İstanbul Sağlık ve Teknoloji Üniversitesi Kurumsal Akademik Arşivi
DSpace@İSTÜN, Üniversite mensupları tarafından doğrudan ve dolaylı olarak yayınlanan; kitap, makale, tez, bildiri, rapor, araştırma verisi gibi tüm akademik kaynakları uluslararası standartlarda dijital ortamda depolar, Üniversitenin akademik performansını izlemeye aracılık eder, kaynakları uzun süreli saklar ve telif haklarına uygun olarak Açık Erişime sunar.
Güncel Gönderiler
Ibuprofen and nimesulide derivatives selectively induce apoptosis in HER2-positive breast cancer via inhibition of the PLA₂–COX-2–NF-κB pathway
(Springer Nature Link, 2026) Çakırlı, Egemen; Bedir, İpek; Biliz, Yağmur; Yılmaz, Özgür; Küçükgüzel, Şükriye Güniz; Telci, Dilek
Background Chronic inflammation contributes to breast cancer development through the phospholipase A₂ (PLA₂)–cyclo oxygenase-2 (COX-2)–nuclear factor κB (NF-κB) cascade, which regulates prostaglandin synthesis, oxidative stress, and transcription of pro-inflammatory and anti-apoptotic genes. This pathway is particularly active in HER2-positive breast can cer, promoting proliferation, invasion, and resistance to apoptosis. Non-steroidal anti-inflammatory drugs such as ibuprofen and nimesulide target COX enzymes and have shown potential in suppressing inflammation-driven tumorigenesis. In this study, we evaluated the anticancer and anti-inflammatory activity of newly synthesized, structurally modified ibuprofen and nimesulide derivatives designed to modulate PLA₂–COX-2–NF-κB axis. Methods and Results Cytotoxicity was assessed in HER2-positive breast cancer cells (AU565 and SKBR3) and compared with normal dermal fibroblasts (HDF) and breast epithelial cells (MCF-12A), using WST-1 assays. Apoptosis, cell cycle distribution, caspase-3/7 activation, and ROS generation were analyzed by imaging-based assays, flow cytometry, and fluo rescence methods. Gene expression of PLA2G2A and PTGS2 was quantified by qRT-PCR, and NF-κB translocation was analyzed by immunocytochemistry. Two ibuprofen triazole derivative (D1) and ibuprofen thioether derivative (D7) and one nimesulide derivative (D8) significantly reduced cell viability in a dose-dependent manner without affecting normal cells. These derivatives induced G₀/G₁ arrest, caspase-3/7 activation, ROS reduction, and increased late apoptosis. Downregula tion of PLA2G2A and PTGS2 expression and inhibition of NF-κB translocation confirmed disruption of the PLA₂–COX-2– NF-κB cascade. Conclusion These findings demonstrate that structurally optimized ibuprofen and nimesulide derivatives exert dual anti inflammatory and anticancer effects in HER2-positive breast cancer by suppressing PLA₂–COX-2–NF-κB pathway and promoting apoptotic cell death.
Synthesis, characterization, biological evaluation, and molecular modeling of novel nimesulide urea derivatives as potential MetAP2 inhibitors
(Nature Research, 2026) Yılmaz, Özgür; Biliz, Yağmur; Kuloğlu, Elif; Arancı, Kübra; Erdoğan, Ömer; Çevik, Özge; Karahasanoğlu, Müfide; Mert Şahin, Naz Mina; Çakır, Ayşe Buse; Tuzcu, Bilge; Yelekçi, Kemal; Küçükgüzel, Şükriye Güniz
A series of nimesulide-derived ureas were synthesized in high yields (69- 91%) via a novel synthetic method under organotin catalysis. The structural characterization of the synthesized compounds was determined using a variety of spectroscopic methods, including ¹H NMR, ¹³C NMR, FTIR, and HRMS. Following initial screening, selected compounds were further evaluated using specific biological assays, including cytotoxicity analysis, apoptosis assessment by Annexin V/PI staining, analysis of Bax and Bcl-2 protein expression, and detection of DNA fragmentation using AO/EB staining. These evaluations were carried out in a variety of cell lines, including MDA-MB-231 (human triple-negative breast cancer cells), HeLa (human cervical cancer cells), PC-3 (androgen-independent human prostate cancer cells), MKN-45 (human gastric cancer cells), U87 (human glioblastoma cancer cells), and HUVEC (human umbilical vein endothelial cells). Three of the compounds demonstrated efficacy in MDA-MB-231 cells, resulting in increased AO/EB staining and annexin-V-PI binding levels, and increased Bax/Bcl-2 ratios. Numerous studies implicate MetAP2 in angiogenesis. MetAP2 stimulates cancer cell proliferation when it is upregulated and appears to play an essential role in tumor progression. In connection with the cell lines studied in this study, a crucial MetAP2 enzyme target was selected for in silico studies to support the experimental outcomes. The three promising compounds have been demonstrated to accelerate cell apoptosis and inhibit cell division by targeting MetAP2. The compounds synthesized in this study potential to overcome the challenges of targeted therapies in triple-negative breast cancer. Alongside these findings, the antioxidant potential of the synthesized compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. One of the compounds exhibited a radical scavenging activity comparable to the reference standard. In-silico molecular modeling studies were conducted in the final phase to evaluate the newly designed inhibitors as potential anticancer and antioxidant drug candidates. The most likely conformations of the MetAP2-ligand complex were sorted according to the free energy of binding score (kcal/mol) and agree with the experimental inhibition values. The computational results suggest that the newly synthesized compounds may be potential anticancer drug candidates.
Scientific accuracy of large language models in tilted implant dentistry: A guideline-based comparative evaluation
(Wolters Kluwer, 2026) Yıldız, Mehmet S.; Alkap, Melek; Özdal, Umut; Özdal Zincir, Özge
Tilted dental implant systems are widely used in the rehabilitation of anatomically compromised jaws and are supported by international consensus guidelines. Concurrently, large language models (LLMs) are increasingly accessed as informational tools in implant dentistry; however, their scien tific accuracy and adherence to guideline-based principles in advanced implant concepts remain insufficiently explored. This study evaluated the scientific accuracy, guideline conformity, and clinical consistency of responses generated by 4 LLMs regarding tilted dental implant systems. A total of 120 guide line-based questions covering 8 predefined domains (definition, indications, contraindications, advantages, surgical procedure content, prosthetic procedure content, complications, and prognosis/survival) were developed in accordance with ITI, EAO, and AAOMS consensus reports. Each question was in dependently submitted to ChatGPT-5.2, Copilot, DeepSeek, and Gemini, and all responses were anonymized and evaluated by a multidisciplinary expert panel using a structured ordinal scoring system. Overall, scientific accuracy scores were high across all models, with near-ceiling performance observed in domains related to indications, advantages, procedural con tent, and prognosis. Statistically significant between-model differences were identified in the definition (P = 0.003), con traindications (P = 0.006), and complications (P < 0.001) do mains, with DeepSeek and Gemini demonstrating consistently higher scores in complication-related content compared with ChatGPT and Copilot. Within-model analyses further revealed significant domain-dependent variability across all LLMs. Al-though LLMs demonstrate a strong capacity to reproduce es tablished, guideline-based knowledge regarding tilted implant systems, limitations remain in safety-critical domains requiring nuanced clinical judgment. Accordingly, LLMs should be re garded as adjunctive educational tools rather than substitutes for expert decision-making in craniofacial implantology.
Impression precision after hydrogen peroxide sterilization of scanner sleeves
(Springer Nature Link, 2026) Yılmaz, Berza; Arslan, Meriç; Kayasaroğlu, Damla Nur; Arslan, Elif Dilara; Sunal Aktürk, Ezgi
Introduction The iTero Element (Align Technologies, San Jose, CA, USA) is a widely used intraoral scanning device, and its protective sleeves for the scanning head are provided for single use. This condition puts the clinical management budget under financial strain and creates a disadvantage for managing environmental waste. The objective of our research was to assess how repeated sterilization of disposable scan head covers with hydrogen peroxide affected the precision of digital impressions. Methods Intraoral scans were carried out using the iTero Element 5D scanner on 26 patients. Hydrogen peroxide was used to sterilize the sleeves for 45min at 45 °C. The sterilization procedure was repeated between the second, third, and fourth intraoral scans. Each tooth was given a score based on the color change between the first and fourth scans, which were superimposed using the iTero TimeLapse technology. The OrthoCAD® software (Align Technologies) was also used to measure the intercanine, interpremolar, and intermolar distances, as well as the mesiodistal dimensions of all the teeth between the first molars. Results No statistically significant difference was found between the mesiodistal dimensions of the teeth and the interca nine, interpremolar, and intermolar distances between the 1st and 4th scans. There was no correlation between the mean differences of the mesiodistal dimensions of the teeth obtained with the 1st and 4th scans and TimeLapse scores. Conclusion After sterilization with hydrogen peroxide, the repeatability of digital measurements of the protective sleeves of the intraoral scanner was not adversely affected, and their clinical performance was maintained.
Localization of a high strength and vibration resistant fastening element for the defense industry
(Liberty Academic Publishers, 2026) Demirel, Yusuf Soner; Şentürk, İsmail Hakkı; Tanrıver, Kürşat; Ay, Mustafa; Şahin, Ethem İlhan
In the modern defense and aerospace industry, maintaining the structural integrity of air platforms and optimizing their operational life cycles are directly dependent on the high-precision domestic production of critical components. The indigenization of strategic parts not only minimizes foreign dependency but also ensures supply chain security against embargo risks and international logistical disruptions. This study comprehensively addresses the localization and technical validation processes of a specialized structural pin, which serves as a primary fastener in aerospace structures, aircraft wings, and missile systems, characterized by high strength and vibration damping capabilities. Within the scope of the research, Al 7075-T6 aluminium alloy, a premium material in aerospace standards known for its superior strength-to-weight ratio, was selected as the raw material. During the manufacturing phase, "Swiss-Type Lathe" (Sliding Headstock) technology was utilized to provide high dimensional stability in tight-tolerance geometries, and samples underwent heat treatment processes in accordance with aerospace norms. The mechanical performances of the manufactured specimens were subjected to static and dynamic tests within the framework of internationally recognized NASM1312 standards. In the design validation phase, non-linear static Finite Element Analysis (FEA) was performed using ANSYS software. In these numerical simulation processes, based on experimental data obtained from physical testing equipment, displacement values of 0.55 mm for tensile analysis and 0.23 mm for double shear analysis were defined as boundary conditions in the system. When the numerical analysis results were compared with the experimental data obtained from production samples, a high-correlation alignment was determined with an acceptable deviation of approximately 5%. The fact that both tensile and double shear strength values exceeded the minimum limits specified by the standards, and that the physical fracture lines perfectly overlapped with the plastic deformation zones in the simulation model, proves the reliable applicability of domestic production in critical defense systems with concrete and scientific data.
