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- Suleyman, Halis(167)
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Yayınlar
- ArticleAçık Erişim2026Design, Synthesis, and Biological Evaluation of Methoxy-Substituted Chalcones and Gypsogenin-Based Hybrids as Anticancer and Antimicrobial Agents
Ulusoy, Nafia Gökçe; Emirdağ, Safiye; Kahriman, Nuran; Demir, Fatma; Serdaroğlu, Vildan; Yaylı, Nurettin; Türkmenoğlu, Burçin
Chalcones and natural product-based hybrids represent important scaffolds in the development of biologically active small molecules. In this study, a series of methoxy-substituted chalcone derivatives (1a–1i) and acetyl gypsogenin-based hybrid compounds (4a–4i) were synthesized and fully characterized by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against five human cancer cell lines (PANC-1, MDA-MB-231, HeLa, A549, and SH-SY5Y) and the normal HEK293 cell line using the MTT assay. Several chalcone derivatives exhibited pronounced antiproliferative activity, whereas the corresponding gypsogenin-based hybrids generally showed reduced cytotoxic effects. Tumor selectivity was further assessed by calculating the selectivity index values. Antimicrobial activity was determined using minimum inhibitory concentration assays against selected bacterial and fungal strains, revealing moderate inhibitory effects for some compounds. In addition, molecular docking studies of the most active chalcones (1g and 1h) were performed to explore potential interactions with key cancer-related targets. Overall, the results highlight the chalcone scaffold as the main contributor to biological activity in this series and demonstrate that hybridization with gypsogenin did not enhance the cytotoxic potency.
- ArticleYalnız künye2026The Effects of Apilarnil and Imatinib on GR/GST/TrxR1 Enzyme Activities and Pentose Phosphate Pathway Enzymes in Rats
Ayna, Adnan; Caglayan, Cuneyt; Türkeş, Cüneyt; Temel, Yusuf; Tahiroğlu, Veysel; Izol, Ebubekir; Inci, Hakan
Apilarnil, a relatively understudied bee-derived product from drone larvae, has recently gained attention due to its diverse chemical content and biological activities. Imatinib, a selective tyrosine kinase inhibitor widely used in cancer treatment, is recognized for its effectiveness but is also associated with off-target toxicities including disturbances in redox homeostasis. While previous studies have mainly focused on the roles of the key antioxidant enzymes glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione-S transferase (GST) and thioredoxin reductase (TrxR1) in tumor resistance mechanisms, their inhibition in non-cancerous cells may contribute systemic toxicity. This study investigated whether co-administration of apilarnil could alleviate the inhibitory effects of imatinib on these enzymes in vivo. The secondary metabolite profile of apilarnil was characterized using liquid chromatography–high resolution mass spectrometry (LC-HRMS) revealing a richness in phenolic compounds, notably isorhamnetin, phenolidzin, ascorbic acid, liquiritigenin, leucoside, 3-(4-hydroxyphenyl) propionic acid and caffeic acid. Enzyme activity assays showed that imatinib significantly suppressed the activities of G6PD, 6PGD, GR, GST and TrxR1 compared to the control group. However, co-treatment with apilarnil particularly at a dose of 400 mg/kg, markedly restored activities of these enzymes. Furthermore, molecular docking analysis was performed to assess the binding affinities and interaction profiles of imatinib with target enzymes, confirming its potent inhibitory potential and revealing distinct but comparable binding interactions. These findings suggest that apilarnil may exert a protective effect against imatinib-induced toxicity by modulating disruptions in metabolic enzyme activities.
- ArticleAçık Erişim2026Hydrazonylthiazole Derivatives as Dual EGFR and ALR2 Inhibitors: Design, Synthesis, and Comprehensive In Vitro and In Silico Evaluation for Potential Anticancer Activity
Sever, Belgin; Türkeş, Cüneyt; Demir, Yeliz; Elamin, Khaled M.; Osman, Wadah; Oral, Kübra; Akıncı Genç, Selenay; Cantürk, Zerrin; Masunaga, Takuya; Kishimoto, Naoki
Background/Objectives: Signaling imbalances involving epidermal growth factor receptor (EGFR) and aldose reductase (ALR2) are frequently associated with the biology of several solid tumors, including non-small-cell lung cancer (NSCLC) and breast cancer. This work sought to prepare and investigate a small set of hydrazonylthiazole derivatives as potential modulators of both targets with relevance to cancer therapy. Methods: Thirteen compounds (1–13) were synthesized and examined for their effects on A549 (NSCLC), MCF-7 (breast cancer), and Jurkat leukemia cells, together with peripheral blood mononuclear cells (PBMCs) to determine selectivity. The most active molecules were further analyzed through apoptosis studies, EGFR and ALR2 inhibition assays, docking calculations, and 200 ns molecular dynamics (MD) simulations. SwissADME was used to estimate pharmacokinetic and drug-likeness features. Results: Among all derivatives, compound 13, prepared here for the first time, showed the strongest activity on A549 and MCF-7 cells (IC50: 1.33 ± 0.41 µM; 1.74 ± 0.38 µM) and displayed a very high selectivity index (SI = 138.9). It also triggered apoptosis in A549 cells and reduced EGFR activity by 74% at 10 µM. In contrast, compound 5 acted as the most efficient ALR2 blocker (KI = 0.08 ± 0.01 µM). MD simulations showed that both compounds maintained stable contact patterns with essential residues in the EGFR and ALR2 binding pockets. SwissADME analysis suggested suitable oral absorption and drug-likeness for both molecules. Conclusions: Compound 13 behaves as a selective EGFR-directed agent capable of inducing apoptotic cell death in NSCLC, while compound 5 shows strong affinity toward ALR2. These outcomes indicate that both structures may serve as useful starting points for further development of small molecules acting on EGFR- and ALR2-related pathways.
- Review ArticleAçık Erişim2026Artificial Intelligence in Arthroplasty: A Comprehensive Structured Critical Review and Descriptive Evidence Map of Validation, Uncertainty, and Workflow Integration
Yapıcı, Furkan
Background/Objectives: Artificial intelligence (AI) in arthroplasty spans clinical prediction, imaging, implant identification, planning, natural language processing, infection support, patient communication, and workflow optimization, but its translational readiness remains uncertain. This review evaluated how often current studies move beyond internal model development toward credible external evaluation, uncertainty-aware reporting, and clinically meaningful integration. Methods: A structured critical narrative review and descriptive evidence map included 252 publications identified and verified between 1 January and 17 August 2026. Of these, 172 were core arthroplasty-specific primary-AI publications used for task mapping, whereas 150 involved an assessable fitted model or operational system suitable for transportability analysis; 139 publications belonged to both analytical sets. Transportability was assessed separately based on geographic/site independence, temporal separation, and model state at the time of evaluation. Results: Strict frozen-model external evaluation was identified in 27/150 publications (18.0%). Twelve of these 27 publications (44.4%) belonged to a single commercial planning program; treating those 12 publications as a single program-level evidence unit reduced the count from 27 to 16. Later, non-overlapping temporal evaluation was established in 7/150 publications (4.7%), while the temporal relationship remained unclear in 86/150 (57.3%). In eight of the 150 transport-assessable publications (5.3%), external-validation terminology mapped to a different operational category under the framework used here. Among the 172 core publications, confirmed-present lower bounds were 27/172 (15.7%) for calibration, 5/172 (2.9%) for uncertainty or out-of-distribution handling, and 8/172 (4.7%) for observed workflow or patient benefit. The strongest near-term evidence concerned bounded, auditable tasks such as implant recognition, measurement, planning, and structured information extraction. Conclusions: Arthroplasty AI is best positioned as clinician-supervised precision-support infrastructure. Credible translation requires clearly defined evaluation settings, transparent reporting of model state, calibration and uncertainty assessment where applicable, and prospective workflow-level evaluation.
- ArticleAçık Erişim2026The mediating role of resilience in the relationship between perceived family social support and general life satisfaction
Sağar, Mehmet Enes; Ateş, Bünyamin
Introduction – Life satisfaction is an important indicator of psychological well-being among university students. Family social support and resilience are considered key protective factors that may contribute to higher levels of life satisfaction. This study aimed to test a hypothesized model examining the relationships among perceived family social support, resilience, and general life satisfaction in university students. Methods – The study group consisted of 357 students (146 males, 40.9%; 211 females, 59.1%; Mage = 22.43) enrolled in various faculties of public universities in Türkiye during the 2024–2025 academic year. Data were collected online via Google Forms using the Adult Life Satisfaction Scale, the Multidimensional Scale of Perceived Social Support, the Adult Resilience Measure, and a Personal Information Form. The data were analyzed using SPSS and Mplus software. Results – The findings revealed statistically significant positive relationships between general life satisfaction and resilience, between general life satisfaction and perceived family social support, and between resilience and perceived family social support. Perceived family social support significantly and positively predicted resilience, while resilience significantly and positively predicted general life satisfaction. In addition, resilience was found to mediate the relationship between perceived family social support and general life satisfaction. The direct and indirect effects included in the model explained approximately 46% of the variance in general life satisfaction. Discussion – The findings underscore the important roles of perceived family social support and resilience in enhancing university students’ life satisfaction. The results suggest that interventions designed to strengthen family support and resilience may contribute to improving students’ psychological well-being and overall life satisfaction. Future research may further investigate these relationships across different cultural contexts and student populations.
- CorrectionAçık Erişim2026Correction: Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities (Naunyn-Schmiedeberg's Archives of Pharmacology, (2025), 398, 7, (8543-8554), 10.1007/s00210-024-03773-6)
Atila Uslu, Gözde; Uslu, Hamit; Çoban, Taha Abdulkadir; Özkaraca, Mustafa; Mendil, Ali Sefa; Aygörmez, Serpil
In the originally published version of this article, inaccuracies were identified in Figure 9. Specifically, the images in Figures 9C and 9D were incorrectly presented due to the misplacement of the representative image for Figure 9D. This error has now been corrected, and Figure 9D has been revised accordingly. Additionally, errors were found in the annotation of Figure 9. Figure 9B was mistakenly labeled as the Nobiletin group; however, it actually represents the negative control group (NFκB). Conversely, Figure 9C was incorrectly labeled as the negative control group, whereas it should be identified as the Nobiletin group (IL-1β). The legend of Figure 9 has been corrected to accurately reflect these revisions. These corrections do not affect the results or conclusions of the study. The corrected figure and legend are provided below. (Figure presented.) Fig. 9 A Negative control group IL-1β, B Negative control group NFκB, C Nobiletin group IL-1β, D Nobiletin group NFκB. (IL-1β and NFκB immune negativities.) IHC
- ArticleAçık Erişim2026Anticancer potential of radioactively activated zinc: mechanisms and therapeutic applications
Kalındemirtaş, Ferdane Danışman; Eroğlu, Güneş Özen; Nazlıgül, Esra; Kariper, İshak Afşin
Zinc (Zn), an essential trace element, has been shown to exhibit antiproliferative effects at high concentrations and to serve various functions in human health. Numerous studies have been undertaken to enhance the efficacy of zinc. In this study, the therapeutic efficacy of zinc in terms of activation by ionizing radiation was investigated, and whether this would increase its efficacy was determined. In this study, Zn-65 was detected by exposing zinc to X-rays using a novel approach. The present study investigates the biological effects of low-dose gamma irradiation with Zn-65 compared with zinc alone on MCF-7 breast cancer cells. Human umbilical cord endothelial cells (HUVECs) were used as a standard cell control. The study investigated the biological effects of Zn-65 (IR-Zn) on MCF-7 breast cancer cells, comparing them with non-irradiated zinc, using human umbilical cord endothelial cells (HUVECs) as a control. Cytotoxic activity, cell proliferation, apoptosis, cell cycle progression, and drug resistance profiles were evaluated. Our findings show that IR-Zn significantly enhances anticancer activity by inducing premature cell cycle arrest at the G0/G1 phase, promoting apoptosis, and suppressing ABCG2-mediated drug resistance mechanisms. This is the first study to demonstrate that low doses of gamma-emitting Zn-65 can elicit potent, selective cytotoxicity against cancer cells without severely damaging normal cells. The findings indicate that weak gamma-emitting Zn-65 may be a viable targeted and low-toxicity radiopharmaceutical candidate for prospective oncological applications.
- ArticleAçık Erişim2026Comparative analysis of free amino acid concentrations in colostrum and transitional breast milk from mothers of term and preterm infantsa
Alkan Polat, Betül; Aydemir Atasever, Meryem; ATASEVER, Mustafa
This study aimed to comprehensively characterize the free amino acid (FAA) composition of human breast milk and to compare profiles between term (TBM; milk of term infants) and preterm (PBM; milk of preterm infants) samples across two lactation stages, colostrum and transitional milk. A total of 200 breast milk samples were collected on the 3rd and 10th postpartum days from 50 healthy mothers of term infants and 50 healthy mothers of preterm infants in Erzurum Province. Forty-five FAAs were quantified using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Significant differences in FAA composition were observed between TBM and PBM. Glutamic acid, the predominant FAA in all samples, was approximately 82% higher in TBM compared to PBM (p < 0.001). TBM also exhibited markedly higher levels of bioactive amines, including anserine, serotonin, and dopamine, whereas PBM was enriched in several amino acids such as aspartic acid (> 200%) and branched-chain amino acids, particularly leucine and isoleucine (p < 0.05–0.001). Among essential amino acids, histidine was more abundant in TBM, while leucine, isoleucine, lysine, and phenylalanine were significantly higher in PBM (p < 0.05–0.001). Lactation stage–dependent variations were evident in both groups. Colostrum exhibited a significantly richer FAA profile than transitional milk in both TBM and PBM (p < 0.05–0.001). In TBM, colostrum contained higher concentrations of several amino acids, including arginine, aspartic acid, asparagine, glycine, proline, serine, histidine, and valine, whereas transitional milk showed higher levels of glutamic acid, beta-alanine, beta-aminoisobutyric acid, and dopamine (p < 0.05–0.001). In PBM, colostrum was particularly enriched in essential amino acids such as lysine, methionine, phenylalanine, threonine, tryptophan, and branched-chain amino acids, while several non-essential amino acids decreased during the transition to transitional milk (p < 0.001). Overall, these findings demonstrate that both gestational age and lactation stage significantly influence the free amino acid composition of human breast milk, highlighting distinct bioactive and nutritional profiles in term and preterm milk with potential implications for early infant nutrition.
- ArticleAçık Erişim2026Measuring Perceived Social Support After Disaster: Development and Validation of the Perceived Social Support in Disasters Scale (PSSDS-28)
Oruç, Abdurrahman; Cengiz, Ekrem
Background/Objectives: Measuring perceived social support after disaster remains an unresolved psychometric problem. Most instruments do not jointly capture the source of support (from whom it comes) and its function (how it operates). None has been validated in a disaster-survivor sample with retrospectively framed items. We developed and validated the Perceived Social Support in Disasters Scale (PSSDS-28), a 28-item measure integrating both dimensions. Methods: In Phase 1, a PRISMA 2020-guided systematic review; a two-round Delphi with eight experts, cognitive interviews (n = 12); and a pilot study (N = 150) produced a 31-item form. In Phase 2, face-to-face data were collected from 607 adults affected by the 6 February 2023 Kahramanmaraş earthquakes (Türkiye). Multiple analytic frameworks converged on a five-factor, 28-item structure comprising family–relative, social environment, institutional, emotional, and instrumental–informational support. Results: The correlated five-factor model fit the independent validation sample well (CFI = 0.954, RMSEA = 0.076, and SRMR = 0.072) and outperformed a one-factor alternative (ΔCFI = 0.222). Blocks showed strong internal consistency (ordinal α = 0.852–0.949), composite reliability (0.865–0.950), and adequate test–retest stability (ICC = 0.542–0.909). Scalar measurement invariance held across six groupings, with no meaningful differential item functioning. Convergent and discriminant evidence supported construct validity, and common-method variance was negligible. Institutional (M = 3.29) and instrumental–informational support (M = 2.99) scored lowest—a profile a global score would conceal. Conclusions: The PSSDS-28 provides promising initial psychometric evidence for a multidimensional post-disaster assessment instrument situated at the perceived–received interface, a target that general-purpose scales are not designed to capture. Criterion-related validity, cross-cultural validity, and cross-disaster replicability remain to be demonstrated.
- ArticleAçık Erişim2026Evaluation of Epithelial Cell Adhesion Molecule, Galectin-3, and Proliferative Cell Nuclear Antigen Expression in Thyroid Papillary Carcinomas and Their Lymph Node Metastases
Daltaban, F.; Sayar, I.; Tayfur, M.; Gürbüzel, M.; Balcı, M.
Background: Thyroid papillary carcinoma (PTC) is the most common carcinoma of thyroid carcinomas and endocrine carcinomas. The diagnosis of thyroid PTC is made mainly by the presence of nuclear features such as nuclear clearing, groove, and nuclear inclusions. Some benign lesions of the thyroid may have nuclear features and growth patterns of papillary thyroid carcinomas, which can make the differential diagnosis difficult. Different immunohistochemical markers have always been needed to reduce diagnostic errors and detect malignancies in routine practice. As in all tumor cases, studies continue to understand carcinogenesis in thyroid carcinomas. One of the ways that can help understand this involves the use of new and effective immunohistochemical markers. Aim: This study aimed to examine the expression of epithelial cell adhesion molecule (EpCAM), Galectin-3 (Gal-3), and proliferative cell nuclear antigen (PCNA), which are immunohistochemical markers that may contribute to the diagnosis and prognosis of thyroid PTCs and lymph node (LN) metastases. Materials and Methods: EpCAM, Gal-3, and PCNA immunohistochemical markers were applied to 26 unifocal (UF) thyroid PTC cases and 25 thyroid PTC cases with LN metastasis or multifocal (MF) tumor field. Results: It was observed that the Gal-3 staining score decreased significantly in the LN metastasis focus compared to the UF tumor. With EpCAM significant loss of membranous expression was observed in the MF tumor compared to the UF tumor. There was no statistically significant difference between the case groups in terms of PCNA staining score. Conclusions: These results may be important in terms of obtaining new immunohistochemical clues for diagnosis and carcinogenesis in thyroid PTCs and their metastases. The number of cases in our study is limited, and we think that supporting the results with a large series of studies may contribute to the diagnosis and prognosis of the patients.
- ArticleYalnız künye2026Novel hydrazone-derived pyrazole-benzofuran compounds inhibit cancer cell growth by targeting MMPs, caspases, and PI3K/AKT/mTOR signaling pathway
El Hassani, Issam Ameziane; Altay, Ahmet; Yeniçeri, Esma; Boukharsa, Youness; Assila, Hamza; Alzahrani, Abdullah Yahya Abdullah; Moussa, Sana Ben; Ansar, M'’hammed; Karrouchi, Khalid
In this research, a series of novel pyrazole-benzofuran hydrazone hybrids (3a-h) were designed, synthesis and evaluated for their anticancer potential. All hybrid pyrazole-benzofuran derivatives were purified and characterized by using 1H NMR, 13C NMR, and ESI-HRMS analyses. Their cytotoxic potentials were evaluated against human lung carcinoma (A-549) and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast (3T3-L1) cells using XTT assay. The findings demonstrated that all compounds exhibited a dose-dependent anti-proliferative effect against the cancer cell lines under investigation. Compound 3d was particularly distinguished by its noteworthy IC50 value of 0.28 μM and a selectivity index of 103.85 on A549 cells. Advanced mechanistic anticancer investigations employing flow cytometry revealed that compound 3d triggered apoptosis in A549 cells by inducing mitochondrial membrane disruption and activating multiple caspases. Furthermore, both flow cytometry and Western blot analysis showed that the 3d molecule significantly suppressed the PI3K/AKT/mTOR signaling pathway, which is vital for cellular proliferation. In summary, the findings suggest that compound 3d has the potential to be evaluated as a therapeutic agent for the treatment of lung cancer.
- ArticleAçık Erişim2026Evaluation of trabecular architecture and bone density in periradicular bone of dilacerated mandibular third molars: a cone beam computed tomography study
Ocak, Ali; Akyüz, Mehmet
Background: This study aimed to evaluate and compare the periradicular trabecular bone density (BD) and microarchitecture of dilacerated and non-dilacerated mandibular third molars using gray values (GVs) and fractal dimension (FD) derived from cone-beam computed tomography (CBCT) images. Methods: This retrospective cross-sectional study included CBCT scans of 54 patients with dilacerated mandibular third molars and 60 controls without dilaceration. Root dilaceration was defined as deviation > 20° from the long axis. The dilaceration group was further divided into subgroups based on severity (angle of dilaceration > 60° vs. ≤60°). Standardized regions of interest were selected adjacent to the curvature of the roots, excluding cortical bones. GVs were automatically measured by Romexis 6.2.1 (R®software, Planmeca, Helsinki, Finland), and FD was calculated via ImageJ using the box-counting method. Appropriate statistical analyses were performed, with significance set at p < 0.05. Results: No significant differences were found between dilacerated and non-dilacerated groups in GV (437.12 ± 184.83 vs. 439.25 ± 148.90, p = 0.645) or FD (1.07 ± 0.15 vs. 1.04 ± 0.17, p = 0.204). However, when dilacerated teeth were stratified by severity, roots with > 60° curvature exhibited significantly higher FD values than those ≤ 60° (p = 0.040), whereas GV values did not differ between curvature groups (p > 0.05). Spearman’s correlation revealed no significant association between dilaceration angle and GV or FD (p > 0.05). Conclusion: Within the limitations of this study, fractal analysis was used as a quantitative method to assess periradicular trabecular bone changes adjacent to dilacerated root apices. Although overall GV- and FD-based metrics did not differ between dilacerated and non-dilacerated teeth, the higher FD observed in severely dilacerated roots (> 60°) suggests increased trabecular complexity in the apical region, reflecting a potential biological bone response associated with pronounced root curvature.
- ArticleAçık Erişim2026Maresin-1 and maresin-2 as synovial fluid biomarkers in psoriatic, rheumatoid, and osteoarthritis
Demir, Sukru; Can, Bugra; Esmez, Omer; Aydin, Mustafa Ata; Gencer, Sevval Yagmur; Bildirici, Furkan; Koca, Süleyman Serdar; Sahin, İbrahim; Aydin, Suleyman
Objective – To investigate synovial fluid levels of maresin-1 (MaR-1) and maresin-2 (MaR-2) in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and controls, and to assess their ability to differentiate PsA from RA. Methods – This prospective cross-sectional study included 88 patients undergoing knee arthrocentesis for joint effusion between September 2025 and February 2026. RA was classified according to the 2010 ACR/EULAR criteria, PsA using CASPAR criteria, and OA based on clinical and radiographic assessment. Synovial fluid MaR-1 and MaR-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and expressed as ng/mL. Group comparisons were performed using parametric or non-parametric statistical tests as appropriate. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of MaR-1 and MaR-2 for distinguishing PsA from RA, including area under the curve (AUC), sensitivity, specificity, and optimal cut-off values. Logistic regression analysis assessed the association between MaR-1 levels and PsA. Results – Significant intergroup differences were observed for age, visual analogue scale (VAS) scores, and synovial MaR-1 concentrations (all p < 0.01). MaR-1 levels were significantly higher in PsA than RA (p < 0.01), whereas MaR-2 showed more modest differences among groups (p < 0.05). ROC analysis demonstrated good discriminatory performance of MaR-1 for differentiating PsA from RA, with an AUC of 0.815 (95% CI, 0.675–0.933). A cut-off value of 3.252 ng/mL provided 68.2% sensitivity and 86.4% specificity. Higher MaR-1 levels were significantly associated with PsA in unadjusted logistic regression analysis (OR = 1.62, 95% CI 1.18–2.22; p = 0.003). MaR-1 and MaR-2 levels were moderately positively correlated (Spearman’s r = 0.620, p < 0.001). Conclusion – Synovial MaR-1 concentrations were markedly elevated in PsA compared with RA and demonstrated good diagnostic discrimination, supporting the potential role of pro-resolving mediators as biomarkers in inflammatory arthropathies. The clinical significance of MaR-2 appears more limited and requires validation in larger studies.
- ArticleAçık Erişim2026Mono- and Bis-Ureido Sulfapyridines as Nanomolar Dual Cholinesterase Inhibitors: Enzyme Kinetics, Molecular Docking, and ADME/Tox Insights
Yapar, Gönül; Akocak, Suleyman; Lolak, Nebih; Topal, Meryem; Türkeş, Cüneyt; Topal, Fevzi; Durgun, Mustafa; Koçyiğit, Ümit Muhammet; Işık, Mesut; Beydemir, Şükrü
A series of mono- and bis-ureido sulfapyridine derivatives (SP-1–SP-10) were synthesized and evaluated as dual cholinesterase inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All compounds exhibited nanomolar inhibition. The most potent AChE inhibitors were SP-8 (Ki = 5.25 ± 0.73 nM), SP-9 (5.09 ± 0.44 nM), and SP-10 (5.74 ± 0.55 nM), significantly outperforming tacrine (Ki = 105.03 ± 8.85 nM) under identical conditions. For BChE, SP-9 showed the strongest inhibition (Ki = 26.38 ± 2.07 nM) compared with tacrine (172.03 ± 32.42 nM). Kinetic analyses revealed competitive inhibition toward AChE for all derivatives, whereas BChE inhibition displayed both competitive and noncompetitive patterns depending on structural features. Glide XP docking using AChE (PDB: 7XN1) and BChE (PDB: 4BDS), complemented by MM-GBSA binding free energy calculations, supported favorable ligand accommodation within the catalytic pockets and highlighted the importance of aromatic and hydrophobic interactions. In silico ADME/Tox analysis revealed a potency–drug-likeness trade-off: mono-ureido derivatives complied with Lipinski's rule of five and showed high predicted oral absorption, whereas bis-ureido derivatives, despite superior enzymatic potency, exhibited multiple drug-likeness violations. These findings identify the ureido–sulfapyridine scaffold as a potent enzymatic dual cholinesterase inhibitory framework, warranting further structural optimization to improve pharmacokinetic properties.
- ArticleAçık Erişim2026Flunarizine attenuates ischemia–reperfusion–induced ovarian injury in rats
Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Paltacı, Şeyma İlayda; Demir, Özlem; Kuzucu, Mehmet; Süleyman, Halis
Background: Ovarian ischemia–reperfusion (I/R) injury is associated with oxidative stress, inflammation, and histopathological damage. The aim of this study was to investigate the potential protective effects of flunarizine against ovarian I/R–induced injury in an experimental rat model. Methods: Rats were divided into four groups: healthy control (HG), sham-operated (SOG), ovarian ischemia–reperfusion (OIR), and flunarizine-treated OIR (FOIR). Ovarian tissues were analyzed in terms of oxidative stress markers, antioxidant enzyme activities, inflammatory cytokines, and histopathological alterations, including follicle counting. Results: Ovarian I/R significantly increased tissue levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) while significantly decreasing total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. Histopathological evaluation revealed severe follicular degeneration, interstitial edema, vascular congestion, and inflammatory cell infiltration in the OIR group. Following flunarizine administration, these biochemical and histopathological alterations were significantly ameliorated, and a partial restoration in follicle counts was observed. Conclusion: The findings of this study demonstrate that flunarizine exerts protective effects against ovarian I/R injury by reducing oxidative stress, inflammation, and histopathological damage.
- ArticleYalnız künye2026Unpacking Profiles of School Burnout in High-Achieving Students in Türkiye: A MSEM Analysis
Ağirkan, Murat; Haspolat, Namık Kemal; Özdoğan, Ahmet Çağlar
Although high-achieving students are often perceived as well-adjusted, there is limited understanding of the varied ways they experience school burnout. Prior research tends to treat burnout as a uniform phenomenon, overlooking subgroups that may differ in psychological risk and academic outcomes. This study addresses this gap by identifying distinct profiles of school burnout and examining their psychological and academic correlates in high-achieving adolescents, defined by their mean grade of 85 or above out of 100 and placement in the top 2%, which earned them admission to science high schools based on their performance on Türkiye’s High School Entrance Exam (LGS). Participants included 443 students (225 females, 50.8%) aged 14 to 19 years (M = 15.9, SD = 1.11). Given the broad age range spanning early to late adolescence, developmental variability in academic expectations and emotional regulation is likely, which may influence how students experience burnout. Using Mixture Structural Equation Modeling (MSEM), in which latent profiles and structural pathways were estimated simultaneously, the study found that parental achievement pressure, self-oriented perfectionism, and socially prescribed perfectionism predicted fear of failure, which in turn negatively impacted grade point average. Both fear of failure and grade point average were significant predictors of burnout, with fear increasing burnout and grade point average serving as a protective factor. Latent Profile Analysis revealed three distinct student profiles: “Calm but Underachieving”, “Burnout Under Pressure”, and “Self-Driven High Achiever”. Three-step regression analyses revealed that psychological symptoms varied meaningfully across profiles. Specifically, the “Calm but Underachieving” group had significantly higher odds of depression compared to the “Self-Driven High Achiever” group, despite reporting lower stress levels. Meanwhile, anxiety levels did not significantly differ across any profile, indicating that anxiety may be a more generalized emotional response among students regardless of their academic engagement. These findings underscore the importance of considering developmental differences and psychological risks unique to high-achieving adolescents. By identifying distinct burnout profiles, this study provides nuanced insights that address gaps in current understanding and support the development of targeted mental health interventions for high-achieving adolescents.
- ArticleAçık Erişim2026Effectiveness of Small-Group Direct Instruction on Science Learning for Students With Mild Intellectual Disability
Demir, Murat; Polat, Recep; Aydin, Orhan; Kenan, Adem
This study examined the effectiveness of direct instruction (i.e., explicit instruction) delivered in a small-group format on the science achievement of students with mild intellectual disability (MID) in the “Support and Movement System” unit, and evaluated maintenance, generalization, and social validity outcomes. A concurrent multiple-baseline design across skills was implemented with three eighth-grade female students attending a special education school. The intervention was delivered by a science teacher using the core components of direct instruction, including attention-getting, modeling, guided practice, and independent practice. Instruction focused on key concepts related to bones, muscles, and joints. Student performance was measured using percentage accuracy scores across the baseline, intervention, post-intervention, and maintenance phases, as well as ongoing generalization data. Social validity data were collected through structured interviews with students, parents, and their special education teacher. Results indicated that baseline performance was low and stable across all participants. Following the introduction of direct instruction, all students demonstrated substantial and stable increases in performance. These gains were largely maintained over time and generalized across different questions. Social validity findings were positive across all respondent groups, indicating that the intervention was perceived as effective, acceptable, and meaningful. Overall, the findings suggest that direct instruction delivered in a small-group format is an effective and feasible approach for supporting science learning in students with MID.
- ArticleAçık Erişim2026Neuroprotective effects of black elderberry (Sambucus nigra) extract through the role of miR-124-5p and miR-144-5p in a streptozotocin-induced Type 2 diabetic rat model
Gezer, Arzu; Sanlı, Fatma; Aslan, Haktan; Özkaraca, Mustafa; Baygutalp, Nurcan Kılıç; Sarı, Ebru Karadağ; Karatas, Omer Faruk; Üstündağ, Hilal
Background: Type 2 diabetes mellitus (T2DM) leads to neurological complications through multiple pathways. Black elderberry (Sambucus nigra, SN) is rich in bioactive compounds with potential neuroprotective properties. This study sought to evaluate the neural-protective potential of SN extract in STZ-diabetic rats using an integrated molecular, biochemical, and histomorphological approach. Methods: Forty male Sprague-Dawley rats were divided into four groups (n = 10/group): control (C; 0.9% NaCl), SN (0.040 g/kg body weight), diabetes mellitus (DM; streptozotocin 50 mg/kg), and DM + SN (streptozotocin + SN). The treatment period was 10 weeks. Brain tissue was analyzed for histopathological changes, caspase-3 expression, microRNA (miRNA) expression, and oxidative stress markers. Results: Histopathological examination revealed severe neuronal degeneration in the DM group, significantly attenuated in the DM + SN group (p < 0.001). Caspase-3 immunoreactivity was markedly increased in DM group compared to controls and significantly reduced by SN treatment (p < 0.01). In situ hybridization showed high ribonucleic acid (rno)-miR-124-5p and rno-miR-144-5p expression in C and SN groups, with reduced expression in DM group (p < 0.05). SN treatment moderated these changes in DM + SN group. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed decreased miR-124 expression in DM group, restored to control levels by SN treatment. Biochemically, SN extract reversed diabetes-induced changes in oxidative stress markers, decreasing malondialdehyde (MDA) levels while increasing glutathione (GSH) and nitric oxide synthase (NOS) levels (p < 0.01). Conclusions: SN extract exerted robust neuroprotective actions in the diabetic brain through apoptosis inhibition, miRNA profile restoration, and amelioration of redox imbalance, underscoring its therapeutic promise for diabetes-associated neuropathy.
- ArticleAçık Erişim2026Hepatoprotective Potential of Eugenol Against Pesticide Glyphosate-Induced Liver Injury via Nrf2/HO-1 Signaling and Modulation of Apoptosis and Inflammation in Rats
Aktas Senocak, Esra; Alat, Omercan; Bolat, Ismail; Lacin, Burak Batuhan; Tekin, Samet; Atasever, Aslıhan; Bolat, Merve; Halici, Mesut Bunyami
Glyphosate (GLY) is a widely used herbicide active ingredient applied in agricultural, residential, and public areas. Although the European Chemicals Agency has stated that current evidence is insufficient to classify GLY as an endocrine disruptor, increasing experimental data indicate that GLY may induce organ toxicity. This study aimed to investigate glyphosate-induced liver toxicity and to evaluate the potential protective effects of eugenol in a rat model. Eugenol is a phenolic compound predominantly found in clove oil (Syzygium aromaticum L.) and is known for its antioxidant, anti-inflammatory, antimicrobial, and analgesic properties. It is classified as generally recognized as safe (GRAS) and non-mutagenic by the World Health Organization. Thirty-five male rats were randomly assigned to five groups: Control, EU-100, GLY, GLY + EU-50, and GLY + EU-100. All treatments were administered orally by gavage. Oxidative stress markers (lipid peroxidation, reduced glutathione, and superoxide dismutase), liver enzyme activities (ALT, AST, and ALP), and the expression of genes involved in antioxidant defense, apoptosis, and inflammation (HO-1, Nrf2, CAT, GPx, Bax, Caspase-3, Bcl-2, COX-2, NF-κB, IL-6, TNF-α, and IL-1β) were analyzed. Short-term GLY exposure resulted in oxidative imbalance, inflammatory activation, and apoptosis in hepatic tissue. Eugenol administration significantly alleviated these alterations by enhancing antioxidant defenses, activating the Nrf2/HO-1 signaling pathway, and suppressing pro-inflammatory responses. These findings suggest that eugenol may represent a promising natural hepatoprotective agent against glyphosate-induced liver toxicity.
- ArticleAçık Erişim2026Modulatory role of endogenous adrenaline in propofol-related nociceptive responses in rats
Gozen, Fusun; Sezgin, Esra Tuba; Yavuzer, Bulent; Sarigul, Cengiz; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Suleyman, Halis
Introduction – Propofol is a short-acting intravenous hypnotic anesthetic widely used for sedation and the induction and maintenance of general anesthesia. Although it reliably produces unconsciousness, its intrinsic analgesic efficacy remains a subject of debate. Accumulating evidence indicates that propofol suppresses catecholaminergic activity, and inhibition of endogenous adrenaline may therefore limit its ability to modulate nociceptive processing. Accordingly, this study aimed to investigate the nociceptive suppressions of subhypnotic and anesthetic doses of propofol in rats and their relationship with endogenous adrenaline levels. Methods – Thirty-six male Wistar rats were randomly allocated into six experimental groups: healthy healthy control, subhypnotic-dose propofol (25 mg/kg; PRO-25, intraperitoneally), anesthetic-dose propofol (50 mg/kg; PRO-50, intraperitoneally), adrenaline-alone (0.3 mg/kg; ADRG, intraperitoneally), and adrenaline combined with subhypnotic or anesthetic-dose propofol (PRAD-25 and PRAD-50). Mechanical paw withdrawal thresholds, anesthetic duration, behavioral responses to standardized scalpel incision, and plasma adrenaline levels were evaluated using statistical analyses. Results – Propofol administered alone failed to produce significant nociceptive suppressionat either dose and induced dose-dependent suppression of circulating adrenaline, whereas adrenaline alone exerted no significant effect on nociceptive thresholds. In contrast, combined administration significantly increased pain thresholds at subhypnotic doses and abolished responses to surgical incision at anesthetic doses despite comparable anesthetic duration. Notably, co-administration restored serum adrenaline levels toward physiological values at lower, but not higher, propofol doses. Conclusion – These findings provide experimental results suggesting that nociceptive responses observed during propofol exposure may be modulated by endogenous adrenergic activity. This interaction may contribute to explaining the dissociation between anesthetic depth and nociceptive suppression and points to a catecholaminergic influence on anesthetic–nociceptive dynamics that has not been sufficiently investigated previously.
