Overview of stimuli-responsive mesoporous organosilica nanocarriers for drug delivery

The application of nanomaterials is regarded nowadays as a highly promising approach for overcoming the limitations of the currently available cancer treatments, contributing for the creation of more effective, precise, and safer therapies. In the last years, organosilica nanoparticles arisen as alternatives to the most common mesoporous silica nanoparticles. The organosilica nanoparticles combine the advantages of the mesoporous silica, such as structural stability and mesoporous structure, with the increased biocompatibility and biodegradability of organic materials. Therefore, the variety of organic bridges that can be incorporated into the silica matrix allowed the development of new and exciting compositions, properties, and functions for improving the therapeutic effectiveness of the anticancer nanomedicines. In this review, the strategies that have been explored to create stimuli-responsive organosilica-based drug delivery systems are highlighted, describing the practical approaches and mechanisms controlling the drug release. Additionally, the organosilica nanoparticles surface modifications aimed for increasing the blood circulation time and the tumor targeting are also described.info:eu-repo/semantics/publishedVersio

Electrospun Asymmetric Membranes as Promising Wound Dressings: A Review

Despite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new wound dressings (hydrogels, films, sponges, membranes) aiming to mimic all the features of native skin. Among them, asymmetric membranes emerged as a promising solution since they reproduce both epidermal and dermal skin layers. Wet or dry/wet phase inversion, scCO2-assisted phase inversion, and electrospinning have been the most used techniques to produce such a type of membranes. Among them, the electrospinning technique, due to its versatility, allows the development of multifunctional dressings, using natural and/or synthetic polymers, which resemble the extracellular matrix of native skin as well as address the specific requirements of each skin layer. Moreover, various therapeutic or antimicrobial agents have been loaded within nanofibers to further improve the wound healing performance of these membranes. This review article provides an overview of the application of asymmetric electrospun membranes as wound dressings displaying antibacterial activity and as delivery systems of biomolecules that act as wound healing enhancers.info:eu-repo/semantics/publishedVersio

Lignin-enriched tricalcium phosphate/sodium alginate 3D scaffolds for application in bone tissue regeneration

The bone is a connective, vascularized, and mineralized tissue that confers protection to organs, and participates in the support and locomotion of the human body, maintenance of homeostasis, as well as in hematopoiesis. However, throughout the lifetime, bone defects may arise due to traumas (mechanical fractures), diseases, and/or aging, which when too extensive compromise the ability of the bone to self-regenerate. To surpass such clinical situation, different therapeutic approaches have been pursued. Rapid prototyping techniques using composite materials (consisting of ceramics and polymers) have been used to produce customized 3D structures with osteoinductive and osteoconductive properties. In order to reinforce the mechanical and osteogenic properties of these 3D structures, herein, a new 3D scaffold was produced through the layer-by-layer deposition of a tricalcium phosphate (TCP), sodium alginate (SA), and lignin (LG) mixture using the Fab@Home 3D-Plotter. Three different TCP/LG/SA formulations, LG/SA ratio 1:3, 1:2, or 1:1, were produced and subsequently evaluated to determine their suitability for bone regeneration. The physicochemical assays demonstrated that the LG inclusion improved the mechanical resistance of the scaffolds, particularly in the 1:2 ratio, since a 15 % increase in the mechanical strength was observed. Moreover, all TCP/LG/SA formulations showed an enhanced wettability and maintained their capacity to promote the osteoblasts' adhesion and proliferation as well as their bioactivity (formation of hydroxyapatite crystals). Such results support the LG inclusion and application in the development of 3D scaffolds aimed for bone regeneration.info:eu-repo/semantics/publishedVersio

Cell‐Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy

Cancer nanomedicines are designed to encapsulate different therapeuticagents, prevent their premature release, and deliver them specifically tocancer cells, due to their ability to preferentially accumulate in tumor tissue.However, after intravenous administration, nanoparticles immediatelyinteract with biological components that facilitate their recognition by theimmune system, being rapidly removed from circulation. Reports show thatless than 1% of the administered nanoparticles effectively reach the tumorsite. This suboptimal pharmacokinetic profile is pointed out as one of themain factors for the nanoparticles’ suboptimal therapeutic effectiveness andpoor translation to the clinic. Therefore, an extended blood circulation timemay be crucial to increase the nanoparticles’ chances of being accumulated inthe tumor and promote a site-specific delivery of therapeutic agents. For thatpurpose, the understanding of the forces that govern the nanoparticles’interaction with biological components and the impact of the physicochemicalproperties on the in vivo fate will allow the development of novel and moreeffective nanomedicines. Therefore, in this review, the nano–bio interactionsare summarized. Moreover, the application of cell-derived vesicles forextending the blood circulation time and tumor accumulation is reviewed,focusing on the advantages and shortcomings of each cell source.info:eu-repo/semantics/publishedVersio

The Influence of Eating at Home on Dietary Diversity and Airway Inflammation in Portuguese School-Aged Children

Considering the negative impact of a lack of dietary diversity on children's nutritional status, we aimed to describe dietary variety according to eating at home frequency and assessed its association with respiratory outcomes in school-aged children. This cross-sectional study included 590 children (49% girls) aged 7 to 12 years from 20 public schools located in city of Porto, Portugal. Daily frequency of eating at home groups were calculated and dietary diversity was calculated using a 10-food group score from a 24 h recall questionnaire. Spirometry and exhaled nitric oxide levels (eNO; = 35 ppb) were assessed. The comparison of diet diversity according to the groups was performed by ANOVA and ANCOVA. The association between dietary diversity and respiratory outcomes was examined using regression models. In multivariate analysis, children in the highest group of eating at home episodes (>= 4 occasions) obtained the lowest dietary diversity mean score, while the lowest group (= 5 food groups) significantly decreased the odds of having an eNO >= 35. Diet diversity might decrease the chance of airway inflammation among children. However, having more eating episodes at home could be a barrier to a more diverse diet

Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI.Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure–volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats.Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading.Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia

Dietary Acid Load: A Novel Nutritional Target in Overweight/Obese Children with Asthma?

Obesity has been repeatedly linked to asthma, and several potential mechanisms have been proposed in the etiologies of the obese-asthma phenotype. Considering that lungs play an important role in systemic pH and acidbase regulation, are a key organ in asthma development, and that nutritional inadequacy of several nutrients and high dietary acid load can affect airway inflammation and reactivity, we aimed to test the hypothesis that dietary acid load may be associated with asthma in children. Data on 699 children (52% females), aged 712 years, were analyzed. Anthropometric measurements were performed to assess body mass index. Dietary acid load was calculated using potential renal acid load (PRAL) equations from a 24 h dietary recall administrated to children. Adjusted PRAL for total energy intake was applied with the use of the residual method. Lung function and airway reversibility were assessed with spirometry. Asthma was defined by a positive bronchodilation or self-reported medical diagnosis with reported symptoms (wheezing, dyspnea, or dry cough) in the past 12 months. After adjustment for energy intake, sex, age, parents education level, and physical activity, positive and significant associations were found between asthma and PRAL [odds ratio (OR) = 1.953, 95% CI = 1.024, 3.730) in overweight/obese children. Our findings suggest that dietary acid load might be a possible mechanism in overweight/obese-asthma phenotype development.</jats:p

Influence of ClearT and ClearT2 Agitation Conditions in the Fluorescence Imaging of 3D Spheroids

3D tumor spheroids have arisen in the last years as potent tools for the in vitro screening of novel anticancer therapeutics. Nevertheless, to increase the reproducibility and predictability of the data originated from the spheroids it is still necessary to develop or optimize the techniques used for spheroids' physical and biomolecular characterization. Fluorescence microscopy, such as confocal laser scanning microscopy (CLSM), is a tool commonly used by researchers to characterize spheroids structure and the antitumoral effect of novel therapeutics. However, its application in spheroids' analysis is hindered by the limited light penetration in thick samples. For this purpose, optical clearing solutions have been explored to increase the spheroids' transparency by reducing the light scattering. In this study, the influence of agitation conditions (i.e., static, horizontal agitation, and rotatory agitation) on the ClearT and ClearT2 methods' clearing efficacy and tumor spheroids' imaging by CLSM was characterized. The obtained results demonstrate that the ClearT method results in the improved imaging of the spheroids interior, whereas the ClearT2 resulted in an increased propidium iodide mean fluorescence intensity as well as a higher signal depth in the Z-axis. Additionally, for both methods, the best clearing results were obtained for the spheroids treated under the rotatory agitation. In general, this work provides new insights on the ClearT and ClearT2 clearing methodologies and their utilization for improving the reproducibility of the data obtained through the CLSM, such as the analysis of the cell death in response to therapeutics administration.info:eu-repo/semantics/publishedVersio