Lung transplantation: Current insights and outcomes.

Until now, the ability to predict or retard immune-mediated rejection events after lung transplantation is still limited due to the lack of specific biomarkers. The pressing need remains to early diagnose or predict the onset of chronic lung allograft dysfunction (CLAD) and its differential phenotypes that is the leading cause of death. Omics technologies (mainly genomics, epigenomics, and transcriptomics) combined with advanced bioinformatic platforms are clarifying the key immune-related molecular routes that trigger early and late events of lung allograft rejection supporting the biomarker discovery.

Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy.

Although there are different data supporting benefits of HLA matching in kidney transplantation, its role in heart transplantation is still unclear. HLA mismatch (MM) between donor and recipient can lead to the development of donor-specific antibodies (DSA) which produces negative events on the outcome of heart transplantation. Moreover, DSAs are involved in the development of antibody-mediated rejection (AMR) and are associated with an increase in cardiac allograft vasculopathy (CAV).

Reduced levels of hepcidin associated with lower ferritin concentration and increased number of previous donations in periodic blood donors: A pilot study.

Background: Hepcidin is one of the major negative regulators of iron balance. Periodic blood donors are highly susceptible to iron deficiency. Our goal was to evaluate the possible association between serum hepcidin levels and iron homeostasis parameters in periodic blood donors.

Novel insights in the clinical management of hyperimmune patients before and after transplantation.

Despite improvements in anti-Human Leucocyte Antigens antibody detection, identification, and characterization offer a better in peri-operative management techniques, antibodies remain a serious cause of morbidity and mortality for patients both before and after organ transplantation. Hyperimmune patients are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. They could benefit from desensitization protocols in both pre- and post-transplantation period.

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts.

Background: High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control.

Objectives: We investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1-9, Ang 1-7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts.

Evaluation of circulating leucocyte populations both in subjects with previous SARS-COV-2 infection and in healthy subjects after vaccination.

Innate immune mechanisms are central players in response to the binding of pathogens to pattern-recognition receptors providing a crucial initial block on viral replication. Moreover, innate immune response mobilizes cells of the cellular-mediated immune system, which develop into effector cells that promote viral clearance. Here, we observed circulating leukocyte T cell response in healthy subjects, COVID-19 infected, and in healthy vaccinated subjects.

Machine Learning and Bioinformatics Framework Integration to Potential Familial DCM-Related Markers Discovery.

Objectives: Dilated cardiomyopathy (DCM) is characterized by a specific transcriptome. Since the DCM molecular network is largely unknown, the aim was to identify specific disease-related molecular targets combining an original machine learning (ML) approach with protein-protein interaction network.

Methods: The transcriptomic profiles of human myocardial tissues were investigated integrating an original computational approach, based on the Custom Decision Tree algorithm, in a differential expression bioinformatic framework.

Radiogenomics and Artificial Intelligence Approaches Applied to Cardiac Computed Tomography Angiography and Cardiac Magnetic Resonance for Precision Medicine in Coronary Heart Disease: A Systematic Review.

The risk of coronary heart disease (CHD) clinical manifestations and patient management is estimated according to risk scores accounting multifactorial risk factors, thus failing to cover the individual cardiovascular risk. Technological improvements in the field of medical imaging, in particular, in cardiac computed tomography angiography and cardiac magnetic resonance protocols, laid the development of radiogenomics. Radiogenomics aims to integrate a huge number of imaging features and molecular profiles to identify optimal radiomic/biomarker signatures.

Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts.

Background: The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment.

and DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome network analysis.

Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease.We performed an epigenome-wide analysis of circulating CD4 and CD8 T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4 T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients HS.

Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte.

Rationale: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance.

Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?

The rapid increase in obesity, metabolic syndrome, and cardiovascular diseases (CVDs) has been related to the rise in sugar-added foods and sweetened beverages consumption. An interesting approach has been to replace sugar with alternative sweeteners (AS), due to their impact on public health. Preclinical and clinical studies, which analyze the safety of AS intake, are still limited.

The human aortic endothelium undergoes dose-dependent DNA methylation in response to transient hyperglycemia.

Background: Glycemic control is a strong predictor of long-term cardiovascular risk in patients with diabetes mellitus, and poor glycemic control influences long-term risk of cardiovascular disease even decades after optimal medical management. This phenomenon, termed glycemic memory, has been proposed to occur due to stable programs of cardiac and endothelial cell gene expression. This transcriptional remodeling has been shown to occur in the vascular endothelium through a yet undefined mechanism of cellular reprogramming.

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study.

Aims: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features.

Methods: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study.

Flow Cytometry Characterization of Pluripotent Transmembrane Glycoproteins on Resident Cervix Uteri Cells in Patients Screened for Cervical Cancer.

The aim of this study was to characterize both by flow cytometry analysis and immunohistochemistry cervix uteri cells of women screened for cervical intraepithelial neoplasia (CIN) in comparison to a group without CIN by using mesenchymal stem cell-like and hematopoietic lineage markers. A significant expression for CD29, CD38, HLA-I, and HLA-II was correlated positively to the CIN degree and it was more relevant in patients positive for human papilloma virus (HPV). Thus, identification and detailed characterization of pluripotent resident in cells could be a promising therapeutic target.

Non-nutritional sweeteners effects on endothelial vascular function.

Aim: Hyperglycemia status induces endothelial dysfunction, although the underlying pathogenic mechanisms are not fully understood. There are several studies connecting sugar/sweetened beverages to the cardiovascular disease. Currently, many sweeteners have been extensively introduced into lifestyle to normalize blood glucose levels without altering the sweet taste.

Genetic and epigenetic-sensitive regulatory network in immune response: a putative link between HLA-G and diabetes.

Introduction: Human leukocyte antigen-G (HLA-G) gene encodes for a tolerogenic molecule constitutively expressed in human pancreas and upregulated upon inflammatory signals. The 14 bp INS/DEL polymorphism in the 3'UTR of HLA-G may influence the susceptibility for diabetes and coronary heart diseases (CHD), thus suggesting a novel candidate gene. DNA hypomethylation at HLA-G promoter may be a putative useful clinical biomarker for CHD onset.

Sweeteners modulate bioactivity of endothelial progenitor cells but not induce detrimental effects both on inflammation and behavioural changes.

This study sought to determine the possible detrimental effects of several low- or non-caloric sweeteners on endothelial progenitor cells (EPCs), inflammation and behavioural changes in mice. C57BL/6 male mice received low and high dose of natural and artificial sweeteners for 4 weeks. EPCs, physical and biochemical variables, inflammation and behavioural changes were evaluated.

Potential clinical benefits of cell therapy in coronary heart disease: an update.

Cell therapy is a central issue of regenerative medicine and is raising a growing interest in the scientific community, but its full therapeutic potential in coronary heart disease (CHD) has not been reached yet. Several different methods, cell types, delivery routes, and supporting techniques have been attempted and improved to elicit cardiac regeneration in CHD, but only some of them showed a really convincing potential for the use in clinical practice. Here we provide an update on approaches and clinical trials of cell therapy applied to CHD, which are ongoing or that have been realized in the last 5 years.

HLA-G and anti-HCV in patients on the waiting list for kidney transplantation.

Purpose: Human leukocyte antigen (HLA)-G is a non-classic major histocompatibility complex HLA class I molecule. HLA-G may have tolerogenic properties which are linked to epigenetic-sensitive pathways. There is a correlation of sHLA-G levels and graft acceptance in transplantation studies.

The epigenetic promise to improve prognosis of heart failure and heart transplantation.

Heart transplantation is still the only possible life-saving treatment for end-stage heart failure, the critical epilogue of several cardiac diseases. Epigenetic mechanisms are being intensively investigated because they could contribute to establishing innovative diagnostic and predictive biomarkers, as well as ground-breaking therapies both for heart failure and heart transplantation rejection. DNA methylation and histone modifications can modulate the innate and adaptive immune response by acting on the expression of immune-related genes that, in turn, are crucial determinants of transplantation outcome.

Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.

Background: Despite left ventricular (LV) dysfunction contributing to mortality in chronic heart failure (HF), the molecular mechanisms of LV failure continues to remain poorly understood and myocardial biomarkers have yet to be identified. The aim of this pilot study was to investigate specific transcriptome changes occurring in cardiac tissues of patients with HF compared to healthy condition patients to improve diagnosis and possible treatment of affected subjects.

Methods: Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family history of the disease were selected with the aim of obtaining a homogeneous population for the study.

Evidence of epigenetic tags in cardiac fibrosis.

In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such as DNA methylation, histone modifications, and miRNAs have been involved in these mechanisms.