Does Diabetes Accelerate the Progression of Aortic Stenosis through Enhanced Inflammatory Response within Aortic valves?

Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74–51.9] mg/l vs. 4.7 [0.59–23.14] mg/l, p = 0.009) and TF (293.06 [192.32–386.12] pg/ml vs. 140 [104.17–177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF−, TFPI−, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5–9]% vs. 0.94 [0–4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

IoT as a Digital Game Changer in Rural Areas: The DESIRA Conceptual Approach

Digital transformation is a process encompassing significant changes in both social and economical domains because of the adoption of digital technologies. The EU H2020 DESIRA (Digitisation: Economic and Social Impacts in Rural Areas) project is working on defining a methodology and creating a knowledge base to characterize digital transformation. The goal is to support those in charge of responding to digitization-related challenges in rural areas, especially considering agriculture and forestry. This work presents preliminary activities in the project aiming to identify (i) Digital Game Changers, like Internet of Things (IoT), facilitating the digital transformation; and (ii) a robust set of exemplary Application Scenarios (ASs). This task will support forthcoming activities aiming to assess the socio-economic impact of digital transformation in rural areas

Polymorphism Gln27Glu of β2 adrenergic receptors in patients with ischaemic cardiomyopathy

Background: Polymorphisms of the Adrenergic Receptors (ARs) might affect the development and progression of Heart Failure (HF) and the response to treatment with β-blockade therapy. Objective: To examine the role of the Gln27Glu polymorphism of β2-AR in HF development and to assess the hypothesis that Gln27Glu is associated with coronary artery disease in patients with ischaemic HF. Methods: In this case control study we enrolled 155 consecutive patients with symptomatic HF of ischaemic aetiology with impaired Left Ventricular Ejection Fraction (LVEF) ≤35%. The control group consisted of 133 patients with no obstructive coronary artery disease and or evidence of HF. Results: Concerning HF and control subjects there was no significant differences in the prevalence of Gln27Gln homozygotes (46 vs. 44%, p=0.82). In HF patients concerning the differences in patient characteristics between allele categories (Gln27Gln vs. Gln27Glu/Glu27Glu) there was no difference in risk factors, LVEF, treatment, the clinical status and NYHA categorization of patients, and in the prevalence of multi-vessel coronary artery disease. Interestingly, participants homozygous for Gln had significant higher prevalence of previous myocardial infarction (Gln27Gln vs. Gln27Glu/Glu27Glu: 77 vs. 23%, p=0.02). Conclusion: The present study shows that the Gln27Gln genotype of β2-AR is the most predominant while the Glu27Glu is the least prevalent in our HF population. There was no difference in the prevalence of polymorphism Gln27Glu between HF patients and control subjects. However, the presence of Glu allele was associated with lower myocardial infarction rate. © 2018 Bentham Science Publishers

Association between plasma levels and immunolocalization of cytokines in heart valve lesions: A possible target for treatment?

Objective: To compare the distribution of pro-inflammatory cytokines in heart valve lesions with their plasma levels. Methods: Plasma leveLs of TNF-α and IL-10 were determined in 70 patients with heart valve lesions. TNF-(α and IL-6 levels were also quantified in tissue specimens obtained from these patients after valve replacement. Results: Plasma concentrations of TNF-α and the extent of calcium deposits were significantly higher in patients with aortic valve stenosis compared with individuals with mitral valve stenosis. A direct relationship was demonstrated between TNF-α blood and tissue levels. There was an increase in TNF-α and IL-6 tissue immunoreactivity with the progression of heart valve disease from mild to advanced inflammation. The increased accumulation of calcium deposits in damaged heart valves correlated with plasma TNF-α and IL-10 levels. Conclusions: The association between plasma and tissue sample cytokine concentrations suggests that plasma cytokine levels reflect the extent and severity of valvular lesions. Statins may attenuate progressive calcific valve stenosis. Statins also affect TNF-α and IL-10 plasma levels. These associations may help not only predict the progression but also attenuate the deterioration of valvular lesions. Verification of these results in larger scale studies is required before definite conclusions can be drawn. © 2008 Informa UK Ltd