2,661 research outputs found
Redox regulation of immunity and the role of small molecular weight thiols
No full textIt is thought that excessive production of reactive oxygen species (ROS) can be a causal component in many diseases, some of which have an inflammatory component. This led to an oversimplification whereby ROS are seen as inflammatory and antioxidants anti-inflammatory. This paper aims at reviewing some of the literature on thiols in host defense. The review will first summarize the mechanisms by which we survive infections by pathogens. Then we will consider how the redox field evolved from the concept of oxidative stress to that of redox regulation and how it intersects the field of innate immunity. A third section will analyze how an oversimplified oxidative stress theory of disease led to a hypothesis on the role of ROS and glutathione (GSH) in immunity, respectively as pro- and anti-inflammatory mediators. Finally, we will discuss some recent research and how to think out of the box of that oversimplification and link the role of thiols in redox regulation to the mechanisms by which we survive an infection outlined in the first section
Environmental risk factors and their footprints in vivo - A proposal for the classification of oxidative stress biomarkers
No full text: Environmental agents, including socioeconomic condition, and host factors can act as causal agents and risk factors in disease. We use biomarkers and sociomarkers to study causal factors, such as overproduction of reactive oxygen species (ROS) which could play a role in disease through oxidative stress. It is therefore important to define the exact meaning of the biomarker we measure. In this review we attempt a classification of biomarkers related to oxidative stress based on their biological meaning. We define as type zero biomarkers the direct measurement of ROS in vivo in patients. Type 1 biomarkers are the most frequently used indicators of oxidative stress, represented by oxidized lipids, proteins or nucleic acids and their bases. Type 2 biomarkers are indicators of the activation of biochemical pathways that can lead to the formation of ROS. Type 3 biomarkers are host factors such as small-molecular weight antioxidants and antioxidant enzymes, while type 4 biomarkers measure genetic factors and mutations that could modify the susceptibility of an individual to oxidative stress. We also discuss whether biomarkers are actionable or not, that is if the specific blockade of these molecules can ameliorate disease or if they are just surrogate markers. The proposed classification of biomarkers of oxidative stress based on their meaning and ambiguities, within the theoretical framework of the oxidative stress theory of disease may help identify those diseases, and individuals, where oxidative stress has a causal role, to allow targeted therapy and personalized medicine
Protein glutathionylation in health and disease
No full textBackground: It is now recognized that protein cysteines exist not only as free thiols or intramolecular disulfides, that help maintain the 3D structure of proteins, but can also undergo different types of oxidation, one of which is glutathionylation, or the formation of mixed disulfides with glutathione (GSH). Scope of the review: We will discuss how proteins can undergo glutathionylation and how this can affect the protein characteristics/function. Glutathionylation is reversible and de-glutathionylation can be catalysed by protein thiol-disulfide oxidoreductases. Genetic modification of the expression of these enzymes, particularly glutaredoxin, using overexpression, knockout mice or siRNA, is becoming an important tool to study the role of protein glutathionylation. While in the past this post-translational modification was mainly known in the context of oxidative stress, measurement of glutathionylated proteins in patients is pointing out a potential importance if this modification in pathogenesis and could identify new biomarkers. We also wanted to point out the main findings in the role of glutathionylation in diseases and drug action. Major conclusions: We identify two major open problems in the field, namely the complexity of the mechanisms responsible for glutathionylation and de-glutathionylation, as well as what makes a protein susceptible to glutathionylation. General significance: This review underlines the peculiarities of this post-translational modification and their biological role. This article is part of a Special Issue entitled Cellular functions of glutathione
Pietro Verri’s Contribution to the Economic Theory of the 18th Century: Commercial Society, Civil Society and Governance of the Economy
No full text'Count Pietro Verri (1728-97) - Schumpeter writes (History, p. 178) - - would have to be included in any list of the greatest economists'. Within the Milanese school, he certainly stands out, alongside with Cesare Beccaria, during one of the most interesting periods from a history of analysis point of view. Luigi Cossa's famous introduction to the study of political economy rates Pietro Verri to be inferior to Beccaria in ingenuity and scientific cultivation, but greatly to be ahead of him as an economist.1 This judgement by Cossa, in particular, seems to echo the relative position of the two men in the history of ideas, particularly after Beccaria's rise to fame with a book - On crimes and punishments - which had in fact been largely inspired by Verri himself and defended by him.2 It is proposed in the present paper to revisit some of the basic tenets of Pietro Verri's political economy, with more in view than dwell on specific intuitions and theorems: namely relate those to Verri's own - quite original - conception of the economy. The scholarly work of Pietro Verri - with a special reference to his Meditazioni sulla economia politica of 1771 - provides the first systematic contribution stemming from the quarters of Lombard enlightenment in the field of political economy, especially so if one considers that Cesare Beccaria's parallel work - namely his Elementi di economia pubblica, conceived and drafted at the same time as Verri's Meditazioni - would only be published posthumously several years later. From the vantage point afforded by Verri's political economy, we gain a considerably attractive view of the most significant elements and characteristic concepts of Lombard enlightenment during the latter half of the 18th century; Verri, moreover, as we shall see, builds on a number of them in a new and original way. This paper is aimed at discussing Verri's political economy mainly along two distinct, but related, lines. In the first place the conception of commercial society is considered such as it is treated by the author particularly in his Meditazioni. In this perspective the analysis of such issues as competition and the market or money and taxation occupy a central place. Secondly it will be necessary to emphasise that Verri's approach has little to do either with forms of pure economics on one side - largely yet to be born throughout the 18th century - or, on the other side, with such conceptions of the polis - contrariwise well alive among his own contemporaries - as are founded on a sovereign authority conceived to be situated above the law. What Verri's political economy ultimately amounts to is an economic conception of civil society. The latter has natural strong connections with his own fact-mindedness - emphasised by Schumpeter - as well as with his deep practical involvement in administrative affairs and in the reforming process taking place during the latter half of the 18th century in Milan. In our view, a thorough investigation along the mentioned lines is the precondition for an understanding of the intellectual stature and of the scholarly contribution of Pietro Verri. His main ground is distinctly analytical and only by appreciating his analysis is it possible to shed light on the meaning and intellectual significance also of his practical contributions. Moreover Verri's pronouncements on the criticism of despotic government, the relevance of intermediate powers or bodies and on multiple levels of governance will be examined in a new and original light, showing how close they are to the gist of his analysis.
Regulation of protein function by glutathionylation
No full text: The main function of reduced glutathione (GSH) is to protect from oxidative stress as a reactive oxygen scavenger. However, in the context of redox regulation, the ratio between GSH and its oxidized form (GSSG) determines the redox state of redox-sensitive cysteines in some proteins and, thus, acts as a signaling system. While GSH/GSSG can catalyze oxido-reduction of intra- and inter-chain disulfides by thiol-disulfide exchange, this review focuses on the formation of mixed disulfides between glutathione and proteins, also known as glutathionylation. The review discusses the regulatory role of this post-translational modification and the role of protein disulfide oxidoreductases (thioredoxin/thioredoxin reductase, glutaredoxin, protein disulfide isomerase) in the reversibility of this process
Quality of online information on breast cancer treatment options
No full text: Offering breast cancer patients treatment choice has become a priority as the involvement of patients in the decision-making process is associated with improved physical and psychological outcomes. As the Internet is increasingly being used by patients as a source of medical information, it is important to evaluate the quality of information relating to breast cancer on the Internet. We analysed 200 websites returned by google.co.uk searching "breast cancer treatment options" in terms of their typology and treatment options described. These were related to standard measures of health information quality such as the JAMA score and the presence of quality certifications, as well as readability. We found that health portals were of higher quality whilst commercial and professional websites were of poorer quality in terms of JAMA criteria. Overall, readability was higher than previously reported for other conditions, and Google ranked websites with better readability higher. Most websites discussed surgical and medical treatments. Few websites, with a large proportion being of commercial typology, discussed complementary and alternative medicine. Google ranked professional websites low whilst websites from non-profit organizations were promoted in the ranking
Thiol regulation of pro-inflammatory cytokines and innate immunity: protein S-thiolation as a novel molecular mechanism
No full text: Inflammation or inflammatory cytokines and oxidative stress have often been associated, and thiol antioxidants, particularly glutathione, have often been seen as possible anti-inflammatory mediators. However, whereas several cytokine inhibitors have been approved for drug use in chronic inflammatory diseases, this has not happened with antioxidant molecules. We outline the complexity of the role of protein thiol-disulfide oxidoreduction in the regulation of immunity and inflammation, the underlying molecular mechanisms (such as protein glutathionylation) and the key enzyme players such as Trx (thioredoxin) or Grx (glutaredoxin)
Redox Proteomics Applied to the Thiol Secretome
No full textSignificance: Secreted proteins are important both as signaling molecules and potential biomarkers. Recent Advances: Protein can undergo different types of oxidation, both in physiological conditions or under oxidative stress. Several redox proteomics techniques have been successfully applied to the identification of glutathionylated proteins, an oxidative post-translational modification consisting in the formation of a mixed disulfide between a protein cysteine and glutathione. Redox proteomics has also been used to study other forms of protein oxidation. Critical issues: Because of the highest proportion of free cysteines in the cytosol, redox proteomics of protein thiols has focused, so far, on intracellular proteins. However, plasma proteins, such as transthyretin and albumin, have been described as glutathionylated or cysteinylated. The present review discusses the redox state of protein cysteines in relation to their cellular distribution. We describe the various approaches used to detect secreted glutathionylated proteins, the only thiol modification studied so far in secreted proteins, and the specific problems presented in the study of the secretome. Future directions: This review focusses on glutathionylated proteins secreted under inflammatory conditions and that may act as soluble mediators (cytokines). Future studies on the redox secretome (including other forms of oxidation) might identify new soluble mediators and biomarkers of oxidative stress. Antioxid. Redox Signal. 26, 299-312
Release of redox enzymes and micro-RNAs in extracellular vesicles, during infection and inflammation
No full textMany studies reported that redox enzymes, particularly thioredoxin and peroxiredoxin, can be released by cells and act as soluble mediators in immunity. Recently, it became clear that peroxiredoxins can be secreted via the exosome-release route, yet it remains unclear how this exactly happens and why. This review will first introduce briefly the possible redox states of protein cysteines and the role of redox enzymes in their regulation. We will then discuss the studies on the extracellular forms of some of these enzymes, their association with exosomes/extracellular vesicles and with exosome micro-RNAs (miRNAs)/mRNAs involved in oxidative processes, relevant in infection and inflammation
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