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The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. Thus, several members of the DAMP family, such as the well-characterized heat shock proteins (HSPs) HSP70 and HSP90, the high-mobility group box 1 protein and calreticulin, and the thymic polypeptide prothymosin α (proTα) and its immunoreactive fragment proTα(100–109), are being studied as potential diagnostic tools and/or possible therapeutic agents. Here, we present the basic aspects and mechanisms of both ICD and other immunogenic RCD forms; denote the role of DAMPs in ICD; and further exploit the relevance of human proTα and proTα(100–109) in ICD, highlighting their possible clinical applications. Furthermore, we present the preliminary results of our in vitro studies, which show a direct correlation between the concentration of proTα/proTα(100–109) and the levels of cancer cell apoptosis, induced by anticancer agents and γ-radiation.

Cardiac arrhythmias are increasingly recognized as dynamic clinical phenotypes arising from the interplay between myocardial substrate, systemic biology, and modifiable exposures rather than as isolated disorders of cardiac electrophysiology. Advances in the field have broadened the conceptual framework of arrhythmia medicine to include structural remodeling, inflammation, autonomic dysfunction, metabolic perturbation, endothelial injury, and aging-related vulnerability as central determinants of arrhythmic risk, progression, and treatment response. In parallel, diagnostic paradigms are evolving from rhythm classification alone toward multidimensional phenotyping that integrates clinical, physiological, and imaging-based markers to identify susceptibility earlier and with greater precision. These developments are also reshaping therapeutic strategy, supporting a shift from uniform treatment algorithms toward individualized care in which rhythm control, surveillance, risk-factor modification, anticoagulation, and antiarrhythmic drug selection are aligned with the underlying biological context. This more integrated view positions arrhythmias not simply as electrical events to be suppressed, but as manifestations of broader cardiovascular and systemic disease processes that require mechanistically informed and phenotype-directed management.

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance.

PurposeAcute high-intensity unaccustomed eccentric exercise performed by naive subjects is accompanied by disturbances in muscle damage biomarkers. The aim of the study was to investigate whether a causal relationship indeed exists between eccentric exercise and muscle damage.MethodsTwenty-four men randomly assigned into a concentric only or an eccentric-only training group and performed 10 weeks of isokinetic resistance exercise (one session/week of 75 maximal knee extensors actions). Physiological markers of muscle function and damage (i.e., range of motion, delayed onset muscle soreness, isometric, concentric and eccentric peak torque) were assessed prior to and 1–3 and 5 days post each session. Biochemical markers of muscle damage (creatine kinase) and inflammation (C-reactive protein) were measured prior and 2 days post each session.ResultsAfter the first bout, eccentric exercise induced greater muscle damage compared to concentric exercise; however, during the nine following sessions, this effect progressively diminished, while after the 10th week of training, no alterations in muscle damage biomarkers were observed after either exercise protocol. Additionally, strength gains at the end of the training period were comparable between the two groups and were mode-specific.Conclusion(1) eccentric exercise per se does not affect muscle damage biomarkers; (2) muscle damage occurs as a result of muscle unaccustomedness to this action type; (3) exercise-induced muscle damage is not a prerequisite for increased muscle strength. Collectively, we believe that muscle unaccustomedness to high-intensity eccentric exercise, and not eccentric exercise per se, is the trigger for muscle damage as indicated by muscle damage biomarkers.

Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays a pivotal role in the pathogenesis of atrial fibrillation (AF), contributing to its onset and progression. The mechanisms underlying atrial fibrosis are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, and coagulation pathways. Variations in fibrosis types—reactive and replacement fibrosis—are influenced by patient-specific factors such as age, sex, and comorbidities, complicating therapeutic approaches. The heterogeneity of fibrosis leads to distinct electrophysiological abnormalities that promote AF via reentrant activity and enhanced automaticity mechanisms. Despite advancements in imaging, such as late gadolinium enhancement CMR and electroanatomical mapping, challenges in accurately quantifying fibrosis persist. Emerging therapeutic strategies include antifibrotic agents targeting the renin–angiotensin–aldosterone system, novel pathways like TGF-β signaling, and cardio-metabolic drugs like SGLT2 inhibitors and GLP-1 receptor agonists. Innovative interventions, including microRNA modulation and lipid nanoparticle-based therapies, show promise but require validation. Knowledge gaps remain in correlating clinical outcomes with fibrosis patterns and optimizing diagnostic tools. Future research should focus on precise phenotyping, integrating advanced imaging with molecular biomarkers, and conducting robust trials to evaluate antifibrotic therapies’ efficacy in reducing AF burden and related complications.

The global rise in diabetes prevalence has significantly contributed to the increasing burden of atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality in this population. Diabetes accelerates atherosclerosis through mechanisms such as hyperglycemia, oxidative stress, chronic inflammation, and epigenetic dysregulation, leading to unstable plaques and an elevated risk of cardiovascular events. Despite advancements in controlling traditional risk factors like dyslipidemia and hypertension, a considerable residual cardiovascular risk persists, highlighting the need for innovative therapeutic approaches. Emerging treatments, including sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, epigenetic modulators, and RNA-based therapies, are showing promise in addressing the unique challenges of diabetes-associated ASCVD. Precision medicine strategies, such as nanoparticle-based drug delivery and cell-specific therapies, offer further potential for mitigating cardiovascular complications. Advances in multiomics and systems biology continue to deepen our understanding of the molecular mechanisms driving diabetes-associated atherosclerosis. This review synthesizes recent advances in understanding the pathophysiology and treatment of diabetes-related atherosclerosis, offering a roadmap for future research and precision medicine approaches to mitigate cardiovascular risk in this growing population.

Obesity-associated inflammation underlies much of cardiometabolic pathology, reflecting the convergence of chronic, low-grade systemic immune activation with region-specific maladaptation of adipose depots. Among these, epicardial adipose tissue (EAT)—a visceral fat layer contiguous with the myocardium and sharing its microvasculature—functions as a cardio-proximal immunometabolic interface that influences atrial fibrillation, heart failure with preserved ejection fraction, and coronary atherogenesis through paracrine crosstalk. These relationships extend beyond crude measures of adiposity, emphasizing the primacy of local inflammatory signaling, adipokine flux, and fibro-inflammatory remodeling at the EAT–myocardium interface. Of importance, substantial weight reduction only partially reverses obesity-imprinted transcriptional and epigenetic programs across subcutaneous, visceral, and epicardial depots, supporting the concept of an enduring adipose memory that sustains cardiovascular (CV) risk despite metabolic improvement. Accordingly, therapeutic strategies should move beyond weight-centric management toward mechanism-guided interventions. Resolution pharmacology—leveraging specialized pro-resolving mediators and their cognate G-protein-coupled receptors—offers a biologically plausible means to terminate inflammation and reprogram immune–stromal interactions within adipose and CV tissues. Although preclinical studies report favorable effects on vascular remodeling, myocardial injury, and arrhythmic vulnerability, clinical translation is constrained by pharmacokinetic liabilities of native mediators and by incomplete validation of biomarkers for target engagement. This review integrates mechanistic, depot-resolved, and therapeutic evidence to inform the design of next-generation anti-inflammatory strategies for obesity-related CV disease.

Cardiac arrhythmias, including atrial fibrillation and ventricular arrhythmias, remain leading causes of morbidity and mortality worldwide. While structural, electrical, and metabolic remodeling have long been recognized as drivers of arrhythmogenesis, emerging evidence identifies inflammation—particularly inflammasome signaling—as a central orchestrator of this pathological triad. Among the various inflammasome complexes, the NLRP3 inflammasome has garnered particular attention due to its activation in cardiomyocytes, fibroblasts, and immune cells in diverse clinical contexts. NLRP3 activation precipitates a cascade of downstream events, including interleukin-1β and -18 maturation, oxidative stress amplification, calcium mishandling, and extracellular matrix remodeling, thereby fostering a proarrhythmic substrate. This review synthesizes mechanistic and translational data implicating inflammasome signaling in both atrial and ventricular arrhythmias, with a focus on cellular specificity and electrophysiological sequelae. We explore upstream triggers, such as metabolic stress, gut dysbiosis, and epicardial adipose inflammation, and delineate the downstream impact on cardiac conduction and structural integrity. Emerging therapeutic strategies—including NLRP3 inhibitors, IL-1 antagonists, colchicine, and SGLT2 inhibitors—are critically appraised for their anti-inflammatory and antifibrotic potential. By bridging molecular insights with clinical application, this review underscores the inflammasome as a unifying mechanistic hub in arrhythmia pathogenesis and a promising target for precision-guided therapy.

The explicit demand response (DR) is a key program for reinforcing the participation of end customers and making the most out of the potential of the smart grid. The DR is a key topic in the field of buildings to make use of the flexibility that they can offer. However, in order to guarantee the correct functionality of a DR system, it is fundamental to perform interoperability tests among the various components/actors. In this paper, we take into consideration the technological solutions suggested in the framework of the DRIMPAC project to enable the DR in buildings. We consider all actors/devices involved in order to reach the objective of executing a flexibility order by an asset. Following a structured interoperability testing methodology created by the Joint Research Centre, we perform interoperability tests regarding all critical links of the full chain of interacting actors to obtain the DR in buildings. The results show that the system functions properly and the benefits from the DR can be exploited. On the other hand, we provide a concrete example of how to apply the interoperability methodology in the field of testing the DR in buildings.

Aortic stenosis (AS), the most prevalent valvular heart disease, is increasingly recognized as an active disease process driven by a convergence of hemodynamic stress, inflammation, oxidative injury, and metabolic remodeling. While transcatheter and surgical valve replacement remain the standard interventions for severe AS, they fail to reverse the chronic myocardial remodeling that underlies adverse outcomes in many patients. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have emerged as promising cardioprotective agents, with effects extending well beyond glycemic control. Recent mechanistic studies reveal that SGLT2 is expressed in the myocardium of patients with AS and is linked to pathways of fibrosis, inflammation, and energetic dysfunction. Experimental models and translational data demonstrate that SGLT2 inhibition attenuates maladaptive remodeling through modulation of TGF-β, NF-κB, NLRP3 inflammasome, and oxidative stress signaling while enhancing mitochondrial energetics and endothelial function. Importantly, clinical evidence from randomized and real-world studies suggests that SGLT2 inhibitors improve heart failure outcomes following valve replacement and may slow AS progression. This review integrates current pathophysiological insights with emerging molecular and clinical data to delineate the therapeutic rationale for SGLT2 inhibition in AS. By targeting both myocardial and valvular components of the disease, SGLT2 inhibitors may offer a novel disease-modifying strategy with potential implications across the AS continuum—from asymptomatic stages to the post-interventional setting. Ongoing and future trials are warranted to define optimal patient selection, timing, and biomarkers for response to SGLT2 inhibitor therapy in this increasingly high-risk population.