Balkan Medical Journal最新文献

Background: Heart failure (HF) represents the terminal stage of many cardiovascular diseases. Doxorubicin (DOX) can induce HF through oxidative stress (OS), inflammation, and apoptosis. Ginkgetin (GK) has potential cardioprotective effects, but its underlying mechanisms remain unclear.

Aims: This study investigated the protective effects of GK against DOX-induced HF and explored its mechanisms, focusing on mitochondrial function and related signaling pathways.

Study design: In vivo and in vitro experimental models.

Methods: HF was induced by DOX in mice and H9c2 cardiomyocytes. Cardiac function, myocardial injury, OS, inflammation, and apoptosis were assessed using echocardiography, biochemical assays, enzyme-linked immunosorbent assay, histopathology, immunofluorescence, and Western blot. Mitochondrial function was evaluated via transmission electron microscopy, RT-qPCR, and Seahorse analysis. Compound C was applied to verify the involvement of the adenosine monophosphate-activated protein kinase (AMPK)/Sirt1/nuclear factor-κB (NF-κB) pathway.

Results: GK markedly improved DOX-induced cardiac dysfunction and myocardial injury, reduced cardiac injury markers and inflammatory cytokines, and alleviated fibrosis, hypertrophy, apoptosis, and reactive oxygen species accumulation. GK restored superoxide dismutase activity, decreased malondialdehyde levels, increased glutathione and ATP, and preserved mitochondrial structure and respiratory function. GK upregulated AMPK and Sirt1, inhibited NF-κB activation, and regulated apoptosis-related proteins, whereas Compound C reversed these effects.

Conclusion: GK protects against DOX-induced HF by activating AMPK/Sirt1 and inhibiting NF-κB signaling, thereby mitigating OS, inflammation, apoptosis, and mitochondrial dysfunction.

Background: Carotid atherosclerosis (CAS) is a key cause of ischemic stroke that is strongly associated with increased risks of cardiovascular disease and vascular death, hence the urgent need to develop therapeutic strategies targeting carotid atherosclerotic plaques that would reduce the overall risk of cerebrovascular events.

Aims: This study performs single-cell sequencing to dissect the cellular subpopulations in CAS. Molecular docking is used to uncover the potential therapeutic targets, consequently providing a theoretical basis for the CAS treatment strategies.

Study design: Integrated single-cell, spatial transcriptomic and molecular docking analysis.

Methods: The single-cell sequencing data were retrieved from the Gene Expression Omnibus. Enrichment analyses were performed to characterize the cellular subpopulation functions. Accordingly, cell-cell communication networks were mapped to uncover the inter-subgroup interactions. Molecular docking was also employed to identify the potential therapeutic targets.

Results: In this study, we identified the multiple cellular subpopulations that are associated with CAS. These CAS-related subpopulations engage in intercellular communication via distinct signaling pathways. Cannabidiol exhibits strong binding affinities for the macrophage, endothelial, and vascular smooth muscle cell markers. Spatial transcriptomics revealed that ACTC1, AKR1C2, and FABP4 exhibit region-specific expression patterns within the plaque.

Conclusion: Dissecting the diverse cellular subpopulations in CAS and elucidating their functions and mechanisms, this study integrates single-cell sequencing, molecular docking, and spatial transcriptomics to offer fresh insights into CAS therapy.

Background: Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in KMT2A. Although several large international cohorts have helped define its broad clinical spectrum, data from underrepresented populations remain limited.

Aims: To characterize the molecular and phenotypic spectrum of Turkish patients with WDSTS and compare these findings with previously published cohorts.

Study design: Multicenter retrospective cohort study.

Methods: Sixteen individuals from 15 unrelated families were recruited across Türkiye. Clinical information was obtained through medical records and systematic phenotyping. Molecular analyses included next-generation sequencing or targeted variant testing, and the variants were classified according to the American College of Medical Genetics and Genomics guidelines.

Results: Fifteen distinct KMT2A variants were identified, including nine novel alleles. Most variants were predicted to result in loss of function; only one was a missense substitution. Neurodevelopmental involvement was prominent, with developmental and speech delays, intellectual disability, and behavioral comorbidities such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Endocrine evaluation revealed growth hormone deficiency in approximately half of the tested patients. Ophthalmologic, cardiac, and dental abnormalities, including delayed tooth eruption, further expanded the known phenotype. Additional systemic features included skeletal, genitourinary, and immunological findings. Comparison with previously reported cohorts displayed no statistically significant genotype-phenotype correlations, although truncating variants appeared to be associated with more pronounced neurodevelopmental and behavioral manifestations.

Conclusion: This report presents the largest Turkish WDSTS cohort to date, expands the known KMT2A variant spectrum with nine novel alleles, and highlights several underreported clinical features. Beyond its immediate clinical relevance, the study further supports KMT2A as a key chromatin regulator and an "umbrella gene" within the chromatinopathy spectrum. Growing recognition of these disorders underscores the need for systematic, multidisciplinary surveillance and contributes to the expanding global understanding of their shared pathogenic mechanisms.

Restorative proctocolectomy with ileal pouch-anal anastomosis restores intestinal continuity and generally provides excellent long-term functional outcomes. However, 5-15% of patients experience pouch failure, most commonly due to septic, mechanical, or inflammatory complications. Surgical management of pouch failure is technically demanding and requires a multidisciplinary approach in high-volume, specialized centers. This narrative review synthesizes contemporary evidence on the transabdominal surgical management of pouch failure, with an emphasis on standardized preoperative evaluation, nomenclature. Key topics include predictors of failure, differentiation of Crohn's-like disease from mechanical etiologies, and technical considerations for pouch reconstruction. The review also emphasizes the importance of a unified team for revisional pouch surgery, involving specialized colorectal surgeons, gastroenterologists, radiologists, physician assistants, dietitians, IBD-specialized psychologists, wound-ostomy nurses, and patient support personnel.