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Öğe An alternative approach wound healing field with polypodium vulgare(Logos Medical Publishing, 2020) Batur, Şebnem; Ayla, Şule; Şakul, Ayşe Arzu; Okur, Mehmet Evren; Karadağ, Ayşe Esra; Daylan, Benay; Özdemir, Ekrem Musa; Kepil, Nuray; Günal, Mehmet YalçınObjective: In this study, we examined the effects of Polypodium vulgare L. (Polypodiaceae) as a candidate to be used for wound healing scarred area. We investigated the antibacterial, and antioxidant activity of P. Vulgare on both in vivo, and in vitro wound healing using an excisional wound model in mice.Method: We used 32 Balb-c mice equally divided into four groups: Group 1 control, Group 2 vehicle, Group 3 Polypodium vulgare, and Group 4 Centella asiatica extract (CAE). All treatments were applied topically once in a day. The scar area, percentage wound closure and epithelization time were measured. PDGF, VEGF, and collagen immunohistochemical staining were used for evaluation.Results: CAE and P. vulgare extract groups were observed to be more effective than the control and vehicle groups in terms of new vascular, epidermal and granulation tissue organization. PDGF, VEGF, and collagen immunohistochemical staining was stronger in the P.vulgare extract and CAE groups compared to the control and vehicle groups. In the P. vulgare and CAE groups, PDGF staining intensity was stronger than the control and vehicle groups, but VEGF and collagen staining in P. vulgare group was not different from the control group.Conclusion: P. vulgare had an effect on the injured area by regenerating the epidermis and increasing vascularization. P. vulgare extract with known antioxidant, and antimicrobial activities may be helpful as a supportive treatment in wound healing.Öğe Anti-inflammatory, analgesic and in vivo-in vitro wound healing potential of the Phlomis rigida Labill. extract(Elsevier Ireland Ltd, 2021) Okur, Mehmet Evren; Karadağ, Ayşe Esra; Özhan, Yağmur; Sipahi, Hande; Ayla, Şule; Daylan, Benay; Kültür, Şükran; Demirci, Betül; Demirci, FatihEthnopharmacological relevance: The preparations of Phlomis aerial parts are used traditionally in Anatolia for wound healing and in inflammatory disorders. Methods: For the identification of the active fraction, the air dried aerial parts of Phlomis rigida Labill. were extracted by methanol and fractionated successively by n-hexane, dichloromethane and ethyl acetate, respectively. The phenolic constituents were characterized by the Folin-Ciocaltheu method; the antioxidant activity was performed by ABTS and DPPH radical scavenging assays. In vitro anti-inflammatory activity was evaluated by LOX enzyme inhibition, spectrophotometrically as well as cell cultures. The wound healing properties of P. rigida extract gels were studied via in vitro cell culture methods and in vivo by excisional wound model using Balb-c mice. The P. rigida extract was analyzed and characterized by GC-FID, GC-MS, and LC-MS. Results: The P. rigida methanol extract showed moderate LOX inhibitory at IC50 = 19.5 ± 2.8 ?g/mL whereas the antioxidant activity was by DPPH• IC50 = 0.89 mg/mL, and by ABTS• IC50 = 0.99 mg/mL, respectively. In addition, a remarkable P. rigida extracts anti-inflammatory activity was observed in the cell culture assay, which was then confirmed by the in vitro wound healing activity applied at 0.125–0.5 mg/mL concentrations, resulting in a dose-dependent increase in wound closure at the final stage. The P. rigida gel formulation was prepared to evaluate the extract in vivo, whereas the experimental results of the new gel formulation supported the findings of the in vitro wound healing activity. Conclusion: The findings of this in vitro and in vivo study suggest that the wound healing and anti-inflammatory properties provide a scientific evidence of the ethnopharmacological application of Phlomis species.Öğe Association of nox5 expression with sperm activity and motility in pathospermic infertile men(2024) Daylan, Benay; Tok, Olgu Enis; Çakıcı, Çağrı; Yiğitbaşı, Türkan; Varlı Yelke, Tuba; Şenel Ustabaş, Tuğba; Ayla, ŞuleBackground: The newest NOX isoform, NOX5, has been found in mammalian spermatozoa. Many physiological and pathological situations in spermatozoa are mediated by reactive oxygen species (ROS). NOX5 is the main source of ROS in spermatozoa. Our purpose was to investigate the changes in NOX5 expression and the effect of NOX5 expression on sperm motility, chromatin integrity, and oxidative status in oligoasthenozoospermic compared to normozoospermic men. Methods: Semen samples were collected from 30 normozoospermic (NS) and 30 oligoasthenozoospermic (OAS) men. NOX5 protein expression in sperm samples was evaluated by immunohistochemistry and western blot. Oxidative stress status was evaluated by total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidative stress index (OSI) parameters. Chromatin integrity in spermatozoa was evaluated by toluidine blue staining. Results: NOX5 expression levels were significantly higher in OAS group than in NS group (p<0.001). In addition, chromatin integrity was significantly higher in the OAS group in comparison to NS group (p<0.001). TAC levels were higher in the NS group, but OSI and TOC levels were significantly higher in OAS group (p<0.001). It was found that NOX5 protein expression was positively correlated with oxidative stress and chromatin integrity and negatively correlated with motility (p<0.01). Conclusion: These results suggest that overexpression of NOX5 may be the source of excessive ROS production and oxidative stress injuries in oligoasthenozoospermic men. Considering that NOX5 expression is positively correlated with oxidative stress and chromatin integrity but negatively correlated with motility, it can be considered a biomarker to be used in assisted reproductive procedures.Öğe Can lactate dehydrogenase inhibition be increased efficiency of 1,25(OH)2 D3 vitamin in prostate cancer animal model?(NLM (Medline), 2022) Çakıcı, Çağrı; Daylan, Benay; Ayla, Şule; Yiğit, Pakize; Yavuz Dokgöz, Elif; Yigitbaşı, TürkanThe Warburg effect explains that the cancer cell's metabolism is programmed based on anaerobic glycolysis to support the proliferation and anabolic growth of cancer cells. LDH-A is the form of LDH found in cancer cells, which is the main regulator of anaerobic glycolysis. Increased LDH-A activity; promotes tumor growth and metastasis, increases migration and invasion. The active form of vitamin D (1,25(OH)2 D3 ), can have a protective effect against cancer by acting on apoptosis induction, stimulation of cell differentiation, anti-inflammatory, anti-proliferative effect, angiogenesis, and invasion through different mechanisms. We hypothesis that reprogramming cancer cell's glucose metabolism to oxidative phosphorylation with LDH-A inhibitor will increase the effectiveness of 1,25(OH)2 D3 vitamin in prostate cancer (PCa). For this purpose, 50 male C57BL/6 mice and Tramp-C2 PCa cell lines were used to develop PCa model (1- Control group; 2- PCa control group; 3- 1,25(OH)2 D3 vitamin group (5 µg/kg 1,25(OH)2 D3 vitamin); 4- LDH-A inhibitor (300 mg/kg sodium oxamate) group; 5- Combined group (LDH-A inhibitor + 1,25(OH)2 D3 ). CK18-M30, lactate and oxidative stress values were calculated from serum samples. TUNEL staining for apoptosis analysis, western blot analysis for epithelial to mesenchymal transition (EMT) to evaluate metastasis were performed from tumor tissue samples. Hematoxylin-eosin staining (HE) was performed in the liver and periodic acid schiff staining (PAS) was performed in the kidney tissues to evaluate toxicity. When the serum lactate levels were examined, it was shown that the LDH-A inhibitor reversed the Warburg effect. 1,25(OH)2 D3 , LDH-A inhibitor, and LDH-A inhibitor + 1,25(OH)2 D3 treatment groups significantly increased oxidative stress and apoptosis (p<0.05). Moreover, 1,25(OH)2 D3 treatment group had more toxic effect on the kidney. However, when the two treatments groups were combined, the toxicity of vitamin D was significantly decreased (p[removed]0.05). When the effect on EMT was examined, it was observed that the 1,25(OH)2 D3 , LDH-A inhibitor increased the expression of E-cadherin and decreased the expression of N-cadherin (p[removed]0.05). Our results suggest that LDH-A inhibitor + 1,25(OH)2 D3 combined treatment group increased apoptosis, oxidative stress, and decreased toxic effect of 1,25(OH)2 D3 in the kidney. So, tumor volume was decreased and the effectiveness of 1,25(OH)2 D3 vitamin was increased. For metastasis, E-cadherin was increased, and N-cadherin was decreased in the LDH-A inhibitor and 1,25(OH)2 D3 vitamin group. However, the transcription factors results were contradictory. For this reason, EMT results needed to be further research to understand the mechanism. Taken together, our current data indicate that LDH-A inhibitor reprogrammed glucose metabolism and increased effectiveness of 1,25(OH)2 D3 vitamin in PCa animal model.Öğe Erkek infertilitesinde reaktif oksijen türevlerine bağlı NOX5'in sperm motilitesi ile ilişkisi(İstanbul Medipol Üniversitesi Sağlık Bilimleri Enstitüsü, 2021) Daylan, Benay; Ayla, Şuleİnfertilite (kısırlık) bir yıl korunmasız cinsel birleşme sonrasında gebelik elde edememe olarak tanımlanmaktadır. Dünya genelinde infertilite her altı çiftten birini ilgilendiren bir konudur ve vakaların yarısında erkek kaynaklı problemler bulunmaktadır. Erkek genital bezindeki enfeksiyon, varikosel, kullanılan ilaçlar, çevresel faktörler, sigara alışkanlığı gibi çeşitli koşullar erkek infertilitesi ile alakalıdır. Bununla beraber, genelde semen plazmasında Reaktif Oksijen Türlerinin (ROT) artması ve buna karşı antioksidan savunma mekanizmalarının yetersiz kalışı infertilite problemlerinin temelini oluşturmaktadır. ROT aşırı miktarda üretildiğinde, antioksidan savunma sistemi zayıf düşer antioksidanlar ile oksidanlar arasındaki dengeyi bozarak süre ve yapısına bağlı oksidatif hasar oluşur. Özellikle DNA'yı hedef alan ROT, lipit, nükleik asid, protein gibi biyolojik makromoleküllerin fonksiyonlarını bozarak, sperm işlevini olumsuz etkiler. Spermatozoonlardaki artan ROT miktarı ise DNA hasarı ve azalan motilite (hareketlilik) ile bağlantılıdır. Aynı zamanda ROT sperm baş ve orta kısmındaki çoklu doymuş yağ asitlerinin çoklu doymuş peroksidasyonu sonucunda sperm morfolojisini bozar ve sperm motilitesinde azalmaya yol açar. Buna bağlı olarak artan ROT seviyesi sperm motilitesini azaltmaktadır. Öte yandan memeli hücrelerinde NADPH oksidazlar (Nox-1-5), süperoksit anyon (O2) ve hidrojen peroksit (H2O2) gibi ROT' ların temel kaynağı olarak belirtilmektedir. Plazma membranında yer alan Nox enzimleri O2- üretimi için gerekli elektron donörü olarak NADPH'ı aktive etmektedirler. Bu O2- molekülü, H2O2 oluşturmak üzere kendiliğinden ya da enzimatik olarak süperoksit dismutaz (SOD) aracılığı ile indirgenebilir. Bu sebep ile Nox5 ekspresyonu arttığında ROT seviyesinde de artış olur ve bu da sperm motilitesini azaltmaktadır. Bu çalışmada 30 Normozoospermik (NS) ve 30 oligoastenozoospermik (OAS) hastalarından alınan kullanılmayan ve tıbbi atık olarak imha edilen semen örnekleri kullanılmıştır. Semen örneklerinde sperm motilite ve fonksiyonu üzerinde etkili olan Nox5'in protein ekspresyon seviyesi belirlenmiştir. Aynı zamanda bu proteinin oksidatif stres, sperm motilitesi ve kromatin yapısı ile ilişkisi açıklanmıştır. Bu bilgiler ışığında ve daha sonra yapacağımız farklı moleküler çalışmaların desteği ile, bu proteinin sperm fonksiyon analizlerinde bir test yöntemi olarak kullanılmasına katkı sağlamayı amaçlamaktayız.Öğe In vivo wound healing and in vitro anti-inflammatory activity evaluation of phlomis russeliana extract gel formulations(MDPI, 2020) Okur, Mehmet Evren; Karadağ, Ayşe Esra; Üstündağ Okur, Neslihan; Özhan, Yağmur; Sipahi, Hande; Ayla, Şule; Daylan, Benay; Demirci, Betül; Demirci, FatihThe air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 mu g/mL, whereas the DPPH center dot assay showed IC50 = 0.89 mg/mL, and the ABTS(center dot) assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC-FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.Öğe In vivo wound-healing and in vitro antibacterial and antioxidant of Carduus extract(Marmara University, 2023) Şakul, Ayşe Arzu; Ayla, Şule; Okur, Mehmet Evren; Karadağ, Ayşe Esra; Daylan, Benay; Güzel, Elif; Özdemir, Ekrem Musa; Günal, Mehmet YalçınCarduus adpressus has been used for its anti-hair loss effect in traditional folk medicine. The plant species is mainly distributed in Turkiye, Bulgaria, and the Western Caucasus. The studies on this specific plant in the genus Carduus is limited which remarks the significance of the current study. This study aims to investigate the antibacterial, antioxidant, and wound-healing properties of the methanolic extract of Carduus adpressus. Extract was obtained by maceration. The broth microdilution assay was performed on Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. DPPH and ABTS radical scavenging assays were performed to detect the antioxidant capacity. Wound-healing activity was tested using alloxan-induced diabetic BALB-c mice. 4 groups, control, vehicle, CAE and Carduus adpressus groups were treated with the relative agent for 10 days. Extract demonstrated 62.5 mu g/mL MIC against S. aureus and E. faecalis, and 125 mu g/mL MIC against P. aeruginosa and E. coli. ABTS assay showed higher antioxidant activity compared to the DPPH assay. Carduus adpressus group demonstrated strong regeneration, epithelisation, and angiogenesis compared to the control group on day 10. Additionally, expression of PDGF, VEGF, and collagen formation was increased in the Carduus adpressus group compared to the control group on day 10. Extract demonstrated strong antibacterial, antioxidant, and wound-healing activities which indicate that it could be a source in developing wound-healing agents.Öğe In vivo wound-healing and in vitro antibacterial and antioxidant properties of Carduus adpressus extract(Marmara University, 2023) Şakul, Ayşe Arzu; Ayla, Şule; Okur, Mehmet Evren; Karadağ, Ayşe Esra; Daylan, Benay; Güzel, Elif; Özdemir, Ekrem Musa; Günal, Mehmet YalçınCarduus adpressus has been used for its anti-hair loss effect in traditional folk medicine. The plant species is mainly distributed in Türkiye, Bulgaria, and the Western Caucasus. The studies on this specific plant in the genus Carduus is limited which remarks the significance of the current study. This study aims to investigate the antibacterial, antioxidant, and wound-healing properties of the methanolic extract of Carduus adpressus. Extract was obtained by maceration. The broth microdilution assay was performed on Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. DPPH and ABTS radical scavenging assays were performed to detect the antioxidant capacity. Wound-healing activity was tested using alloxan-induced diabetic BALB-c mice. 4 groups, control, vehicle, CAE and Carduus adpressus groups were treated with the relative agent for 10 days. Extract demonstrated 62.5 µg/mL MIC against S. aureus and E. faecalis, and 125 µg/mL MIC against P. aeruginosa and E. coli. ABTS assay showed higher antioxidant activity compared to the DPPH assay. Carduus adpressus group demonstrated strong regeneration, epithelisation, and angiogenesis compared to the control group on day 10. Additionally, expression of PDGF, VEGF, and collagen formation was increased in the Carduus adpressus group compared to the control group on day 10. Extract demonstrated strong antibacterial, antioxidant, and wound-healing activities which indicate that it could be a source in developing wound-healing agents.Öğe LDH-A inhibitor as a remedy to potentiate the anticancer effect of docetaxel in prostate cancer(Ivyspring International Publisher, 2024) Çakıcı, Çağrı; Daylan, Benay; Ünlüer, Rüveyde Safiye; Emekli Alturfan, Ebru; Ayla, Şule; Eren Gözel, Hilal; Yiğit, Pakize; Yavuz Dokgöz, Elif; Yiğitbaşı, TürkanIncreased LDH-A activity promotes tumor growth, migration, invasion, and metastasis. This study aimed to investigate the effects of the combination of LDH-A inhibitor and Docetaxel on apoptosis and epithelial-mesenchymal transition (EMT) in the murine prostate cancer (PCa) model. The prostate cancer murine model was developed subcutaneously in 50 male B57CL/6 mice using the Tramp-C2 prostate cancer cell line. From the tumor tissue samples, apoptosis analysis was performed using TUNEL staining, and EMT was investigated using western blot and qPCR. Hematoxylin-eosin staining (HE) and Periodic acid-Schiff staining were used to histopathologically examine liver and kidney tissues. Lactate levels revealed that the Warburg effect was reversed with the LDH-A inhibitor. Both serum and tumor tissue apoptosis increased, and tumor sizes reduced in PCa+LDH-A inhibitor + Docetaxel treatment groups (p<0.05). The combination of LDH-A inhibitor and Docetaxel inhibited EMT mechanism by causing a decrease in Snail, Slug, Twist, and HIF-1? expressions as well as a decrease in N-cadherin and an increase in E-cadherin levels. Reprogramming glucose metabolism with an LDH-A inhibitor can increase the effectiveness of Docetaxel on apoptosis and metastasis mechanisms in PCa.Öğe Wound healing activity of arum maculatum(Istanbul Medeniyet University, 2023) Arzu Şakul, Ayşe; Okur, Mehmet Evren; Ayla, Şule; Daylan, Benay; Karadağ, Ayşe Esra; Batur, Şebnem; Özdemir, Ekrem Musa; Altınalan, Ebrar; Günal, Mehmet YalçınObjective: In this study, the antioxidant properties of Arum maculatum plant were evaluated. This study reported for the first time the wound healing activity of the methanol extract of A. maculatum fruits. This study aimed to assess and determine the possible pharmacological activities of A. maculatum and evaluate its potential to act as a wound care plant. Methods: The antioxidant and antimicrobial activities of A. maculatum were investigated using excisional in vivo and in vitro wound healing mouse models. A total of 32 Balb-c mice were used, which were equally, divided into four groups: saline control group, control group, A. maculatum group, and Centella asiatica extract group. Treatment applications were performed topically once per day. Wound area narrowing, wound healing percentage, and epithelialization time were analyzed. Results: A. maculatum application supported the healing process in in vivo and in vitro wound models. A. maculatum contributed to the healing process by promoting granulation tissue formation, epidermal regeneration, and angiogenesis. Conclusions: Wound healing is a complex and well-organized process that requires communication between cells. The antioxidant and antimicrobial activities of A. maculatum extract have been determined by current studies. A. maculatum extract may provide significant benefits in promoting the wound healing process.Öğe Wound healing effect of naringin gel in alloxan induced diabetic mice(Ankara University Faculty of Pharmac, 2020) Okur, Mehmet Evren; Şakul, Ayşe Arzu; Ayla, Şule; Karadağ, Ayşe Esra; Şahin Şenyüz, Cemre; Batur, Şebnem; Daylan, Benay; Özdemir, Ekrem Musa; Palabıyık-Yücelik, Sezin; Sipahi, Hande; Aydın, AhmetObjective: The aim of this study was to investigate the effects of naringin, a known flavonoid, on in vitro cytotoxicity, irritation and in vivo potential efficacy when topically applied to the diabetic wound. Material and Method: In vitro direct contact assay and hen's egg chorio-allantoin membrane tests were used to evaluate irritation, and cytotoxicity potential of Naringin. In vitro antimicrobial activity was also tested. Topical treatments were administered once a day on the wound. Wound lesions were photographed and statistically analyzed. After the 10th day, histopathological parameters of tissues were assessed. Result and Discussion: The results showed that naringin gel has no cytotoxicity and irritation potential. Also, it displayed a weak antimicrobial effect. Aside from these, in vivo studies revealed that naringin gel showed statistically higher wound contraction and re-epithelialization, the thickness of granulation tissue, angiogenesis scores. The results indicated that naringin gel effectively enhanced diabetic wound healing, and so this formulation could be considered a promising therapeutic alternative for treating diabetic wounds.
