Araştırmacılar(11)

• Atila Uslu, Gözde
• Bardas, Ebru
• Bardaş Özkan, Ebru
• Beytut, Ebru
• Cicek, Betul
• Danışman-Kalındemirtaş, Ferdane
• Gursul, Cebrail
• Gül, Mustafa
• Gürsu, Cebrail
• Uslu, Hamit
• Ustundag, Hilal

• ArticleYayıncıda açık erişim2026/r/ebyu/11155
  Association between postoperative arterial blood gas parameters and cognitive dysfunction following coronary artery bypass grafting: a prospective observational study

  Demir, Özge; Üstündağ, Hilal; Onk, Oruç Alper

  Background: Postoperative cognitive dysfunction (POCD) is a significant complication of coronary artery bypass grafting (CABG), with impaired quality of life and long-term outcomes. The association between postoperative arterial blood gas (ABG) abnormalities and early cognitive outcomes remains unclear. Objectives: To investigate the association between perioperative ABG parameters and SMMSE-assessed cognitive function in patients undergoing elective CABG. Methods: This prospective study of 41 CABG patients recorded SMMSE scores and ABG parameters (pH, PO₂, PCO₂, HCO₃⁻, SO₂, base excess) preoperatively and 3–7 days postoperatively; POCD was defined as a ≥ 2-point SMMSE decline. Analyses included correlation, regression with VIF diagnostics, logistic regression, ROC analysis, and FDR correction. Results: Age was 63.15 ± 7.42 years; 29 of 41 patients (70.7%) met POCD criteria, with SMMSE declining (p < 0.001). Postoperative pH, PO₂, SO₂, HCO₃⁻, and base excess correlated with SMMSE change (ρ = 0.567–0.608, all p < 0.001) and differed between groups (all p ≤ 0.003); PCO₂ showed neither association. In multivariable regression, the model was significant (adjusted R² = 0.332, p = 0.002), but no individual parameter remained significant, reflecting multicollinearity (VIF up to 5.21); these also predicted POCD by logistic regression, and ROC analysis identified HCO₃⁻ as the strongest discriminator (AUC = 0.885), followed by pH (0.866) and base excess (0.851). Conclusions: Postoperative ABG derangements, metabolic acidosis and hypoxemia, are significantly associated with early cognitive decline after CABG. No single parameter was an independent predictor, reflecting interrelation; pH, HCO₃⁻, and base excess showed the strongest discriminative accuracy. These observational associations warrant confirmation in interventional studies.

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• ArticleAçık Erişim2026/r/ebyu/10894
  Synthesis and characterization of NIR-sensitive curcumin-gelatin nanoparticles for targeted drug delivery in 3D colon cancer

  Özerkan, Dilşad; Danışman-Kalındemirtaş, Ferdane; Kariper, İshak Afşin

  Curcumin (CUR) exhibits potent anti-cancer effects; however, its poor water solubility limits its clinical use. This study explores gelatin nanoparticles (GelNPs) as nanocarriers to improve curcumin delivery. We aimed to enhance the release and efficacy of photosensitive curcumin-loaded GelNPs (Cur-GelNPs) using infrared (IR) light-induced localized hyperthermia in a 3D co-culture cancer model. Cur-GelNPs were synthesized and characterized via DLS, FTIR, STEM, Raman, HPLC, and DSC. Cytotoxicity, migration, invasion, apoptosis, and drug resistance were assessed using MTT, Transwell, Hoechst/PI staining, and Rho123 assays, respectively. Optimal results were achieved by IR treatment at 38 °C for 30 s. Cur-GelNPs localized in the cytoplasm due to curcumin’s natural fluorescence. At 25 µg/ml, Cur-GelNPs significantly reduced the viability, invasion, and migration of colon cancer cells, while promoting apoptosis and mitochondrial damage—more effectively when combined with IR. Importantly, minimal toxicity was observed in healthy cells, suggesting selective cancer targeting. This method enables spontaneous drug-macromolecule binding, reducing time, cost, and labor. Overall, IR-activated Cur-GelNPs represent a promising approach for targeted colon cancer therapy and may offer broader contributions to nanomedicine and drug delivery systems.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10892
  Effects of Subconjunctival Bevacizumab and Ranibizumab on Corneal and Systemic Oxidative Stress Biomarkers in an Alkali Injury Model

  Yarbağ, Abdulhekim; Bardaş Özkan, Ebru; Ulaş, Mustafa; Arslan, Yusuf Kemal

  The study tests the efficacy of subconjunctival ranibizumab and bevacizumab treatments in determining the oxidant and antioxidant levels during alkali-induced corneal neovascularisation. The researchers assigned 24 New Zealand White rabbits into four different groups, which included a healthy control, an alkali-injured control, a BV-treated group, and an RN-treated group, with six rabbits per group. All animals received alkali injury treatment except for the HC group. The AC group received six doses of subconjunctival saline 24 h after their injury, while the BV group and RN group received one dose of 0.5 mg of their respective treatment. The researchers conducted 14-day assays on normal tissue, blood plasma, and erythrocytes to determine total antioxidant status and total oxidant status. The researchers performed biochemical assays for total antioxidant status TAS and total oxidant status TOS on samples that were collected after the 14-day observation period. The corneal TOS levels increased in all injured groups when matched against the HC group. The RN group showed the highest corneal TOS levels, but the difference between the RN and AC and BV groups did not reach statistical significance. The injured groups showed higher corneal TAS levels than HC (p = 0.002), but the AC, BV, and RN groups showed no differences. The injured groups showed a significant decrease in erythrocyte TAS compared with HC (p < 0.001), but the injured groups showed lower plasma TOS levels than HC (p < 0.001). The researchers found no other systemic differences between the groups that received anti-VEGF treatment. The study results show that alkali injury leads to both local and systemic changes in redox status. The two anti-VEGF agents caused numerical changes in corneal oxidative parameters, but these changes did not achieve statistical significance. The research requires further investigation to understand potential agent-related effects on corneal redox balance, which should take place in larger, more detailed studies.

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• ArticleYalnız künye2026/r/ebyu/10857
  Herniarin mitigates inflammation, oxidative stress, and apoptosis in experimental serous otitis media via NRF2/HO-1 and NLRP3/Caspase-1 pathways

  Kozan, Günay; Erbaş, Elif; Üstündağ, Hilal; Kara, Adem

  Objective Serous otitis media (SOM) is a prevalent inflammatory condition of the middle ear. Herniarin (7-methoxycoumarin) is a coumarin derivative with anti-inflammatory and antioxidant properties. This study aimed to investigate the therapeutic potential of herniarin against experimentally induced SOM in rats, focusing on the NRF2/HO-1 and NLRP3/Caspase-1 pathways. Methods Thirty six adult male Wistar rats were allocated into six groups (n = 6): Control, Herniarin 200 mg/kg, Otitis, Otitis + Herniarin 100 mg/kg, Otitis + Herniarin 200 mg/kg, and Otitis + Dexamethasone. SOM was induced by established experimental protocols, and treatments were administered for seven consecutive days. Serum cytokines (IL-1β, TNF-α, IL-18), oxidative stress markers (GSH, SOD, MDA), histopathology, RT-qPCR, and Western blot analyses were performed. Results Serum levels of IL-1β, TNF-α, and IL-18 were significantly elevated in the otitis group compared with controls (p < 0.0001) and were markedly attenuated by herniarin and dexamethasone. Herniarin restored depleted GSH and SOD levels while reducing elevated MDA concentrations. Histopathological examination demonstrated dose-dependent attenuation of inflammatory cell infiltration, hemorrhage, and tympanic membrane damage. RT-qPCR showed that herniarin suppressed the upregulation of HO-1, NRF2, NF-κB, and Caspase-3 gene expression induced by otitis, while restoring Bcl-2 expression toward control levels. Western blot confirmed that herniarin reduced the expression of NLRP3, Caspase-1, and Caspase-3, and of NF-κB, while increasing Bcl-2 levels. Conclusion Herniarin exerts protective effects against experimental SOM by modulating the NRF2/HO-1 antioxidant defense system and suppressing NLRP3 inflammasome-mediated inflammation and apoptosis, suggesting its potential as a therapeutic candidate for otitis media.

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• ArticleYalnız künye2026/r/ebyu/10832
  Astaxanthin and omega-3 fatty acids enhance endometrial receptivity in a rat model of polycystic ovary syndrome

  Bal Taştan, Tuğba; Selli, Jale; Toktay, Erdem; Üstündağ, Hilal; Ugan, Rüstem Anıl

  Polycystic ovary syndrome (PCOS) adversely affects endometrial receptivity and fertility outcomes. This study investigated whether combining high-dose antioxidants (astaxanthin or omega-3 fatty acids) with metformin improves endometrial receptivity markers, reduces oxidative stress, and normalizes hormone profiles in a PCOS rat model compared to metformin alone or no treatment. Fifty-six female Sprague–Dawley rats (200-250g) were divided into seven groups: Control, PCOS, PCOS + Met, and groups receiving metformin plus either astaxanthin (PCOS + Met + AX5 or PCOS + Met + AX10) or omega-3 (PCOS + Met + OMG400 or PCOS + Met + OMG1000). PCOS was induced using letrozole for 21 days, followed by one week of treatment. After establishing endometrial receptivity, uterine tissues were analyzed histopathologically, immunohistochemically, and biochemically on day 5. The PCOS group demonstrated significant increases in body weight and oxidative stress markers (malondialdehyde) compared to controls (p < 0.001). High-dose antioxidant supplementation (PCOS + Met + AX10 and PCOS + Met + OMG1000) significantly improved these parameters (p < 0.001). Immunohistochemically, integrin β3 expression increased while mucin 1 (MUC-1) decreased in high-dose groups compared to PCOS (p < 0.001). The LH:FSH ratio normalized to control levels in PCOS + Met + AX10 and PCOS + Met + OMG1000 groups. Histological examination revealed enhanced endometrial morphology and increased pinopode-like structure formation in antioxidant-supplemented groups. High-dose astaxanthin and omega-3 fatty acid supplementation, combined with metformin, may enhance endometrial receptivity in PCOS by reducing oxidative stress and modulating key implantation markers. This therapeutic approach could potentially improve fertility outcomes in women with PCOS.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10820
  Liraglutide Attenuates Multiorgan Oxidative, Astroglial, and Mitochondrial Stress Responses in Thioacetamide-Induced Hepatic Encephalopathy

  Bilgin, Yasin; Sari, Fatih Mehmet; Cicek, Betul; Kurt, Engin; Ozkaraca, Mustafa; Gungor, Ali; Kurt, Nezahat; Bilgin, Asli Ozbek

  Hepatic encephalopathy (HE) is a complex complication of liver failure involving oxidative stress, astroglial activation, mitochondrial dysfunction, and multiorgan disturbances along the gut–liver–brain axis. This study investigated the therapeutic effects of liraglutide (LIRA) in a thioacetamide (TAA)-induced rat model of HE. Thirty male Sprague–Dawley rats were assigned to control, TAA, and TAA+LIRA 100, 200, or 400 µg/kg groups. HE was induced with TAA (200 mg/kg, intraperitoneally) for three consecutive days, followed by subcutaneous LIRA treatment for 14 days. Serum biochemical parameters, tissue oxidative and inflammatory markers, histopathology, and Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity were evaluated. TAA caused marked hepatic and cerebral structural injury, increased serum and brain glutamine concentrations, disrupted redox homeostasis, elevated MPO activity, and increased cerebral GFAP and multiorgan VEGFA immunoreactivity. LIRA partially improved hepatic and cerebral histopathology, reduced glutamine disturbances, attenuated selected oxidative, nitrosative, and inflammatory alterations, and modulated Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity in a tissue- and dose-specific manner. The 200 µg/kg dose produced the most consistent overall improvement, whereas the 400 µg/kg dose was less favorable for several endpoints. LIRA may therefore alleviate multiorgan stress associated with experimental HE, although further studies are required to confirm functional and mechanistic relevance.

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• ArticleAçık Erişim2026/r/ebyu/10779
  Assessment of methylene blue and NAD on LPS-induced acute brain injury: effects on neuroinflammation, oxidative stress, and blood–brain barrier integrity in a rat endotoxemia model

  Doganay, Songul; Üstündağ, Hilal; Erbaş, Elif; Yanar, Sevinc; Hayme, Serhat; Kurt, Nezahat

  Sepsis-induced brain dysfunction remains a significant challenge with limited therapeutic options, warranting exploration of multi-target approaches. Methylene blue (MET) is a phenothiazine derivative with mitochondrial-enhancing and electron transport chain regulatory properties, while nicotinamide adenine dinucleotide (NAD) serves as a crucial cofactor in cellular energy metabolism and redox reactions. This study investigated the therapeutic effects of MET and NAD, individually and in combination, in lipopolysaccharide (LPS)-induced sepsis model. Male Sprague–Dawley rats (n = 35) were randomized into five groups: control, LPS (8 mg/kg), LPS + NAD (250 mg/kg), LPS + MET (15 mg/kg), and LPS + NAD + MET. Brain tissues were analyzed for oxidative stress, inflammation, and blood–brain barrier integrity. The combination therapy demonstrated the most pronounced improvements across clinical parameters, antioxidant capacity evidenced by significantly elevated superoxide dismutase levels (p < 0.001) and cerebral histopathological outcomes. It also significantly reduced myeloperoxidase activity (p < 0.001) compared to the LPS group. Pro-inflammatory cytokines IL-6 and IL-8 were significantly decreased in both MET and NAD monotherapy groups (p < 0.05), while TNF-α showed a decreasing trend without statistical significance. Brain-derived neurotrophic factor levels were maintained in the combination group, comparable to controls, while TGF-β showed differential modulation across treatment groups. Immunohistochemical analysis revealed LPS-induced blood–brain barrier disruption, evidenced by reduced occludin expression (p < 0.01), increased aquaporin-4 expression in perivascular astrocytic end-feet (p < 0.05), and elevated glial fibrillary acidic protein reactivity in protoplasmic astrocytes (p < 0.01). In conclusion, MET and NAD individually provided significant protection against LPS-induced brain injury by reducing neuroinflammation, oxidative stress, and neuronal damage. The combined treatment offered incremental benefits in certain outcomes. These findings suggest that both agents may have therapeutic potential in SAE.

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• Review ArticleYayıncıda açık erişim2026/r/ebyu/10770
  The P2X7 receptor/NLRP3 inflammasome signaling axis in sepsis: molecular mechanisms, organ-specific pathophysiology, and emerging therapeutic strategies

  Üstündağ, Hilal

  Sepsis remains a leading cause of mortality in intensive care units worldwide, representing life-threatening organ dysfunction arising from dysregulated host responses to infection. The purinergic P2X7 receptor (P2X7R) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome have emerged as critical regulators of inflammatory responses during sepsis pathogenesis. Extracellular adenosine triphosphate (ATP), released as a danger-associated molecular pattern from damaged and dying cells, activates the P2X7R, triggering potassium efflux that serves as the cardinal signal for NLRP3 inflammasome assembly. The activated inflammasome complex mediates caspase-1-dependent proteolytic maturation of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, while simultaneously inducing gasdermin D (GSDMD)-mediated pyroptotic cell death—an inflammatory form of programmed cell death characterized by membrane pore formation, cellular swelling, and release of intracellular contents. Paradoxically, emerging evidence indicates that excessive P2X7R activation during sepsis progression induces profound mitochondrial dysfunction in circulating monocytes, leading to impaired NLRP3 inflammasome function and a state of immunoparalysis that coincides with an increased mortality. This comprehensive review examines the molecular mechanisms governing P2X7/NLRP3 signaling in sepsis; critically evaluates its dual and seemingly contradictory roles in hyperinflammation versus immunosuppression; delineates organ-specific manifestations across the lung, kidney, heart, brain, liver, and intestine; and systematically evaluates emerging therapeutic strategies including direct NLRP3 inhibitors such as MCC950, selective P2X7R antagonists, IL-1 receptor blockade, GSDMD inhibitors, and natural compounds with inflammasome-modulating properties. Understanding the temporal dynamics of this signaling axis is crucial for developing precision-targeted interventions that appropriately balance pathogen clearance with prevention of excessive inflammatory tissue damage.

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• ArticleYalnız künye2026/r/ebyu/10693
  UV-synthesized albumin-based doxorubicin nanoparticles induce apoptosis and modulate leukemia surface markers while overcoming drug resistance

  Danışman-Kalındemirtaş, Ferdane; Sert, Esra; Kariper, İ. Afşin; Korkut, Işık Neslişah; Erdem-Kuruca, Serap

  Although chemotherapeutic agents such as doxorubicin (DOX) are used to treat leukemia, their application is often limited by systemic toxicity, low specificity, and the development of drug resistance. The development of drug delivery systems can overcome the problems associated with conventional delivery methods. In this study, innovative albumin-based UV-DOX-NPs were synthesized by UV irradiation and evaluated for their leukemia inhibitory activity; they represent a novel formulation strategy that has seen limited application to date. Their effects on leukemic Jurkat and THP-1 cells were extensively studied. Advanced techniques such as dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX) were used for characterization. UV-DOX-NPs exhibited increased cytotoxicity and significantly lower IC50 values compared to free DOX. Apoptosis rates were also higher in both cell lines following DOX-NP treatment. Flow cytometry revealed a significant downregulation of leukemia-associated surface markers, including CD5, CD7, and CD3 in Jurkat cells and CD7, CD14, and CD33 in THP-1 cells. In addition, UV-DOX-NPs significantly reduced the expression of ABCG2, an important MDR-associated transporter. Our results demonstrate that UV-synthesized, albumin-based UV-DOX-NPs not only enhance antileukemic efficacy but also modulate the leukemic immunophenotype and overcome multidrug resistance. These results provide a promising platform for a more targeted and safer leukemia therapy.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10671
  Comparative Study on the Protective Effect of Thiamine and Thiamine Pyrophosphate Against Hydroxychloroquine-Induced Cardiomyopathy in Rats

  Emir, Izzet; Yavuzer, Bulent; Suleyman, Bahadir; Sarigul, Cengiz; Mendil, Ali Sefa; Sezgin, Esra Tuba; Altuner, Durdu; Gursul, Cebrail; Suleyman, Halis

  Background: Hydroxychloroquine (HCQ), widely used in autoimmune and inflammatory diseases, has been associated with cardiotoxicity driven by oxidative, mitochondrial, and metabolic disturbances. However, no comparative evidence exists regarding whether thiamine, thiamine pyrophosphate (TPP), or their combination (TTPC) can mitigate HCQ-induced myocardial injury. Objective: This study examined the biochemical and histopathological effects of thiamine, TPP, and their combination in a rat model of HCQ-induced cardiomyopathy. Methods: Thirty male Wistar rats were assigned to five groups: healthy control, HCQ, thiamine + HCQ, TPP + HCQ, and TTPC + HCQ. Thiamine (20 mg/kg, intraperitoneal), TPP (20 mg/kg, intraperitoneal), or TTPC (20 mg/kg each, intraperitoneal) was administered once daily, followed by HCQ (120 mg/kg, oral, twice daily). After seven days, cardiac tissue was analyzed for MDA, tGSH, SOD, and CAT, while serum TnI, lactate, and LDH were measured from tail-vein blood samples. Cardiac samples underwent histopathological examination. Results: HCQ exposure markedly increased MDA, TnI, LDH, and lactate levels while reducing tGSH, SOD, and CAT, indicating severe oxidative and metabolic insult. Thiamine co-treatment failed to ameliorate these disturbances. Conversely, TPP restored redox balance, attenuated biomarker elevations, and improved cardiac biochemical profiles. TTPC produced comparable improvements but did not exceed those of TPP alone. Histopathologically, HCQ caused pronounced myocyte degeneration and mononuclear infiltration, whereas TPP and TTPC groups showed only mild inflammatory changes with preserved myocardial architecture. Conclusions: HCQ induces a marked redox imbalance accompanied by well-defined histopathological myocardial degeneration. TPP afforded robust cardio-protection, whereas thiamine offered no meaningful benefit. Collectively, these findings position TPP as a biologically plausible, clinically relevant candidate for mitigating HCQ-induced cardiomyopathy.

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