Inflammasome, T Lymphocytes and Innate-Adaptive Immunity Crosstalk: Role in Cardiovascular Disease and Therapeutic Perspectives

AbstractOver the past few decades, lot of evidences have shown atherosclerosis as a chronic progressive disease with an exquisite inflammatory feature. More recently, the role of innate immune response in the onset and progression of coronary artery disease (CAD) and an adaptive immunity imbalance, mostly involving T cell sub-sets, have been documented. Therefore, like in many other inflammatory and autoimmune disorders, an altered innate-adaptive immunity crosstalk could represent the key of the inflammatory burden leading to atherosclerotic plaque formation and progression and to the breakdown of plaque stability. In this review, we will address the role of inflammasome in innate immunity and in the imbalance of adaptive immunity. We will discuss how this altered immune crosstalk is related to CAD onset and progression. We will also discuss how unravelling the key molecular mechanisms is of paramount importance in the development of therapeutic tools to delay the chronic progression and prevent the acute destabilization of atherosclerotic plaque

The Brief Strategic Treatment of Cardiophobia: A Clinical Case Study

AbstractMany individuals presenting to medical settings with heart-related symptoms for which no medical explanation is found might suffer from cardiophobia, but this condition is still poorly identified and addressed. This article presents a case of cardiophobia treated in an outpatient cardiac rehabilitation unit and, for the first time, describes the application of brief strategic therapy for the treatment of this condition. In the case reported, the first therapeutic encounter and the key elements of the strategic approach are described in detail with the aim to explain how brief strategic therapy works and how it can be used to identify and address cardiophobia-related behaviors. A 64-year-old male presented to cardiac rehabilitation reporting intense anxiety-provoking heart palpitations, and believing he was at risk of dying from a heart attack. After 3 sessions, an overall improvement in heart-related bodily sensations followed a decrease in the patient's continuous checking of his heartbeat and seeking reassurance—factors that were largely responsible for the persistence of the problem. Moreover, quantitative evaluation showed increased scores of mood state at the end of treatment. This improvement persisted at the 18-month follow-up. This case is an interesting example of how brief strategic therapy can contribute to the development of a new conceptual model for the diagnosis and treatment of cardiophobia. Still, more systematic research in the field is needed to prove the efficacy and effectiveness of this therapeutic approach on symptoms of heart-focused anxiety

How to manage KRAS G12C-mutated advanced non-small-cell lung cancer

Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 – 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3’UTR polymorphism (rs371194629) shows that the HLA-G 3’UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3’UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 – 0.7), PM = 6.5 x 10-4]. Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients

Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion

Background: Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown. Objectives: The authors sought to assess the role of hyaluronan (HA) metabolism in ACS. Methods: Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis. Results: Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively). Conclusions: HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability

Acqua e salute per la popolazione

Riflessioni della Water Decade 2005-215 e Giornate Mondiali dell'acqu

Mineral water or tap water? An endless debate

The consumption of mineral water has been increasing because of the frequent and unjustified reports of the water supply contamination. However some authors have shown that bottled waters are not always better than tap water. Mineral waters are more palatable for organoleptic characteristic because, being pure at source, they do not undergo disinfection treatments and are sometimes enriched with CO2. In fact, they are characterized by their microbial facies subject to changes during the production cycle which can contribute to their contamination. It is necessary to provide people with the tools necessary to operate a critical choice of the type of water to be consumed not exclusively for their organoleptic characteristics or marketing strategies

[Mushroom consumption and toxicity, state of the art]

Mushroom consumption is widespread throughout the world and mushroom foraging is often seen as a recreational activity. However, mushroom hunters, especially if inexperienced, may not fully perceive the risks associated with ingesting potentially toxic mushroom species. It is fundamental that mushrooms must be professionally inspected and their quality and safety approved before being ingested. This article analyzes the main scientific documents and current regulations regarding this topic

Steam Reforming of Bioethanol Using Metallic Catalysts on Zeolitic Supports: An Overview

Hydrogen is considered one of the energy carriers of the future due to its high mass-based calorific value. Hydrogen combustion generates only water, and it can be used directly as a fuel for electricity/heat generation. Nowadays, about 95% of the hydrogen is produced via conversion of fossil fuels. One of the future challenges is to find processes based on a renewable source to produce hydrogen in a sustainable way. Bioethanol is a promising candidate, since it can be obtained from the fermentation of biomasses, and easily converted into hydrogen via steam catalytic reforming. The correct design of catalysts and catalytic supports plays a crucial role in the optimization of this reaction. The best results have to date been achieved by noble metals, but their high costs make them unsuitable for industrial application. Very satisfactory results have also been achieved by using nickel and cobalt as active metals. Furthermore, it has been found that the support physical and chemical properties strongly affect the catalytic performance. In this review, zeolitic materials used for the ethanol steam reforming reaction are overviewed. We discuss thermodynamics, reaction mechanisms and the role of active metal, as well as the main noble and non-noble active compounds involved in ethanol steam reforming reaction. Finally, an overview of the zeolitic supports reported in the literature that can be profitably used to produce hydrogen through ethanol steam reforming is presented