Browsing by Author "Boyacioglu, Ozge"

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Citation - WoS: 3
Citation - Scopus: 3
Clinic-Oriented Injectable Smart Material for the Treatment of Diabetic Wounds: Coordinating the Release of Gm-Csf and Vegf
(Elsevier, 2024) Kinali, Hurmet; Kalaycioglu, Gokce Dicle; Boyacioglu, Ozge; Korkusuz, Petek; Aydogan, Nihal; Vargel, Ibrahim; Basic Sciences
Chronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles. GM-CSF promotes inflammation, while VEGF facilitates angiogenesis. The hybrid particles (200 -1000 nm) designed within the scope of the study can encapsulate the model proteins Bovine Serum Albumin 65 +/- 5 % and Lysozyme 77 +/- 10 % and can release stably for 21 days. In vivo tests and histological findings revealed that in the hydrogels containing GM-CSF/VEGF-loaded hybrid particles, wound depth decreased, inflammation phase increased, and fibrotic scar tissue decreased, while mature granulation tissue was formed on day 10. These findings confirm that the hybrid particles first initiate the inflammation phase by delivering GM-CSF, followed by VEGF, increasing the number of vascularization and thus increasing the healing rate of wounds. We emphasize the importance of multi-component and sequential release in wound healing and propose a unifying therapeutic strategy to sequentially deliver ligands targeting wound healing stages, which is very important in the treatment of the diabetic wounds.
Citation - WoS: 1
Citation - Scopus: 1
Development and Validation of a Sensitive Assay for the Quantification of Arachidonoylcyclopropylamide (acpa) in Cell Culture by Lc-ms/Ms
(Springer int Publ Ag, 2023) Boyacioglu, Ozge; Recber, Tuba; Kir, Sedef; Korkusuz, Petek; Nemutlu, Emirhan; Basic Sciences
Synthetic and natural cannabinoid derivatives are highly investigated as drug candidates due to their antinociceptive, antiepileptic and anticancer potential. Arachidonoylcyclopropylamide (ACPA) is a synthetic cannabinoid with antiproliferative and apoptotic effects on non-small cell lung cancer and pancreatic and endometrial carcinoma. Thus, ACPA has a great potential for being used as an anticancer drug for epithelial cancers. Therefore, determining the levels of ACPA in biological fluids, cells, tissues and pharmaceutical dosage forms is crucial in monitoring the effects of various pharmacological, physiological and pathological stimuli on biological systems. However, the challenge in the quantification of ACPA is its short half-life and lack of UV signal. Therefore, we developed a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for sensitive and selective quantification of ACPA in cell culture medium and intracellular matrix. Multiple reaction monitoring in the positive ionization mode was used for detection with 344 -> 203 m/z transitions. The separation of ACPA was performed on C18 column (50 x 3.0 mm, 2.1 mu m) with the mobile phase run in the gradient mode with 0.1% formic acid (FA) in water and 0.1% FA in acetonitrile at a flow rate of 0.3 ml/min. The assay was linear in the concentration range of 1.8-1000 ng/mL (r = 0.999). The validation studies revealed that the method was linear, sensitive, accurate, precise, selective, repeatable, robust and rugged. Finally, the developed method was applied to quantify ACPA in cell culture medium and intracellular matrix.
Does Dexmedetomidine Induce Bone Regeneration in Cranial Defects in Rabbits
(Taylor & Francis Ltd, 2025) Erkan, Gozde Nur; Tekin, Umut; Boyacioglu, Ozge; Korkusuz, Petek; Orhan, Kaan; Kirman, Betul; Onder, Mustafa Ercument; Basic Sciences
Dexmedetomidine has been shown to exert protective and curative effects on various tissues and organs in different pathological processes. This study aimed to investigate the effect of dexmedetomidine on the regeneration process after making holes in the parietal bones of rabbits. Twenty-four male Oryctolagus cuniculus rabbits were allocated to three groups, and an 8-mm circular parietal critical-sized bone defect was induced in each animal. Group_C (control) received saline; Group_LD (low dose) was given dexmedetomidine 2.75 mu g/kg; Group_HD (high dose), dexmedetomidine 5.5 mu g/kg; all were administered intraperitoneally for 7 days. After 8 weeks the bones were examined by micro-computed tomography (micro-CT) and histomorphometry. The results indicated that regeneration was improved in both the dexmedetomidine-treated groups. The lower dose increased the bone volume ratio (BV/TV) more than the higher dose. Trabecular thickness, connectivity value, and connectivity density were also higher in Group_LD than in Group_HD. Significant intramembranous ossification was observed in the dexmedetomidine-treated groups, and active osteoblasts were seen at the margins of new bone trabeculae. We conclude that dexmedetomidine, especially at the lower dosage, increases osteoblastic activity and regeneration quality.
Citation - WoS: 1
Citation - Scopus: 1
A Novel Injectable Nanotherapeutic Platform Increasing the Bioavailability and Anti-Tumor Efficacy of Arachidonylcyclopropylamide on an Ectopic Non-Small Cell Lung Cancer Xenograft Model: A Randomized Controlled Trial
(Elsevier, 2025) Boyacioglu, Ozge; Varan, Cem; Bilensoy, Erem; Aykut, Zaliha Gamze; Recber, Tuba; Nemutlu, Emirhan; Korkusuz, Petek; Basic Sciences
Rapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro. Hydrophobic polymers like polycaprolactone (PCL) offer prolonged circulation time and slower drug clearance which is suitable for hydrophobic molecules like ACPA. Thus, the extended circulation time with enhanced bioavailability and half-life of nanoparticular ACPA is crucial for its therapeutic performance in the tumor area. We assumed that a novel high technology-controlled release system increasing the bioavailability of ACPA compared to free ACPA could be transferred to the clinic when validated in vivo. Plasma profile of ACPA and ACPA-loaded PCL-based nanomedicine by LC-MS/MS and complete blood count (CBC) was assessed in wild-type Balb/c mice. Tumor growth in nanomedicine-applied NSCLC-induced athymic nude mice was assessed using bioluminescence imaging (BLI) and caliper measurements, histomorphometry,immunohistochemistry, TUNEL assay, and Western blot on days 7-21. Injectable NanoACPA increased its systemic exposure to tissues 5.5 times and maximum plasma concentration 6 times higher than free ACPA by substantially improving bioavailability. The potent effect of NanoACPA lasted for at least two days on ectopic NSCLC model through Akt/PI3K, Ras/MEK/Erk, and JNK pathways that diminished Ki-67 proliferative and promoted TUNEL apoptotic cell scores on days 7-21. The output reveals that NanoACPA platform could be a chemotherapeutic for NSCLC in the clinic following scale-up GLP/GMP-based phase trials, owing to therapeutic efficacy at a safe low dose window.
Citation - WoS: 4
Citation - Scopus: 3
Thioredoxin System and Mir-21, Mir-23a/B and Let-7a as Potential Biomarkers for Brain Tumor Progression: Preliminary Case Data
(Elsevier Science inc, 2022) Kilic, Nedret; Boyacioglu, Ozge; Saltoglu, Gamze Turna; Bulduk, Erkut Baha; Kurt, Gokhan; Korkusuz, Petek; Basic Sciences; Surgical Sciences
BACKGROUND: The thioredoxin system and microRNAs (miRNAs) are potential targets for both cancer progression and treatment. However, the role of miRNAs and their relation with the expression profile of thioredoxin system in brain tumor progression remains unclear. METHODS: In this study, we aimed to determine the expression profiles of redox components Trx-1, TrxR-1 and PRDX-1, and oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade. We studied Trx-1, TrxR-1, and PRDX-1 messenger RNA expression levels by quantitative real-time polymerase chain reaction and protein levels by Western blot and miR-23a, miR-23b, miR-125a, miR-21, and let-7a miRNA expression levels by quantitative real-time polymerase chain reaction in 16 glioma, 15 meningioma, 5 metastatic, and 2 benign tumor samples. We also examined Trx-1, TrxR-1, and PRDX-1 protein levels in serum samples of 36 patients with brain tumor and 37 healthy volunteers by enzyme-linked immunosorbent assay. RESULTS: We found that Trx-1, TrxR-1, and PRDX-1 presented high messenger RNA expression but low protein expression in low-grade brain tumor tissues, whereas they showed higher protein expression in sera of patients with low-grade brain tumors. miR-23b, miR-21, miR-23a, and let-7a were highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity. CONCLUSIONS: Our findings showed that Trx-1, TrxR-1, miR-21, miR-23a/b, and let-7a might be used for brain tumor diagnosis in the clinic. Further prospective studies including molecular pathway analyses are required to validate the miRNA/Trx system regulatory axis in brain tumor progression.