Search Results (895)

Postpericardiotomy syndrome (PPS) is the most frequent inflammatory after-effect of cardiac surgery and is characterized by high morbidity, delayed hospitalization, and increased long-term mortality rates. Although PPS is common, empirical anti-inflammatory therapy has historically been employed for its prevention, and mechanism-based approaches have not yet been standardized. In this literature review, which was conducted on the basis of randomized controlled trials, meta-analyses, cohort studies, and mechanistic research regarding pharmacologic interventions, surgical modalities, and biomarker-based preventive strategies, the deficiencies of a critical synthesis of existing preventive strategies and emerging risk stratification instruments for PPS are addressed. The review affirms that the most evidence-based pharmacologic intervention is colchicine, which demonstrates a consistent reduction in PPS incidence across a range of randomized trials. Nonsteroidal anti-inflammatory drugs show variable responses, whereas corticosteroids are no longer recommended for routine prophylaxis due to relapse. Specific anti–interleukin-1 therapies represent a promising novel approach for high-risk patients. Surgical interventions, such as pericardial closure using biomaterials and posterior pericardiotomy, are important and do not lead to increased hemodynamic complications, while postoperative effusions, atrial fibrillation, and tamponade are reduced. Less invasive methods may also be employed to mitigate inflammatory causes, particularly in valve-sparing procedures and congenital operations. Emerging biomarker data, including postoperative neutrophil-to-lymphocyte ratios, C-reactive protein levels, and pericardial fluid cytokines, enable the identification of high-risk patients and form the basis for a personalized prevention approach. In summary, pharmacologic prophylaxis, innovative surgical techniques, and biomarker-based risk stratification represent a pathway toward reducing the incidence and burden of PPS in modern cardiac surgery. Full article

Premelanosomal protein (Pmel, also known as Pmel17) is the major component of melanosomal fibrils and plays a key role in melanin polymerization, making it an important factor in melanogenesis. We investigated how the absence of Pmel affects the properties of B16F10 melanoma cells. Pmel-knockout B16F10 cells were generated using CRISPR/Cas9-mediated genome editing. A viability assay revealed no significant differences between wild-type (WT) and Pmel-knockout (KO) sublines; however, melanosome maturation was impaired. In Pmel KO cells, the cell cycle was disrupted, and higher levels of reactive oxygen species (ROS) were observed compared with WT cells. Moreover, the migration capacity and tube formation of melanoma cells were increased. Tumors derived from Pmel KO cells exhibited unchanged growth kinetics but reduced melanin content, along with enhanced vascularization and oxygenation. Thus, knockout of the Pmel17 gene in melanoma cells alters pigmentation, vascularization, and oxygenation of tumors. These parameters are crucial for both tumor progression and therapeutic response. Full article

Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality, and its initiation and progression are closely associated with multiple molecular mechanisms. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and antimicrobial proteins that are released by neutrophils during inflammation or infection. They play a crucial role in innate immune defense. However, when the dynamic balance of NETs is disrupted by excessive formation, persistent accumulation, or impaired clearance, NETs are no longer merely bystanders. Instead, they actively drive pathological processes in multiple CVDs and serve as a critical link between inflammation and cardiovascular injury. Given the central role of NETs in CVD pathogenesis, including atherosclerosis, myocardial ischemia–reperfusion injury, pulmonary arterial hypertension, atrial fibrillation, and heart failure, therapeutic strategies targeting NETs, such as inhibiting aberrant formation, enhancing clearance, or neutralizing toxic components, have emerged as promising approaches. In recent years, traditional Chinese medicine (TCM) and natural products have shown potential therapeutic value by modulating NET formation and promoting NET degradation, owing to their multitarget, multipathway regulatory effects. This article reviews the mechanisms by which NETs operate in CVDs and explores potential pathways through which TCM and natural active ingredients prevent and treat CVDs by regulating NETs. This review provides theoretical support for further research and clinical application. Full article

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion. Full article

(1) Background: The synthetic eleven-amino acid peptide P₁₁-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P₁₁-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P₁₁-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P₁₁-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca²⁺ influx and a slight increase in ROS. Among the 84 genes examined, P₁₁-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P₁₁-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P₁₁-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells. Full article

The aggregation of tau protein is a central pathological event in Alzheimer’s disease, and this pathology is hypothesized to spread via a prion-like mechanism driven by tau “seeds”. While aggregated tau from Alzheimer’s disease brains is known to contain age-related d-isomerized aspartic acid (d-Asp) residues, it remains unknown how this modification affects the seeding activity that drives disease propagation. Here, we investigated the impact of site-specific d-isomerization within R2 and R3 tau repeat-domain peptides, which form the core of tau fibrils. We demonstrate that the stereochemical integrity of these peptides is critical for their seeding function. d-isomerization at Asp314 within the R3 peptide seed severely impaired its ability to template the fibrillization of full-length tau in vitro. This finding was validated in a cellular model, where R3 seeds containing d-Asp314 were significantly less potent at inducing the formation of phosphorylated tau aggregates compared to wild-type seeds. Our results establish that Asp d-isomerization within tau seeds acts as a potent attenuator of their pathological seeding activity, suggesting this spontaneous modification may intrinsically modulate the progression of Alzheimer’s disease. Full article

Background: Device-detected subclinical atrial fibrillation (SCAF) and atrial high-rate episodes (AHRE) are increasingly recognized in patients with cardiac implantable electronic devices and through long-term rhythm monitoring. Although often asymptomatic, these episodes are associated with a higher risk of clinical atrial fibrillation (AF), stroke, and heart failure. Aims: This narrative review summarizes clinical, electrocardiographic, echocardiographic, and circulating biomarkers associated with the development and progression of device-detected SCAF/AHRE. Methods: We performed a comprehensive search of PubMed, Embase, and Scopus using combinations of the terms “subclinical atrial fibrillation”, “atrial high-rate episodes”, “device-detected AF”, “predictive factors”, “P-wave morphology”, “echocardiographic parameters”, “left atrial strain”, and “biological markers”. We included English-language-only studies of patients with cardiac implantable electronic devices or long-term monitoring and reporting incident SCAF/AHRE or AF as outcomes, published in the last 10 years. Results: Older age, high body mass index, heart failure, obstructive sleep apnea, and C₂HEST score are consistently associated with SCAF. On-surface electrocardiogram (ECG) and device electrograms, prolonged and dispersed P-wave indices, low atrial sensing amplitude, and specific pacing configurations, particularly right ventricular apical pacing with wide QRS, predict incident and longer-lasting AHRE. Echocardiographic markers of atrial cardiomyopathy, including increased left atrial volume and impaired atrial strain, together with indices of left ventricular diastolic dysfunction, further refine risk. Among circulating biomarkers, galectin-3 and high-sensitivity C-reactive protein show the most reproducible associations with incident AHRE. Conclusions: A multiparametric approach combining clinical profile, ECG features, advanced echocardiography, and selected biomarkers may improve identification of patients at risk for device-detected SCAF. Further prospective studies are needed to define risk thresholds that justify intensified rhythm surveillance and early initiation of anticoagulation or rhythm control strategies, especially in AHRE shorter than 24 h. Full article

Necroptosis is an antiviral form of programmed cell death modulated by proteins that interact via RIP Homotypic Interaction Motifs (RHIMs). The result of the signaling pathways depends on which RHIM-containing proteins are involved: although both host and viral proteins contain RHIMs, virally encoded RHIM proteins, such as murine cytomegalovirus (MCMV)-encoded viral inhibitor of RIP activation (vIRA) serve to prevent cell death. Although every RHIM contains the same core four-amino-acid pattern, there are variations in individual sequences that we hypothesized would determine the differential outcomes in necroptotic signaling. As such, we replaced the RHIM in vIRA with the RHIMs from other proteins involved in the signaling cascade (RIPK1, RIPK3, ZBP1, ICP6) to assess the effect on necroptosis during MCMV infection. Although these RHIM-swap vIRA constructs remained able to bind to RIPK3, in the context of MCMV infection, they lost the ability to prevent necroptosis. These results are consistent with other studies that demonstrate that RHIM-containing proteins form amyloid fibrils unique to the proteins interfacing. Our results provide biological context for the growing model that the outcome of RHIM-based signaling is influenced by the specific amyloid fibril structures that are driven by the unique amino-acid sequences of each RHIM present. Full article

Despite the efficacy of catheter ablation in preventing recurrences of atrial fibrillation (AF), the reasons for its lack of success in some patients remain unknown. The aim of this study was to try to identify a new predictor of AF recurrence following catheter-based treatment. This prospective study enrolled a cohort of patients with AF. Based on the results of a one-year follow-up, patients were divided into two groups: Group 1 (“vein-dependent” AF)—patients who achieved a successful outcome after 1–2 catheter ablation procedures—and Group 2 (“non-vein-dependent” AF)—patients with confirmed complete pulmonary vein isolation (PVI) or with an identified “non-vein-dependent” AF substrate. Blood samples were collected prior to the procedure and biobanked. Initial proteomic profiling of the serum using protein microarrays identified several candidate proteins, whose elevated levels were subsequently confirmed by an enzyme-linked immunosorbent assay (ELISA). This article presents data on one such protein—TAG72. A comparison of TAG72 levels (%OD normalized units) between Group 1 (“vein-dependent” AF) and Group 2 (“non-vein-dependent” AF) revealed a statistically significant increase in the latter group (128.9 [98.2; 284.4] vs. 84.3 [73.8; 92.1], p < 0.001). These data provide the first evidence implicating TAG72 in the pathogenesis of AF. Full article

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. Full article

Aim: To analyse the importance of inflammation in the disease burden and prognosis of patients with type 2 diabetes (T2DM) and atrial fibrillation (AF). We assessed these patients according to their neutrophil-to-lymphocyte ratio (NLR) values, examining their baseline characteristics and their prognosis at one year of follow-up based on a prospective AF registry in Spain (Sumamos-FA-SEMI). Methods: A prospective, multicentre, observational study of patients with AF (Sumamos-FA-SEMI) was conducted. We categorised the patients into four groups according to the presence of T2DM and NLR levels with a reference cut-off point of three. We compared the characteristics of the four groups and evaluated the prognosis using the mean values of all-cause mortality and all-cause mortality plus readmissions during a year of follow-up. Results: We analysed 1071 patients, 482 of whom had T2DM. This group had significantly higher rates of obesity and comorbidities. Groups with an NLR greater than three points had a higher prevalence of cancer, lower HDL cholesterol levels, and more albuminuria. Other inflammatory markers, such as C-reactive protein, were also higher in these groups. Regarding prognosis, groups (both with and without T2DM) with an NLR greater than three had significantly higher mortality, with a higher probability in those without T2DM (HR 3.58, 95% CI: 1.99–6.43, p < 0.00). In terms of mortality and readmissions, only the group without T2DM and with an NLR greater than three had significantly higher mortality (HR 2.19, 95% CI: 1.51–3.19, p < 0.00). Conclusions: Among atrial fibrillation patients, the combination of T2DM and high inflammation (NLR) was linked to higher comorbidity, worse metabolic and kidney disease, and the poorest prognosis. Surprisingly, the highest risk of readmission or death was in non-T2DM patients with higher NLR levels, suggesting that T2DM treatments may mitigate risk. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia, and its initiation and progression involve multiple mechanisms, including electrical remodeling, structural remodeling, inflammatory responses, and oxidative stress. In recent years, the ubiquitin–proteasome system (UPS), a central pathway for maintaining intracellular protein homeostasis, has attracted increasing attention in the pathogenesis of AF. By regulating the degradation and expression of ion channel proteins, Ca²⁺-handling molecules, and pro-fibrotic signaling factors, the UPS plays a pivotal role in key pathological processes such as electrical and structural remodeling. Several E3 ubiquitin ligases (e.g., NEDD4-1/2, MuRF1, WWP1/2, TRAF6), deubiquitinating enzymes (e.g., JOSD2), and immunoproteasome subunits (e.g., β5i) have been shown to exert critical regulatory effects on atrial electrophysiological disturbances, interstitial remodeling, and inflammation. This review provides a comprehensive summary of the regulatory mechanisms of the UPS in AF-associated pathological processes, outlines potential therapeutic targets, and highlights current intervention strategies, including proteasome inhibitors, selective E3 ligase modulators, and natural compounds. Moreover, we discuss the latest advances and future perspectives regarding the application of UPS-based interventions in AF, aiming to provide theoretical foundations and research insights for the mechanistic exploration and innovative therapeutic development of AF. Full article

Background/Objectives: New-onset atrial fibrillation (NOAF) frequently develops in patients with chronic coronary syndrome (CCS) and is associated with adverse cardiovascular outcomes. The C-reactive protein–to–albumin ratio (CAR) reflects systemic inflammation, whereas left atrial diameter (LAD) indicates structural cardiac remodeling. Their combined predictive role for NOAF in CCS remains uncertain. This study evaluated the predictive value of combined CAR and LAD for NOAF in CCS patients. Methods: We retrospectively analyzed 2431 CCS patients treated at the Third Affiliated Hospital of Sun Yat-sen University between 2012 and 2019. The primary endpoint was NOAF occurrence during follow-up. Receiver operating characteristic (ROC) analysis determined exploratory cutoff values for CAR (0.0429) and LAD (33.96 mm). Patients were categorized into four groups: Group 1 (low CAR–low LAD), Group 2 (high CAR–low LAD), Group 3 (low CAR–high LAD), and Group 4 (high CAR–high LAD). Cox proportional hazards, Kaplan-Meier, and subgroup analyses were conducted to evaluate associations with NOAF risk. Results: During a median follow-up of 4.96 years, 93 NOAF events were identified. Compared with the Group 1, patients with higher CAR and LAD showed significantly elevated NOAF risk (HR = 2.67, 95%CI 1.99–3.57, p < 0.001). The combined CAR–LAD model demonstrated superior predictive accuracy (AUC = 0.731, 95% CI = 0.654–0.765; p < 0.001) and consistent effects across most subgroups. Decision curve analysis confirmed greater net clinical benefit for the combined model. Conclusions: The integration of CAR and LAD serves as a simple, non-invasive, and effective tool for predicting NOAF in CCS patients. This dual-marker model facilitates early identification of high-risk individuals and support personalized preventive strategies in clinical practice. Full article

The formation of mixed adsorption layers of amyloid fibrils of a plant protein, oat globulin (OG), and a strong polyelectrolyte, sodium polystyrene sulfonate (PSS), at the liquid–gas interface was studied by measurements of the kinetic dependencies of surface tension, dynamic surface elasticity, and ellipsometric angle. The micromorphology of the layers was determined by atomic force microscopy. A strong increase in the surface elasticity was discovered when both components had similar concentrations and formed a network of threadlike aggregates at the interface, thereby explaining the high foam stability in this concentration range. The sequential adsorption of PSS and OG resulted in the formation of thick mixed multilayers and the surface elasticity increased with the number of duplex layers. Full article

Bacterial biofilms are critical contributors to chronic infections and antimicrobial resistance. Among the diverse extracellular matrix components, extracellular DNA (eDNA) and amyloid proteins have recently emerged as pivotal structural and functional molecules. Both individually contribute to biofilm stability and antibiotic tolerance, yet their cooperative roles remain underappreciated. This review aims to summarize current knowledge on the origins and functions of eDNA and amyloid proteins in biofilms, to highlight their molecular interactions, and to discuss how their synergistic effects promote biofilm-mediated resistance to antimicrobial agents. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases up to September 2025. Keywords included “biofilm”, “extracellular DNA”, “amyloid proteins”, “matrix”, and “antimicrobial resistance”. Relevant original research and review articles were systematically screened and critically analyzed to integrate emerging evidence on eDNA–amyloid interactions in bacterial biofilms. Current studies demonstrate that eDNA originates primarily from autolysis, active secretion, and host-derived DNA, while amyloid proteins are produced by multiple bacterial species, including Escherichia coli (curli), Pseudomonas aeruginosa (Fap), Bacillus subtilis (TasA), and Staphylococcus aureus (phenol-soluble modulins). Both molecules independently strengthen biofilm integrity and provide protective functions against antimicrobial agents. Importantly, recent evidence shows that eDNA can act as a nucleation template for amyloid fibrillation, while amyloid fibers stabilize and protect eDNA from degradation, creating a dense extracellular network. This synergistic eDNA–amyloid assembly enhances biofilm robustness, impedes antibiotic penetration, sequesters antimicrobial peptides, protects persister cells, and facilitates horizontal gene transfer of resistance determinants. The interplay between eDNA and amyloid proteins represents a central but underexplored mechanism driving biofilm-mediated antimicrobial resistance. Understanding this cooperative network not only deepens our mechanistic insights into bacterial pathogenesis but also highlights novel therapeutic targets. Strategies that disrupt eDNA–amyloid interactions may offer promising avenues for combating persistent biofilm-associated infections. Full article