Juvenile idiopathic arthritis (JIA) represents the most common cause of chronic arthritis in childhood; however, not all early-onset arthropathies are inflammatory in origin. We report the case of a 4-year-old girl initially diagnosed with oligoarticular JIA and treated with methotrexate followed by a tumor necrosis factor inhibitor, without significant clinical improvement and despite persistently normal inflammatory markers. Clinical reassessment raised suspicion of a non-inflammatory arthropathy, supported by characteristic radiographic findings including metaphyseal flaring of the distal femora and proximal tibiae. Genetic analysis identified compound heterozygous pathogenic variants in the PRG4 gene, confirming the diagnosis of camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (OMIM #208250). PRG4 encodes lubricin, a mucin-like glycoprotein essential for boundary lubrication of articular cartilage and maintenance of synovial joint homeostasis. Loss-of-function variants disrupt joint lubrication, leading to mechanical synovial hyperplasia and chronic non-inflammatory joint effusion. This case highlights common diagnostic pitfalls in pediatric rheumatology and underscores the importance of considering genetic causes of chronic arthropathy when clinical and laboratory features are atypical for inflammatory disease. Early molecular diagnosis prevents unnecessary immunosuppressive therapy and enables appropriate multidisciplinary management.

Myocardial ischemia-reperfusion injury (MIRI) significantly limits the clinical benefits of reperfusion therapy, underscoring a pressing need for effective interventions. This study examines the cardioprotective effects and underlying mechanisms of the natural amide alkaloid N-p-trans-Coumaroyltyramine (p-CT). Using hypoxia/reoxygenation (H/R) models in neonatal rat cardiomyocytes and in vivo rat MIRI models, we assessed p-CT pretreatment on cell viability, cardiac function, serum injury markers (lactate dehydrogenase, creatine kinase-MB, cardiac troponin T, and myoglobin), myocardial histopathology, ultrastructural alterations, and infarct size. The systematic screening and validation of potential targets were conducted via label-free quantitative proteomics, molecular docking, and Western blot. The results demonstrated that p-CT pretreatment dose-dependently mitigated H/R-induced cellular injury, improved cardiac function in MIRI rats, reduced serum markers of myocardial damage, alleviated pathological and ultrastructural injury in myocardial tissue, and significantly diminished infarct size. Proteomic analysis revealed 19 differentially expressed proteins specifically reversed by p-CT, with Titin-cap (Tcap) exhibiting the most pronounced downregulation in the MIRI model-a change effectively restored by p-CT pretreatment. Molecular docking indicated strong binding affinity between p-CT and Tcap protein. In summary, p-CT represents a promising cardioprotective agent, likely exerting its effects by targeting Tcap protein and upregulating its expression, thereby helping preserve cardiomyocyte structural and functional integrity.

Endovascular therapies have transformed cardiovascular medicine, yet restenosis, thrombosis, and device failure remain common and poorly predictable complications. Increasing evidence suggests that immunothrombotic processes critically shape vascular recovery after device implantation. This includes neutrophil extracellular trap (NET) formation, innate immune polarization, and endothelial damage responses. Concurrently, advances in artificial intelligence (AI) are increasingly enabling continuous multimodal monitoring and adaptive clinical decision-making throughout the medical device life cycle. Here, we propose the concept of immunologically adaptive endovascular devices: a closed-loop paradigm in which patient immune status informs device selection, device-tissue interactions are interpreted via mechanistic biomarkers, and real-world monitoring dynamically updates risk and management. The study introduces (i) an immune-device interaction phenotype taxonomy linking device design features to measurable thrombo-inflammatory trajectories, (ii) a mechanistic framework defining interface signaling processes that enhance or resolve NET-driven responses, (iii) a minimum evidence model encompassing preclinical testing, clinical validation, and post-market surveillance, and (iv) a reference AI architecture for risk prediction, drift detection, and safety monitoring. This study also outlined testable predictions and a translational roadmap toward precision endovascular intervention and next-generation adaptive cardiovascular devices.

Myocardial fibrosis is a key pathological process driving the progression of cardiovascular diseases toward heart failure, closely linked to persistent inflammation and immune dysregulation. Among CC chemokines, CCL17 has emerged as an important mediator connecting immune cell dynamics with fibrotic remodeling. This review outlines current understanding of the cellular sources, regulatory mechanisms, and functional roles of CCL17, with particular attention to its impact on regulatory T cell (Treg) recruitment through ligand-biased signaling. Beyond this mechanism, CCL17 likely operates within a broader inflammatory network, with potential interactions involving CCR2⁺ macrophages and IL-17-related pathways. Experimental studies show that disruption of CCL17 signaling attenuates fibrosis and improves cardiac function, while clinical data link elevated circulating CCL17 to cardiac dysfunction and adverse outcomes. However, the absence of clinical trials and the redundancy of chemokine networks remain key challenges for translation. Overall, CCL17 may serve as a biomarker and therapeutic target, although its clinical application will require a more integrated, network-based understanding.

Cardiovascular diseases (CVDs) remain the leading cause of mortality globally, characterized by myocardial injury, pathological structural remodeling, and progressive deterioration of cardiac function. Clinical manifestations include post-infarct functional impairment, pathological cardiac hypertrophy, interstitial fibrosis, malignant arrhythmias, and end-stage heart failure. Although the dual-specificity tyrosine-regulated kinase (DYRK) family has been extensively investigated in cancer and neurodegenerative disorders, emerging evidence highlights DYRKs as critical upstream regulators in a wide spectrum of cardiovascular pathological processes. However, current research is largely confined to individual isoforms or isolated signaling pathways, lacking systematic integration of isoform-specific functions, dose- and spatiotemporal-dependent effects, as well as bidirectional regulatory roles in chronic cardiac remodeling. This review systematically summarizes the molecular mechanisms of the DYRK family across major cardiovascular disease models, with particular emphasis on the functional specificity of distinct DYRK isoforms and their translational potential as therapeutic targets. We further provide an integrated theoretical framework to facilitate the development of isoform-selective, context-dependent precision therapies for cardiovascular diseases.

The present review discusses vitamin A/retinoid metabolism as a cross-organ axis in which hepatic clock-dependent retinoid handling may affect immune clock gene expression through the stimulation of retinoic acid 6-Janus kinase 2-signal transducer and activator of transcription 5 signaling, potentially promoting pro-inflammatory monocyte states. We further highlight mechanosensory signaling as a second convergent layer that integrates hemodynamic forces with tissue microenvironmental cues. Among these pathways, G protein-coupled receptor 68, a proton- and flow-sensitive G protein-coupled receptor, is discussed as a representative druggable node linking mechanical and inflammatory signaling in chronic kidney disease-associated cardiac injury. Finally, we outline potential therapeutic directions, including (i) circadian alignment/chronopharmacology, (ii) modulation of retinoid metabolism and signaling, and (iii) targeted inhibition of primary immune and mechanosensory effectors.

Acute myocardial infarction (AMI) results from a lack of oxygen supply to the myocardium, leading to the loss of cardiomyocytes and their replacement with fibrotic scar tissue. This process is closely associated with the development of heart failure. Regenerative medicine has emerged as a promising strategy to enhance treatment outcomes in severe cases of heart failure. This study aimed to evaluate myocardial regeneration after AMI using a biomaterial composed of mononuclear stem cells and human amniotic membrane. A total of 120 Wistar rats were subjected to experimentally induced AMI. On the 7th day post-infarction, rats with an ejection fraction of <50% on echocardiography were randomized into four groups: (1) control; (2) stem cells; (3) amniotic membrane; and (4) amniotic membrane combined with stem cells. On the 30th day, the surviving animals underwent a second echocardiographic evaluation and were subsequently euthanized. The group treated with the combination of amniotic membrane and stem cells showed reduced systolic and diastolic ventricular volumes. Histological analysis revealed that these animals exhibited less fibrosis and a lower percentage of type I collagen. Based on the results of the study, it was concluded that the combination of human amniotic membrane and mononuclear stem cells decreased ventricular volumes and myocardial fibrosis, suggesting more favorable ventricular remodeling in this experimental model.

Inflammation occurs throughout the entire process of atherosclerosis. So, reducing the inflammatory response remains one of the main therapeutic strategies for atherosclerosis. Chensinin-1b, a derivative of the natural antimicrobial peptide extracted from the skin secretions of the Rana chensinensis, has been shown to effectively mitigate the occurrence of inflammatory responses. Here, the anti-inflammatory activity of the peptide by suppressing the canonical Wnt/β-catenin signaling pathway was investigated in ox-LDL-induced AS. The results showed that the classical Wnt/β-catenin signaling pathway was activated in ox-LDL-induced THP-1-derived foam cells. The inhibitor of Wnt reduced the release of pro-inflammatory cytokines by downregulating the NF-κB signaling pathway. Cyclooxygenase-2, a target protein of the canonical Wnt/β-catenin signaling pathway, inhibited the phosphorylation of NF-κB. Chensinin-1b and its analogs effectively downregulated the expression of Wnt signaling proteins by inhibiting the nuclear translocation of the key pathway protein β-catenin, resulting in a decrease in COX-2 expression and simultaneously reducing the release of pro-inflammatory cytokines. In summary, our study suggests the potential of chensinin-1b and its analogs as therapeutic agents for AS.

Optimization of guideline-directed medical therapy in chronic heart failure remains challenging in real-world practice, particularly outside settings with routine cardiopulmonary exercise testing. In this context, cardiovascular rehabilitation can improve functional capacity, symptoms, and quality of life, while structured follow-up may also facilitate treatment adjustment. We therefore evaluated whether exposure to a structured multimodal functional assessment pathway, embedded within a more intensive follow-up model, was associated with pharmacological optimization and functional change in chronic heart failure.

We conducted a retrospective, single-center cohort study including adults with chronic heart failure with reduced or mildly reduced ejection fraction managed in a tertiary university clinic. Patients were classified according to documented exposure to an integrated pathway that combined standardized 6 min walk testing, heart rate dynamics, oxygen saturation response, perceived exertion, validated quality-of-life assessment, and prespecified interim reassessment, versus usual care. The integrated pathway involved more frequent clinical contact than usual care. The primary outcome was change in 6 min walk distance over 6 months. Secondary outcomes included changes in heart rate recovery, oxygen saturation nadir, Borg perceived exertion score, quality-of-life score, intensity of guideline-directed medical therapy, treatment intensification rates, and heart failure hospitalization.

The study included 250 patients with comparable baseline demographic and clinical characteristics. Patients managed within the structured pathway showed greater improvement in 6 min walk distance at 6 months than those receiving usual care, together with more pronounced improvement in secondary functional parameters and quality-of-life scores. Pharmacological optimization, reflected by higher uptake and intensification of guideline-directed medical therapy, also occurred more frequently in the structured pathway group. The integrated group, however, also had higher follow-up intensity, which limits causal interpretation of the observed between-group differences.

In this real-world heart failure cohort, exposure to a structured care pathway combining repeated multimodal functional profiling with closer follow-up was associated with greater functional improvement and more intensive pharmacological optimization. These findings should be interpreted as pathway-level associations rather than proof that functional assessment alone drove benefit, and they require prospective validation.

Giant cell myocarditis (GCM) is a rare condition with an incompletely understood immune pathogenesis, characterized by inflammatory damage to the myocardium and the presence of multinucleated giant cells on histopathological examination. The frequently fulminant and severe course requires rapid intervention for a correct diagnosis and the initiation of immunosuppressive therapy, which is often life-saving.

This article contains information from observational studies and case reports, systematically collected from prestigious publications such as JACC, NEJN, ESC, JCC, Heliyon, and Cureus found in the PubMed and ClinicalTrials.gov databases. Thus, 25 patients diagnosed with giant cell myocarditis between March 2019 and May 2025 were analyzed, with a focus not only on the initial clinical evolution, mortality incidence, and the need for heart transplantation but also on the incidence of major complications such as cardiogenic shock and malignant rhythm and conduction disorders refractory to drug treatment. These parameters were studied according to certain intrinsic factors that cannot be influenced, such as age at onset, gender, and associated pathology of the patient, as well as extrinsic factors that can be influenced, such as the time of diagnosis and the start of immunosuppressive therapy. The results obtained were compared with those in the literature from previous years, considering the limitations of the current study.

The selected patients were 13 women (52%) and 12 men (48%), mostly from the US and Japan, aged between 22 and 76 years, with an average age of 44.92 years. An associated autoimmune pathology was found in 40% of patients in this group, and previous cardiovascular pathology in 28%. Only 8% had a history of GCM. The clinical onset of new-onset heart failure, refractory to usual therapy, with progressive dyspnea as the cardinal symptom was found in 12 patients, representing 48% of cases; palpitations as an expression of rhythm or conduction disorders were found in five patients, representing 20%; precordial discomfort to precordial pain accompanied or not by ST-T segment changes was present in four patients, representing 16%; and general signs and symptoms or those of other organs were present in three (12%) cases. The diagnosis was made by histological examination of the biopsy fragment obtained by endomyocardial biopsy or from the myocardial fragment obtained during the implantation of mechanical cardiovascular support devices and, less frequently, on the explanted heart and at autopsy. In terms of progression, of the 25 patients, four (16%) died, four (16%) required heart transplantation, and 16 (64%) had a severe progression with cardiogenic shock, which required mechanical circulatory support in 11 (44%) cases. The outcome was mainly influenced by the early diagnosis and administration of immunosuppressive medication, but also by the age of the patients and associated chronic diseases.

Giant cell myocarditis is a serious condition that, in the absence of rapid diagnosis and appropriate immunosuppressive therapy, has a fulminant, often fatal course. Clinical suspicion of giant cell myocarditis remains important in the initial diagnosis. Raising this suspicion, together with modern and improved paraclinical investigations compared to previous years, has led to faster diagnosis and administration of immunosuppressive therapy in this pathology. Histological examination remains the gold standard for final diagnosis, but it should be noted that it may be non-diagnostic. In the face of a strong suspicion of giant cell myocarditis, the best approach is to start immunosuppressive therapy and monitor the patient's progress. Immunosuppressive treatment remains decisive in influencing the evolution of this condition, both through prompt administration and through the adaptation of therapeutic regimens to the evolution of patients. A more detailed understanding of the immune-mediated pathogenesis of GCM and the identification of clinical risk factors for unfavorable short- and long-term outcomes may enable earlier risk stratification and the development of more targeted, individualized therapeutic strategies.