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  • Article
    Enhanced Doxorubicin Cytotoxicity on Breast Cancer Spheroids by Aptamer Targeted Co-Delivery With Hyaluronidase
    (Wiley, 2025) Kavruk, Murat; Demirel, Dide Su; Bonyadi, Farzaneh; Guner, Buket Cakmak; Dursun, Ali Dogan; Vakifahmetoglu, Cekdar; Ozalp, Veli Cengiz
    Breast cancer is one of the most prevalent solid tumors in women and can be classified into subtypes based on molecular characteristics, such as hormone receptor status and HER2 expression. Aptamers, highly specific affinity molecules, are extensively studied for targeted drug delivery using nanocarriers to enhance anti-cancer efficacy. This study focused on HER2-responsive co-delivery of doxorubicin and hyaluronidase via aptamer-gated mesoporous silica nanoparticles to improve therapeutic outcomes in solid tumors. SK-BR-3 spheroids are employed as a model for resistant tumor environments in solid tumors. Previous research is shown that conjugating cytotoxic drugs with nanoparticles or cells enhances drug penetration into tumor spheroids. In this work, doxorubicin is loaded into mesoporous silica nanoparticles and capped with HER2-specific aptamers, while the particle surface is functionalized with hyaluronidase. This dual-functionalized nanocarrier system achieves an approximate to 8.5-fold increase in cytotoxicity compared to aptamer-targeted delivery lacking hyaluronidase. The enhanced effect is attributed to hyaluronidase-mediated loosening of the spheroid structure, facilitating nanoparticle penetration and localized release of doxorubicin at high concentrations on HER2-positive cells.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Is increased activator protein 1 in cerebrospinal fluid as a potential biomarker that distinguishes idiopathic intracranial from sclerosis?
    (Aepress Sro, 2024) Karabork, Seyda; Celik, Humeyra; Dursun, Ali Dogan; Ankarali, Handan; Turkoglu, Sule Aydin
    OBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein -1 (AP -1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP -1 as biomarkers for the discrimination of IIH and MS. METHODS: AP -1, TNF-alpha, and IL -6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP -1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-alpha, IL -6, CSF, and serum biochemistry analyses. However, it was determined that the AP -1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP -1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP -1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-alpha and IL -6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP -1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31) . Text in PDF www.elis.sk
  • Article
    Citation - WoS: 7
    Citation - Scopus: 7
    Surface Plasmon Resonance Aptasensor for Soluble Icam-1 Protein in Blood Samples
    (Royal Soc Chemistry, 2022) Dursun, Ali Dogan; Dogan, Soner; Kavruk, Murat; Tasbasi, B. Busra; Sudagidan, Mert; Yilmaz, M. Deniz; Tuna, Bilge G.
    Intercellular Adhesion Molecule-1 (ICAM-1) is considered to be a cancer biomarker in the assessment of metastatic potential in patients and an early indicator of atherosclerosis. A labelless biosensor based on the surface plasmon resonance (SPR) signal from the specific affinity interaction of an aptamer and a soluble ICAM-1 protein was developed for blood samples. The developed aptasensor provided real-time information on the concentration of the ICAM-1 protein in blood when integrated to a purification step based on a magnetic pull-down separation. The SPR aptasensor was highly specific with a limit of detection of 1.4/0.2 ng ml(-1), which was achieved through aptamer-functionalized silica-coated magnetic nanoparticles.
  • Article
    Investigation of Sars-Cov Antibody Levels After Covid-19 Vaccine in Chronic Hepatitis B Patients
    (Aepress Sro, 2024) Kinikli, Sami; Afsar, Fatma Elcin; Dursun, Ali Dogan; Aksoy, Altan; Karahan, Gizem; Cesur, Salih; Urtimur, Ufuk
    AIM: The aim was to compare SARS-CoV-2 IgG antibody levels in chronic hepatitis B patients and healthcare personnel selected as the control group and to determine factors such as age, gender, vaccine type, and number of vaccines that may affect the antibody levels. MATERIALS AND METHODS: 87 chronic hepatitis B (CHB) patients followed in Ankara Training and Research Hospital Infectious Diseases Clinic and Mamak State Hospital Infectious Diseases outpatient clinic and 89 healthcare personnel selected as the control group were included in the study. SARS-CoV-2 IgG antibody levels in the serum samples of patients and healthcare personnel who received the COVID-19 vaccine were studied with the ELISA method in the Microbiology Laboratory of Ankara Training and Research Hospital, using a commercial ELISA kit (Abbott, USA) in line with the recommendations of the manufacturer. In the study, SARS-CoV-2 IgG levels were compared in CHB patients and healthcare personnel. In addition, the relationship between SARS-CoV-2 antibody level, gender, average age, natural history of the disease, number of vaccinations, vaccine type (Coronavac TM vaccine alone, BNT162b2 vaccine alone or Coronavac TM and BNT162b2 vaccine (heterologous vaccination)), treatment duration of CHB was investigated. Statistical analyses were made in the SPSS program. A value of p <= 0.05 was considered statistically significant. FINDINGS: A total of 167 people, including 87 CKD patients and 80 healthcare personnel as the control group, were included in the study. SARS-CoV-2 IgG antibody levels were detected above the cut-off level in the entire study group, regardless of the vaccine type. No difference was detected in SARS-CoV-2 IgG titers after COVID-19 vaccination between CHB patients and healthcare personnel. There was a statistically significant difference in SARS-CoV-2 IgG antibody levels among individuals participating in the study according to vaccine types. Compared to those who received Coronavac TM vaccine alone, the average SARS-CoV-2 IgG level was found to be statistically significantly higher in those who received BNT162b2 vaccine alone or heterologous vaccination with Coronavac TM + BNT162b2 vaccine. There was no difference between the groups in terms of age, gender, number of vaccinations, natural transmission of the disease, and duration of antiviral therapy in the CHD patient group. CONCLUSION: As a result, SARS-CoV-2 IgG antibody levels above the cut-off value were achieved with Coronavac TM and BNT162b2 vaccines in both CHD patients and healthy control groups. however, both CHD patients and healthcare personnel had higher antibody levels than those who received BNT162b2 alone or those who received heterologous vaccination had higher antibody levels than those with Coronavac TM alone. Therefore, if there are no contraindications, BNT162b2 vaccine may be preferred in CHB and health personnel (Tab. 2, Ref. 14) .
  • Article
    Citation - WoS: 2
    Citation - Scopus: 3
    Irisin Pathways in Hearts of Type 1 Diabetic Adult Male Rats Following 6 Weeks of Moderate and High-Volume Aerobic Exercise on a Treadmill
    (Springernature, 2023) Celik, Humeyra; Dursun, Ali Dogan; Tatar, Yakup; Omercioglu, Goktug; Bastug, Metin
    Purpose Exercise-mediated protection from cardiomyopathy in diabetes through myokines raises the question of what volume of exercise should be performed. Irisin pathway molecules (consisting of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), irisin, peroxisome proliferator-activated receptors-alpha (PPAR-alpha) and uncoupling protein 1 (UCP1)), which have been shown to be mostly expressed in the heart, are thought to have beneficial effects on diabetic heart. The aim of the study is to evaluate the effects of different exercise protocols on irisin pathway in Type 1 diabetic heart. Methods Diabetic (60 mg/kg streptozotocin i.p.) and healthy Wistar Albino rats (n = 60) were trained under moderate and high-volume exercise protocols on rat treadmill for 6 weeks. After killing, mRNA transcript and protein abundance of PGC-1 alpha, irisin, PPAR-alpha, and UCP1 were determined in the left ventricles of healthy and diabetic rats. Results PPAR-alpha, FNDC5, and UCP1 mRNA levels increased significantly in healthy moderate-volume exercise group (HMVE) compared to healthy high-volume exercise (HHVE) and diabetic moderate-volume exercise groups (DMVE). Moreover, protein levels of irisin and UCP1 also elevated significantly in the diabetic high-volume exercise group (DHVE) compared to the healthy control group (HC), although there was no significant difference between the groups in PPAR-alpha. Conclusion Irisin and UCP1 protein values increased due to HHEV in the heart of Type 1 diabetic rats, but PPAR-alpha values did not change; it shows that HHEV is suitable for the heart of Type 1 diabetic rats in terms of the benefits of the pathway of irisin.
  • Article
    Citation - WoS: 29
    Citation - Scopus: 32
    Effects of Exercise Training on Anxiety in Diabetic Rats
    (Elsevier, 2019) Caliskan, Hasan; Akat, Firat; Tatar, Yakup; Zaloglu, Nezahet; Dursun, Ali Dogan; Bastug, Metin; Ficicilar, Hakan
    Diabetes mellitus (DM) is a common health problem, which manifests itself with chronic hyperglycemia and impaired insulin action. The prevalence of anxiety disorders tends to be high in the diabetic population. Exercise has a well-known anxiolytic effect, also demonstrated on rodents, but the effect of exercise on the DM-induced anxiety is still unknown. Female, Wistar albino rats were randomly divided into four groups (n=8) (C; EX; DM; DM+EX). DM was induced by injection (i.p.; 50 mg/kg) of Streptozotocin (STZ). Rats exercised in moderate intensity on the treadmill (15m/min; 5 degrees; 30 min) for 5 weeks. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT) and Elevated Plus Maze (EPM). According to OFT, central time and central entry have increased with in EX but not in DM+EX. There was no difference between C and DM. Central latency time didn't differ among groups. Unsupported rearing increased in both EX and DM+EX. There was no significant decrease in DM. Freezing time was significantly increased in the DM group. Exercise training reduced freezing time both in diabetic and non-diabetic animals. EPM results were similar. Time spent in open arm was increased significantly in exercise groups compared to their sedentary matches, and freezing time data were also parallel to OFT. Our study revealed that diabetes had shown an anxiogenic effect, which was not severe, and it only manifested itself on some behavioral parameters. Exercise training was reduced anxiety-like behavior both in diabetic and non-diabetic rats. However, because of the nature of exercise studies, it is hard to separate the anxiolytic effect of exercise from the alteration of locomotion.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Chronic Pregabalin Treatment Reduced Anxiety, and Acute Pregabalin Treatment Increased Depression-Like Behaviors in Rats
    (Bmc, 2024) Caliskan, Hasan; Akat, Firat; Dursun, Ali Dogan; Zaloglu, Nezahet
    BackgroundPregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors.MethodsFifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment.ResultsIn the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia.ConclusionAcute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.
  • Article
    Citation - WoS: 5
    Citation - Scopus: 5
    Serum Irisin Levels and Osteoporosis in Patients With Advanced Chronic Kidney Disease and Renal Transplant Recipients
    (Springer, 2023) Demir, Canan; Dursun, Ali Dogan; Sariyildiz, Guelcin Tuerkmen; Arslan, Aykut Ilker
    AimTo elucidate the association of serum irisin levels with bone mineral density (BMD) and calcium-phosphorus metabolism parameters in chronic kidney disease (CKD) patients and renal transplant recipients (RTRs).MethodsThis is a cross-sectional study involving CKD patients and RTRs. Healthy volunteers served as controls. Age, gender, and dialysis vintage were recorded. Serum irisin, creatinine, glucose, calcium, albumin, 25(OH) vitamin D, ferritin, C-reactive protein, A1C, and lipid profile were studied in all participants. Estimated glomerular filtration rate (eGFR), corrected calcium, and body mass index (BMI) were calculated.ResultsOverall, 49 patients (23 hemodialysis, 26 RTRs) and 25 control subjects were included. In hemodialysis (HD) group, 8 patients (34.8%) had osteoporosis, and 12 patients (52.2%) had osteopenia. In RTR group, 3 patients (11.5%) had osteoporosis, while 15 patients (57.7%) had osteopenia. Among controls, one had osteoporosis, and 7 had osteopenia. There was no significant difference between HD and RTRs; however, osteoporosis rate was significantly lower in control subjects. BMD measurements (femur and lumbar T- and Z-scores) were comparable between HD and RTR groups. Control group DEXA values were similar to RTRs; however, they were significantly higher compared to HD group. 25(OH) vitamin D levels were comparable between the HD and RTR groups, and these were significantly lower compared to values of the control group. Mean serum irisin level was 426.6 +/- 191.2 pg/mL in hemodialysis group, 342.6 +/- 174.8 in the RTR group, and 208.0 +/- 186.1 in controls. Serum irisin levels were similar in RTR and HD groups, but their values were significantly higher compared to controls. When we compared serum irisin levels between patients with and without osteoporosis in the whole cohort and hemodialysis and RTR groups, there was no difference. Serum irisin was positively correlated with lumbar T-score both in hemodialysis and RTR groups.ConclusionOur study is the first in the literature revealing the positive correlation of serum irisin level with femur T-score in RTRs. Serum irisin level was also positively correlated with femur T-scores in hemodialysis patients.
  • Article
    Clinical and Laboratory Evaluation of Acute Pericarditis Associated With Antinuclear Antibodies Positivity
    (Bentham Science Publ Ltd, 2023) Dursun, Ali Dogan; Saricam, Ersin; Erdem, Hakan; Sariyildiz, Gulcin Turkmen; Ozyer, Esref Umut; Bozkurt, Engin; Cantekin, Omer Faruk
    Background Up to 30% of patients with acute pericarditis develop recurrent pericarditis. Acute pericarditis may be a manifestation of an underlying systemic autoimmune disease. Therefore, we evaluated the characteristics of patients with acute pericarditis according to antinuclear antibodies (ANA) positivity/negativity. Methods Participants with acute pericarditis and negative ANA (n=29), recurrent pericarditis with positive ANA (n=30) and healthy controls (n=11) were examined. The groups were compared using serum parameters (ANA, C-reactive protein, leucocyte count, erythrocyte sedimentation rate, total antioxidant status, nitric oxide (NO), and oxidative stress index (OSI)) and imaging techniques (electrocardiogram, echocardiography, cardiovascular magnetic resonance, and venous Doppler ultrasound). Results In females, acute pericarditis associated with ANA occurred more frequently (p<0.001). ANA-positive acute pericarditis had significantly lower NO and OSI (p<0.05 and p<0.001, respectively) and pericardial inflammation on magnetic resonance. We found a pulmonary embolism in one patient with positive ANA. Slow venous flow (SVF) occurred more often in acute pericarditis associated with ANA than in the ANA-negative group on venous ultrasound (p<0.05). The prevalence of positive ANAs was 1.6 times higher among SVF patients than in controls. Conclusion This study suggests that acute pericarditis associated with ANA is more common in middle-aged females. SVF and lower oxidative stress tests were more common in patients with ANA-associated acute pericarditis. Acute pericarditis associated with ANA could be considered as a hypercoagulable state. Therefore, all newly diagnosed pericarditis patients (especially females) should be checked for ANA positivity. Awareness of this coexistence should be promptly addressed to establish management strategies.