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evaluation of the individual effects of melatonin and umbilical cord-derived mesenchymal stem cell exosomes on cell viability and apoptosis in be(2)-c neuroblastoma cells in vitro
(MDPI, 06/2026) Şengül, Ahmet; Kaan, Dilek; Güler, Hatice; Yiğit, Hüseyin
The study aimed to investigate the individual therapeutic effects of melatonin and umbilical cord-derived mesenchymal stem cell exosomes (UC-MSC-Exo) separately on BE(2)-C neuroblastoma cells. Melatonin is recognized for its anti-cancer, antioxidant, and apoptosis-inducing properties, and its ability to cross the blood-brain barrier. UC-MSC-Exos are nanovesicles from mesenchymal stem cells that can also cross the blood-brain barrier and transport biologically active molecules. The potential therapeutic benefits of each independent agent in treating BE(2)-C neuroblastoma cells were investigated. Melatonin and UC-MSC-Exos were examined on BE(2)-C neuroblastoma cells at varying concentrations and time intervals to evaluate cell viability and apoptosis. Both melatonin and UC-MSC-Exo independently reduced cell viability and induced apoptosis in a manner that depended on the dosage and duration of exposure. Melatonin had an IC50 of 2.68 mM after 24 h, while UC-MSC-Exo showed an IC50 of 25.3 μg/mL after 48 h, with no cytotoxic effects observed at 24 h. Specifically, individual concentrations of 2.5 mM and 5 mM of melatonin, as well as 50 µg/mL and 100 µg/mL of UC-MSC-Exo, led to significant levels of apoptotic and necrotic cells at 48 and 72 h (p < 0.001). Our findings suggest that the individual administration of melatonin and UC-MSC-Exo may hold therapeutic potential for neuroblastoma cells, particularly given their ability to cross the blood-brain barrier. Further in vivo research is required to evaluate their clinical utility.
Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis Yiğit H, Gökoğlu A, Gökoğlu S. Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis. World J Clin Pediatr 2026; 15(3): 118192 [DOI: 10.5409/wjcp.118192]
(Baishideng, Haziran 2026) Yiğit, Hüseyin; Gökoğlu, Abdulkerim; Gökoğlu, Sonay
This letter discusses the pilot study by Kotb et al published in World Journal of Clinical Pediatrics, which identifies significantly reduced serum cytochrome P450 1A2 (CYP1A2) levels in neonates with biliary atresia and neonatal hepatitis compared to healthy controls. While these findings highlight a potential role for detoxification mechanisms in neonatal cholestasis, critical methodological issues regarding the interpretation of results warrant attention. The primary concern is the causality dilemma; it is crucial to distinguish between an innate ‘defect’ (congenital deficiency) and ‘downregulation’ (secondary suppression). Low CYP1A2 levels may be a secondary consequence of systemic inflammation rather than an inherent susceptibility factor. Furthermore, the reliance on enzyme-linked immunosorbent assay for protein abundance lacks the resolution of functional activity assays. Future research should integrate single-cell multi-omics and gut-metabolite signaling to decode the complexity of the hepatic microenvironment.
Distinct thalamic volumetric profiles in cervical and upper limb dystonia
(ARQUIVOS DE NEURO-PSIQUIATRIA, 06/2026) Yiğit, Hüseyin; Gökoğlu, Abdulkerim
Abstract
Dystonia is a large-scale motor network disorder involving the basal ganglia, cerebellum, and thalamus.
This study investigated the volumetric characteristics of thalamic subnuclei in patients with isolated cervical (CD) and upper limb (ULD) dystonias, and their relationship with disease severity.
We analyzed high-resolution T1-weighted MR-images from the OpenNeuro database. The sample included 37 healthy controls, 25 CD, and 29 ULD patients. Thalamic nuclei were automatically segmented using the DeepThalamus pipeline. Group differences were analyzed using analysis of covariance (ANCOVA), controlling for age, sex, and total intracranial volume (TIV). Relationships between disease severity and volumetry were assessed using Spearmans correlation.
A volumetric reduction trend was observed in the CD group compared with controls, particularly in the left lateral geniculate, right ventral lateral posterior, and right intermediate nuclei. Although statistical significance remained borderline after FDR correction (p = 0.078), high Cohens values (d > 1.4) were detected. In contrast, thalamic volumes were largely preserved in the ULD group. Correlation analyses showed that increased disease severity was associated with decreased volumes of the mammillothalamic tract in the CD group and the anterior ventral nuclei in the ULD group.
Observed volumetric trends may provide preliminary insights into the role of specific thalamic substructures in cervical dystonia pathophysiology. Further studies in larger cohorts, supported by functional and diffusion imaging, are needed to clarify these findings.
Bilimsel Metinlerde Anlamsal Özetleme: Derin Öğrenme Yaklaşımlarının Performans Analizi
(Gazi Üniversitesi Bilişim Teknolojileri Dergisi, 31/07/2026)
Bu çalışmada biyomedikal soyutlayıcı metin özetleme görevinde alan odaklı ve genel amaçlı Transformer tabanlı modeller karşılaştırılmıştır. BART Large CNN, PEGASUS Large, FLAN T5 XL ve BioMistral 7B modelleri, 133120 PubMed makalesinden oluşan hazır bir veri seti üzerinde eğitilmiş ve test edilmiştir. Tüm modeller 1024 token girdi ve 256 token çıktı sınırı ile eğitilmiş, performansları ROUGE 1, ROUGE 2, ROUGE L ve ROUGE Lsum metrikleri kullanılarak değerlendirilmiştir. Sonuçlar, BioMistral 7B modelinin ROUGE 1 değerinde 47.74, ROUGE 2 değerinde 21.08 ve ROUGE L değerinde 27.99 skorları ile en yüksek genel performansı elde ettiğini göstermektedir. Niteliksel değerlendirmeler, BioMistral 7B modelinin biyomedikal terminolojiye daha yüksek uyum sağladığını ve klinik bilgileri daha tutarlı biçimde özetleyebildiğini ortaya koymuştur. Bu bulgular, alan uyarlamalı ön eğitimin biyomedikal soyutlayıcı özetleme görevlerinde model performansını artırdığını göstermektedir.
Epirubicin Alters Pancreatic Autophagy and Insulin Synthesis Through a Zinc-Dependent Mechanism
(John Wiley & Sons Ltd. (Wiley), 27.05.2026) Afşar, Ebru; Eranıl, Işıl
ABSTRACT
Epirubicin (EPI) can cause metabolic side effects, including chemotherapy-related diabetes, partly through oxidative stress that disrupts zinc (Zn) homeostasis and impairs autophagy. This study investigated the effects of EPI on Zn regulation and autophagy in the pancreas, as well as the modulatory role of N-acetylcysteine (NAC). Rats received EPI (9.6 mg/kg) by intraperitoneal injection (i.p.) followed 1 h later by NAC (50 or 300 mg/kg, i.p.). Glucose homeostasis was assessed using the Homeostatic Model Assessment (HOMA-IR), and β-cell function was assessed using HOMA-β levels. Plasma insulin levels, as well as insulin, proinsulin, beclin, autophagy-related proteins (ATG5), Microtubule-Associated Protein 1 Light Chain 3 (LC3), phosphorylated Akt (p-Akt), mechanistic target of rapamycin complex 1 (mTOR1), cleaved caspase-3, Zrt/Irt-like Protein 10 (ZIP10), and the proliferation marker Ki-67 in pancreatic tissue, were measured using commercial ELISA kits. Total oxidant status (TOS) and total antioxidant status (TAS) were measured using commercial colorimetric assay kits, and the oxidative stress index (OSI) was calculated. Zn levels in pancreatic tissue and plasma samples were measured using a colorimetric method. Morphological changes in the pancreas were assessed by hematoxylin and eosin staining. As a result, in the EPI group, oxidative stress and ZIP10 levels increased, whereas Zn levels decreased, as well as pancreatic autophagy, proliferation, and insulin synthesis increased. Oxidative stress decreased in both the EN-50 and EN-300 groups, with a more pronounced decrease in the EN-300 group. Furthermore, in the EN-300 group, pancreatic Zn, ZIP10, autophagy, and proliferation levels decreased, whereas mTOR1 levels increased. The pancreatic insulin synthesis observed in the EN-50 group was not observed in the EN-300 group. In conclusion, the increased autophagy observed in the Epi group may reflect an adaptive response to oxidative stress. The effects of NAC on oxidative stress may be dose-dependent, and high-dose NAC administration may suppress EPI-induced autophagy via mTOR1-mediated signaling. Furthermore, the relationship among Zn levels, autophagy, and insulin synthesis observed in the experimental groups may contribute to a better understanding of EPI-associated diabetogenic alterations.
