results Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around − 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage. Conclusion TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment. Graphical Abstract

Abstract Increasing life expectancy has led to an aging population, which has consequently increased the prevalence of dementia. Alzheimer's disease (AD), the most common form of dementia worldwide, is estimated to make up 50–80% of all cases. AD cases are expected to reach 131 million by 2050, and this increasing prevalence will critically burden economies and health systems in the next decades. There is currently no treatment that can stop or reverse disease progression. In addition, the late diagnosis of AD constitutes a major obstacle to effective disease management. Therefore, improved diagnostic tools and new treatments for AD are urgently needed. In this review, we investigate and describe both well-established and recently discovered AD biomarkers that could potentially be used to detect AD at early stages and allow the monitoring of disease progression. Proteins such as NfL, MMPs, p-tau217, YKL-40, SNAP-25, VCAM-1, and Ng / BACE are some of the most promising biomarkers because of their successful use as diagnostic tools. In addition, we explore the most recent molecular strategies for an AD therapeutic approach and nanomedicine-based technologies, used to both target drugs to the brain and serve as devices for tracking disease progression diagnostic biomarkers. State-of-the-art nanoparticles, such as polymeric, lipid, and metal-based, are being widely investigated for their potential to improve the effectiveness of both conventional drugs and novel compounds for treating AD. The most recent studies on these nanodevices are deeply explained and discussed in this review. Graphic Abstract

Abstract Infectious diseases kill over 17 million people a year, among which bacterial infections stand out. From all the bacterial infections, tuberculosis, diarrhoea, meningitis, pneumonia, sexual transmission diseases and nosocomial infections are the most severe bacterial infections, which affect millions of people worldwide. Moreover, the indiscriminate use of antibiotic drugs in the last decades has triggered an increasing multiple resistance towards these drugs, which represent a serious global socioeconomic and public health risk. It is estimated that 33,000 and 35,000 people die yearly in Europe and the United States, respectively, as a direct result of antimicrobial resistance. For all these reasons, there is an emerging need to find novel alternatives to overcome these issues and reduced the morbidity and mortality associated to bacterial infectious diseases. In that sense, nanotechnological approaches, especially smart polymeric nanoparticles, has wrought a revolution in this field, providing an innovative therapeutic alternative able to improve the limitations encountered in available treatments and capable to be effective by theirselves. In this review, we examine the current status of most dangerous human infections, together with an in-depth discussion of the role of nanomedicine to overcome the current disadvantages, and specifically the most recent and innovative studies involving polymeric nanoparticles against most common bacterial infections of the human body.

Considerando que el poder blando se desarrolla a largo plazo y que la cultura y los eventos deportivos forman parte de su estrategia, este artículo presenta el múltiple análisis de casos de tres ciudades: Madrid, Río de Janeiro y Doha, a partir del inicio del siglo XXI y antes de la pandemia de 2020. El objetivo es estudiar las diferentes acciones propuestas por las ciudades elegidas que pueden impactar la diplomacia pública y el poder blando, enfocando en las acciones culturales y deportivas, turismo y canales y herramientas de comunicación locales. A través del análisis comparativo de múltiples casos y la recopilación de datos, se pretende contribuir al debate académico sobre el papel de las ciudades en la geopolítica y responder a la pregunta de investigación planteada sobre la relevancia de las acciones urbanas para la imagen y reputación de la ciudad en el escenario internacional.

Tomando como punto de referencia el marco Europeo de Educación Superior, el artículo que a continuación se presenta tiene como objetivo principal conocer desde la percepción del alumnado -aún en proceso de formación- del Grado de Maestro en Educación Primaria, cuáles son las variables que han influido en la adquisición de las competencias específicas que debe adquirir para el desarrollo de su perfil profesional. Para llevar a cabo este trabajo, se ha empleado una metodología no experimental de naturaleza descriptiva, aplicando para la recogida de datos de la muestra (n=109) un cuestionario cerrado ad-hoc. A partir del análisis de las respuestas, se revelan cuáles son las variables más influyentes en la adquisición de las competencias específicas y las que los alumnos universitarios consideran menos desarrolladas para alcanzar dichas competencias. Entre los resultados a destacar y según el alumnado, el tipo de evaluación es la variable que menos ha influido en la adquisición de las competencias específicas del título. Con los datos que se muestran a continuación, se pretende realizar un acercamiento a los procesos educativos que tienen lugar en las aulas universitarias desde las percepciones de los alumnos y, sobre todo, analizar su desarrollo competencial como futuros docentes que influirá, de manera inevitable, en su práctica en las aulas escolares.

Introduction: The metabolic syndrome presents obesity among its manifestations, which is related to the development of cancer. However, we had not found any cases of malignant neoplasms in animals with metabolic syndrome in four years. Materials and Methods: The experimental biomodel was achieved by the application of a 35% sucrose solution for 20 weeks to 50 weaned male Wistar rats. The diagnosis of nephroblastoma was made by necropsy with morphological observation of the renal lesion. Results: It was detected palpable abdominal mass, after the metabolic syndrome had been confirmed. On macroscopic inspection, a tumor was observed in the lower pole of the right kidney, grayish-brown, hemorrhaging and with cystic changes. Histologically, alterations of a mixed nephroblastoma were observed with blastema, mesenchymal and epithelial components. Conclusions: It is described for the first time, in pathological study the presence of a nephroblastoma case in a rat with experimental metabolic syndrome.

DNA:RNA hybrids constitute a well-known source of recombinogenic DNA damage. The current literature is in agreement with DNA:RNA hybrids being produced co-transcriptionally by the invasion of the nascent RNA molecule produced in cis with its DNA template. However, it has also been suggested that recombinogenic DNA:RNA hybrids could be facilitated by the invasion of RNA molecules produced in trans in a Rad51-mediated reaction. Here, we tested the possibility that such DNA:RNA hybrids constitute a source of recombinogenic DNA damage taking advantage of Rad51-independent single-strand annealing (SSA) assays in the yeast Saccharomyces cerevisiae. For this, we used new constructs designed to induce expression of mRNA transcripts in trans with respect to the SSA system. We show that unscheduled and recombinogenic DNA:RNA hybrids that trigger the SSA event are formed in cis during transcription and in a Rad51-independent manner. We found no evidence that such hybrids form in trans and in a Rad51-dependent manner.

Abstract Background Memantine, drug approved for moderate to severe Alzheimer’s disease, has not shown to be fully effective. In order to solve this issue, polylactic-co-glycolic (PLGA) nanoparticles could be a suitable solution to increase drug’s action on the target site as well as decrease adverse effects. For these reason, Memantine was loaded in biodegradable PLGA nanoparticles, produced by double emulsion method and surface-coated with polyethylene glycol. MEM–PEG–PLGA nanoparticles (NPs) were aimed to target the blood–brain barrier (BBB) upon oral administration for the treatment of Alzheimer’s disease. Results The production parameters were optimized by design of experiments. MEM–PEG–PLGA NPs showed a mean particle size below 200 nm (152.6 ± 0.5 nm), monomodal size distribution (polydispersity index, PI

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug carriers for pathologies affecting the posterior ocular segment. Eye anatomy and the most relevant diseases affecting the posterior segment will be summarized. Moreover, preparation methods and different types and subtypes of lipid nanoparticles will also be reviewed. Lipid nanoparticles used as carriers to deliver drugs to the posterior eye segment as well as their administration routes, pharmaceutical forms and ocular distribution will be discussed emphasizing the different targeting strategies most recently employed for ocular drug delivery.

Metal nanoparticles have been extensively investigated for different types of pharmaceutical applications. However, their use has raised some concerns about their toxicity involving the increase of reactive oxygen species causing cellular apoptosis. Therefore, in this review we summarize the most relevant toxicity mechanisms of gold, silver, copper and copper oxide nanoparticles as well as production methods of metal nanoparticles. Parameters involved in their toxicity such as size, surface charge and concentration are also highlighted. Moreover, a critical revision of the literature about the strategies used to reduce the toxicity of this type of nanoparticles is carried out throughout the review. Additionally, surface modifications using different coating strategies, nanoparticles targeting and morphology modifications are deeply explained.

The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.

Benzodiazepines (BZDs) and Z-drugs are compounds widely prescribed in medical practice due to their anxiolytic, hypnotic, and muscle relaxant properties. Yet, their chronic use is associated with cases of abuse, dependence, and relapse in many patients. Furthermore, elderly people are susceptible to alterations in pharmacodynamics, pharmacokinetics as well as to drug interaction due to polypharmacy. These situations increase the risk for the appearance of cognitive affectations and the development of pathologies like Alzheimer's disease (AD). In the present work, there is a summary of some clinical studies that have evaluated the effect of BZDs and Z-drugs in the adult population with and without AD, focusing on the relationship between their use and the loss of cognitive function. Additionally, there is an assessment of preclinical studies focused on finding molecular proof on the pathways by which these drugs could be involved in AD pathogenesis. Moreover, available data (1990–2019) on BZD and Z-drug use among elderly patients, with and without AD, was compiled in this work. Finally, the relationship between the use of BZD and Z-drugs for the treatment of insomnia and the appearance of AD biomarkers was analyzed. Results pointed to a vicious circle that would worsen the condition of patients over time. Likewise, it put into relevance the need for close monitoring of those patients using BZDs that also suffer from AD. Consequently, future studies should focus on optimizing strategies for insomnia treatment in the elderly by using other substances like melatonin agonists, which is described to have a much more significant safety profile.

Nowadays, Alzheimer’s disease (AD) is a severe sociological and clinical problem. Since it was first described, there has been a constant increase in its incidence and, for now, there are no effective treatments since current approved medications have only shown short-term symptomatic benefits. Therefore, it is imperative to increase efforts in the search for molecules and non-pharmacological strategies that are capable of slowing or stopping the progress of the disease and, ideally, to reverse it. The amyloid cascade hypothesis based on the fundamental role of amyloid has been the central hypothesis in the last 30 years. However, since amyloid-directed treatments have shown no relevant beneficial results other theories have been postulated to explain the origin of the pathology. The brain is a highly metabolically active energy-consuming tissue in the human body. It has an almost complete dependence on the metabolism of glucose and uses most of its energy for synaptic transmission. Thus, alterations on the utilization or availability of glucose may be cause for the appearance of neurodegenerative pathologies like AD. In this review article, the hypothesis known as Type 3 Diabetes (T3D) will be evaluated by summarizing some of the data that has been reported in recent years. According to published research, the adherence over time to low saturated fatty acids diets in the context of the Mediterranean diet would reduce the inflammatory levels in brain, with a decrease in the pro-inflammatory glial activation and mitochondrial oxidative stress. In this situation, the insulin receptor pathway would be able to fine tune the mitochondrial biogenesis in neuronal cells, regulation the adenosine triphosphate/adenosine diphosphate intracellular balance, and becoming a key factor involved in the preservation of the synaptic connexions and neuronal plasticity. In addition, new targets and strategies for the treatment of AD will be considered in this review for their potential as new pharmacological or non-pharmacological approaches.

El proyecto europeo H2020 RISEWISE (Rise Women with Disabilities in Social Engagement) trata de analizar las barreras que afronta el colectivo de mujeres con discapacidad en distintos entornos de la vida cotidiana, e identificar buenas prácticas que puedan exportarse de unos lugares a otros. El proyecto es el primer estudio relevante a escala global que se realiza en Europa en este colectivo. Este se aborda mediante la movilidad de investigadores en varias ciudades, de distintas disciplinas, tratando diferentes ámbitos de la vida cotidiana, para luego compartir las observaciones y analizarlas en común. En este artículo se presenta la experiencia de dos investigadoras del proyecto durante su estancia en la ciudad de Génova (Italia) durante el mes de julio de 2018. La mayor parte del trabajo se realizó en coordinación con Asociación Italiana de Esclerosis Múltiple (AISM).

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable “light-to-heat” conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model.

Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions with a customized lipid corneal membrane model were studied. Ex vivo permeation through ocular tissues and in vivo anti-inflammatory efficacy have also been studied.

Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.

The measurement of sustainable development presents considerable difficulties that have limited the capacity in analyzing environmental questions in local systems. The intention of this study is to make a contribution in the measurement of sustainable development at the local level. In order to undertake this study, an Index of Sustainable Local Development (IDSL) was created drawing on the theory of fuzzy logic. This index permits us to analyze and compare sustainable development in three dimensions of the environmental system at the local level: social, environmental and economic. Empirical evidence is presented from the results of the application of the Index in 11 municipalities in the State of Jalisco, Mexico. These municipalities include the three largest metropolitan areas of the region.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia together with disturbances in the metabolism of carbohydrates, proteins and fat, which in general results from an insulin availability and need imbalance. In a great number of patients, marketed anti-glycemic agents have shown poor effectiveness in maintaining a long-term glycemic control, thus being associated with severe adverse effects and leading to an emerging interest in natural compounds (e.g., essential oils and other secondary plant metabolites, namely, flavonoid-rich compounds) as a novel approach for prevention, management and/or treatment of either non-insulin-dependent diabetes mellitus (T2DM, type 2 DM) and/or Metabolic Syndrome (MS). In this review, some of these promising glucose-lowering agents will be comprehensively discussed.

Progress in the field of biocompatible SERS nanoparticles has promising prospects for biomedical applications. In this work, we have developed a biocompatible Raman probe by combining anisotropic silver nanoparticles with the dye rhodamine 6G followed by subsequent coating with bovine serum albumin. This nanosystem presents strong SERS capabilities in the near infrared (NIR) with a very high (2.7 × 107) analytical enhancement factor. Theoretical calculations reveal the effects of the electromagnetic and chemical mechanisms in the observed SERS effect for this nanosystem. Finite element method (FEM) calculations showed a considerable near field enhancement in NIR. Using density functional quantum chemical calculations, the chemical enhancement mechanism of rhodamine 6G by interaction with the nanoparticles was probed, allowing us to calculate spectra that closely reproduce the experimental results. The nanosystem was tested in cell culture experiments, showing cell internalization and also proving to be completely biocompatible, as no cell death was observed. Using a NIR laser, SERS signals could be detected even from inside cells, proving the applicability of this nanosystem as a biocompatible SERS probe.

O presente artigo investiga as estratégias criativas da publicidade centradas em conceitos da retórica clássica (precisamente, paráfrase e memória), bem como em teorias mais recentes da linguagem (hipertexto). Escrito por pesquisadores da Espanha e do Brasil, que reúnem interesses comuns no estudo desse objeto, o texto traz, em suas análises, anúncios de ambos os países, demonstrando como os publicitários acionam, num primeiro momento, o tesouro cultural de sua comunidade durante o processo criativo, para, em seguida, ampliá-lo com o conteúdo das peças que elaboram a partir de referências já conhecidas do público.

Este articulo se enmarca dentro de la línea de investigación que el gruposocmedia (www.gruposocmedia.es) está desarrollando desde hace varios años sobre Nativos Digitales y su relación con las Nuevas Tecnologías. Se trata de investigar cómo construyen realidad Social los jóvenes a través de los servicios y contenidos digitales abiertos. En este artículo se expone la implantación de los conocimientos extraídos de las investigaciones del grupo a las clases prácticas dentro de la universidad durante el curso académico 2009-2010. Se intenta transferir los conocimientos adquiridos en investigación a las clases de la Facultad de Ciencias de la Información de la Universidad Complutense .AbstractThis article is part of the research that gruposocmedia (www.gruposocmedia.es) is developed over several years on Digital Natives and their relationship to new technologies. The research focuses on how young people construct social reality through services and open digital content. This article describes the implementation of knowledge from the group research to practical classes in the university during the academic year 2009-2010. Attempting to transfer the knowledge acquired in research classes at the School of Information Sciences at the Complutense University.

Abstract The development of biocompatible hybrid nanosystems for advanced functional applications presents significant challenges to the research community. Key obstacles include the poor solubility of these nanosystems in water and the difficulty of precisely controlling their nanostructure dimensions and composition. A promising approach to overcoming these challenges is the self-assembly of surfactant-based building blocks into well-ordered hybrid nanostructures. In this study, we explore the relationship between structure and self-assembly in novel low molecular weight amphiphilic molecules to produce stable and biocompatible hybrid nanostructures. We investigated the self-assembly behavior of two families of amphiphiles derived from alkenyl lipids with one or two double bonds, leading to distinct hybrid supramolecular structures facilitated by the incorporation of hydrophobic iron oxide nanoparticles (IONPs) as templates. The presence of double bonds in the lipid tail and the morphology of the amphiphile influence the arrangement on the hydrophobic NPs. Amphiphiles with a single double bond in the lipid tail form highly water-soluble, well-ordered micellar-like structures on the IONP surfaces, while those with two double bonds create disordered lipid nanoparticles. Furthermore, these amphiphilic molecules can self-organize into higher-order hybrid supramolecular structures, such as vesicles, with potential applications in magnetic resonance imaging (MRI).

Cancer affects 9 million people every year constituting one of the main causes of death. However, current treatments are frequently associated with adverse effects and can exhibit limitations in therapeutic efficacy. Therefore, the combination of the pharmaceutical properties of the natural flavone Apigenin (APG) and the neurohormone Melatonin (MEL), could represent a key finding for tumoral processes. However, both possess low aqueous solubility and photosensitivity. To overcome these limitations, APG and MEL are encapsulated into nanostructured lipid carriers (NLC) based on rosehip oil, to increase their bioavailability and efficacy. Optimization, physicochemical characterization, biopharmaceutical behaviour, and in vitro studies were assessed and compared to individually-loaded NLC. Optimized APG-MEL-NLC owned suitable physicochemical properties with an average size below 200 nm, low polydispersity index, negative charge and high encapsulation efficiency. Biopharmaceutical studies demonstrated that both compounds were released from NLC in a prolonged and sustained manner, following a biphasic behaviour with an initial fast release followed by a slow phase. Cytotoxicity studies showed selective cytotoxicity in tumoral cell lines, especially in the leukaemia cells, where co-encapsulation resulted in an additive pharmacological effect against individually loaded NLC. This novel and natural treatment could open a new therapeutical window in cancer treatment.