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Öğe 3D Bioprinting Strategies for Melatonin-Loaded Polymers in Bone Tissue Engineering(Wiley-V C H Verlag Gmbh, 2025) Aykora, Damla; Oral, Ayhan; Aydeğer, Cemre; Uzun, MetehanBone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer-based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell-derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next-generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer-based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well-known antioxidant with many osteoinductive properties and is one of the key hormones in the brain-bone axis. 3D bioprinted melatonin-loaded polymers with unique lipophilic, anti-inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.Öğe Development of melatonin-embedded PLGA-PEG6000 nanofiber biomaterial, and investigation of the effects on abdominal adhesion formation(SAGE Publications Ltd, 2024) Gökçe, Oruç Numan; Aykora, Damla; Danışman, Merve; Demir, Ufuk; Aydeğer, Cemre; Süner, Salih Can; Oral, Ayhan; Karaboğa, İhsan; Uzun, MetehanAbdominal adhesions are still among the most common postsurgical peritoneal inflammation-related complications. Adhesion-related disorders are still highly costly and prevalent due to advances in surgical techniques, treatment methods, and various drugs. The present study aimed to investigate the effects of Poly (D,L-lactide-co-glycolide) (PLGA)- polyethylene glycol (PEG6000) Nanofiber + Melatonin on the abdominal adhesion model in rats. For this purpose, PLGA-PEG6000 Nanofiber + Melatonin matrix was fabricated and implanted in an experimental abdominal adhesion model in rats. Our study consisted of an in vitro and an in vivo part. The degradation and release profile of the matrix and Melatonin (Mel) embedded matrix was performed in vitro. In vivo, the procedure was carried out with 18 Wistar male rats. Rats were divided into three groups as follows: Sham, Matrix, and Mel + Matrix, respectively. Consequent to degradation and release profiling in vitro, an experimental adhesion model was created and fabricated pure matrix (2 × 2 cm2), and matrix (2 × 2 cm2, 0.25 mg melatonin/per matrix embedded) was applied to injury area in related groups. Intra-abdominal adhesion scores were determined on post-op 21st day, under general anesthesia. Following, cecum, peritoneal tissue, and adhesive bands were harvested. Macroscopic analysis (severity of adhesion formation), Hematoxlyn&Eosin and Masson’s Trichrome staining (for the examination of the levels of infiltration of inflammatory cells, fibrosis, and neovascularization) were performed for the evaluation of the effects of Mel embedded and pure matrix Our results indicated that PLGA-PEG6000 Nanofiber + Melatonin matrix was degraded completely in rats abdominal cavity and significantly reduced adhesion formation compared to other groups macroscopically (p < 0.05). On the other hand, the histopathological analysis indicated that the fabricated matrix reduced inflammatory cell infiltration, fibrosis, and neovascularization levels.Öğe Effects of Ozone Therapy on Chronic Arsenic Poisoning in Rats(Springer, 2023) Büyük, Başak; Aydeğer, Cemre; Öztopuz, Özlem; Ovalı, Mehmet Akif; Makav, Mustafa; Eroğlu, Hüseyin AvniArsenic (As) is a toxic metalloid that affects many organs through drinking water. This study aims to examine the efficacy of ozone therapy on chronic arsenic toxicity. Twenty-four male Wistar albino rats were housed in individual cages and grouped as control, As, O3, and As + O3. As was applied by adding 5 mg/kg/day in drinking water for 60 days. Ozone therapy was applied at 0.5 mg/kg/day (i.p.) O3 in the last 5 days of the experimental period. Tissues were harvested and analyzed for histopathological injury and apoptotic markers. There was no significant difference between the As + O3 and O3 groups (p = 0.186 and p = 0.599) for light microscopic criteria: inflammatory cell infiltration and hydropic degeneration in liver tissue. In TUNEL assessments, similar outcomes were obtained in the control and As + O3 groups. A statistically significant increase was observed in p53 and Caspase 3 (Casp-3) expression levels in the As group compared to the O3 and As + O3 groups. There was no significant difference between the As + O3 and O3 groups on peritubular hemorrhage and desquamation parameters in kidneys (p = 0.147 and p = 0.094). The KIM-1 expression level was significantly increased in the As group compared to the As + O3 group (p = 0.01), and the Casp-3 expression level was not significantly changed in the O3 group compared to the As + O3 group (p = 0.59). In conclusion, it is determined that ozone therapy has ameliorative effects on the microscopic injury of liver and kidney tissues. In addition to microscopic improvement, KIM-1 gene expression levels were ameliorated in the kidneys. The apoptotic cell counts and the Casp-3 and p53 gene expression levels were decreased by O3 administration. Thus, ozone therapy can be a treatment choice for As toxicity.Öğe Investigation of Lycium barbarum Effects on Ovarium Damage Exposed to N-Methyl-N-Nitrourea(Springer, 2025) Eroğlu, Hüseyin Avni; Büyük, Başak; Aydeğer, Cemre; Demir, Ufuk; Makav, MustafaN-Methyl-N-nitrourea (MNU), is one of the N-nitroso compounds that people are commonly exposed to in various exogenous ways such as diet, tobacco smoke, cosmetics, household goods, indoor air, occupational exposure, etc. It is known that the compound damages organs and tissues in the body, and one of the affected structures is the ovarium. Lycium barbarum, used in medication in ancient China, has become more popular in recent years. Previous studies have mentioned that polysaccharide ingredients are the most bioactive parts of Lycium barbarum. Therefore, this study aims to investigate the effects of Lycium barbarum polysaccharides (LBP) on ovarian tissue damage exposed to MNU. In accordance with this purpose, a total of 12 21-day-old female Wistar Albino rats were divided into two groups: sham and treatment. The animals were administrated with 50 mg/kg MNU (i.p.) on days 21, 28, 35, and 42. The treatment group was treated with 800 mg/kg LBP via intragastric for 30 days. At the end of the study, animals were sacrificed under general anaesthesia, and the ovarian tissues were harvested. Shrinkage of follicles, lytic oocytes, and disintegrated stroma parameters were evaluated histopathologically. The genetic assessment of the Bcl-2, Bax, Bcl-2/Bax ratio, Caspase 3, p53, and p27 expression levels were determined. The histopathological parameters between the groups were statistically significant (for all parameters p < 0.001). Moreover, the Bcl-2, Bcl-2/Bax ratio, and p53 relative fold changes were significantly increased in the treatment group (p < 0.001, p = 0.045, and p = 0.011, respectively). The results revealed that LBP has ameliorative effects on MNU-induced ovarian tissue damage. Further studies are required to clarify the main underlying mechanisms.Öğe Investigation of the Effects of Dimethyl Sulfoxide in Experimental Gout with Comparison of Dexamethasone and Indomethacin(Springer, 2024) Aydeğer, Cemre; Adalı, Yasemen; Makav, Mustafa; Eroğlu, Hüseyin AvniGout arthritis is an inflammatory arthritis characterized by increased serum uric acid and accumulation of monosodium urate (MSU) crystals in soft tissues. The treatment for gout arthritis is centered on reducing uric acid agents with long-term and anti-inflammatory agents during attack times. In recent studies, it is noteworthy that Indomethacin and Dexamethasone have positive effects in the treatment of gout. Dimethyl sulfoxide (DMSO) is a lipophilic solvent and has an anti-inflammatory effect at appropriate doses. Based on this information, for this study, the effects of these three agents were investigated in rats using a gut model to compare their efficacy. In the study, a total of 48 female 3-4-month rats were divided equally into 8 groups: Control, Indomethacin, DMSO, Dexamethasone, Gout, Gout+Indomethacin, Gout+DMSO, Gout +Dexamethasone. During the eight-week study, a gout arthritis model was used that included 10 mg MSU given intra-articularly in the right foot. Indomethacin 12.5 mg/kg intragastric, DMSO 0.1 ml intraperitoneally and dexamethasone 0.2 mg/kg were administered subcutaneously to the related groups once a day for seven days. At the end of the study, collected articular tissues were stained with haematoxylin and eosin after the fixation and decalcification processes were done. The findings obtained showed that inflammation was reduced in treatment groups compared to the Control groups (all p values 0.002). Also, synovial proliferation was remarkably decreased in the Gout+Dexamethasone group compared to the Gout group (p = 0.019). As a result of these findings, although the three agents all reduced inflammation in gout arthritis, DMSO was shown to be more advantageous due to its having fewer side-effects.Öğe Physiopathology of Wound Healing in Central Nervous System(Hacettepe University, Faculty of Pharmacy, 2023) Aydeğer, Cemre; Eroğlu, Hüseyin AvniWound healing refers to regeneration of damaged tissue under various circumstances and activation of specific physiologic mechanisms. A wound is an immediate onset of tissue damage, contusion, or degeneration. Wounds are common pathological actions of body. After wounds happened, they should lean on healing at specific processes. Wound healing contains 4 phases initially as follows: haemostasias, inflammation, proliferation, and remodelling. Novel studies demonstrated those 4 phases with dermis wound healing process. Nevertheless, every tissue has its own healing pattern. Especially central nervous system differs from dermis in healing process. Therefore, the physiopathological wound healing mechanisms of central nervous system have been referred under novel information in this review. Healing of central nervous system is a complicated process, and the mechanisms of healing are still lacking due to several bunch of studies. Thus, clarification of underlying mechanisms of healing in central nervous system is indispensable for the sufferers. © 2023, Hacettepe University, Faculty of Pharmacy. All rights reserved.Öğe Sağlıklı sıçanlarda dallı zincirli amino asit takviyesi ve dirençli yüzme egzersizinin böbrek dokusu üzerine etkileri(Çanakkale Onsekiz Mart Üniversitesi, 2020) Aydeğer, Cemre; Eroğlu, Hüseyin AvniGünümüzde egzersizin vücut kompozisyonunu geliştirmek amacıyla spor salonlarında yapımının yaygınlaşması, kişileri bilinçli/bilinçsiz olarak besin takviyeleri kullanımına yönlendirmektedir. Bu besin takviyelerinden birisi de dallı zincirli amino asit (BCAA) takviyeleridir. Lösin, izolösin ve valinden oluşan esansiyel amino asitlerinden oluşan BCAA takviyeleri, bu amino asitlerin kas protein sentezini arttırıcı ve intrasellüler sinyal yolaklarını uyarıcı etkisinden dolayı tercih edilmektedir. BCAA takviyeleri hakkında farklı dokular üzerinde çalışmalar bulunmakla beraber dirençli egzersizle böbrek üzerine etkilerini inceleyen herhangi bir çalışma mevcut değildir. Çalışma bu eksikliğin giderilmesi amacıyla planlandı. Çalışmada toplam 24 adet 2 aylık erkek Wistar Albino sıçan her bir grupta 6 adet olacak şekilde 4 grup oluşturuldu: Kontrol, BCAA, Egzersiz, Egzersiz+BCAA. BCAA gruplarına 2,5 mg/kg olarak her gün oral gavaj şeklinde BCAA takviyesi uygulandı. Egzersiz gruplarına ise haftanın 5 günü 6 hafta süresince dirençli yüzme egzersizi yaptırıldı. Çalışmanın bitiminde sıçanlardan alınan böbrek dokuları uygun koşullarda saklanarak histopatolojik, immünohistokimyasal ve genetik incelemeler yönünden değerlendirildi. Bu değerlendirmeler neticesinde, BCAA takviyelerinin böbrekte doğrudan tübüler nekroza sebebiyet vermese bile egzersiz ile birlikte tüketiminin böbrek hasarını arttırdığı belirlendi. Bununla birlikte immünohistokimyasal ve genetik bulgular birlikte değerlendirildiğinde egzersiz ile BCAA'ların apoptoz mekanizması üzerinde antagonist bir etkinlik gösterdiği tespit edildi. Bu iki sonuca ek olarak egzersizin özellikle proksimal tübül, egzersizin yanında BCAA tüketiminin ise böbreğin diğer bölümleri olan bowman kapsülü ve glomerüler membranda sorunlara yol açabileceği kanatine varıldı. Sonuç olarak BCAA takviyesi kullanımının, böbreklerde oluşturabileceği hasar/lara karşı hekim kontrolünde kullanılması tavsiye edilmektedir.Öğe The Effect of Topically Applied Boric Acid on Ephrin-Eph Pathway in Wound Treatment: An Experimental Study(SAGE Publications, Early Access) Büyük, Başak; Aydeğer, Cemre; Adalı, Yasemen; Eroğlu, Hüseyin AvniBackground: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated. Methods: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as Control, Fito, Boron and Plu groups. After the applications performed twice a day and lasting 7 days, skin tissues obtained and evaluated histopathological (inflammatory cell infiltration, oedema, and fibroblast proliferation density) and immunohistochemical (TNF-α, EphrinA1, EphrinB1, EphrinB2 and EphB4). Results: Inflammatory cell infiltration score was found to be higher in the Fito group compared to Boron group (p =.018). Fibroblast proliferation density was higher in Plu group than Boron group (p=.012). While TNF-α was lower in boron group than Plu (p =.027) and Fito (p =.016) groups, EphrinA1 was higher in Boron group than Plu group (p =.005). EphrinB1 expression was higher in Boron group compared to Plu (p= .015) and Fito (p =.015) groups, and the same difference was also observed in EphrinB2 (p values .000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to Plu (p=.000) and Fito (p =.002). Conclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.Öğe The Effects of Thiopental on Cold Ischemic Injury in Renal Transplantation(Medical University of Plovdiv, 2023) Büyük, Başak; Adalı, Yasemen; Karakoç, Ebru; Eroğlu, Hüseyin Avni; Aydeğer, CemreIntroduction: One of the most important factors influencing post-transplant success in kidney transplantation is preserving the viability of the organ from removal to transfer into the recipient. Aim: This study aimed to reduce the energy requirement with thiopental doses administered before organ transplantation, and to increase the organ viability by minimizing the tissue damage during the cold ischemia process. Materials and methods: Twenty female Wistar albino rats were divided into two groups: control group (group C), and thiopental group (group T). In group C, a midline incision was performed, and the renal artery was isolated under ketamine and xylazine anesthesia. A standard organ storage solution (cooled to +4°C) was used for kidney perfusion. Nephrectomy was applied, and the removed kidneys were placed into +4°C standard organ storage solution and stored at +4°C for 12 hours. Animals in group T were subjected to the procedures explained above under 85 mg/kg thiopental sodium anesthesia. After 12-hour storage, samples from the kidney tissues were fixed in 10% neutral buffered formalin. Histopathological evaluation and apoptosis detection via TUNEL method were performed. Results: Tubular necrosis was more extensive in group C compared with that in group T and this difference was statistically significant. Similarly, vacuolization was widely observed in group C, and this increase was also statistically significant. For the ‘dilatation of Bowman’s space’ parameter, a significant decrease was observed in group T compared with group C. When the apoptotic index values of both groups were examined, it was seen that they were lower in group T than those in group C. This result was statistically significant. Conclusions: These data suggest that thiopental provides protection to the kidney tissue during the cold storage process. Thiopental has been shown to decrease the number of apoptotic cells in the kidney tissue when administered to the donor before organ transplantation, increasing the organ viability.Öğe Ultraviyole-A ve B radyasyonu ile oluşturulan cilt hasarı modelinde mirna-330-3P'nin etkilerinin araştırılması(Çanakkale Onsekiz Mart Üniversitesi, 2024) Aydeğer, Cemre; Eroğlu, Hüseyin AvniGüneşten salınan ışınlardan biri olan Ultraviyole (UV) radyasyon sağlığı olumlu olduğu kadar olumsuz olarak da etkileyebilmektedir. Cilt, UV radyasyona en çok maruz kalan doku olup maruziyet sonucunda DNA hasarı, inflamasyon ve eritem, güneş yanığı, gen mutasyonları, immünsupresyon ve ilerleyen süreçte cilt kanserlerinin de dahil olduğu birçok komplikasyon meydana gelebilmektedir. Bu bilgiler ışığında amacımız güneş ışığından kaynaklanan UV radyasyonun zararlı etkilerini engellemek veya azaltmak için miRNA-330-3p içeren pomat geliştirilmesi ve bunun in vivo etkilerinin belirlenmesidir. Çalışmamızda lipofectamin ile enkapsüle edilen miRNA-330-3p pluronik jel ile karıştırılarak pomat elde edildi. Ardından 36 adet Wistar albino cinsi erkek sıçan rasgele eşit bir şekilde (n=6); A (Kontrol), B (UV), C (UV+Plu), D (Plu+UV), E (UV+Pomat) ve F (Pomat+UV) olmak üzere gruplara ayrıldı. Sıçanlara UV uygulaması 30 gün, günde 2 saat olarak gerçekleştirildi. Bu süreçte E ve F gruplarındaki sıçanların dorsal sırt bölgesine geliştirilen 1 µl miRNA 330-3p mimic içeren pomat uygulanırken; C ve D gruplarının aynı bölgesine pomat bazı olan pluronik jel uygulaması yapıldı. Çalışmanın 31. gününde anestezi altında sıçanların tedavi uygulanan ve işaretlenmiş olan dorsal sırt bölgesi makroskobik değerlendirme için fotoğraflandı. Ardından uygulama yapılan işaretli alanlardan tam kat deri dokuları eksize edildi. Elde edilen dokular histopatolojik, immünohistokimyasal ve genetik analizler için kullanıldı. Sonuçlara göre, pomat uygulaması yapılan E ve F gruplarında apoptotik hücre yüzdesinin A grubu ile aynı düzeyde olduğu belirlendi. Pomat uygulamasının UV radyasyonun neden olduğu epitel incelmesinin, kontrol ile aynı seviyeye getirdiği ortaya konuldu. Buna ek olarak F grubunda p27 ekspresyonunun A grubuna göre yaklaşık 4,5 kat arttırdığı belirlendi. TUNEL sonuçları ve kaspaz-3 ekspresyon bulguları birlikte değerlendirildiğinde miRNA 330-3p içeren pomat uygulamasının p27 ekspresyonunu arttırarak koruma gerçekleştirildiği düşünüldü.
