With cancer cells encompassing consistently higher production of reactive oxygen species (ROS) and with an induced antioxidant defense to counteract the increased basal ROS production, tumors have a ...limited reserve capacity resulting in an increased vulnerability of some cancer cells to ROS. Based on this, oxidative stress has been recognized as a tumor-specific target for the rational design of new anticancer agents. Among redox modulating compounds, selenium compounds have gained substantial attention due to their promising chemotherapeutic potential.
This review aims in summarizing and providing the recent developments of our understanding of the molecular mechanisms that underlie the potential anticancer effects of selenium compounds.
It is well established that selenium at higher doses readily can turn into a prooxidant and thereby exert its potential anticancer properties. However, the biological activity of selenium compounds and the mechanism behind these effects are highly dependent on its speciation and the specific metabolic pathways of cells and tissues. Conversely, the chemical properties and the main molecular mechanisms of the most relevant inorganic and organic selenium compounds as well as selenium-based nanoparticles must be taken into account and are discussed herein.
Elucidating and deepening our mechanistic knowledge of selenium compounds will help in designing and optimizing compounds with more specific antitumor properties for possible future application of selenium compounds in the treatment of cancer. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
•Selenium compounds are evolving as promising chemotherapeutic agents.•Inorganic and organic forms as well as selenium-based nanoparticles are described.•The chemical properties and the main mechanisms of these compounds are discussed.•Redox active selenium compounds seem to be more efficient as anticancer agents.
Abstract Porous artificial bone substitutes, especially bone scaffolds coupled with osteobiologics, have been developed as an alternative to the traditional bone grafts. The bone scaffold should have ...a set of properties to provide mechanical support and simultaneously promote tissue regeneration. Among these properties, scaffold permeability is a determinant factor as it plays a major role in the ability for cells to penetrate the porous media and for nutrients to diffuse. Thus, the aim of this work is to characterize the permeability of the scaffold microstructure, using both computational and experimental methods. Computationally, permeability was estimated by homogenization methods applied to the problem of a fluid flow through a porous media. These homogenized permeability properties are compared with those obtained experimentally. For this purpose a simple experimental setup was used to test scaffolds built using Solid Free Form techniques. The obtained results show a linear correlation between the computational and the experimental permeability. Also, this study showed that permeability encompasses the influence of both porosity and pore size on mass transport, thus indicating its importance as a design parameter. This work indicates that the mathematical approach used to determine permeability may be useful as a scaffold design tool.
Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world ...(especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.
Selenium(Se)-containing compounds have attracted a growing interest as anticancer agents over recent decades, with mounting reports demonstrating their high efficacy and selectivity against cancer ...cells. Typically, Se compounds exert their cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis. However, the precise intracellular targets, signalling pathways affected and mechanisms of cell death engaged following treatment vary with the chemical properties of the selenocompound and its metabolites, as well as the cancer model that is used. Naturally occurring organic Se compounds, besides encompassing a significant antitumor activity with an apparent ability to prevent metastasis, also seem to have fewer side effects and less systemic effects as reported for many inorganic Se compounds. On this basis, many novel organoselenium compounds have also been synthesized and examined as potential chemotherapeutic agents. This review aims to summarize the most well studied natural and synthetic organoselenium compounds and provide the most recent developments in our understanding of the molecular mechanisms that underlie their potential anticancer effects.
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•Selenium compounds have gained substantial interest as anticancer agents.•The review covers naturally occurring and synthetic organoselenium compounds.•Their chemical properties and main mechanisms of action are discussed herein.
Road traffic poses negative externalities on society and represents a key challenge in sustainable transportation. However, the existing literature about the assessment of traffic externalities drawn ...on a common measure is scarce.
This paper develops a sustainability indicator that integrates traffic-related externalities as means of traffic congestion, noise, greenhouse gases (GHG) and nitrogen oxides emissions, health impacts and road crash related costs, and adjusted to local contexts of vulnerability.
Traffic, road crashes, acoustic and vehicle dynamic data were collected from one real-world intercity corridor pair comprising three alternative routes. The site-specific operations were characterized using a modeling platform of traffic, emissions, noise and air quality. A specific methodology is applied for each road traffic externality and translated in a single factor – external cost.
The results indicated that road crashes presented the largest share in the partly rural/urban route while GHG emissions had the highest contribution in external costs for the highway routes. Also, the distribution of external cost component varied according to the type of road, mostly due to different levels of exposed inhabitants.
This paper offers a line of research that produced a method for decision-makers with a reliable and flexible cost analysis aimed at reducing the negative impacts of road traffic. It also encourages the design of eco-traffic management policies considering the perspective of drivers, commuters and population.
Sustainability Indicator (congestion, noise, GHG, NOX, health impacts and road crash) in €/veh. Display omitted
•Sustainability indicator for integrating road traffic externalities was developed.•External costs focused on congestion, noise, GHG, NOX, health impacts and crashes.•The methodology was tested in real-world corridor pair with three alternative routes.•Crashes and GHG represented the largest share in external costs.•Share of externalities varied according the road type and population exposure.
The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox homeostasis and signaling ...pathways. Recently, these selenoproteins have emerged as promising therapeutic targets for anticancer drug development, often being overexpressed in tumor cells and contributing to drug resistance. Herein, we summarize the current knowledge on metal- and semimetal-containing molecules capable of hampering mammalian TrxRs, with an emphasis on compounds reported in the last decade.
Linear regression is one of the oldest statistical modeling approaches. Still, it is a valuable tool, particularly when it is necessary to create forecast models with low sample sizes. When ...researchers use this method and have numerous potential regressors, choosing the group of regressors for a model that fulfills all the required assumptions can be challenging. In this sense, the authors developed an open-source Python script that automatically tests all the combinations of regressors under a brute-force approach. The output displays the best linear regression models, regarding the thresholds set by users for the required assumptions: statistical significance of the estimations, multicollinearity, error normality, and homoscedasticity. Further, the script allows the selection of linear regressions with regression coefficients according to the user’s expectations. This script was tested with an environmental dataset to predict surface water quality parameters based on landscape metrics and contaminant loads. Among millions of possible combinations, less than 0.1 % of the regressor combinations fulfilled the requirements. The resulting combinations were also tested in geographically weighted regression, with similar results to linear regression. The model's performance was higher for pH and total nitrate and lower for total alkalinity and electrical conductivity.•A Python script was developed to find the best linear regressions within a dataset.•Output regressions are automatically selected based on regression coefficient expectations set by the user and the linear regression assumptions.•The algorithm was successfully validated through an environmental dataset.
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Fire is infrequent in the oak woodlands of southern Portugal (montado) but large and severe fires affected these agro-forestry systems in 2003–2005. We hypothesised transition from forest to ...shrubland as a fire-driven process and investigated the links between fire incidence and montado change to other land cover types, particularly those related with the presence of pioneer communities (generically designed in this context as “transitions to early-successional communities”). We present a landscape-scale framework for assessing the probability of transition from montado to pioneer communities, considering three sets of explanatory variables: montado patterns in 1990 and prior changes from montado to early-successional communities (occurred between 1960 and 1990), fire patterns, and spatial factors. These three sets of factors captured 78.2% of the observed variability in the transitions from montado to pioneer vegetation. The contributions of fire patterns and spatial factors were high, respectively 60.6% and 43.4%, the influence of montado patterns and former changes in montado being lower (34.4%). The highest amount of explained variation in the occurrence of transitions from montado to early-successional communities was related to the pure effect of fire patterns (19.9%). Low spatial connectedness in montado landscape can increase vulnerability to changes, namely to pioneer vegetation, but the observed changes were mostly explained by fire characteristics and spatial factors. Among all metrics used to characterize fire patterns and extent, effective mesh size provided the best modelling results. Transitions from montado to pioneer communities are more likely in the presence of high values of the effective mesh size of total burned area. This cross-boundary metric is an indicator of the influence of large fires in the distribution of the identified transitions and, therefore, we conclude that the occurrence of large fires in montado increases its probability of transition to shrubland.
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•Transitions in Mediterranean oak woodlands (montados) were assessed;•Low spatial connectedness in montado landscape increases its vulnerability;•Changes were mostly explained by fire characteristics and spatial factors;•Large fires have a major role in transitions from montado to pioneer communities.
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