Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.     

Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights

Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.     

An approach to accidents modeling based on compounds road environments

The most common approach to study the influence of certain road features on accidents has been the consideration of uniform road segments characterized by a unique feature. However, when an accident is related to the road infrastructure, its cause is usually not a single characteristic but rather a complex combination of several characteristics. The main objective of this paper is to describe a methodology developed in order to consider the road as a complete environment by using compound road environments, overcoming the limitations inherented in considering only uniform road segments. The methodology consists of: dividing a sample of roads into segments; grouping them into quite homogeneous road environments using cluster analysis; and identifying the influence of skid resistance and texture depth on road accidents in each environment by using generalized linear models. The application of this methodology is demonstrated for eight roads. Based on real data from accidents and road characteristics, three compound road environments were established where the pavement surface properties significantly influence the occurrence of accidents. Results have showed clearly that road environments where braking maneuvers are more common or those with small radii of curvature and high speeds require higher skid resistance and texture depth as an important contribution to the accident prevention.     

Forecasting with unequally spaced data by a functional principal component approach

The Principal Component Regression model of multiple responses is extended to forccast a continuous-time stochastic process. Orthogonal projection on a subspace of trigonometric functions is applied in order to estimate the principal components using discrete-time observations from a sample of regular curves. The forecasts provided by this approach are compared with classical principal component regression on simulated data.     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.     

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.     

Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action

Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.     

Obesity and Bone Health: A Complex Relationship

Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.     

Pixel selection for near-infrared chemical imaging (NIR-CI) discrimination between fish and terrestrial animal species in animal protein by-product meals

This paper proposes a method based on near-infrared hyperspectral imaging for discriminating between terrestrial and fish species in animal protein by-products used in livestock feed. Four algorithms (Mahalanobis distance, Kennard-Stone, spatial interpolation, and binning) were compared in order to select an appropriate subset of pixels for further partial least squares discriminant analysis (PLS-DA). The method was applied to a set of 50 terrestrial and 40 fish meals analyzed in the 1000-1700 nm range. Models were then tested using an external validation set comprising 45 samples (25 fish and 20 terrestrial). The PLS-DA models obtained using the four subset-selection algorithms yielded a classification accuracy of 99.80%, 99.79%, 99.85%, and 99.61%, respectively. The results represent a first step for the analysis of mixtures of species and suggest that NIR-CI, providing valuable information on the origin of animal components in processed animal proteins, is a promising method that could be used as part of the EU feed control program aimed at eradicating and preventing bovine spongiform encephalopathy (BSE) and related diseases.