Browsing by Author "Eken, Ahmet"

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Alantolactone ameliorates graft versus host disease in mice
(ELSEVIER, 2024) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Şerife; Çakır, Mustafa; Özcan, Alper; Yılmaz, Ebru; Karakukcu, Musa; Donmez-Altuntas, Hamiyet; Yay, Arzu Hanim; Deniz, Kemal; Altay, Derya; Arslan, Duran; Canatan, Halit; Eken, Ahmet; Unal, Ekrem; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Kendirli, Perihan Kader
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2–18 (n = 4) and non-GVHD patients between ages 2–50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44− ). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
Immunomagnetic separation of B type acute lymphoblastic leukemia cells from bone marrow with flow cytometry validation and microfluidic chip measurements
(TAYLOR & FRANCIS INC, 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA, 2020) Icoz, Kutay; Eken, Ahmet; Cinar, Suzan; Murat, Aysegul; Ozcan, Servet; Unal, Ekrem; Deniz, Gunnur; 0000-0002-8330-7010; 0000-0002-0947-6166; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
In order to detect the blast cells from bone marrow of patients, one strategy is to first isolate the cells using immunomagnetic beads. The aim of this study was to report the experimental results of the immunomagnetic separation efficiency of the blast cells from bone marrow of pediatric leukemia patients. To test the efficiency of immunomagnetic separation, flow cytometry measurements at critical steps were performed. We here reported 94.5% capture efficiency for CD10 nano beads. Patients samples were also analyzed with a microfluidic chip to test the feasibility for further developments.
Synthesis and Comprehensive in Vivo Activity Profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in Experimental Autoimmune Encephalomyelitis: A Natural Remyelinating and Anti-Inflammatory Agent
(American Chemical Society(ACM), 2023) Senol, Halil; Ozgun-Acar, Ozden; Daǧ, Aydan; Eken, Ahmet; Guner, Hüseyin; Aykut, Zaliha Gamze; Topcu, Gulacti; Sen, Alaattin; 0000-0002-8444-376X; 0000-0002-0220-5224; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Sen, Alaattin; Güner, Hüseyin
Multiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG35-55-induced experimental autoimmune/allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treatment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory regulators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment since OPCA not only normalizes the pro- and anti-inflammatory immunological bias but also stimulates remyelination in EAE.