This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.
Extracellular Vesicles , MicroRNAs , Retinal Degeneration , Humans , Retina/metabolism , Retinal Degeneration/metabolism , Extracellular Vesicles/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Oxidative Stress
Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying a diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs in hyperglycemia or inflammation. In fact, sEVs release has been associated with the promotion of physio-pathological processes. Among the sEVs cargo, microRNAs play an essential role in cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim of this study is to understand the specific role of sEVs containing miR-205-5p under high glucose conditions. ARPE-19 cells were cultured with high glucose (HG) for 5 days. sEVs were isolated and characterized. sEVs from ARPE-19 were used for angiogenesis and cell proliferation. HG increased sEVs release but downregulated miR-205-5p cargo expression compared to the control. sEVs from HG-treated ARPE-19 cells promoted tube formation and migration processes. In contrast, miR-205-5p overexpression (by mimic transfection) decreased angiogenesis and cell migration. Our results demonstrate how ARPE-19 cells respond to HG challenge by increasing sEVs with weak miR-205-5p cargo. The absence of this miRNA in sEVs is enough to promote angiogenesis. In contrast, restoring sEVs-miR-205-5p levels decreased it. These findings open new possibilities in sEVs-based therapies containing miR-205-5p against angiogenesis.
Angiogenesis , MicroRNAs , Cell Communication , Cell Movement/genetics , MicroRNAs/genetics , Glucose
This case report presents a real example of a study which introduces the use of reconfigurable platforms in the teaching of electronics engineering to establish a bridge between theory and practice. This gap is one of the major concerns of the electronics engineering students. Different strategies, such as simulation tools or breadboard implementations, have been followed so far to make it easier for students to practice what they study in lectures. However, many students still claim to have problems when they face real practical implementations. The use of reconfigurable platforms as a teaching tool is proposed to provide the students the possibility of fast experimentation, reducing both development time and the learning curve. In addition, reconfigurable platforms available on the market make this methodology suitable to be applied throughout the different courses of their curricula. The feasibility of this approach is demonstrated in a course at the M.Eng. level, where the objective is the study, design and development of electronic sensor nodes. We firmly consider, based on the students' results and reflections collected during the course, that this methodology helps students to address the theoretical framework from a practical viewpoint, as well as to acquire some of the fundamental skills for their professional careers, such as the usage of communication protocols and embedded systems programming, in a more intuitive way when compared to traditional teaching methodologies.
Cocaine can induce severe neurobehavioral changes, among others, the ones involved in learning and memory processes. It is known that during drug consumption, cocaine-associated memory and learning processes take place. However, much less is known about the effects of this drug upon the mechanisms involved in forgetting.The present report focuses on the mechanisms by which cocaine affects memory consolidation of experiences acquired prior to drug administration. We also study the involvement of hippocampus in these processes, with special interest on the role of Nuclear factor kappa B (NF-κB), N-methyl-D-aspartate glutamate receptor 2B (GluN2B), and their relationship with other proteins, such as cyclic AMP response element binding protein (CREB). For this purpose, we developed a rat experimental model of chronic cocaine administration in which spatial memory and the expression or activity of several proteins in the hippocampus were assessed after 36 days of drug administration. We report an impairment in memory acquisition of experiences gathered prior to cocaine administration, associated to an increase in GluN2B expression in the hippocampus. We also demonstrate a decrease in NF-κB activity, as well as in the expression of the active form of CREB, confirming the role of these transcription factors in the cocaine-induced memory impairment.
Behavior, Animal/drug effects , Cocaine/toxicity , Gene Expression Regulation/drug effects , Memory Disorders/pathology , NF-kappa B/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Anesthetics, Local/administration & dosage , Anesthetics, Local/toxicity , Animals , Cocaine/administration & dosage , Male , Memory Consolidation/drug effects , Memory Consolidation/physiology , Memory Disorders/chemically induced , Memory Disorders/genetics , Memory Disorders/metabolism , NF-kappa B/genetics , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/genetics , Spatial Memory/drug effects , Spatial Memory/physiology
Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in the biochemical composition of human milk, especially in terms of oxidative status. Given that newborns are subject to a significant increase in total ROS burden in their transition to neonatal life and that their antioxidant defense system is not completely developed, the aim of this study was to evaluate antioxidant defense (glutathione peroxidase (GPx), reduced glutathione (GSH), total polyphenol content (TPP), and total antioxidant capacity (TAC)) in milk samples from mothers suffering from mastitis and controls. We also measured the oxidative damage to lipids (malondyaldehyde (MDA)) and proteins (carbonyl group content (CGC)) in these samples. Finally, we tested whether dietary supplementation with cranberries (a product rich in antioxidants) in these breastfeeding mothers during 21 days could improve the oxidative status of milk. GPx activity, TPP, and TAC were increased in milk samples from mastitis-affected women, providing a protective mechanism to the newborn drinking mastitis milk. MDA concentrations were diminished in the mastitis group, confirming this proposal. Some oxidative damage might occur in the mammary gland since the CGC was increased in mastitis milk. Cranberries supplementation seems to strengthen the antioxidant system, further improving the antioxidative state of milk.
This work demonstrates a cost-effective manufacturing method of flexible and fully printed microheaters, using carbon nanotubes (CNTs) as the heating element. Two different structures with different number of CNT layers have been characterized in detail. The benchmarking has been carried out in terms of maximum operating temperature, as well as nominal resistance and input power for different applied voltages. Their performances have been compared with previous reports for similar devices, fabricated with other technologies. The results have shown that the heaters presented can achieve high temperatures in a small area at lower voltages and lower input power. In particular, the fully printed heaters fabricated on a flexible substrate covering an area of 3.2 mm2 and operating at 9.5 V exhibit a maximum temperature point above 70 °C with a power consumption below 200 mW. Therefore, we have demonstrated that this technology paves the way for a cost-effective large-scale fabrication of flexible microheaters aimed to be integrated in flexible sensors.
Herein, we present, for the first time, a 2D-MOF based on copper and 4-hydroxypyrimidine-5-carbonitrile as the linker. Each MOF layer is perfectly flat and neutral, as is the case for graphene. High pressure X-ray diffraction measurements reveal that this layered structure can be modulated between 3.01 to 2.78 Å interlayer separation, with an evident piezochromism and varying conductive properties. An analysis of the band structure indicates that this material is conductive along different directions depending on the application of pressure or H doping. These results pave the way for the development of novel layered materials with tunable and efficient properties for pressure-based sensors.
The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.
Nowadays, the study of kinanthropometric parameters is an important tool for both early talent selection and for evaluating the efficacy of a training program. This study aimed to determine the anthropometric characteristics, body composition indicators and somatotype components of individual (athletics, swimming and triathlon), collective (handball and volleyball) and fight (karate and taekwondo) sportsmen and sportswomen from the Valencian Sports Technification Centre. This study involved a total of 62 men and 56 women, they were divided in three subgroups, including individual (athletics, swimming and triathlon), collective (handball and volleyball) and fight (karate and taekwondo) sports. The assessment was carried out according to the one established by the International Society for Advancement of Kinanthropometry (ISAK). For men, the highest value of femur breath, ectomorphy and medial calf and front thigh skinfolds are obtained for triathletes, athletics, volleyball and karate, respectively. The highest values of triceps, biceps and abdominal skinfolds, relaxed arm girth, endomorphy and body fat percentage are shown for taekwondo, while the other highest values are obtained with handball. For women, the highest value of ectomorphy is obtained for athletics. The identified kinanthropometric parameters are useful when comparing between sports and sports subgroups for the selection of subjects and to help in their performance assessment.
En la actualidad, el estudio de los parámetros cineantropométricos es una herramienta importante tanto para la selección temprana del talento como para evaluar la eficacia de un programa de capacitación. Este estudio tuvo como objetivo determinar las características antropométricas, los indicadores de composición corporal y los componentes somatotípicos de deportistas y deportistas individuales (atletismo, natación y triatlón), colectivos (balonmano y voleibol) y de lucha (karate y taekwondo) del Centro Valenciano de Tecnificación Deportiva. Este estudio involucró a un total de 62 hombres y 56 mujeres, se dividieron en tres subgrupos, que incluyen deportes individuales (atletismo, natación y triatlón), colectivos (balonmano y voleibol) y peleas (karate y taekwondo). La evaluación se realizó de acuerdo con la establecida por la Sociedad Internacional para el Avance de la Cineantropometría (ISAK). Para los hombres, el valor más alto de la respiración del fémur, la ectomorfia y los pliegues de la pantorrilla y el muslo frontal se obtienen para triatletas, atletismo, voleibol y karate, respectivamente. Los valores más altos de tríceps, bíceps y pliegues abdominales, circunferencia relajada del brazo, endomorfia y porcentaje de grasa corporal se muestran para el taekwondo, mientras que los otros valores más altos se obtienen con balonmano. Para las mujeres, el mayor valor de la ectomorfía se obtiene para el atletismo. Los parámetros cineantropométricos identificados son útiles cuando se comparan entre deportes y subgrupos deportivos para la selección de sujetos y para ayudar en su evaluación del rendimiento.
Humans , Male , Female , Sports , Anthropometry , Somatotypes , Spain , Body Composition , Kinanthropometry
In this paper, we present a comparative study of a cost-effective method for the mass fabrication of electrodes to be used in thin-film flexible supercapacitors. This technique is based on the laser-synthesis of graphene-based nanomaterials, specifically, laser-induced graphene and reduced graphene oxide. The synthesis of these materials was performed using two different lasers: a CO2 laser with an infrared wavelength of λ = 10.6 µm and a UV laser (λ = 405 nm). After the optimization of the parameters of both lasers for this purpose, the performance of these materials as bare electrodes for flexible supercapacitors was studied in a comparative way. The experiments showed that the electrodes synthetized with the low-cost UV laser compete well in terms of specific capacitance with those obtained with the CO2 laser, while the best performance is provided by the rGO electrodes fabricated with the CO2 laser. It has also been demonstrated that the degree of reduction achieved with the UV laser for the rGO patterns was not enough to provide a good interaction electrode-electrolyte. Finally, we proved that the specific capacitance achieved with the presented supercapacitors can be improved by modifying the in-planar structure, without compromising their performance, which, together with their compatibility with doping-techniques and surface treatments processes, shows the potential of this technology for the fabrication of future high-performance and inexpensive flexible supercapacitors.
A portable reconfigurable platform for hemoglobin determination based on inner filter quenching of room-temperature phosphorescent carbon dots (CDs) in the presence of H2O2 is described. The electronic setup consists of a light-emitting diode (LED) as the carbon dot optical exciter and a photodiode as a light-to-current converter integrated in the same instrument. The reconfigurable feature provides adaptability to use the platform as an analytical probe for CDs coming from different batches with some variations in luminescence characteristics. The variables of the reaction were optimized, such as pH, concentration of reagents, and response time; as well as the variables of the portable device, such as LED voltage, photodiode sensitivity, and adjustment of the measuring range by a reconfigurable electronic system. The portable device allowed the determination of hemoglobin with good sensitivity, with a detection limit of 6.2 nM and range up to 125 nM.
In this paper, we present a simple, fast, and cost-effective method for the large-scale fabrication of high-sensitivity humidity sensors on flexible substrates. These sensors consist of a micro screen-printed capacitive structure upon which a sensitive layer is deposited. We studied two different structures and three different sensing materials by modifying the concentration of poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT:PSS) in a graphene oxide (GO) solution. The results show that the aggregation of the PEDOT:PSS to the GO can modify its electrical properties, boosting the performance of the capacitive sensors in terms of both resistive losses and sensitivity to relative humidity (RH) changes. Thus, in an area less than 30 mm2, the GO/PEDOT:PSS-based sensors can achieve a sensitivity much higher (1.22 nF/%RH at 1 kHz) than other similar sensors presented in the literature which, together with their good thermal stability, time response, and performance over bending, demonstrates that the manufacturing approach described in this work paves the way for the mass production of flexible humidity sensors in an inexpensive way.
The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive component obtained from the spice turmeric (Curcuma longa) rhizome has been used for centuries in Asian countries for cooking and for curing all kinds of diseases like dysentery, chest congestion and pain in general, due to its antioxidant effects. Curcumin prevents the formation of reactive oxygen species and so it is a good protective agent. Curcumin has shown also anti-inflammatory, and antitumor properties. Curcumin is a natural product, which can be a therapeutic option in a variety of retinal diseases due to its pleiotropic properties. Some drawbacks are its poor solubility, bioavailability and lack of stability at physiological conditions; which have been shown in curcumin skeptical publications. In this review, we provide some lights and shadows on curcumin administration on the major retinal pathologies.
In this paper, we present a simple and inexpensive method for the fabrication of high-performance graphene-based heaters on different large-scale substrates through the laser photothermal reduction of graphene oxide (laser-reduced graphene-oxide, LrGO). This method allows an efficient and localized high level of reduction and therefore a good electrical conductivity of the treated films. The performance of the heaters is studied in terms of steady-state temperature, power consumption, and time response for different substrates and sizes. The results show that the LrGO heaters can achieve stable steady-state temperatures higher than 200 °C when a voltage of 15 V is applied, featuring a time constant of around 4 s and a heat transfer coefficient of ~200 °C cm2/W. These characteristics are compared with other technologies in this field, demonstrating that the fabrication approach described in this work is competitive and promising to fabricate large-scale flexible heaters with a very fast response and high steady-state temperatures in a cost-effective way. This technology can be easily combined with other fabrication methods, such as screen printing or spray-deposition, for the manufacturing of complete sensing systems where the temperature control is required to adjust functionalities or to tune sensitivity or selectivity.
Finding an inexpensive and scalable method for the mass production of memristors will be one of the key aspects for their implementation in end-user computing applications. Herein, we report pioneering research on the fabrication of laser-lithographed graphene oxide memristors. The devices have been surface-fabricated through a graphene oxide coating on a polyethylene terephthalate substrate followed by a localized laser-assisted photo-thermal partial reduction. When the laser fluence is appropriately tuned during the fabrication process, the devices present a characteristic pinched closed-loop in the current-voltage relation revealing the unique fingerprint of the memristive hysteresis. Combined structural and electrical experiments have been conducted to characterize the raw material and the devices that aim to establish a path for optimization. Electrical measurements have demonstrated a clear distinction between the resistive states, as well as stable memory performance, indicating the potential of laser-fabricated graphene oxide memristors in resistive switching applications.
Wearable monitoring devices are now a usual commodity in the market, especially for the monitoring of sports and physical activity. However, specialized wearable devices remain an open field for high-risk professionals, such as military personnel, fire and rescue, law enforcement, etc. In this work, a prototype wearable instrument, based on reconfigurable technologies and capable of monitoring electrocardiogram, oxygen saturation, and motion, is presented. This reconfigurable device allows a wide range of applications in conjunction with mobile devices. As a proof-of-concept, the reconfigurable instrument was been integrated into ad hoc glasses, in order to illustrate the non-invasive monitoring of the user. The performance of the presented prototype was validated against a commercial pulse oximeter, while several alternatives for QRS-complex detection were tested. For this type of scenario, clustering-based classification was found to be a very robust option.
Electrocardiography, Ambulatory/instrumentation , Electrocardiography/instrumentation , Monitoring, Physiologic , Wearable Electronic Devices , Humans , Oximetry/instrumentation , Signal Processing, Computer-Assisted
Autophagy and exosome secretion play important roles in a variety of physiological and disease states, including the development of age-related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways of activation. Low oxidative damage in ARPE-19 cells, alters both autophagy and exosome biogenesis. Moreover, oxidative stress modifies the protein and genetic cargo of exosomes, possibly affecting the fate of surrounding cells. In order to understand the connection between these two mechanisms and their impact on angiogenesis, stressed ARPE-19 cells were treated with a siRNA-targeting Atg7, a key protein for the formation of autophagosomes. Subsequently, we observed the formation of multivesicular bodies and the release of exosomes. Released exosomes contained VEGFR2 as part of their cargo. This receptor for VEGF-which is critical for the development of new blood vessels-was higher in exosome populations released from stressed ARPE-19. While stressed exosomes enhanced tube formation, exosomes became ineffective after silencing VEGFR2 in ARPE-19 cells and were, consequently, unable to influence angiogenesis. Moreover, vessel sprouting in the presence of stressed exosomes seems to follow a VEGF-independent pathway. We propose that abnormal vessel growth correlates with VEGFR2-expressing exosomes release from stressed ARPE-19 cells, and is directly linked to autophagy.
Autophagy/genetics , Macular Degeneration/genetics , Neovascularization, Physiologic/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Autophagosomes/metabolism , Cells, Cultured , Exosomes/genetics , Humans , Macular Degeneration/pathology , Oxidative Stress/genetics , Retinal Pigment Epithelium/metabolism
This work presents a detailed study of the photothermal ablation of Kapton® polyimide by a laser diode targeting its electrical conductivity enhancement. Laser-treated samples were structurally characterized using Scanning Electron Microscopy (SEM), Raman spectroscopy, X-ray Photoelectron Spectroscopy (XPS), as well as Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. The results show that the laser-assisted ablation constitutes a simple one-step and environmental friendly method to induce graphene-derived structures on the surface of polyimide films. The laser-modified surface was also electrically characterized through the Transmission Line Method (TLM) aiming at the improvement of the conductivity of the samples by tuning the laser power and the extraction of the contact resistance of the electrodes. Once the laser-ablation process is optimized, the samples increase their conductivity up to six orders of magnitude, being comparable to that of graphene obtained by chemical vapor deposition or by the reduction of graphene-oxide. Additionally, we show that the contact resistance can be decreased down to promising values of ∼2 Ω when using silver-based electrodes.
