Genetic Factors Associated with Longevity in Humans

Introduction: Life expectancy and the rate of survival into old age have risen dramatically throughout the past century. The positive ageing outcomes may be due to a variety of factors including healthy lifestyle behaviors, but it is clear that longevity has a genetic basis, with heritability estimate of 20–35%. In this contest, it was emerged that human longevity seems strongly influenced by gender defined as the combination between biological sexual characteristics and factors related to behavior, social role, lifestyle and life experiences. Body—research methods: Successful ageing seems to be related to gene involved in different pathways of regulation, such as immune-inflammatory responses and oxidative stress. The aims of the present review are to discuss recent findings and highlight the genetic basis of longevity. For these reasons we are aimed to describe the most important underpinning which is the gender differences in longevity between males and females. Conclusion—key results: It appears clear that longevity may represent a complex polygenic trait that is influenced by the interaction of multiple genetic variants, as was demonstrated by several genetic studies conducted in the last years. Furthermore, epigenetic and environmental factors actin on the longevity phenotype

RAGE gene polymorphism in heart failure patients with and without angiographic evidence of significant coronary atherosclerosis.

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE-RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) <45%, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (p<0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin

A proof-of-concept analysis of plasma-derived exosomal microRNAs in interstitial pulmonary fibrosis secondary to antisynthetase syndrome

Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD?. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-?B and TGF-?1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD.Funding: This research was supported by the Ministry of Health IRCCS Foundation Policlinico San Matteo Grant [grant number 948-rcr2019i2-46]

Anti-Ro52 antibodies positivity in antisynthetase syndrome: a single centre cohort study

Objectives: Although antisynthetase antibodies (ARS) are the established markers of the so-called antisynthetase syndrome (ASSD), in these patients the concomitant positivity of anti-Ro52 antibodies, reported in up to the 50% of cases, is not rare. Several studies focused on the effect of different ARS specificities on the evolution of ASSD, the most recent showing no effects. On the contrary, the role of co-occurring anti-Ro52 antibodies in ASSD is still debated. We investigated the potential of anti-Ro52 antibodies in identifying a clinical phenotype of ASSD or influencing prognosis, irrespectively to the underlying ARS specificity. Methods: Retrospective analysis of clinical, imaging and laboratory characteristics, therapeutic approaches and outcome at baseline and at last follow-up, of 60 ASSD patients progressively enrolled at our Hospital. Results: We identified 34 anti-Ro+ and 26 anti-Ro- ASSD patients. Classic triad prevalence at baseline was similar between the two groups, whereas interstitial lung disease (ILD) (p value=0.01) and myositis (p value=0.03) were significantly more prevalent in anti-Ro52+ and in anti-Ro52- patients at last follow up, respectively. No differences in therapeutic approaches, oxygen need and ILD patterns were observed. Overall mortality was 25% (15 subjects). No differences in mortality, overall and disease related, between anti-Ro52+ and anti-Ro52- patients were observed (p value=0.764), despite the more frequent ILD occurrence in anti-Ro52+ patients. Survival curves were not different at any time point (Log-rank test, p value 0.98). Conclusions: Anti-Ro52 antibodies affect time course and clinical characteristics of ASSD. Although ILD is significantly more associated to anti-Ro52 antibodies, no difference in mortality was observed compared to anti-Ro52 negative patients

Hyaluronic acid-decorated liposomes as innovative targeted delivery system for lung fibrotic cells

Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1\u3b2, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-\u3b2 mRNA. However, upon analyzing TGF-\u3b2 release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients

Application and uses of electronic noses for clinical diagnosis on urine samples: A review

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents

Soluble RAGE Plasma Levels in Patients with Coronary Artery Disease and Peripheral Artery Disease

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE

Fourth European Congress on Computational Methods in Applied Sciences and Engineering (ECCOMAS 2004)

L’ European Congress on Computational Methods in Applied Sciences and Engineering è un importante congresso europeo, organizzato ogni quattro anni dall’associazione ECCOMAS (European Community on COmputational Methods in Applied Sciences), con lo scopo di favorire scambi di esperienze tra i ricercatori europei nei diversi ambiti di applicazione dei metodi matematici e computazionali. Per l’edizione del 2004, la quarta, gli organizzatori hanno scelto come sede la città di Jyväskylä (Finlandia), dove si sono riuniti più di mille esponenti dell’ambiente scientifico internazionale

Expo e-Learning 2005

Si é svolta a Ferrara, (Ottobre 2005), la seconda edizione dell'Expo e-Learning, ottima occasione per uno scambio di esperienze tra gli operatori del settore e per discutere delle linee guida per il futuro dell'e-learning a livello nazionale e internazionale