The role of apelin in atrial fibrosis linked to postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) is not fully understood. This exploratory study investigated apelin's association with POAF-related atrial fibrosis and its impact on profibrotic signaling. The study included 18 patients: six CABG patients with POAF, six CABG patients without POAF, and six patients with congenital heart disease in sinus rhythm (serving as a secondary reference). Left atrial appendage tissue was analyzed histologically and molecularly, and serum apelin levels were measured on postoperative day 2 in CABG patients. Primary neonatal rat atrial fibroblasts were treated with transforming growth factor-β1 (TGF-β1) both with and without apelin, or subjected to apelin silencing. Compared with CABG patients without POAF, the POAF group exhibited lower atrial apelin expression and serum concentrations, increased collagen deposition, elevated TGF-β1 expression, and enhanced phosphorylation of mothers against decapentaplegic homolog 2 (Smad2), while total Smad2 remained unchanged. Experimentally, apelin attenuated TGF-β1-induced fibroblast activation, collagen expression, and Smad2 phosphorylation. Conversely, apelin silencing increased the expression of fibrosis-associated proteins. These preliminary findings suggest a link between reduced apelin and atrial fibrosis, as well as POAF after CABG. They also indicate antifibrotic effects of apelin, potentially mediated through TGF-β1/Smad2 signaling. Further research with larger clinical cohorts and complementary experimental models is necessary to fully elucidate the pathway mediation and clinical significance of these findings.
Precision oncology has revolutionized cancer treatment, improving outcomes and extending survival even in aggressive cancers like small-cell lung cancer. Molecularly targeted therapies and immune checkpoint inhibitors (e.g., PD-1/PD-L1) are now standard. Recently, the immune checkpoint regulator B7-H3 (CD276) has emerged as a promising therapeutic target, especially for novel antibody-drug conjugates (ADCs). This article highlights recent advances in B7-H3-targeted ADCs, emphasizing the urgent need for reliable predictive biomarkers to guide patient selection and optimize treatment.
The online symposium “The role of exercise in managing immunotherapy-related chronic fatigue during cancer treatment,” taking place on November 6, 2026, brings together European researchers and clinicians to explore the relationship between exercise, cancer immunotherapy, and fatigue. Organized by the Center for Integrated Oncology (CIO) Aachen Bonn Cologne Düsseldorf, with Biomolecules and Biomedicine as a project partner, the symposium connects basic and clinical research to advance individualized approaches to supportive cancer care.This book presents an editorial and eight invited keynote abstracts addressing fatigue and fatigability assessment, skeletal muscle and mitochondrial adaptations, exercise-induced immune responses, and clinical exercise interventions. The contributions examine current evidence, ongoing studies, and challenges in translating research into practice, with an emphasis on managing treatment-related symptoms, improving physical function and quality of life, and advancing precision exercise oncology.
Biofilm-associated reductions in antifungal susceptibility complicate Candida albicans infection management. This in vitro study assessed farnesol, lyticase, and tyrosol, alone and in combination with fluconazole or micafungin, against established C. albicans biofilms. We screened 25 clinical isolates from patients with suspected vulvovaginal candidiasis using crystal violet staining. Sessile minimum inhibitory concentrations (SMICs), defined as ≥80% reductions in metabolic activity, were determined by a tetrazolium reduction assay. Checkerboard interactions were evaluated using fractional inhibitory concentration indices, with upper-bound estimates for fluconazole due to single-agent values reaching the assay ceiling. Twenty-one isolates (84%) formed biofilms. All three compounds alone reduced biofilm metabolic activity. Fluconazole SMICs were ≥64 µg/mL, while micafungin SMICs ranged from 0.5–2 µg/mL. Fluconazole–farnesol and micafungin–farnesol combinations demonstrated synergy in 61.9% and 57.1% of isolates, respectively, with no observed antagonism. Farnesol reduced fluconazole SMICs to 2–8 µg/mL and median micafungin SMICs from 1 to 0.25 µg/mL (Holm-adjusted p < 0.001). Micafungin–lyticase interactions were predominantly indifferent (90.5%). In contrast, tyrosol combinations were antagonistic with fluconazole in 33.3% of isolates and with micafungin in 28.6%. Farnesol combinations consistently exhibited the most potent antibiofilm effects. However, the small sample size, unreplicated biofilm susceptibility assays, and estimated fluconazole interaction indices necessitate cautious interpretation. Future research should investigate reproducibility, safety, and in vivo efficacy.
Sonic Hedgehog (SHH) signaling is implicated in B-cell acute lymphoblastic leukemia (B-ALL) and represents a potential therapeutic target. This proof-of-concept study evaluated glasdegib, alone and combined with inotuzumab ozogamicin, in primary B-ALL cells using a stromal co-culture model. Peripheral blood or bone marrow samples from seven patients were co-cultured with HS-5 stromal cells and treated for four days. Viability relative to vehicle controls was assessed using an adenosine triphosphate (ATP)–based luminescence assay after mechanical separation from stromal cells. Expression of four SHH pathway genes was examined by quantitative polymerase chain reaction (qPCR) in four patient samples following treatment with 20 μM glasdegib, with or without 10 ng/mL inotuzumab ozogamicin. Co-culture showed descriptively more stable viability measurements than monoculture, although the between-condition difference in changes in dispersion was not statistically significant (p = 0.154). Glasdegib reduced B-ALL cell viability in a dose-dependent manner by day 4, while HS-5 stromal cells showed negligible sensitivity. Adding inotuzumab ozogamicin did not clearly enhance the response to glasdegib at the tested concentration. Gene expression changes were heterogeneous and inconclusive, with downregulation of selected genes observed in some samples. These preliminary findings support further investigation of glasdegib in B-ALL. Larger studies are needed to determine the value of combination treatment and clarify treatment-associated transcriptional effects.
