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Öğe Development of anti-VEGF prolonged release drug delivery system containing PLL dendrimer and hyaluronic acid(Maik Nauka/Interperiodica/Springer, 2022) Gedik, Gülşah; Öztabağ, Cansu Kara; Sarp, Önder; Nazlı, Hakan; Tıranbeşli, Görkem; Kurt, Akif HakanIn this study we aimed to develop anti-vascular endothelial growth factors (anti-VEGF) drug delivery systems that long-term sustained release using dendrimer technology and to evaluate its possible cytotoxic effects on the retina pigment epithelial cells (ARPE-19) and the irritation potential by Hen's Egg Test on a chorioallantoic membrane (HET-CAM) analysis. The drug carrier gel formulation was prepared by adding hyaluronic acid (HA) after bevacizumab (BEV) was complexed with poly-L-lysine (PLL) dendrimer. The formulations were determined by the particle size, polydispersity index (PDI) values, zeta potential, pH, optical clarity, and their content. The UV- spectrophotometric analytical methods were developed, validated and applied for the kinetic studies. Prolonged BEV release from formulations has been observed for up to 21 days. Cell viability was evaluated with the XTT assay. VEGF and BEV levels in the medium were measured using a human VEGF and BEV ELISA kit, respectively. HET-CAM assays were conducted to determine the irritation potential. The clarity of gel formulation was found to be clear and satisfactory (double +). The pH of gel formulation ranged between 6.39 and 6.95. The zeta potential of formulations ranged between +3.9 and -1.5 mV. The particle size of formulations ranged between 15 and 302 nm. The loading efficiency (LE) of the complex formulation was found 79.04%. The formulation's kinetic behavior was determined by the Higuchi and Korsmeyer-Peppas model. The formulations did not cause any irritation. According to the results obtained, gel formulation was innovative, effective and suitable for treatment. However, animal experiments and clinical studies should also be performed.Öğe Effects of bone marrow and adipose-derived mesenchymal stem cells on microRNA expressions in acute alkaline corneal burn(Mary Ann Liebert, Inc., 2021) Dinç, Erdem; Ayaz, Lokman; Kurt, Akif Hakan; Dursun, Özer; Yılmaz, Gülşen; Vatansever, MustafaPurpose: The aim of this study was to investigate the microRNA (miRNA) expressions of the corneal tissue after an alkaline burn and to compare the efficiency of adipose- and bone marrow-derived mesenchymal stem cells (MSCs) on expressions. Methods: Thirty-two rats were divided into 4 groups. No intervention was made in the control group. A chemical burn was created by applying 4 mu L NaOH soaked in 6 mm filter paper to the right eye of each animal in the other groups. Whereas only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 x 10(6) adipose- or bone marrow-derived MSC in 0.1 mL PBS was injected subconjunctivally to the animals in the remaining groups (groups 2 and 3, respectively). Tissue samples were collected for miRNA analysis on the third day after the burn. Results: When group 1 was compared with the control group, the expression of 3 of 93 miRNAs increased significantly, whereas the expression of 50 miRNAs decreased significantly. Significant changes in miRNA expressions were observed when group 1 was compared with groups 2 and 3. Although a significant change was observed in the expression of 6 miRNAs in the adipose-derived MSC group, it was found that the expression of 65 miRNAs significantly changed in the bone marrow-derived MSC group. Conclusion: This study shows that there are significant changes in some miRNA expressions after corneal alkaline burn and these changes can be reversed with the subconjunctival injection of MSCs.Öğe Effects of mesenchymal stem cells on microRNA expressions in acute alkaline corneal burn(Mary Ann Liebert, Inc, 2023) Dinç, Erdem; Ayaz, Lokman; Kurt, Akif Hakan; Dursun, Özer; Yılmaz, Gülsen; Vatansever, Mustafa; Özer, ÖmerÖğe Effects of music therapy on pain and oxidative stress in oocyte pick-up: a randomized clinical trial(Elsevier Science Inc, 2020) Orak, Yavuz; Bakacak, Süleyman Murat; Yaylalı, Aslı; Tolun, Fatma İnanç; Kiran, Hakan; Boran, Ömer Faruk; Kurt, Akif HakanBackground and objective: The aim was to investigate the effects of Turkish classical music on pain and oxidative stress in patients undergoing oocyte pick-up. Methods: The study was a randomized, controlled trial. The groups included were Group NM (Non-Music), control group; Group PM, which comprised patients who listened to music before the operation; and Group CM, which comprised patients who listened to music both before and during the operation. Blood was drawn prior to the operation to measure the oxidative stress values. Pain, hemodynamic parameters, oxidative stress values were assessed postoperatively. Results: The number of patients requiring additional propofol was higher in Group PM than in Groups NM and CM (p = 0.003). The postoperative Visual Analog Scale (VAS) score were lower in Groups PM and CM than in Group NM (p = 0.001, p = 0.007) in the 1st and 60th minutes. The postoperative VAS score was lower in Group CM than in Group NM (p = 0.045) in the 5th minute. The postoperative additional analgesic requirements were lower in Groups PM and CM than in Group NM (p = 0.045). The postoperative blood glutathione peroxidase values were significantly higher in Groups PM and CM than in Group NM (p = 0.001). The postoperative catalase values were significantly higher in Groups PM and CM than in Group NM (p = 0.008 and p < 0.001). The preoperative malondialdehyde values were significantly lower in Groups PM and CM than in Group NM. The preoperative nitric oxide values were higher in Groups PM and CM than in Group NM (p < 0.001), whereas the postoperative nitric oxide values were lower in Groups PM and CM than in Group NM (p < 0.001). Conclusion: Turkish classical music has beneficial effects on pain and oxidative stress in oocyte pick-up patients. (C) 2020 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.Öğe Effects of music therapy on pain and oxidative stress in oocyte pick?up: a randomized clinical trial(Elsevier Editora Ltda, 2020) Orak, Yavuz; Bakacak, Suleyman Murat; Yaylali, Asli; Tolun, Fatma Inanc; Kiran, Hakan; Boran, Omer Faruk; Kurt, Akif HakanBackground and objective: The aim was to investigate the effects of Turkish classical music on pain and oxidative stress in patients undergoing oocyte pick?up. Methods: The study was a randomized, controlled trial. The groups included were Group NM (Non?Music), control group; Group PM, which comprised patients who listened to music before the operation; and Group CM, which comprised patients who listened to music both before and during the operation. Blood was drawn prior to the operation to measure the oxidative stress values. Pain, hemodynamic parameters, oxidative stress values were assessed postoperatively. Results: The number of patients requiring additional propofol was higher in Group PM than in Groups NM and CM (p = 0.003). The postoperative Visual Analog Scale (VAS) score were lower in Groups PM and CM than in Group NM (p = 0.001, p = 0.007) in the 1st and 60th minutes. The postoperative VAS score was lower in Group CM than in Group NM (p = 0.045) in the 5th minute. The postoperative additional analgesic requirements were lower in Groups PM and CM than in Group NM (p = 0.045). The postoperative blood glutathione peroxidase values were significantly higher in Groups PM and CM than in Group NM (p = 0.001). The postoperative catalase values were significantly higher in Groups PM and CM than in Group NM (p = 0.008 and p ? 0.001). The preoperative malondialdehyde values were significantly lower in Groups PM and CM than in Group NM. The preoperative nitric oxide values were higher in Groups PM and CM than in Group NM (p ? 0.001), whereas the postoperative nitric oxide values were lower in Groups PM and CM than in Group NM (p ? 0.001). Conclusion: Turkish classical music has beneficial effects on pain and oxidative stress in oocyte pick?up patients. © 2020 Sociedade Brasileira de AnestesiologiaÖğe Evaluation of anti-inflammatory and antiapoptotic effects of bone marrow and adipose-derived mesenchymal stem cells in acute alkaline corneal burn(Mary Ann Liebert, Inc, 2021) Dinç, Erdem; Dursun, Özer; Yılmaz, Gülsen; Kurt, Akif Hakan; Ayaz, Lokman; Vatansever, Mustafa; Özer, ÖmerPurpose: The aim of the present study is to comparatively evaluate the anti-inflammatory and antiapoptotic effects of bone marrow and adipose-derived mesenchymal stem cells (MSCs) applied subconjunctivally after alkaline corneal burn. Methods: Thirty-two rats were divided into 4 groups and included in the study (n = 8). While no intervention was made in the control group, a chemical burn was created by applying 4 mu L of NaOH soaked in 6 mm filter paper to the right eye of each subject in the other groups under general anesthesia. While only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 x 10(6) adipose or bone marrow-derived MSC in 0.1 mL PBS was applied subconjunctivally to the subjects in the remaining groups (Group 2 and 3, respectively). Tissue samples were collected for histological analysis on the third day after the burn. Tissue samples were evaluated light microscopically and immunohistochemically stained for interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), caspase-3 (Cas-3), and CD68. Results: The IL-1 beta and TNF-alpha staining scores and the number of CD68- and Cas-3-positive stained cells were significantly lower in the groups given bone marrow and adipose-derived MSC compared to the alkaline burn group (P < 0.0001, for all parameters). Epithelial IL-1 beta and TNF-alpha staining scores were significantly lower in the bone marrow-derived MSC group compared to the adipose-derived MSC group (P < 0.0001, for all parameters). Conclusions: The presented study shows that both bone-marrow and adipose-derived MSCs support wound healing in the corneal tissue and strongly suppress the inflammation occured in the tissue.Öğe Expression of ER stress markers (GRP78 and PERK) in experimental nephrotoxicity induced by cisplatin and gentamicin: Roles of inflammatory response and oxidative stress(Springer, 2023) Metin, Tuba Özcan; Bayrak, Gülsen; Yaman, Selma; Doğaner, Adem; Yoldaş, Atila; Eser, Nadire; Kurt, Akif HakanThis study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)–induced and gentamicin (GEN)–induced nephrotoxicity. The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for 7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney. CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7 days. These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress–related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs insteadÖğe Melatonin metabolites protect human retinal pigment epithelial cells from death caused by oxidative stress(Springer, 2021) Uras, Ebru; Kılıçaslan, Derya; Kurt, Akif Hakan; Allı, Bilge; Doğaner, AdemThis study was aimed to determine the efficacy of 6-hydroxy melatonin and N-acetyl serotoninin protecting human retinal pigment epithelial cells from death brought about by oxidative-stress. The ARPE-19 cells (one of the retinal pigment epithelial cell lines) were used as the test cell culture. Following the application of 500 mu M H2O2, ARPE-19 cell line culture was incubated for 20 h to induce oxidative stress damage. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay was used to evaluate the oxidative injury to ARPE-19 cells caused by H2O2 and the effectiveness of 6-hydroxy melatonin and N-acetyl serotonin application in preventing this damage. The results indicated that 6-hydroxy melatonin and N-acetyl serotonin exhibited a therapeutic effect on cells damaged by exposure to oxidative stress. It was concluded that these melatonin metabolites might be useful in treating many retinal conditions linked to the oxidative stress-induced damage. In addition, this study proposed a new idea for developing chemical approaches to the design and synthesis/semisynthesis of new drugs.Öğe Microwave-assisted ultra-fast synthesis of carbon quantum dots from linter: Fluorescence cancer imaging and human cell growth inhibition properties(Elsevier, 2020) Eskalen, Hasan; Uruş, Serhan; Cömertpay, Sabahattin; Kurt, Akif Hakan; Özgan, ŞükrüThe water dispersed-fluorescent carbon quantum dots (CDs) were synthesized using microwave-assisted hydrothermal process in the closed system from the waste cotton linter as a new carbon source. This method provided an ultra-fast, more effective, economical and easier synthesis for cancer-imaging applications compared to the other methods presented in literature. The morphological and optical properties of the hydrothermally produced carbon quantum dots were characterized by using FT-IR, transmission electron microscopy (TEM), SEM, EDX, UV-vis and fluorescent spectrophotometry techniques. An emission peak was observed at 420 nm when the CDs were excited at 376 nm. CDs were calculated to have an average particle diameter of 10.14 nm by TEM. In order to determine the usability of the CDs in cell imaging, two different concentrations (50 mu L/mL and 100 mu L/mL) of the CDs colloidal solution were applied to a human mesothelioma cell line, H2452, and human umbilical vein endothelial cells (HUVEC) for varying durations. While the fluorescent photos revealed that 2 h of exposure was sufficient for the cells to take the C-dots in and higher concentrations appeared brighter in the wavelengths studied (red channel (excitation/emission 586/646 nm), blue channel (390/446 nm) and the green channel (482/532 nm)), cell viability and proliferation assays indicated that the material was cytotoxic against the both cell lines and inhibited the cell growth in a time- and dose- dependent manner.Öğe A novel donepezil-caffeic acid hybrid: Synthesis, biological evaluation, and molecular docking studies(Maik Nauka/Interperiodica/Springer, 2023) Kılıçaslan, Derya; Kurt, Akif Hakan; Köse, Muhammet; Çeşme, Mustafa; Güngör, Özge; Öztabağ, Cansu Kara; Doğaner, AdemA novel donepezil-caffeic acid (DP-CA) hybrid molecule was designed, synthesis, and investigated by molecular modeling. Its biological activity and protective effect were investigated by the IR spectroscopy, H-1 and C-13 NMR spectroscopy, and mass spectrometry. DP-CA was highly active against acetylcholine esterase and inhibited it at the micromolar concentrations. Fluorescence and UV-Vis spectroscopy studies showed strong binding of DP-CA to DNA. Moreover, DP-CA exhibited protective effects against H2O2-induced toxicity in U-118 MG glioblastoma cells. Finally, molecular docking showed a high affinity of DP-CA in all concentrations, and the active 4EY7 site exhibited essential residues with polar and apolar contacts. Taken together, these findings indicate that DP-CA could be a prospective multifunctional agent for the treatment of neurodegenerative diseases.Öğe Protective effects of pinocembrin and pinostrobin against hydrogen peroxide-induced stress in retina pigment epithelial cells(Springer, 2020) Kılıçaslan, Derya; Kurt, Akif Hakan; Doğaner, AdemThis work was aimed at examining the protective effect of pinocembrin and pinostrobin in retinal pigment epithelial cells exposed to oxidative stress caused by hydrogen peroxide (H2O2). In the present study, the ARPE-19 cell line, one of the retinal pigment epithelial cell lines, was selected as the test cell culture. The incubation was performed on the basis of a 16-h application time of 500 mu MH2O2 to induce the oxidative stress damage in the ARPE-19 cell line. The protective effect of applying pinocembrin and pinostrobin in H2O2-induced oxidative damage was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The obtained results showed evidence of therapeutic effects of pinocembrin and pinostrobin in cells exposed to oxidative stress-induced damage. Pinocembrin and pinostrobin can find direct medical application as pharmaceutical agents and may contribute to the design, synthesis and semi-synthesis of new drugs and to the development of chemical templates for treatment of diseases.Öğe Protective effects of quercetin in combination with donepezil against H2O2-induced oxidative stress in glioblastoma cells(Springer, 2023) Albayrak, Ahmet; Kurt, Akif Hakan; Kılıçaslan, Derya; Çelik, Mustafa; Öztabağ, Cansu Kara; Doğaner, AdemPolyphenols are natural antioxidants found in the human diet, which are known to have protective effects against neurodegenerative diseases by scavenging free radicals. Recently, combination therapies including cholinesterase (ChE) inhibitors and neuroprotective agents have been shown to be more efficacious in the prevention and treatment of Alzheimer's disease. Therefore, the purpose of this work was to assess the neuroprotective impact of the combination of quercetin, a major polyphenolic compound, and donepezil, a cholinesterase inhibitor, against hydrogen peroxide-induced oxidative damage of glioblastoma (U-118 MG) cells. Following pretreatment with quercetin and donepezil, the glioblastoma cell line was subjected to H2O2-induced oxidative stress damage via application of 250 mu MH2O2 and incubation for a period of 24 h. In this study, four test groups were selected for the investigation of quercetin and donepezil as protective agents against H2O2 oxidative stress. First, quercetin and donepezil were examined in terms of their effects on glioblastoma cell viability. Next, pre- and post-application of quercetin and donepezil were used to determine their concentrations effective against the H2O2-induced oxidative damage in the U-118 MG cell line. Finally, the effect of the combined application of quercetin and donepezil on the cell viability was investigated. Viability testing of the cell lines was carried out via the advanced XTT assay using sulfonated tetrazolium. As a result of testing, no protective or therapeutic effects of donepezil alone were observed on the cell damage caused by oxidative stress. On the other hand, quercetin and combination applications exhibited protective or therapeutic effects on the cell damage. Thus, the neuroprotective effect of quercetin and its combination with donepezil provide a new approach to the search for drugs in the clinical treatment of neurodegenerative diseases.Öğe Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: One-pot synthesis, characterization, and anticancer and antibacterial activities(Beilstein-Institut, 2023) Kurt, Akif Hakan; Olutaş, Elif Berna; Avcıoğlu, Fatma; Karakuş, Hamza; Sungur, Mehmet Ali; Öztabağ, Cansu Kara; Yıldırım, MuhammetThe presented study comprises the one-pot synthesis and the characterization of quercetin-and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles (Ch/Q-and Ch/CA-Ag NPs), and their antibacterial and anticancer activities. The formation of Ch/Q-and Ch/CA-Ag NPs has been confirmed by ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The characteristic surface plasmon resonance (SPR) absorption band has been found at 417 and 424 nm for Ch/Q-and Ch/CA-Ag NPs, respectively. The formation of a chitosan shell comprising quercetin and caffeic acid, which surround the colloidal core Ag NPs, was confirmed by UV-vis, and FTIR analyses, and moni-tored by TEM microscopy. The size of nanoparticles has been determined as 11.2 and 10.3 nm for Ch/Q-and Ch/CA-Ag, respec-tively. The anticancer activity of Ch/Q-and Ch/CA-Ag NPs has been evaluated against U-118 MG (human glioblastoma) and ARPE-19 (human retinal pigment epithelium) cells. Both NPs showed anticancer activity, but Ch/Q-Ag NPs seemed to be more effective on cancer cell lines (U-118 MG) in comparison to healthy ones (ARPE-19). Furthermore, the antibacterial activity of Ch/Q-and Ch/CA-Ag NPs against Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus and S. epidermidis) bacteria was determined, and dose-dependent antibacterial effects were found.Öğe A Review on the Design, Synthesis, and Structure-activity Relationships of Benzothiazole Derivatives against Hypoxic Tumors(NLM (Medline), 2022) Kurt, Akif Hakan; Ayaz, Lokman; Ayaz, Furkan; Seferoglu, Zeynel; Nural, YahyaThere has been a growing body of studies on benzothiazoles and benzothiazole derivatives as strong and effective anti-tumor agents against lung, liver, pancreas, breast, and brain tumors. Due to the highly proliferative nature of the tumor cells, the oxygen levels get lower than that of normal tissues in the tumor microenvironment. This situation is called hypoxia and has been associated with increased ability for carcinogenesis. For the drug design and development strategies, the hypoxic nature of the tumor tissues has been exploited more aggressively. Hypoxia itself acts as a signal initiating system to activate the pathways that eventually lead to the spread of the tumor cells into the different tissues, increases the rate of DNA damage, and eventually ends up with more mutation levels that may increase the drug resistance. As one of the major mediators of hypoxic response, hypoxia-inducible factors (HIFs) have been shown to activate angiogenesis, metastasis, apoptosis resistance, and many other protumorigenic responses in cancer development. In the current review, we will be discussing the design, synthesis, and structureactivity relationships of benzothiazole derivatives against hypoxic tumors such as lung, liver, pancreas, breast, and brain as potential anti-cancer drug candidates. The focus points of the study will be the biology behind carcinogenesis and how hypoxia contributes to the process, recent studies on benzothiazole and its derivatives as anti-cancer agents against hypoxic cancers, conclusions, and future perspectives. We believe that this review will be useful for researchers in the field of drug design during their studies to generate novel benzothiazole-containing hybrids against hypoxic tumors with higher efficacies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.Öğe Yaşa Bağlı Makula Dejenerasyonunda Yeni Tedavi Yaklaşımlarında Polifenoller(2022) Kurt, Akif Hakan; Öztabag, Cansu Kara; Kaymaz, AbdulganiYaşa bağlı makula dejenerasyonu (YBMD), dünya çapında milyonlarca insanı etkileyen bir retina hastalığıdır. Gözün retina pigment epiteli (RPE) ve fotoreseptörlerinin nörodejenererasyonu sonucu görme kaybı ile karakterize multifaktöriyel bir hastalıktır. 65 yaş üstü kişilerde geri dönüşü olmayan görme bozukluğunun önde gelen sebepleri arasında yer alan, YBMD’nin prevalansı hızla artmasına karşın, oluşan görme kaybının etkin bir tedavisi yoktur. Güncel çalışmalar ile, YBMD’nin farmakoterapisi hala istenen düzeyde olmasa da antioksidan tedaviler ile hastalığın seyri yavaşlatılmaktadır. Bir çok meyve ve sebzede bulunan polifenollerin antikanser, anti-inflamatuar, antiapoptotik özelliklerinin yanı sıra antioksidan özelliğe de sahip olması YBMD’nin önlenmesi için bir umut olmuştur. Son zamanlarda, polifenollerin YBMD’nin önlenmesinde rolü olduğuna işaret eden çalışmalar yayınlanmıştır. Güçlü antioksidan özelliğe sahip polifenollerin oksidatif hasara karşı doğrudan reaktif oksijen türlerini (ROS) süpürme dışında, kronik inflamasyon ve apoptotik yolaklar üzerinden nöroprotektif etkisi olduğunu gösteren çalışmalar da bu görüşü desteklemektedir. Bu derleme yazısında polifenollerin YBMD gibi retina hastalıklarının önlenmesinde ki rolü ve etkin tedavi yaklaşımları irdelenmiştir.
