Risultati per: Scoperto nuovo biomarker per il cancro al colon-retto

Circulation, Volume 150, Issue Suppl_1, Page A4136687-A4136687, November 12, 2024. Background:Peripheral artery disease (PAD) is associated with high morbidity and mortality and is closely related to diabetes mellitus (DM) and atherosclerosis. Recent advances in epigenetics have highlighted the critical relationships of non-coding RNA Vault RNA 2-1 (VTRNA2-1) promoter methylation and periconceptional nutritional status. Furthermore, the abundance of methylation of the VTRNA2-1 promoter is associated with glucose metabolism and cell aging. This study investigates the association between VTRNA2-1 promoter methylation and clinical outcomes in PAD patients requiring revascularization.Hypothesis:VTRNA2-1 promoter methylation status is associated with clinical outcomes in PAD patients requiring revascularization.Methods:A total of 133 PAD patients requiring revascularization were enrolled. Inclusion criteria included adults over 20 years old, consent to participate, and a requirement for angioplasty. Blood samples were processed to isolate leukocytes, and DNA was extracted using the DNeasy blood kit. Bisulfite pyrosequencing was performed to quantify CpG site-specific DNA methylation at the VTRNA2-1 promoter locus. General population samples from the National Health Research Institutes were used as the control group to compare the methylation status. Patients’ one-year clinical outcomes were evaluated.Results:The study found significant differences in VTRNA2-1 promoter methylation status between PAD patients and the control group (P < 0.001). Hypomethylation of VTRNA2-1 promoter was associated with a higher amputation rate in PAD patients (HR 2.19, 95% CI 1.09-4.42, p=0.027). Among patients without ESRD (N=79), those with hypomethylation had a significantly increased risk of major adverse limb events (MALE) (HR 2.78, 95% CI 1.11-6.97, p=0.024), amputations (HR 2.58, 95% CI 1.02-6.57, p=0.044), and progression to ESRD (p=0.039).Conclusion:The methylation status of VTRNA2-1 promoter is significantly different between PAD patients and the normal population, with hypomethylation linked to poorer clinical outcomes in PAD patients undergoing revascularization. These findings suggest that VTRNA2-1 promoter methylation status could serve as a valuable biomarker for predicting prognosis and guiding treatment strategies in PAD. Our results open a molecular link between the periconceptional environment and the risks of PAD.

Circulation, Volume 150, Issue Suppl_1, Page A4143940-A4143940, November 12, 2024. Introduction:Ischemia/reperfusion (I/R) injury occurs after coronary revascularization, contributing to infarct size. Circulating mitochondrial DNA (mtDNA) levels are elevated in acute myocardial infarction (MI) patients, and act as Damage Associated Molecular Patterns (mtDNA DAMP), which are recognized by the Toll-like receptor 9 (TLR9), initiating pro-inflammatory responses. Prior studies have shown that loss of TLR9 prevents I/R injury in isolated mouse hearts. However, mtDNA DAMP levels have not been measured in ST-elevation MI (STEMI) patients, and whether blocking TLR9 in mice can reduce I/R injury remains unknown.Hypothesis:MtDNA DAMP levels serve as markers of STEMI related cardiac injury. Blocking the activation of TLR9 will decrease cardiac I/R injury.Methods:MtDNA DAMP levels in serum were measured pre- and 24 hours post- PCI in 55 STEMI patients and 37 healthy controls by qPCR. To evaluate the role of TLR9 on I/R injury, ODN2088 was used to block TLR9 receptor, wild type and TLR9 germline KO mice were subjected to close-chest I/R surgery with minimal systemic inflammation. The cardiac systolic function and infarct size were assessed. Immune cells were isolated from the injured left ventricle and spleens and detected by flow cytometry.Results:Pre- PCI mtDNA DAMP levels were increased ~200 folds in STEMI patients compared to healthy controls. After PCI, the elevated mtDNA DAMP levels reduced significantly, while the troponin T levels increased, suggesting mtDNA is an early marker of MI. Compared with negative ODN, ODN2088 treatment at reperfusion reduced infarct size and total leukocytes, myeloid cells, neutrophils and TNF-α+cells, and a trend of reduced IL-1β+cells, and there was no difference in IL-6+cells, total macrophages and residential macrophages. Loss of TLR9 in male and female mice significantly reduced infarct size by ~40% and preserved the systolic function. Meanwhile, there is no difference between genders.Conclusions:Circulating mtDNA DAMP level is an early marker of STEMI and may predict the success of PCI. Blocking the mtDNA DAMP-TLR9 signaling pathway during reperfusion significantly reduces I/R injury, indicating it is a viable therapy to mitigate cardiac I/R injury after prompt coronary revascularization.

Chi ne consuma molti ha rischio ridotto di avere vari tumori

Chi ne consuma molti ha rischio ridotto di avere vari tumori

Il numero 1 al mondo per l’iniziativa ‘Un ace per la ricerca’

Illustrato Bilancio sociale. Parte secondo lotto della Biobanca

Illustrato Bilancio sociale. Parte secondo lotto della Biobanca

Illustrato Bilancio sociale. Parte secondo lotto della Biobanca

Illustrato Bilancio sociale. Parte secondo lotto della Biobanca

Ricerca esamina correlazioni tra alimentazioni e patologia

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