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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 CengizBreast 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: 2Citation - Scopus: 3Irisin 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, MetinPurpose 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: 5Evaluation of the Efficacy of Silymarin and Dexmedetomidine on Kidney and Lung Tissue in the Treatment of Sepsis in Rats With Cecal Perforation(Spandidos Publ Ltd, 2024) Yavuz, Aydin; Kucuk, Aysegul; Ergorun, Aydan Iremnur; Dursun, Ali Dogan; Yigman, Zeynep; Alkan, Metin; Arslan, MustafaSepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 mu g/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.Article Citation - WoS: 5Citation - Scopus: 5Serum 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 IlkerAimTo 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 FarukBackground 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.
