Yazarlar
- Suleyman, Halis(167)
- Mammadov, Renad(95)
- Türkeş, Cüneyt(84)
- Aydin, Sonay(83)
- Altuner, Durdu(74)
- Suleyman, Bahadir(68)
- Isik, Arda(67)
- Beydemir, Şükrü(66)
- Kantarci, Mecit(64)
- Kurt, Nezahat(57)
- Demir, Yeliz(54)
- Bulut, Seval(51)
- Arslan, Yusuf Kemal(50)
- Sofu, Hakan(50)
- Coban, Taha Abdulkadir(49)
- Karakeçili, Faruk(47)
- Altay, Ahmet(46)
- Huyut, Mehmet Tahir(46)
- Aydin, Suleyman(45)
- Türkmenoğlu, Burçin(45)
- Kuzucu, Mehmet(40)
- Yazici, Gulce Naz(40)
- Peker, Kemal(39)
- Algul, Oztekin(38)
- Cicek, Betul(37)
- Mertoglu, Cuma(36)
- Camurcu, Yalkin(35)
- Suleyman, Zeynep(34)
- Bozkurt, Aliseydi(32)
- Mendil, Ali Sefa(32)
- Gunay, Murat(31)
- Gözcü, Sefa(31)
- Köksal, Ekrem(31)
- Yuca, Hafize(31)
- Dilek, Esra(30)
- Karakurt, Papatya(30)
- Ozcicek, Fatih(30)
- Süleyman, Halis(30)
- Onk, Didem(29)
- Ucpunar, Hanifi(29)
Yayınlar
- MakaleAçık Erişim2025Salivary mitofusin levels in periodontal disease: a cross-sectional case-control study
Okumuş, Ömer F.; Kurt, Nezahat; Kantarcı, Alpdoğan
Background: Mitofusin (Mfn) is a mitochondrial fusion protein. It has two isoforms (Mfn1 and 2) and is critical in intracellular energy production, calcium transfer, and phospholipid metabolism. Based on previous evidence linking mitochondrial function with the pathophysiology of periodontal inflammation, we hypothesized that salivary Mfn1 and Mfn2 levels may differ across periodontal health, gingivitis, and periodontitis, and that these levels correlate with markers of inflammatory and oxidative stress. Although previous studies have suggested that Mfn2 plays a role in inflammatory and oxidative pathways, clinical evidence regarding its role in periodontal disease is lacking. The null hypothesis of this study was that salivary Mfn levels are not significantly altered with periodontal conditions and are not correlated with inflammation or oxidative stress markers in saliva. Methods: A total of 81 participants were included in this cross-sectional case-control study, with 27 individuals per group. Periodontally healthy patients, patients with gingivitis, and patients with stage 3 or stage 4 grade C periodontitis were recruited for the study. Mfn-1 and Mfn-2 levels were measured. To identify their correlation with inflammatory mechanisms, interleukin-1β levels, total oxidative status (TOS), and total antioxidant status (TAS) were determined using enzyme-linked immunosorbent assay and colorimetric measurements. The oxidative stress index (OSİ) was calculated. Results: Salivary Mfn1 levels were significantly higher in patients with periodontitis compared to healthy controls (36.54 ± 13.15 ng/mL, 24.67 ± 8.69 ng/mL, p < 0.001). No significant difference was observed between the groups in terms of Mfn2 levels (p > 0.05). While significant differences were found between Group P and Group H in TAS and OSI values (p < 0.05), TOS values did not show any significant difference between the groups (p > 0.05). A positive correlation was found between Mfn1 and Mfn2 and IL-1β levels (p < 0.05). Mfn1 and Mfn2 did not have any significant correlation with TAS, TOS, or OSI values (p > 0.05). Conclusions: Elevated Mfn1 levels in the saliva of patients with periodontitis suggested that mitochondrial function was disrupted in severe periodontitis. Mitofusin levels showed no significant correlation with oxidative stress markers in this study. Trial registration: This study was registered in ClinicalTrials.gov under the number NCT06510608 on July 18, 2024.
- MakaleYalnız künye2025Improved apoptosis and mitochondrial dysfunction: the potential of carmofur-platinum nanoparticles
Erdemir-Cilasun, Gökçe; Özerkan, Dilşad; Kariper, İshak Afşin; Sert, Esra; Korkut, Işık Neslişah; Danışman-Kalındemirtaş, Ferdane
Despite their impact on cancer therapy, limitations such as systemic toxicity and drug resistance are encountered with platinum-based drugs. This study explores the potential of combining PtIV-based NP with carmofur (Car) to address these issues. In this study, platinum nanoparticles (PtNPs) and Car-loaded PtNP (Car@PtNP) were synthesized and their cytotoxic and apoptotic effects on colorectal and breast cancer cells were evaluated. Following characterization of the synthesized NPs by dynamic light scattering, UV-VIS spectroscopy, FTIR, and STEM, it was found that the average size of PtNPs was 55.42 nm and the size increased to approximately 186.06 nm upon synthesis of Car@PtNP. MTT assays demonstrated that Car@PtNP exhibited higher levels of cellular toxicity than carmofur alone. While it significantly decreased cell viability in both colon and breast cancer cells, its toxicity to HUVEC cells was minimal. Treatment of MCF-7 and HCT116 cells with 50 µg ml−1 of free Car resulted in cell viabilities of 65.2% and 76.93%, respectively, whereas the viability of cells treated with Car@PtNP decreased to 49.60% and 55.47%. Flow cytometric analysis confirmed that apoptosis was increased in healthy HCT116 cells treated with Car@PtNP, with a marked increase in both early and late apoptotic cell populations. Furthermore, these results were confirmed by Hoescht and Rhodamin123 immunofluorescence staining, and significant mitochondrial dysfunction and apoptotic morphological changes were observed in treated cells. The findings underscore the promise of Car@PtNP as a novel chemotherapeutic approach, integrating the benefits of PtIV complexes and Car to enhance antitumor efficacy while mitigating the drawbacks of conventional platinum-based therapies.
- MakaleAçık Erişim2025Columnar cell variant of papillary thyroid carcinoma in an adolescent: a comprehensive histopathological, immunohistochemical, and molecular analysis
Issin, Gizem; Demir, Fatih; Cagatay, Diren Vuslat; Yilmaz, Ismail
The columnar cell variant (CCV) of papillary thyroid carcinoma (PTC) is a rare histological subtype with distinct morphological and immuno-histochemical (IHC) features, which can present diagnostic challenges. We report a case of a 13-year-old girl diagnosed with CCV of PTC (CCV–PTC) following a total thyroidectomy for a solitary thyroid nodule. Histopathological (HP) examination revealed aggressive features, including vascular invasion and extrathyroidal extension. However, no metastases or recurrences were observed during six years of follow-up. This case report provides a comprehensive analysis of a rare CCV–PTC in an adolescent, focusing on its HP, IHC, and molecular characteristics. It also discusses diagnostic pitfalls and differential diagnoses that should be considered.
- MakaleYalnız künye2025Synthesis and evaluation of sulfonamide-chalcone hybrid compounds as inhibitors of VEGFR1/VEGFR2-mediated angiogenesis
Barlak, Neslisah; Sanli, Fatma; Celik, Suleyman; İskender, Burhan; Anil, Derya Aktas; Gambacorta, Nicola; Burmaoglu, Serdar; Nicolotti, Orazio; Algul, Oztekin; Karatas, Omer Faruk
Cancer continues to be a major worldwide health concern, with angiogenesis playing a pivotal role in its progression and metastasis. The capacity of tumors to induce angiogenesis is crucial for their proliferation and metastasis, rendering it a significant target for treatment strategies. This study involved the synthesis of sulfonamide-chalcone hybrid compounds and the evaluation of their anti-angiogenic activity by the assessment of their effects on vascular endothelial growth factor receptors (VEGFR1/VEGFR2) in human umbilical vein endothelial cells (HUVECs). Among the synthesized compounds, 28 and 31 exhibited the most promising inhibitory effects similar to sorafenib as positive control, with IC50 values superior to 10 μM. They dramatically diminished endothelial cell proliferation and tube formation without exhibiting significant cytotoxicity against healthy human cells. Molecular docking simulations validated their binding affinity to VEGFR1/VEGFR2 receptors, elucidating their molecular mechanisms. Moreover, compounds 28 and 31 exhibited significant anti-angiogenic activity in both 2D and 3D angiogenesis assays, indicating their potential as novel anti-cancer agents. These findings underscore the therapeutic potential of these compounds in blocking angiogenesis and necessitate additional in vivo research to confirm their clinical relevance.
- MakaleAçık Erişim2025Alleviation of LPS-induced acute lung injury by propolis-based nanocomposites through the TLR4/NFKB and P2X7/AKT pathways: Randomized-controlled experimental study
Üstündağ, Hilal; Kara, Adem; Gökhan Taş, Necip; Danişman Kalindemi̇rtaş, Ferdane; Kurt, Nezahat; Erbaş, Elif; Tahir Huyut, Mehmet; Gül, Mustafa; Afşin Kari̇per, İshak
Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i.p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1β, TNF-α) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1β, TNF-α, NF-κB, and TLR4, and increased GSH content in lung tissue (p < 0.05). The anti-apoptotic protein BCL-2 was upregulated, while pro-apoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion, propolis-based treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.
- MakaleAçık Erişim2025Thyroid Imaging Reporting and Data System on the Basis of Cost and Effectiveness
Aydin, Sonay; Gulmez, Ali Osman; Memis, Kemal Bugra
Background: We aim to evaluate thyroid imaging reporting and data system (TIRADS) on the basis of cost and effectiveness through the numbers of fine‑needle aspiration biopsies (FNABs) and sonographic examinations in a tertiary health‑care institution. Methods: The 50‑day intervals before and after the start of TIRADS use (October 10, 2022) were evaluated to carry out this assessment. The reason for choosing 50‑day periods was because it covers the initial phase when the study is most optimally performed in our hospital. The number of thyroid ultrasound (US) and FNAB procedures carried out in our facility during that time was tallied. Exclusion standards were not applied. Results: One thousand nine hundred eighty‑two people made up the study population. Fifty days before the October 10, 2022, there were 975 instances (49.2%), and 50 days after that, there were 1007 cases (50.8%). Out of 1982 cases, it was discovered that 190 (9.6%) underwent a biopsy, and 1792 (90.4%) underwent a US examination. It was found that the first period’s rate of biopsy examination was significantly higher than the second period’s rates of 11.1% and 8.1%, respectively. The rate of biopsy examination in males during the first period was found to be substantially higher than the second period. Individuals between the ages of 35 and 50 years had a rate of biopsy examination that was considerably higher in the first period than the second period. Conclusion: The TIRADS Risk Scale has the capacity to reduce unnecessary biopsies, hence mitigating potential psychological distress, burden, and financial expenses for the patient.
- MakaleAçık Erişim2025Echinococcus granulosus in atypical localizations: Five case reports
Celik, Ayse Sena; Yosunkaya, Hacer; Ozyilmaz, Aysel Yayilkan; Memis, Kemal Bugra; Aydin, Sonay
BACKGROUND Hydatid cyst disease, caused by Echinococcus granulosus, primarily affects the liver and lungs, but it can also develop in rare locations such as the kidneys, thyroid, subcutaneous tissues, bones, and the mediastinum. These atypical presentations often pose diagnostic challenges, as they can mimic benign and malignant pathologies, leading to potential misdiagnoses and inappropriate treatments. Early and accurate detection of hydatid cysts in uncommon sites is crucial for optimal patient management. CASE SUMMARY This case report series presents five patients with hydatid cysts located in atypical anatomical regions: The kidney, lumbar subcutaneous tissue, gluteal soft tissue, posterior mediastinum, and thyroid gland. The patients exhibited diverse clinical symptoms, including hematuria, palpable masses, localized pain, and chronic cough. Diagnosis was confirmed through a combination of imaging techniques-ultrasound, computed tomography, and magnetic resonance imaging-along with serological testing. All cases were managed with antiparasitic therapy (alben-dazole), and in selected cases, surgical excision was performed to prevent complications such as cyst rupture or secondary infections. Post-treatment follow-up demonstrated complete resolution or stable cystic lesions, with no signs of recur-rence. CONCLUSION Recognizing hydatid cysts in atypical locations is essential to avoid misdiagnosis and ensure appropriate treatment strategies. Radiological imaging plays a key role in distinguishing hydatid cysts from other cystic and neoplastic conditions, while serological tests can aid in confirmation, particularly in endemic regions. A multidisciplinary approach, integrating radiology, clinical evaluation, and surgical expertise, is critical for effective diagnosis and management. This report highlights the need for increased awareness of extrapulmonary and extravisceral hydatid disease, emphasizing its significance in differential diagnosis and clinical practice.
- MakaleAçık Erişim2025Pyridostigmine Mitigates Methotrexate-Induced Liver Fibrosis in Rats: Association with Changes in BMP-9, SIRT1, and Endoglin Expression
Ulusan, Mehmet; Erdogan, Mumin Alper; Simsek, Ozkan; Ustundag, Hilal; Dogan, Zafer; Ciftci, Bertug Bekir; Kocamuftuoglu, Mesih; Orhan, Imdat; Erbas, Oytun
Background and Objectives: Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. Methods: Thirty-six female Wistar albino rats randomly assigned to three groups: control (n = 12), MTX + saline (n = 12), and MTX + pyridostigmine (n = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. Results: Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (p < 0.05) and cytokeratin-18 levels (p < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (p < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (p < 0.05), bone morphogenetic protein-9 (p < 0.001), and endoglin levels (p < 0.05), as well as increased sirtuin 1 level (p < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. Conclusions: Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity.
- MakaleYalnız künye2025Syringic acid alleviates cadmium-induced neurotoxicity in rats by modulating cellular signaling pathways
Bolat, Merve; Yilmaz, Tuğçe Ertek; Çeğindir, Murat; Atasever, Aslıhan; Doğan, Tuba; Yildirim, Serkan; Sağlam, Yavuz Selim; Çomakli, Selim; Bolat, İsmail
Cadmium (Cd) is a metal found widely in nature that negatively affects brain health by affecting the DNA repair mechanisms of the cell through the effect it creates on various reactive oxygen species in the body. Antioxidants provide the potential to reduce the neurotoxic effects of cadmium. Therefore, we aimed to investigate the protective properties of syringic acid (SA) in cadmium-induced neurotoxicity. Fifty male Sprague Dawley rats were used in the study. The rats were divided into 5 groups: Control, SA100, Cd, SA50 + Cd and SA100 + Cd. Cd (6.5 mg/kg) was administered intraperitoneally, and SA (50–100 mg/kg) intragastrically for seven days. Our results showed that SA significantly mitigated Cd-induced brain damage. The up-regulation of MDA and down-regulation of GSH, SOD, and CAT in brain tissues induced by Cd was significantly reversed by SA treatment. Additionally, the decreased expression of Nrf2/HO-1/SIRT1, impaired by ROS induced by Cd, was enhanced by SA. While Cd caused inflammation by triggering proinflammatory cytokines such as IL-1β and TNF-α via TLR4/NF-κB and suppressing IL-10, SA reduced inflammation in the tissue. This study demonstrated that SA treatment significantly reversed Beclin-1 and LC3A/B expression. Finally, it was revealed that SA treatment inhibited Cd-induced apoptosis by decreasing Bax, Caspase3 levels, and increasing Bcl2 levels. Collectively, our data revealed that SA exerts its neuroprotective effects by regulating various Cd-induced cellular signaling pathways in rat brains.
- MakaleAçık Erişim2025Panax Ginseng Protects Against Doxorubicin-Induced Testicular Injury in Male Rats by Modulating NF-κB/COX-2 and AR Pathways
Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Mokhtare, Behzad
Panax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague–Dawley rats (200–250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1β (IL-1β), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-α, IL-1β, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-κB and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.
- MakaleAçık Erişim2025High-Frequency Oscillations in Self-Limited Epilepsy With Centrotemporal Spikes: Potential Predictors of Attention Deficit Hyperactivity Disorder?
Kart, Pinar Ozkan; Özdemir, Cihad; Kayikcioglu, Temel; Cansu, Ali
Objective: The aim of this study was to examine the possible effect of HFOs detected in children with SeLECTS, who have rolandic spikes with or without ADHD, in predicting cognitive comorbidities with the fully automatic ripple detector program we developed. Methods: A total of 40 patients diagnosed with SeLECTS with at least a 1-year follow-up were included in this study. The patients were divided into two groups: those diagnosed with SeLECTS only and those diagnosed with SeLECTS+ADHD. For ripple detection, EEG data recorded for at least 10 min during non-REM stage 2 sleep with a sampling frequency of 2000 Hz was analysed in the MATLAB environment. After the data in each channel was filtered at 80–200 Hz, ripple detection was made with the fully automatically developed ripple detector program. Results: At least one ripple was detected in 29 of 40 patients (72.5%). The total number of spikes in both groups had a mean of 1435.8 ± 1626.9 (5–6183). The number of spikes in the rolandic region was found to be statistically significantly higher in the SeLECTS+ADHD group (p = 0.042). The total number of ripples in both groups was the mean: 9.5 ± 26.5 (0–158). The highest ripples count was detected in a patient in the SeLECTS+ADHD group; 158 ripples were counted, and the ripple distribution was found to be 33 ripples in the centrotemporal region and 125 ripples in the frontal region. The ripple of number (p = 0.009) and ripple ratio in the ‘Fz-Cz’ electrode were found to be statistically significantly higher in the SeLECTS + ADHD group (p = 0.009, p = 0.019, respectively). Significance: Our study showed that the presence of interictal scalp HFOs has the effect of predicting neurocognitive comorbidities. We think that ripple analysis with the can be used as a potential biomarker to predict neurocognitive comorbidities.
- MakaleYalnız künye2025Evaluation of the mechanical properties and cell cultural behavior of diamond lattice scaffolds with different porosities
Ghahramanzadeh Asl, Hojjat; Çelik Uzuner, Selcen; Çam, Salim; Uzuner, Uğur
Metal porous structures are a common treatment for bone tissue loss when the loss exceeds the self-repair capacity of the human body. The structural characteristics, mechanical properties, and biological behavior of scaffold biomaterials exert a significant influence on the formation of new bone cells. The objective of this study was to ascertain the mechanical and cell biological behavior of scaffold structures with four distinct porosities (60%, 70%, 80%, and 90%). Scaffold structures with a diamond lattice unit cell were manufactured by the selective laser melting method using a CoCr alloy powder with a diameter of 4 mm and a height of 5 mm and were then subjected to a static compression test. Subsequently, human gingival fibroblast cells were seeded into each sample via the cell culture process, and cell formation was observed. According to the results obtained from the compression test, the sample with 60% porosity demonstrated optimal mechanical performance and effective modulus of elasticity. In the cell culture process, the sample with 60% porosity exhibited the highest adherence rate.
- MakaleAçık Erişim2025Identification of right ventricular dysfunction with LogNNet based diagnostic model: A comparative study with supervised ML algorithms
Huyut, Mehmet Tahir; Velichko, Andrei; Belyaev, Maksim; Izotov, Yuriy; Karaoğlanoğlu, Şebnem; Sertoğullarından, Bünyamin; Keskin, Sıddık; Korzun, Dmitry
Right ventricular dysfunction (RVD) is strongly associated with increased mortality in patients with acute pulmonary embolism (PE), making its early detection crucial. Identifying RVD risk factors rapidly, accurately, and economically within the acute PE population could significantly improve diagnosis and treatment, potentially reducing mortality rates. This study evaluates the performance of LogNNet and supervised machine learning (ML) models for diagnosing RVD using a repeated stratified hold-out validation procedure. An ensemble-based LogNNet model is proposed for practical application. The LogNNet model identified gender, coronary artery disease, Comorbid Disease (especially hypertension), age (above 74-years), Thrombus segment and un/bilateral Thrombus as the most significant predictors for RVD diagnosis. Additionally, combinations of these features demonstrated high predictive power. LogNNet achieved robust results with only a few selected features, making it suitable for applications in resource-limited environments. LogNNet provides a practical and accessible tool for early RVD detection using PE patient data and has been shown to support applications in healthcare innovations aimed at improving patient outcomes and resilience in edge devices, clinical decision support systems, and challenging environments. Furthermore, these findings could be used as promising applications by integrating with advances in digital health and human health monitoring systems, such as bionic clothing and smart sensor networks.
- MakaleAçık Erişim2025Protective Role of Thiamine Pyrophosphate Against Erlotinib-Induced Oxidative and Inflammatory Damage in Rat Optic Nerve
Karatas, Ezgi; Yavuzer, Bulent; Demir, Ozlem; Sezgin, Esra Tuba; Hendem, Engin; Cinici, Emine; Coban, Taha Abdulkadir; Suleyman, Halis
Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are widely used in non-small-cell lung cancer treatment, and accumulating evidence indicates they can markedly increase ocular toxicity. Nonetheless, whether erlotinib causes optic nerve injury has not been investigated before and remains a subject worth investigating. This study aimed to examine the impact of erlotinib on oxidative stress, inflammation, and histopathological changes in rat optic nerve tissue and evaluate the potential neuroprotective role of thiamine pyrophosphate (TPP). Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control, TPP alone, erlotinib alone, and erlotinib + TPP. Erlotinib (10 mg/kg, orally, on alternate days) and TPP (20 mg/kg, intraperitoneally, daily) were administered for two consecutive weeks. Optic nerve samples were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), followed by histopathological examination. Results: Erlotinib treatment significantly increased MDA, IL-1β, and TNF-α levels while reducing tGSH, SOD, and CAT activity, demonstrating oxidative stress and an inflammatory response. Co-administration of TPP ameliorated these changes by lowering reactive oxygen species, restoring antioxidant capacity, and attenuating inflammation. Histopathological alterations, including astrocyte degeneration, edema, and vascular congestion, were evident after erlotinib exposure but were significantly alleviated when TPP was administered concurrently. Conclusions: Erlotinib induces oxidative and inflammatory optic nerve injury, while TPP co-treatment offers significant neuroprotection. These findings support TPP as a potential adjunct to reduce EGFR-TKI-related ocular toxicity and highlight importance of redox modulation in limiting treatment-associated side effects.
- MakaleYalnız künye2025N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling
Zognjani, Blinera; Nixha, Arleta Rifati; Duran, Hatice Esra; Arslan, Mustafa; Yıldıztekin, Gizem; Ece, Abdulilah; Türkeş, Cüneyt
Aldose reductase (ALR2; AKR1B1), a NADPH-dependent cytosolic oxidoreductase, plays a central role in the polyol pathway and is implicated in hyperglycemia-induced tissue injury. Beyond its metabolic function, elevated ALR2 expression has been reported in several malignancies, including hepatocellular and pulmonary carcinomas, highlighting its potential as a therapeutic target in metabolic-oncologic interface. In this study, a novel set of eleven N-substituted phthalimide–carboxylic acid derivatives (5a–5k) was synthesized and evaluated for ALR2 inhibition, pharmacokinetic characteristics, and cancer-selective safety. Among the series, compound 5f demonstrated the highest inhibitory potency (KI = 7.34 nM), outperforming epalrestat (KI = 232.1 nM). Glide docking positioned 5f within the ALR2 active site (GlideScore: −6.71 kcal/mol), stabilized via key contacts with Tyr48, His110, and Cys298, along with π–π stacking at Trp219. MM-GBSA analysis corroborated strong binding affinity (ΔG = −64.86 kcal/mol). DFT-derived quantum descriptors, logP, TPSA, and solvation energies supported its favorable interaction profile. ADME/Tox predictions indicated high GI absorption, no P-gp or CYP liabilities, and acceptable bioavailability. In vitro cytotoxicity assays showed negligible activity of 5f against A549 and Hep3B cancer cell lines (IC₅₀ > 160 μM) and no toxicity toward L929 fibroblasts, reflecting safety for long-term use. Transcriptomic data from CCLE and DepMap confirmed AKR1B1 overexpression in these cancer models. Network analysis linked ALR2 to redox imbalance and inflammation, suggesting its broader role in tumorigenesis.
- MakaleAçık Erişim2025Evaluating artificial intelligence for a focal nodular hyperplasia diagnosis using magnetic resonance imaging: preliminary findings
Kantarcı, Mecit; Kızılgöz, Volkan; Terzi, Ramazan; Kılıç, Ahmet Enes; Kabalcı, Halime; Durmaz, Önder; Tokgöz, Nil; Harman, Mustafa; Kahraman, Ayşegül Sağır; Avanaz, Ali
PURPOSE This study aimed to evaluate the effectiveness of artificial intelligence (AI) in diagnosing focal nodular hyperplasia (FNH) of the liver using magnetic resonance imaging (MRI) and compare its perfor mance with that of radiologists. METHODS In the first phase of the study, the MRIs of 60 patients (30 patients with FNH and 30 patients with no lesions or lesions other than FNH) were processed using a segmentation program and introduced to an AI model. After the learning process, the MRIs of 42 different patients that the AI model had no experience with were introduced to the system. In addition, a radiology resident and a radiology specialist evaluated patients with the same MR sequences. The sensitivity and specificity values were obtained from all three reviews. RESULTS The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AI model were found to be 0.769, 0.966, 0.909, and 0.903, respectively. The sensitivity and specificity values were higher than those of the radiology resident and lower than those of the radiology specialist. The results of the specialist versus the AI model revealed a good agreement level, with a kappa (κ) value of 0.777. CONCLUSION For the diagnosis of FNH, the sensitivity, specificity, PPV, and NPV of the AI device were higher than those of the radiology resident and lower than those of the radiology specialist. With additional studies focused on different specific lesions of the liver, AI models are expected to be able to diagnose each liver lesion with high accuracy in the future. CLINICAL SIGNIFICANCE AI is studied to provide assisted or automated interpretation of radiological images with an accurate and reproducible imaging diagnosis.
- MakaleYalnız künye2025Phthalimide–benzoic acid hybrids as potent aldose reductase inhibitors: Synthesis, enzymatic kinetics, and in silico characterization
Hoti, Dafina; Nixha, Arleta Rifati; Duran, Hatice Esra; Arslan, Mustafa; Yıldıztekin, Gizem; Ece, Abdulilah; Türkeş, Cüneyt
Aldose reductase (ALR2; AKR1B1) is implicated in hyperglycemia-driven tissue injury and remains a tractable enzymatic target. We developed a concise, chromatography-free two-step route to phthalimide–benzoic acid hybrids ( 5a–5m) and profiled their biochemical activity against human ALR2. Across the series, halogenated analogs were most active, with the para-bromophenyl derivative5demerging as the top hit (KI = 7.56 nM). Steady-state kinetic analysis indicated a competitive inhibition mechanism. Molecular docking to the ALR2 active site (PDB4JIR), supported by MM-GBSA rescoring, yielded a catalytically consistent binding mode featuring hydrogen-bonding within the anion-binding region (Tyr48, His110) and complementary hydrophobic contacts (Trp111, Trp219), with Cys298 contributing as a proximal hydrophobic contact. In cell-based assays (A549, Hep3B, L929), the compounds generally showed low intrinsic cytotoxicity at the tested concentrations, suggesting a favorable preliminary safety margin aligned with their ALR2-directed pharmacology. In silico ADME/Tox assessments further supported oral drug-likeness. Overall, these results identify phthalimide–benzoic acid hybrids as tractable ALR2 inhibitor scaffolds that combine potent biochemical inhibition with a competitive kinetic profile and encouraging early safety signals, warranting in vivo evaluation and SAR-guided optimization.
- MakaleAçık Erişim2025Association between health literacy and medication adherence in patients with hypertension: a cross-sectional study
Karakurt, Papatya; Bilgin, Sonay; Özdemir, Selen
This study aimed to determine the levels of medication adherence and health literacy among patients with hypertension at a family health center in eastern Türkiye. This was a descriptive, cross-sectional study conducted in a family health center with 200 hypertensive patients (≥ 18 years). Data were collected using the “Patient Identification Form”, the “Health Literacy Scale”, and the “Short Drug Questionnaire”. The mean score on the Health Literacy Scale was 81.83 ± 13.73, indicating above-average health literacy. The mean score on the Short Drug Questionnaire was 0.62 ± 0.60, with 40.5% of patients showing nonadherence with their medications. Importantly, 40.5% of participants scored ≥ 1 on the BMQ, indicating a clinically meaningful risk of non-adherence in almost half of the sample. The most common reasons for nonadherence were diet (30.5%) and personal beliefs (14.5%). A moderate positive correlation was found between health literacy and medication adherence (r = 0.545, p = 0.023). In the regression analysis, health literacy significantly predicted medication adherence (β = 0.545, p < 0.05), explaining 29.7% of the variance in adherence (R²= 0.297). Participants with higher education, income, and prior disease education showed better medication adherence and higher health literacy scores (p < 0.05). Patients’ medication adherence improved as their health literacy levels increased. These findings highlight the importance of enhancing health literacy to promote better medication adherence in hypertensive individuals. Nurses should implement strategies such as personalized education, effective communication, and regular follow-up to increase patients’ health literacy and ensure consistent medication adherence.
- MakaleAçık Erişim2025The relationship between rheumatoid arthritis and epicardial fat thickness, and serum levels of chemerin, adropin, and betatrophin
Ekinci, Bilge; Mertoglu, Cuma; Coskun, Resit; Arslan, Yusuf Kemal; Coban, Taha Abdulkadir; Ozcicek, Fatih
Background. Cardiovascular diseases (CVDs) are highly prevalent among patients with rheumatoid arthritis (RA). Epicardial adipose tissue, serum betatrophin, chemerin, and adropin levels are factors associated with atherosclerosis and cardiovascular involvement. Objectives. This study aimed to investigate the relationship between RA and epicardial fat thickness (EFT), as well as serum betatrophin, chemerin and adropin levels. Materials and methods. This cross-sectional study included 80 patients (62 women and 18 men) diagnosed with RA according to the American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 RA classification criteria and 80 healthy controls (64 women and 16 men). Exclusion criteria comprised other autoimmune diseases, CVDs, diabetes mellitus, other endocrine disorders, acute or chronic pancreatic disorders, malignancy, pregnancy, breastfeeding, or antihyperlipidemic drug usage. Serum betatrophin, chemerin and adropin concentrations were measured. Epicardial fat thickness was evaluated with transthoracic echocardiography. Results. Adropin levels were significantly lower in the RA group compared to the control group (p < 0.001). Chemerin levels and EFT were significantly higher in the RA group than in the control group (p = 0.016, p < 0.001, respectively). When assessing the relationship between biomarkers and EFT in RA patients, a strong positive correlation was observed between chemerin and EFT (r = 0.73, p = 0.046) in patients with high disease activity. Conclusions. Epicardial fat thickness, as an indicator of cardiovascular involvement, is higher in patients with RA. Moreover, high chemerin levels and low adropin levels in these patients may be indicative of cardiovascular involvement. Copyright by Author(s)
- MakaleYalnız künye2025Bioactive Properties and Chemical Compositions of Essential Oils From Three Nepeta L. Species, Two Endemic, Grown in Türkiye
Aydin, Bilge; Kararenk, Ayşe Cemre; Yuca, Hafize; Çeçen, Ömer; Bona, Gülnur Ekşi; Demirci, Betül; Bona, Mehmet; Karakaya, Songul
Nepeta is one of the largest genera in the Lamiaceae family. The aim of this study is to evaluate (DPPH• and ABTS+ scavenging tests), antidiabetic (α-amylase and α-glucosidase enzymes inhibition), and anticholinesterase (acetylcholinesterase and butyrylcholinesterase enzymes inhibition) activities of methanolic, aqueous extracts and essential oils obtained from flowering aerial parts of N. cilicia Boiss. ex Benth., N. isaurica Boiss. & Heldr. ex Benth., and N. sulfuriflora P.H.Davis. Furthermore, essential oils extracted from these plants were analysed for their chemical composition by GC–MS/MS. Also, anatomy and morphology of these plants were evaluated. Total phenolic and tannin contents were analysed. The major compounds identified in the essential oils of Nepeta species were as follows: caryophyllene oxide (24.8%) and phytol (17.7%) in N. cilicia, α-cadinol (13.6%) and ledol (8.0%) in N. isaurica, and 1,8-cineole (70.4%) in N. sulfuriflora. The plants are perennial, and they have unicellular to multicellular non-glandular and multicellular glandular trichomes. In antidiabetic assays, N. cilicia methanolic extract showed the highest α-amylase inhibition (31.66%), while N. isaurica essential oil had the strongest α-glucosidase inhibition (14.25%). For anticholinesterase activity, N. sulfuriflora essential oil was most effective against acetylcholinesterase (8.63%), and N. isaurica MeOH extract had the highest butyrylcholinesterase inhibition (13.24%). It was determined that especially methanolic extracts had higher % inhibition value on ·+ABTS and DPPH•. When a comparison was made in terms of total phenol and total tannin content, it was observed that N. sulfuriflora species was one step ahead. In conclusion, the study revealed that the three Nepeta species—N. cilicia, N. isaurica, and N. sulfuriflora—possess significant bioactive properties, particularly in their antioxidant, antidiabetic, and anticholinesterase activities.
