1,721,268 research outputs found
Fluid-based assays and precision medicine of cardiovascular diseases: The hope' for Pandora's box?
No full textProgresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field
ERK2 Is a Promoter of Cancer Cell Growth and Migration in Colon Adenocarcinoma
Full text linkERK1/2 phosphorylation is frequently downregulated in the early phase of colon tumorigenesis with subsequent activation of ERK5. In the current work, we studied the advantages of ERK1/2 downregulation for tumor growth by dissecting the individual functions of ERK1 and ERK2. The patient sample data demonstrated decreased ERK1/2 phosphorylation in the early phase of tumorigenesis followed by increased phosphorylation in late-stage colon adenocarcinomas with intratumoral invasion or metastasis. In vitro results indicated that SOD3-mediated coordination of small GTPase RAS regulatory genes inhibited RAS-ERK1/2 signaling. In vitro and in vivo studies suggested that ERK2 has a more prominent role in chemotactic invasion, collective migration, and cell proliferation than ERK1. Of note, simultaneous ERK1 and ERK2 expression inhibited collective cell migration and proliferation but tended to promote invasion, suggesting that ERK1 controls ERK2 function. According to the present data, phosphorylated ERK1/2 at the early phase of colon adenocarcinoma limits tumor mass expansion, whereas reactivation of the kinases at the later phase of colon carcinogenesis is associated with the initiation of metastasis. Additionally, our results suggest that ERK1 is a regulatory kinase that coordinates ERK2-promoted chemotactic invasion, collective migration, and cell proliferation. Our findings indicate that ROS, especially H2O2, are associated with the regulation of ERK1/2 phosphorylation in colon cancer by either increasing or decreasing kinase activity. These data suggest that ERK2 has a growth-promoting role and ERK1 has a regulatory role in colon tumorigenesis, which could lead to new avenues in the development of cancer therapy
Differential epigenetic factors in the prediction of cardiovascular risk in diabetic patients
No full textHyperglycaemia can strongly alter the epigenetic signatures in many types of human vascular cells providing persistent perturbations of protein-protein interactions both in micro- and macro-domains. The establishment of these epigenetic changes may precede cardiovascular (CV) complications and help us to predict vascular lesions in diabetic patients. Importantly, these epigenetic marks may be transmitted across several generations (transgenerational effect) and increase the individual risk of disease. Aberrant DNA methylation and imbalance of histone modifications, mainly acetylation and methylation of H3, represent key determinants of vascular lesions and, thus, putative useful biomarkers for prevention and diagnosis of CV risk in diabetics. Moreover, a differential expression of some micro-RNAs (miRNAs), mainly miR-126, may be a useful prognostic biomarker for atherosclerosis development in asymptomatic subjects. Recently, also environmental-induced chemical perturbations in mRNA (epitranscriptome), mainly the N6-methyladenosine, have been associated with obesity and diabetes. Importantly, reversal of epigenetic changes by modulation of lifestyle and use of metformin, statins, fenofibrate, and apabetalone may offer useful therapeutic options to prevent or delay CV events in diabetics increasing the opportunity for personalized therapy. Network medicine is a promising molecular-bioinformatic approach to identify the signalling pathways underlying the pathogenesis of CV lesions in diabetic patients. Moreover, machine learning tools combined with tomography are advancing the individualized assessment of CV risk in these patients. We remark the need for combining epigenetics and advanced bioinformatic platforms to improve the prediction of vascular lesions in diabetics increasing the opportunity for CV precision medicine
Follicular variant of papillary carcinoma: cytologic findings on FNAB samples-experience with 16 cases
No full textCardiovascular involvement during COVID-19 and clinical implications in elderly patients. A review
No full textSARS-CoV-2 betacoronavirus is responsible for the Corona Virus Disease 2019 (COVID-19) which has relevant pathogenic implications for the cardiovascular system. Incidence and severity of COVID-19 are higher in the elderly population (65 years and older). This may be due to higher frequency of comorbidities, but increased frailty and immunosenescence linked with aging may also contribute. Moreover, in elderly individuals, SARS-CoV-2 may adopt different molecular strategies to strongly impact on cardiac aging that culminate in exacerbating a pro-inflammatory state (cytokine storm activation), which, in turn, may lead to pulmonary vascular endothelialitis, microangiopathy, diffuse thrombosis, myocarditis, heart failure, cardiac arrhythmias, and acute coronary syndromes. All these events are particularly relevant in elderly patients, and deserve targeted cardiovascular treatments and specific management of repurposed drugs against COVID-19. We discuss current evidence about the cardiovascular involvement during COVID-19, and elaborate on clinical implications in elderly patients
Precision medicine in distinct heart failure phenotypes: Focus on clinical epigenetics
No full textHeart failure (HF) management is challenging due to high clinical heterogeneity of this disease which makes patients responding differently to evidence-based standard therapy established by the current reductionist approach. Better understanding of the genetic and epigenetic interactions may clarify molecular signatures underlying maladaptive responses in HF, including metabolic shift, myocardial injury, fibrosis, and mitochondrial dysfunction. DNA methylation, histone modifications and micro-RNA (miRNAs) may be major epigenetic players in the pathogenesis of HF. DNA hypermethylation of the kruppel-like factor 15 (KLF15) gene plays a key role in switching the failing heart from oxidative to glycolytic metabolism. Moreover, hypomethylation at H3K9 promoter level of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes also leads to reactivation of fetal genes in man. The role of miRNAs has been investigated in HF patients undergoing heart transplantation, for whom miR-10a, miR-155, miR-31, and miR-92 may be putative useful prognostic biomarkers. Recently, higher RNA methylation levels have been observed in ischemic human hearts, opening the era of “epitranscriptome” in the pathogenesis of HF. Currently, hydralazine, statins, apabetalone, and omega-3 polyunsatured fatty acids (PUFA) are being tested in clinical trials to provide epigenetic-driven therapeutic interventions. Moreover, network-oriented analysis could advance current medical practice by focusing on protein–protein interactions (PPIs) perturbing the “cardiac” interactome. In this review, we provide an epigenetic map of maladaptive responses in HF patients. Furthermore, we propose the “EPi-transgeneratIonal network mOdeling for STratificatiOn of heaRt Morbidity” (EPIKO-STORM), a clinical research strategy offering novel opportunities to stratify the natural history of HF
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