Search Results (51,748)

Early engagement with psychotherapy is a public mental health issue because potential patients’ first appraisals of psychological care may shape treatment expectations, willingness to continue, and openness to receiving effective support. In first-contact therapeutic encounters, people respond not only to the content of a therapist’s intervention but also to the interpersonal meaning conveyed by the therapist’s response style. Guided by a recognition–resistance framework and models of narcissistic self-regulation, we examined how therapist response style and trait narcissistic admiration and rivalry shape early appraisals of psychological care in a vignette-based psychotherapeutic encounter. In a between-subjects vignette experiment, Hebrew-speaking adults in Israel (N = 972) were randomly assigned to read a validation-based, recognition-supportive, autonomy-supportive therapist response or a more directive and challenging response to the same clinical scenario. Participants then reported perceived recognition, autonomy-related resistance, anticipated alliance, therapist credibility, expected benefit, and willingness to continue. The validation-based response elicited higher perceived recognition, lower autonomy-related resistance, and greater willingness to continue. Perceived recognition and autonomy-related resistance mediated the effects of response style on all therapy-related outcomes. Narcissistic admiration predicted more favorable appraisals, and narcissistic rivalry predicted lower recognition and greater resistance, but neither moderated style effects nor indirect pathways. Recognition and autonomy-related resistance emerged as proximal appraisal pathways linking therapist response style to anticipated engagement with psychological care in this analogue vignette context. However, the predicted moderation and moderated-mediation effects involving narcissistic admiration and rivalry were not supported. This pattern suggests that, in the present design, admiration and rivalry functioned more as general appraisal orientations than as differential-susceptibility moderators of therapist response style. The moderated-mediation component of the recognition–resistance framework should therefore be regarded as unsupported pending independent replication and more ecologically valid tests. These findings position first-contact therapist communication as a candidate modifiable feature of public mental health engagement, with implications for future research on treatment uptake, early retention, trust in services, and access to effective psychological care. Full article

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus–host interactions, especially protein–protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction. Full article

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance. Full article

Stingless bees, or meliponines, are essential pollinators in Brazil, with over 300 described species. These bees produce propolis or geopropolis (characterized by the incorporation of mineral material and clay) used to protect their nests. This product has aroused increasing scientific interest due to its therapeutic potential, including antimicrobial and anti-inflammatory activities. However, there is still limited knowledge about its volatile composition, which can vary according to the bee species and the botanical origin of the resins, influencing their biological and aromatic properties. The purpose of this study was to characterize the volatile composition of (geo)propolis produced by different species of native stingless bees from the Southeastern region of Brazil (São Paulo and Minas Gerais) and to detect if this composition is influenced by the species or by the region. The samples were analyzed by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography–mass spectrometry (GC-MS). The results indicated that, despite some variations, the chemical profile for each species was mostly constant between regions. In São Paulo, about 25% of the features varied between species, whereas in Minas Gerais, only 5% showed significant differences, although one species (Melipona quadrifasciata) presented a very constant composition. Although the local vegetation determines the supply of resins for these bees, differences in the chemical composition of propolis are a result of a species’ choice of plant species. Full article

Background/Objectives: Diagnostic metabolites measured in newborn screening, inherited metabolic disease, lysosomal storage disease, oncometabolite testing and routine clinical biochemistry are direct read-outs of human metabolic state. Their mechanistic interpretation requires linking measured metabolites to enzymes, pathways, regulatory context, disease knowledge and, increasingly, AI-assisted quantitative systems pharmacology (AI-QSP) workflows. We developed EHMN2026^®T as a license-aware AI-QSP integration framework that connects the EHMN2026^® metabolic backbone with licensed geneXplain knowledge resources while keeping ownership, licensing and redistribution constraints explicit. Methods: EHMN2026^®T integrates the SBML-encoded EHMN2026^® metabolic backbone with licensed TRANSFAC^® 2025.2, TRANSPATH^® 2025.2 and HumanPSD™ 2025.2 resources. TRANSFAC^® position weight matrices were used for promoter-level analysis of EHMN metabolic genes. The resulting transcription factor (TF)–gene connections were mapped to EHMN genes, TRANSPATH^® signalling/molecular-state entries and HumanPSD™ disease/drug context. The framework is positioned as a controlled component of the IQANOVA AI-QSP environment, but only aggregate statistics, non-proprietary EHMN-derived summaries and manuscript-level examples are reported publicly unless separate permission is obtained from the relevant rightsholders. Results: Promoter analysis of 1681 EHMN2026^® metabolic genes using 1147 mapped TRANSFAC^® matrices identified 291,387 ENSG-level TF–gene regulatory-potential connections involving 398 TFs and 1,107,264 predicted binding sites. The diagnostic panel contained 80 covered genes (63.5%), including complete coverage of oncometabolite enzymes and high coverage of organic acidaemia, steroidogenesis and fatty-acid oxidation categories. Mapping to TRANSPATH^® expanded the EHMN genes into 144,529 molecular-state representations and 14,879 gene–pathway or gene–chain pairs. HumanPSD™ was used as a licensed translational context layer; EHMN-specific HumanPSD™ outputs are treated as license-controlled derived outputs and are therefore not redistributed as open detailed tables in this manuscript. Conclusions: EHMN2026^®T provides a license-aware AI-QSP integration framework for tracing a diagnostic metabolite from a measured clinical value to candidate enzyme nodes, regulatory potential, signalling/molecular-state context and disease or therapeutic interpretation. PWM-derived TF–gene links are presented as regulatory hypotheses, not proof of active regulation. Public release should be limited to aggregate statistics and non-proprietary EHMN-derived components; detailed TRANSFAC^®, TRANSPATH^® and HumanPSD™-derived edges, mappings, annotations and SBML outputs remain subject to geneXplain ownership and licensing terms. Full article

Since 2020, recurrent waves of SARS-CoV-2 infection have persisted globally. Despite the advancements in vaccines and pharmacological treatments, a subset of patients still exhibits an aggressive form of COVID-19 requiring prolonged stays in the intensive care unit (ICU) or experiences major acute infections (or reinfections) and long-term symptoms. Endothelial dysfunction is one of the key events contributing to both the severity of acute COVID-19 and the development of long COVID (LC)/post-acute sequelae of SARS-CoV-2 infection (PASC) syndrome. Since the beginning of the pandemic, the efficacy of nutraceuticals, particularly essential micronutrients, has been investigated as a complementary treatment to prevent disease onset and improve clinical outcomes. One such bioactive molecule is folate (vitamin B9), a member of the B-vitamin family involved in the pathogenesis of multiple diseases, including viral infections and vascular disorders. This review examines the role of folic acid in COVID-19 and its interaction with homocysteine metabolism, which is frequently dysregulated in inflammatory endothelial diseases. It further discusses the potential benefits of folic acid supplementation for the prevention and treatment of COVID-19 in both the acute and long-term phases of the disease, alongside the therapeutic role of vitamin B12 supplementation in LC syndrome. Full article

Chronic hyperglycemia and excessive reactive oxygen species (ROS) production are defining features of endothelial dysfunction, a key driver of diabetic vascular complications such as diabetic nephropathy. Microvesicles (MV-enriched fraction), a subtype of extracellular vesicles, and the stress-responsive antioxidant protein Sestrin2 (SESN2) have emerged as important contributors to these processes. This study investigated the role of the MV-enriched fraction in endothelial cell communication under diabetic conditions, with a particular focus on oxidative stress signaling. To model diabetic injury, EA.hy926 endothelial cells were treated with methylglyoxal (MGO), and the resulting MV-enriched fraction was isolated and then applied to two recipient models: naïve endothelial cells and SESN2 knockdown (KD) cells. Protein expression of key antioxidant markers, including endothelial nitric oxide synthase (eNOS), was assessed by Western blot. Nitric oxide (NO) bioavailability was quantified via nitrite measurement using 2,3-diaminonaphthalene (DAN), while mitochondrial and cytosolic ROS levels were evaluated using MitoSOX and dihydroethidium (DHE), respectively. Results demonstrated that the MV-enriched fraction derived from diabetic conditions triggers a complex antioxidant response in healthy endothelial cells, characterized by upregulation of SESN2, superoxide dismutase 1 (SOD1), and heme oxygenase-1 (HO-1). This suggests a compensatory mechanism that mitigates oxidative stress. Notably, SESN2 KD cells exhibited increased ROS production and reduced NO levels upon MV treatment, underscoring the essential role of SESN2 in maintaining redox homeostasis. Overall, this study highlights the dual role of the MV-enriched fraction as a mediator of both protective and detrimental redox signaling in diabetic endothelial dysfunction and suggests potential therapeutic targets for managing diabetic vascular complications. Full article

Diabetes mellitus (DM) is a highly prevalent metabolic disorder and a major public health concern. Pioglitazone, a widely used antidiabetic agent, exhibits limited therapeutic efficiency due to poor water solubility and suboptimal pharmacokinetic properties. Similarly, curcumin (Cur), a natural polyphenol with pleiotropic biological activities, is hindered by low oral bioavailability. In this study, chitosan-based nanocarriers were developed for the delivery of pioglitazone (CS-Pio NPs), curcumin (CS-Cur NPs), and their co-encapsulation (CS-Pio-Cur NPs), aiming to enhance their biological performance and therapeutic efficacy. The co-loaded nanosystem (CS-Pio-Cur NPs) demonstrated significantly enhanced antioxidant activity, as evidenced by DPPH (71.29 ± 0.09%), ABTS (86.08 ± 0.04%), and hydroxyl radical scavenging (87.08 ± 0.06%) assays, along with a strong reducing capacity (IC₅₀ = 25.39 ± 0.23 μg/mL). In a diabetic rat model, CS-Pio-Cur NPs significantly reduced blood glucose level and HbA1c (6.60 ± 0.83%), while also improving liver and kidney function parameters and lipid profile. These findings suggest that co-delivery of Pio and Cur via CS-based nanocarriers provides a combined therapeutic effect by simultaneously targeting hyperglycemia, oxidative stress, and associated metabolic dysfunctions. This nanosystem represents a promising approach for improving the management of DM and its complications. Full article

Atherosclerosis is a chronic multifactorial inflammatory vascular disease and the major risk factor for cardiovascular diseases (CVDs), characterized by arterial wall thickening, loss of arterial elasticity and the progressive accumulation of lipids and immune cells, ultimately leading to plaque formation and the development of unstable, rupture-prone plaques. Several studies suggest that gut microbiota might contribute to atherosclerosis, mainly by converting dietary and endogenous molecules into bioactive metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and the Gram-negative cell-wall component lipopolysaccharide (LPS). Such metabolites can promote key mechanisms involved in the development and progression of atherosclerotic plaque, and, importantly, plaque vulnerability. Specifically, they can worsen endothelial dysfunction, induce macrophage-driven inflammatory responses, and cause oxidative stress and extracellular matrix degradation. These processes are crucial for thinning of the fibrous cap and destabilization of atherosclerotic plaques. As a result, the risk of plaque rupture and related cardiovascular events increases. In this review, we summarize potential mechanisms by which the gut microbiota and their compounds induce the formation of vulnerable atherosclerotic plaques and discuss findings from experimental models and clinical studies that reveal the crucial role of microbiota–host dynamics in atherosclerosis. In contrast to previous reviews that primarily focused on atherosclerosis development, we specifically highlight the cellular and molecular mechanisms linking gut microbiota to plaque vulnerability and destabilization. We also address future research priorities to define microbiota-driven pathways better and develop targeted therapeutic interventions to reduce plaque vulnerability and cardiovascular risk. Full article

Satureja nepeta essential oil (EO) is gaining prominence for its multifaceted pharmacological and biotechnological potential. This study aimed to characterize its volatile profile and evaluate its functional capacity as an antioxidant, antibacterial, and antiproliferative agent. Gas Chromatography Mass Spectrometry (GC–MS) profiling was conducted to identify the volatile constituents of the EO. Antioxidant activity was assessed using DPPH, ABTS, TAC, and FRAP assays. Antibacterial activity was evaluated against Gram-positive and Gram-negative pathogens using disk diffusion and MIC determination. In silico molecular docking against bacterial DNA gyrase B was performed to explore potential mechanisms of action. Antiproliferative activity was assessed on the P3X63Ag8.653 myeloma cell line. Chemical profiling identified nine major constituents, dominated by pulegone (68.63%), menthol (6.64%), and cis-pulegol (2.04%). The EO demonstrated significant free radical-scavenging activity, particularly in the TAC assay (EC₅₀ = 3.747 ± 0.577 µg/mL). Antimicrobial evaluations revealed robust inhibitory effects, with Pseudomonas aeruginosa and Salmonella enterica exhibiting the highest susceptibility. In silico modeling corroborated these findings, identifying menthol as the lead ligand (ΔG = −6.09 kcal/mol), suggesting a synergistic mechanism of action. Notably, the EO displayed potent antiproliferative activity (LC₅₀ = 14.060 ± 1.364 µg/mL), falling well within the high-cytotoxicity threshold. Collectively, these findings underscore the pharmacological significance of S. nepeta EO as a potent reservoir of bioactive monoterpenes with antioxidant, antimicrobial, and anticancer properties, meriting further in vivo validation and mechanistic exploration toward its development as a therapeutic or nutraceutical candidate. Full article

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disorder often leading to demyelination of the spinal cord. Progression to HAM/TSP is closely associated with the high proviral load and the presence of virally infected CD4+ T cells that release extracellular vesicles (EVs). Exosomes, an EV subtype released by many cell types, transport proteins and nucleic acids that regulate intercellular communication and have been implicated in the progression of cancer and neuroinflammatory diseases. Herein, we have studied the effect of exosomes from HTLV-1 infected cells on the Peripheral Blood Mononuclear Cells (PBMCs) of HAM/TSP patients by single-cell sequencing utilizing innovative Honeycomb technology. We observed a distinct transcriptional response in monocyte populations compared with other immune cell types. Given that monocytes remain understudied in HTLV-1 pathogenesis, these findings highlight a potential role for infection-derived exosomes in shaping monocyte-driven immune dysregulation in HAM/TSP. A total of 41 genes were identified to be differentially expressed in HAM/TSP monocytes treated with exosomes; 28 were upregulated and 13 were downregulated. The most significantly altered genes are involved in chemokine activity and signaling, macrophage differentiation, lipid metabolism, and lysosomal function. Overall, our data suggests that exosome-treated HAM/TSP monocytes undergo immune remodeling that favors cell recruitment, activation, and a shift toward a mixed M1/M2-like phenotype. Such a shift may support viral persistence and chronic inflammation. These findings highlight a potential therapeutic pathway for addressing HTLV-1-induced neuroinflammation by modulating exosome-mediated signaling. Full article

Background: MEIS1::NCOA1/2 fusion sarcomas are a recently described molecular entity arising predominantly in the genitourinary and gynecologic tracts. Their clinical presentation is often misleading, and no standardized treatment guidelines currently exist. Methods: A literature review was conducted using PubMed to identify all reported cases of molecularly confirmed MEIS1::NCOA1/2 fusion sarcomas. Clinicopathological, molecular, treatment, and outcome data were extracted for comparative analysis. Case: We report the case of a 38-year-old nulliparous woman who presented with a right vulvar induration clinically consistent with a Bartholin gland cyst. Surgical excision revealed a spindle cell mesenchymal tumor harboring a MEIS1::NCOA2 fusion transcript and a CTNNB1 exon 3 mutation, with probable incomplete resection margins. A local recurrence was documented by MRI and PET–CT at eight months. Surgical re-excision revealed diffuse involvement and complete excision was considered uncertain. Adjuvant external beam radiotherapy followed by an MR-Linac boost was administered. Discussion: This case highlights the diagnostic challenge of Bartholin gland masses. We provide a review of the literature on MEIS1::NCOA1/2 fusion sarcomas and examine the potential aggressiveness of tumors that additionally harbor a CTNNB1 mutation. Given the nonspecific immunophenotype of this entity, this case underscores the indispensable role of RNA-based molecular sequencing in the diagnosis of low-grade spindle cell tumors when immunohistochemistry proves inconclusive. We further discuss the surgical challenges inherent to this anatomical region and explore intention-to-treat radiotherapy as a potential therapeutic option. Conclusions: We report a rare case of a MEIS1::NCOA2 fusion-positive sarcoma arising in the Bartholin gland region, and, to our knowledge, the first case in which radiotherapy with curative intent has been explored for this entity. This observation expands the limited literature on this emerging clinicopathological entity. Full article

The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm², p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation. Full article