Background: Schizophrenia in adolescence disrupts neurodevelopment and long-term functioning. While symptom reduction remains a primary treatment goal, quality of life (QoL) represents a critical, patient-centered outcome. Pharmacogenetic variability, particularly in CYP2D6 metabolism of second-generation antipsychotics, may influence tolerability and subjective well-being beyond symptom control. Materials and Methods: Forty-seven adolescents (aged 14-18 years) diagnosed with schizophrenia (DSM-5) were followed in routine clinical care. CYP2D6 genotyping classified patients as normal metabolizers (NM, n = 27) or reduced-function metabolizers (RFM, including intermediate/poor, n = 20). Symptom severity was assessed with PANSS, QoL was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and adverse effects (hyperprolactinemia, extrapyramidal symptoms, sedation, metabolic changes) were monitored. Non-parametric tests and multiple linear regression were applied. Results: At 12 months, RFM patients showed significantly higher PANSS scores, markedly more adverse reactions (95% vs. 48.1%), and lower PQ-LES-Q total and domain scores (all p < 0.0001) compared to NM patients. A regression analysis identified the metabolizer status (β = -0.410, p = 0.001), extrapyramidal symptoms (β = -0.248, p = 0.003), sedation (β = -0.193, p = 0.029), and hyperprolactinemia (β = -0.190, p = 0.012) as independent predictors of a reduced QoL, explaining 84% of the variance. The residual symptom severity was not independently associated. Conclusions: In adolescent schizophrenia, the CYP2D6-reduced metabolizer status is the strongest independent predictor of long-term QoL impairment, associated primarily through a substantially higher burden of treatment-related adverse effects (metabolic, endocrine, neurological, and sedative) rather than through persistence of psychotic symptoms alone. These findings support early pharmacogenetic testing to guide individualized dosing and improve tolerability and patient-reported outcomes.

Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro-B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024-2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers-CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)-as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS.

Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. Increased B-type natriuretic peptide (BNP) levels have been associated with HF. The NPPB:rs198389 (c.-381T > C) promoter polymorphism has been found to modulate BNP levels.

To investigate possible associations among the NPPB:rs198389 polymorphism, N-terminal pro-BNP (NT-proBNP) concentrations, and phenotypic features in Polish patients with HF.

The study group comprised 250 patients with HF. Genomic DNA was extracted from blood, and genotyping was performed using PCR-RFLP.

There were no significant differences in the distributions of NPPB genotypes or alleles between HF females and HF males. Except for body height, there were no significant differences in phenotypic features among HF patients regarding NPPB:rs198389 genotypes. There were also no significant differences in the distributions of either NPPB:rs198389 genotypes or alleles across NT-proBNP concentration terciles. However, age, left-ventricular-mass index, C-reactive-protein levels, serum-creatinine concentrations, and the incidence of myocardial infarction, left ventricular hypertrophy, or reduced ejection fraction (EF) were significantly lower in patients from the lower tercile (LT) than in patients from the middle and/or upper terciles. EF and the frequency of preserved EF in LT patients were significantly higher than those from other terciles.

Our results did not confirm associations between NPPB:rs198389 and NT-proBNP serum concentrations or clinical phenotypes in Polish patients with HF.

Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy.

We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG/AMP criteria.

The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T>A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation.

This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling.

Background/Objectives: Cardiac embryonic development is a highly coordinated and dynamic process governed by precise spatiotemporal gene regulation. Increasing evidence indicates that cellular heterogeneity and lineage specification during heart development are tightly controlled by complex gene regulatory networks (GRNs) and epigenetic mechanisms. Recent advances in single-cell multi-omics technologies provide unprecedented resolution to dissect these regulatory processes. This review aims to summarise current applications of single-cell multi-omics approaches to elucidate gene regulatory mechanisms underlying cardiac embryogenesis and their implications for congenital heart disease (CHD). Methods: We systematically reviewed recent literature on single-cell RNA sequencing (scRNA-seq), single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), spatial transcriptomics, and integrative multi-omics analyses applied to embryonic heart development. Studies were analysed to evaluate how these technologies contribute to cell-type identification, lineage trajectory reconstruction, GRN inference, and epigenetic landscape characterisation. Results: Single-cell multi-omics approaches have enabled the construction of high-resolution cardiac cell atlases, revealing previously unrecognised cellular heterogeneity and transitional states during heart development. Integrative analyses of transcriptomic and chromatin accessibility data have provided insights into lineage commitment, key transcription factors, enhancer-promoter interactions, and dynamic GRNs. These findings have advanced understanding of developmental genetics in cardiac morphogenesis and offered new perspectives on the molecular mechanisms underlying CHD. Conclusions: Single-cell multi-omics technologies provide a powerful framework for investigating gene regulatory mechanisms during cardiac embryogenesis. Continued methodological refinement and integrative analyses are expected to further clarify developmental processes and facilitate translational insights into CHD.

Ulcerative colitis (UC) is an intestinal disease characterized by long-term inflammation. Circadian rhythm disorder (CRD) affects various biological activities and has been linked to several diseases, including UC. This study aimed to investigate the role and significance of CRD in UC.

Bulk RNA-seq data from five independent UC cohorts were obtained from the Gene Expression Omnibus (GEO) database and integrated into a single dataset. The dataset underwent differential analysis to identify differentially expressed genes (DEGs) in association with CRD. Expression levels and pathway enrichment of CRD genes were analyzed, and signature genes were identified using machine learning algorithms. Based on these signature genes, a UC risk prediction model and CRD-related molecular subtypes were established. Furthermore, single-cell RNA-seq data of UC were analyzed to discuss the key role of CRD and signature genes in the UC microenvironment. RT-PCR analysis was employed to validate the expression levels of the identified signature genes.

247 DEGs associated with CRD in UC were identified (referred to as CRD-DEGs). Gene set enrichment analysis (GSEA) revealed a strong association between CRD and inflammation, as well as immune cell infiltration in UC. This association potentially impacts intestinal fibrosis. A comparison of three machine learning algorithms (Lasso, SVM-RFE, and Random Forest) resulted in the identification of 12 signature genes. A UC risk prediction model and two UC CRD subtypes were developed using these genes. Among them, STXBP1 was identified by all three machine learning algorithms and was further analyzed. STXBP1 was predominantly enriched in pathways related to inflammatory response. Elevated levels of STXBP1 are mainly caused by reduced levels of methylation of its gene promoter. RT-PCR confirmed elevated expression of certain genes in mouse UC models.

This study is the first to establish a strong association between CRD and the onset of UC. The newly developed UC nomogram based on CRD demonstrated high predictive accuracy, although further clinical validation is required. Understanding the intrinsic relationship between CRD and UC enhances our understanding of the potential pathogenesis of UC. This study introduces novel ideas and methods for early diagnosis, treatment, and prognosis of UC.

Inherited cardiomyopathies represent a major cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), frequently occurring in the absence of advanced systolic dysfunction. Traditional strategies for the primary prevention of SCD have relied predominantly on left ventricular ejection fraction (LVEF), an approach that fails to capture the substantial biological and clinical heterogeneity of non-ischemic cardiomyopathies. Over the past decade, advances in cardiac genetics and cardiac magnetic resonance imaging have identified specific genotypes associated with a disproportionate arrhythmic risk, which often precedes overt ventricular remodeling. The 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies formalize this paradigm shift by integrating etiology, myocardial substrate, and electrical phenotype into contemporary risk stratification. In this narrative review, we focus on cardiomyopathy-associated genotypes consistently linked to high arrhythmic risk-LMNA, truncating variants in FLNC, RBM20, PLN p.Arg14del, and desmosomal genes-and examine their molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles. We discuss how genotype-specific patterns of myocardial fibrosis, conduction disease, and VA inform implantable cardioverter-defibrillator (ICD) decision-making beyond LVEF-based thresholds. By synthesizing genetic, imaging, and clinical evidence in light of ESC 2023 recommendations, this review highlights the evolving role of genotype-informed strategies in the personalized prevention of SCD and underscores remaining gaps in evidence and risk prediction.

Myocardial infarction remains a leading cause of mortality worldwide as the most severe clinical presentation of coronary artery disease, with an increasing trend in young adults. In the early phase of myocardial infarction, the mean blood pressure regulates the pressure distal to the occluded artery in the presence of well-developed collateral coronary circulation. Hypotensive medication administered after the myocardial infarction could compromise collateral recruitment and exacerbate myocardial ischemia. Collateral coronary circulation develops through angiogenic processes as a network of small blood vessels. After the myocardial infarction, the collateral arteries open and begin a process of arteriogenesis in order to mature into functional arteries. Although there are several well-known biochemical and molecular biomarkers for both myocardial infarction and angiogenesis, we need to associate these with arteriogenesis biomarkers in order to be able to fully determine the level of collateral coronary circulation development after myocardial infarction. In this review, we summarize some of the most important biomarkers that could provide insight into the collateral coronary arteriogenesis process. Our aim is to identify specific biomarkers that can be identified in the early processes of arteriogenesis after the myocardial event in order to quickly determine the best therapeutic strategy.

Chronic kidney disease is a global public health concern, representing a critical global public health challenge with increasing morbidity and mortality rates. The disease is a long-term condition characterized by the progressive loss of renal function. Early detection of declining kidney health and timely intervention are crucial to slow disease progression and improve prognosis, mitigating complications, including cardiovascular events. Current diagnostic standards are unable to detect early stages of kidney disease, reflecting early signs of glomerular and tubular damage. This creates an urgent need to identify reliable biomarkers for early detection, prognosis and therapeutic monitoring of kidney diseases. Novel biomarkers, including urinary microRNA, exosomal components, proteomic signatures and integrated multi-omics profiles, facilitated by up-to-date technologies offer strong promise for enhancing early diagnosis, risk assessment and monitoring of the disease. We focus on the fundamental biological significance and clinical application of these markers, discussing a critical evaluation of novel methodologies and clinical evidence supporting their potential for earlier and more precise diagnosis. This review summarizes innovative urinary biomarkers and advanced analytical technologies that can provide a more comprehensive and accurate assessment of the kidney status towards early diagnosis, better prognosis and better quality of life for patients with chronic kidney disease.

CRISPR technologies are transforming cardiovascular therapy development by creating an increasingly seamless pipeline from potential target discovery to clinical translation. What began as a genome-editing tool has evolved into a versatile platform that enables researchers to precisely interrogate and modulate cardiac biology with tools such as base- and prime-editors, and CRISPR inhibition and activation. In this review, we follow the use of CRISPR across the stages of biomedical research through to bench-to-bedside application. This review begins by addressing how genome-wide and focused CRISPR screens discover developmental regulators, disease drivers, and drug-response pathways, making the first steps in identifying therapeutic targets. We then explore how CRISPR engineering creates progressively more relevant disease model systems to validate mechanisms of disease and test interventions, helping bridge the translational gaps between the lab and the clinic. Finally, we consider how CRISPR technologies are beginning to enter cardiovascular clinical trials, while highlighting the key challenges that still limit this translation. By linking the latest advances of modern CRISPR platforms to the stages of therapeutic development, this review highlights how CRISPR technology is reshaping the pipeline from molecular insight to clinical innovation in cardiac disease.