Aims
Differential microRNA expression in peripheral blood has been observed in patients with heart failure, suggesting their value as potential biomarkers and likely contributors to disease ...mechanisms. In the present study, we aimed to evaluate the transcardiac gradient of 84 cardio‐microRNAs in healthy and failing hearts to determine which microRNAs are released or absorbed by the myocardium in heart failure.
Methods and results
Eight healthy volunteers and nine patients with congestive heart failure were included. Arterial and coronary sinus blood samples were collected, and microRNAs were extracted. The expression of microRNAs was analysed using real‐time PCR by the miScript miRNA PCR Array Human Cardiovascular Disease. In coronary sinus samples, the microRNAs miR‐16‐5p, miR‐27a‐3p, miR‐27b‐3p, miR‐29b‐3p, miR‐29c‐3p, miR‐30e‐5p, miR‐92a‐3p, miR‐125b‐5p, miR‐140‐5p, miR‐195‐5p, miR‐424‐5p, and miR‐451a were significantly down‐regulated, and let‐7a‐5p, let‐7c‐5p, let‐7e‐5p, miR‐23b‐3p, miR‐107, miR‐155‐5p, miR‐181a‐5p, miR‐181b‐5p and miR‐320a were up‐regulated in heart failure. Left ventricular filling pressure was negatively correlated with miR‐195, miR‐16, miR‐29b‐3p, miR‐29c‐3p, miR‐451a, and miR‐92a‐3p. The failing heart released let‐7b‐5p, let‐7c‐5p, let‐7e‐5p, miR‐122‐5p, and miR‐21‐5p, and absorbed miR‐16‐5p, miR‐17‐5p, miR‐27a‐3p, miR‐30a‐5p, miR‐30d‐5p, miR‐30e‐5p, miR‐130a‐3p, miR‐140‐5p, miR‐199a‐5p, and miR‐451a. In silico analyses suggest that the transcardiac gradient of microRNAs in heart failure may target pathways related to heart disease.
Conclusion
We determined the transcardiac gradient of cardio‐microRNAs in failing hearts, which supports the use of these microRNAs as potential biomarkers. The microRNAs described here may have a role in the pathophysiology of heart failure as they might be involved in pathways related to disease progression, including fibrosis.
Cardiac Complications of Thoracic Irradiation Jaworski, Catherine, MBBS; Mariani, Justin A., MBBS, PhD; Wheeler, Greg, MBBS ...
Journal of the American College of Cardiology,
06/2013, Letnik:
61, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Adjuvant radiation therapy in the management of early stage breast cancer, Hodgkin’s disease, and to a lesser extent other thoracic malignancies has led to a significant improvement in ...disease-specific survival. Cardiovascular disease is now the most common nonmalignancy cause of death in radiation-treated cancer survivors, most often occurring decades after treatment. The spectrum of radiation-induced cardiac disease is broad, potentially involving any component of the heart. The relative risk of coronary artery disease, congestive heart failure, valvular heart disease, pericardial disease, conduction abnormalities, and sudden cardiac death is particularly increased. Over the years contemporary techniques have been introduced to reduce cardiac morbidity and mortality in radiation-treated cancer survivors; however, the long-term effects on the heart still remain unclear, mandating longer follow-up. Awareness and early identification of potential cardiac complications is crucial in cancer survivors, with the management often being quite complex. This review examines the epidemiology of radiation-induced cardiac disease together with its pathophysiology and explores the available treatment strategies and the potential utility of various screening strategies for affected cancer survivors.
This paper aims to contribute to the current debate on the inclusion of nutritional information and health warnings on wine labels, exploring consumers' interest and preferences. The results of a ...survey conducted on a sample of Italian wine consumers (N = 300) show the strong interest of respondents in the inclusion of such information on the label. Conjoint analysis reveals that consumers assign greater utility to health warnings, followed by nutritional information. Cluster analysis shows the existence of three different consumer segments. The first cluster, which included mainly female consumers (over 55) and those with high wine involvement, revealed greater awareness of the links between wine and health and better knowledge of wine nutritional properties, preferring a more detailed nutritional label, such as a panel with GDA%. By contrast, the other two clusters, consisting of individuals who generally find it more difficult to understand nutritional labels, preferred the less detailed label of a glass showing calories. The second and largest cluster comprising mainly younger men (under 44), showed the highest interest in health warnings while the third cluster – with a relatively low level of education - preferred the specification of the number of glasses not to exceed. Our results support the idea that the policy maker should consider introducing a mandatory nutritional label in the easier-to-implement and not-too-costly form of a glass with calories, rotating health warnings and the maximum number of glasses not to exceed.
•We analyse consumer preferences for nutritional and health information on wine labels.•Health warning is the attribute to which consumers assign greater utility.•Nutritional information is preferred via a logo + claim and a glass with kcal amount.•We examine differences among three identified consumer segments.
Extraintestinal pathogenic Escherichia coli (ExPEC) are a common cause of disease in both mammals and birds. A vaccine to prevent such infections would be desirable given the increasing antibiotic ...resistance of these bacteria. We have determined the genome sequence of ExPEC IHE3034 (ST95) isolated from a case of neonatal meningitis and compared this to available genome sequences of other ExPEC strains and a few nonpathogenic E. coli. We found 19 genomic islands present in the genome of IHE3034, which are absent in the nonpathogenic E. coli isolates. By using subtractive reverse vaccinology we identified 230 antigens present in ExPEC but absent (or present with low similarity) in nonpathogenic strains. Nine antigens were protective in a mouse challenge model. Some of them were also present in other pathogenic non-ExPEC strains, suggesting that a broadly protective E. coli vaccine may be possible. The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains.
Aims
The impact of atrial fibrillation (AF) ablation in early heart failure with preserved ejection fraction (HFpEF) is unknown. Our aim was to determine the impact of AF ablation on symptoms and ...exercise haemodynamic parameters of early HFpEF.
Methods and results
Symptomatic AF patients referred for index AF ablation with ejection fraction ≥50% underwent baseline quality of life questionnaires, echocardiography, cardiac magnetic resonance imaging, exercise right heart catheterisation (exRHC), and brain natriuretic peptide (BNP) testing. HFpEF was defined by resting pulmonary capillary wedge pressure (PCWP) ≥15 mmHg or peak exercise PCWP ≥25 mmHg. Patients with HFpEF were offered AF ablation and follow‐up exRHC ≥6 months post‐ablation. Of 54 patients undergoing baseline evaluation, 35 (65%) had HFpEF identified by exRHC. HFpEF patients were older (64 ± 10 vs. 54 ± 13 years, P < 0.01), and more frequently female (54% vs. 16%, P < 0.01), hypertensive (63% vs. 16%, P < 0.001), and suffering persistent AF (66% vs. 11%, P < 0.001), compared to those without HFpEF. Twenty HFpEF patients underwent AF ablation and follow‐up exRHC 12 ± 6 months post‐ablation. Nine (45%) patients no longer fulfilled exRHC criteria for HFpEF at follow‐up. Patients remaining arrhythmia free (n = 9, 45%) showed significant improvements in peak exercise PCWP (29 ± 4 to 23 ± 2 mmHg, P < 0.01) and Minnesota Living with Heart Failure (MLHF) score (55 ± 30 to 22 ± 30, P < 0.01) while the remainder did not (PCWP 31 ± 5 to 30.0 ± 4 mmHg, P = NS; MLHF score 55 ± 23 to 25 ± 20, P = NS).
Conclusion
Heart failure with preserved ejection fraction frequently coexists in patients with symptomatic AF and preserved ejection fraction. Restoration and maintenance of sinus rhythm in patients with comorbid AF and HFpEF improves haemodynamic parameters, BNP and symptoms associated with HFpEF.
Overview of the study illustrating the proportion of patients referred for consideration of atrial fibrillation (AF) ablation who met the criteria for heart failure with preserved ejection fraction (HFpEF) in panel A. Three‐dimensional reconstruction of the left atrium with radiofrequency lesions used to achieved pulmonary vein electrical isolation at the time of AF ablation in panel B and results of the follow‐up exercise right heart catheterisation at ≥6 months following AF ablation based on arrhythmia recurrence status in panel C. Panel D illustrates the potential interaction between AF and HFpEF. BNP, brain natriuretic peptide; LA, left atrial; LAPW, left atrial posterior wall; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; PCWP, pulmonary capillary wedge pressure; QoL, quality of life; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
Recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs during cell differentiation. However, recruitment of all TFs, ...including pioneer factors, is impeded by condensed H3K27me3-containing chromatin. Single-cell and gene-specific analyses revealed that, during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical “window of opportunity” for recruitment of lineage-specific TFs to DNA. Increasing the levels of post-replicative H3K27me3 or preventing S phase entry inhibited recruitment of new TFs to DNA and significantly blocked cell differentiation. These findings suggest that recruitment of lineage-specifying TFs occurs soon after replication and is facilitated by a decondensed chromatin structure. This insight may explain the developmental plasticity of stem cells and facilitate their exploitation for therapeutic purposes.
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•Induction of h/mESCs leads to increased association of UTX with nascent DNA•UTX prevents methylation of H3K27me3, creating a temporal window of “open” chromatin•“Open” nascent chromatin allows recruitment of lineage-specifying TFs to DNA•Blocking DNA replication or inhibiting UTX prevents association of TFs with DNA
Recruitment of TFs, including pioneer factors, is impeded by condensed H3K27me3-containing chromatin. Petruk et al. find that, following induction of ESC differentiation, accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, thus providing a “window of opportunity” for recruitment of lineage-specific TFs to nascent DNA.
Spinal cord injury (SCI) is an acute neurodegenerative disorder caused by traumatic damage of the spinal cord. The neuropathological evolution of the primary trauma involves multifactorial processes ...that exacerbate the pathology, worsening the neurodegeneration and limiting neuroregeneration. This complexity suggests that multi-therapeutic approaches, rather than any single treatment, might be more effective. Encouraging preclinical results indicate that stem cell-based treatments may improve the disease outcome due to their multi-therapeutic ability. Mesenchymal Stem Cells (MSCs) are currently considered one of the most promising approaches. Significant improvement in the behavioral outcome after MSC treatment sustained by hydrogel has been demonstrated. However, it is still not known how hydrogel contribute to the delivery of factors secreted from MSCs and what factors are released in situ.
Among different mediators secreted by MSCs after seeding into hydrogel, we have found CCL2 chemokine, which could account for the neuroprotective mechanisms of these cells. CCL2 secreted from human MSCs is delivered efficaciously in the lesioned spinal cord acting not only on recruitment of macrophages, but driving also their conversion to an M2 neuroprotective phenotype. Surprisingly, human CCL2 delivered also plays a key role in preventing motor neuron degeneration in vitro and after spinal cord trauma in vivo, with a significant improvement of the motor performance of the rodent SCI models.
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