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Öğe Achillea goniocephala Extract Loaded into Nanochitosan: In Vitro Cytotoxic and Antioxidant Activity(Marmara Univ, Inst Health Sciences, 2021) Taskin, Duygu; Dogan, Murat; Ermanoglu, Mizgin; Arabaci, TuranIntroduction: The present study aimed to prepare Achillea goniocephala chloroform extract and evaluate antioxidant and cytotoxic effects. Then, the nanoparticles (NPs) were synthesized on the most efficient extracts and the biological activities of the free forms of the extracts were compared with the NPs forms. Methods: Antioxidant capacities of 14 extracts (A-N) prepared using column chromatography were determined by FRAP, DPPH and CUPRAC methods. Again, the cytotoxic activities of all fractions were evaluated on MCF-7 and HT-29 cell lines using the XTT cell viability assay. Chitosantripolyphosphate (TPP) NPs of the extracts with the most active biological properties were formed using the ionic gelation method. Results: The particle size of the NPs synthesized from the two most efficient extracts was found to be between 274.12 and 296.25 nm. The extract-encapsulation and loading-efficiency of the most active NPs were found 77.6 +/- 0.04% and 7.76 +/- 0.01% for the F extract and 10.2 +/- 0.02 and 1.39 +/- 0.07% for the H extract, respectively. Conclusions: While antioxidant activity results of chitosan NPs were close to unencapsulated extracts, cytotoxic activity results were found to be better than unencapsulated extracts. Based on these results, it is thought that it would be more effective to use the encapsulated forms of A. goniocephala instead of the raw extract of the plant in the treatment.Öğe Additional Therapeutic Effect of Balneotherapy in Low Back Pain(LIPPINCOTT WILLIAMS & WILKINS, 2011) Dogan, Murat; Sahin, Ozlem; Elden, Hasan; Hayta, Emrullah; Kaptanoglu, EceObjectives: Balneotherapy has been widely used for treatment of chronic low back pain recently. However there are only a few clinical controlled trials on balneotherapy. The aim of the present study was to evaluate the effects of balneotherapy in patients with chronic low back pain. Methods: Sixty patients with lumbar spondylosis were included in the study. In Group 1, patients received both balneotherapy and physiotherapy and in Group 2, patients received only physiotherapy for three weeks. The intensity of the pain was evaluated by Visual Analog Scale (VAS) and functional disability was scored according to Revised Oswestry Index (ROI). Spinal mobility was assessed by the Schober and lateral flexion tests. Variables were evaluated before and after the three weeks of treatment. Results: The groups were comparable regarding age (P = 0.970) and sex (P = 0.357). There was no statistically significant difference between the two groups for baseline VAS (P = 0.838), Schober test (P = 0.226), and right (P = 0.642) and left (P = 0.674) lateral flexion measurements, and ROI scores (P = 0.798). At the end of the therapy, all clinical parameters significantly improved in patients in both of the groups (P < 0.05). VAS, Schober test, and ROI scores after the therapy were clearly superior in Group 1 in comparison to Group 2 (P < 0.05). Conclusion: The results of the present study reiterate that besides conventional physiotherapy, balneotherapy may be effective in the treatment of patients with chronic low back pain.Öğe Analysis of the mechanisms underlying the anticancer and biological activity of retinoic acid and chitosan nanoparticles containing retinoic acid(Humana Press Inc, 2024) Dogan, MuratRetinoic acid (RA) has been shown in earlier investigations to have anticancer properties in various cancer cells. RA's effect on breast cancer treatment remains uncertain, though. This study investigated whether RA and chitosan nanoparticles (NPs) loaded with RA could be harmful to the MCF-7 cell line. In this study, NPs with RA were used in characterization tests. Using ELISA kits, the amounts of 8-okso-2 '-deoksiguanozin (8-oxo-dG), BCL-2, Bcl-2-Associated X-protein (Bax), cleaved Poly (ADP-ribose) polymerases (PARP), total oxidant and antioxidant, and cleaved caspase-3 capacities were determined. The analysis of chitosan NPs showed that their drug-release profile, encapsulation efficiency (EE), and particle size were suitable for cell culture experiment. The EE value of NPs including RA was calculated as 83.32 +/- 0.04%. The IC50 value for RA was 2.89 +/- 0.03 mu g/mL, while the IC50 value for RA-loaded NPs was significantly lower at 2.28 +/- 0.02 mu g/mL. In ELISA testing, RA and chitosan NPs containing RA at a concentration of 2 mu g/mL dramatically increased the concentrations of total oxidant, cleaved caspase-3. Cleaved caspase-3 levels were quantified as 614.90 +/- 3.40 pg/mg protein in the control group, 826.37 +/- 5.82 pg/mg protein in RA-treated cells, and 863.52 +/- 4.32 pg/mg protein in RA-NP-treated cells. Interestingly, no substantial variations were observed in the levels of the anti-apoptotic protein BCL-2. Overall, studies revealed that RA and RA-NPs promoted apoptosis in MCF-7 cells by upregulating the expression of pro-apoptotic proteins Bax, cleaved caspase-3, and cleaved PARP.Öğe Assessment of mechanism involved in the apoptotic and anti-cancer activity of Quercetin and Quercetin-loaded chitosan nanoparticles(Humana Press Inc, 2022) Dogan, MuratIn prior studies, Quercetin was revealed to exhibit anti-cancer features in a variety of cancer cell lines. However, the impact of Quercetin on neuroblastoma is unknown. This study looked into the potential cytotoxic effects of Quercetin and Quercetin-loaded chitosan nanoparticles (NPs) on the SH-SY5Y cell line. In this study, NPs containing Quercetin was prepared and characterization studies were performed. The vitality of the cells was measured using the XTT test after 24 h of treatment with various concentrations of Quercetin (0.5, 1, 2, 4, and 8 mu g/mL). ELISA kits were used to detect the amounts of cleaved PARP, BCL-2, 8-Hydroxy-deoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant status, and total antioxidant status in the cells. The results of the chitosan NPs characterization investigation revealed that the particle size, encapsulation effectiveness, and drug release profile of NPs were all appropriate for cell culture studies. Quercetin and Quercetin-loaded chitosan NPs significantly reduced cell viability in SH-SY5Y cells at different concentrations (**p < 0.05). 2 mu g/mL Quercetin and Quercetin-loaded chitosan NPs significantly enhanced the levels of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, and total oxidant in ELISA testing. However, treatment with 2 mu g/mL of Quercetin and Quercetin-loaded chitosan NPs did not affect the amount of BCL-2 protein. Overall, Quercetin and Quercetin-loaded chitosan NPs caused significant cytotoxicity in SH-SY5Y cells via producing oxidative stress, DNA damage, and eventually apoptosis.Öğe Assessment of sphenoid sinus related anatomic variations with computed tomography(AFRICAN FIELD EPIDEMIOLOGY NETWORK-AFENET, 2017) Turkdogan, Figen Tunali; Turkdogan, Kenan Ahmet; Dogan, Murat; Atalar, Mehmet HaydarIntroduction: Frequent and broad application of endoscopic sinus surgery (ESS) in parallel with experience makes it imperative to know the anatomy and the existing pathology very well before surgery. This study examines the association between anomalies in the sphenoid sinus area in paranasal sinuses computed tomography (PNS-CT) and pathological findings and determines variations of sphenoid sinus. Methods: A total of 200 cases (100 women, 100 men) who had PNS-CT in the emergency and radiology polyclinics within the period of one year were included in this study. Bone tissue anomalies and soft tissue pathologies were assessed in the CT. Results: Pterygoid process was found in 36.75% of our cases, anterior clinoid pneumatization was found in 21.25%; vidian canal in 34.25%, foramen rotundum in 17.5% and ICA in 12.75% had protrusion into the sphenoid sinus; 8.25% were found to have onodi cell, 11.25% were found to have multiple septation, 16.75% were found to have mucosal thickening and 2.5% were found to have retention cyst. Conclusion: The importance of PNS-CT in terms of determining anatomic variations before ESC and predicting possible complications during surgery has been emphasized once more. In our study, as sphenoid sinus pneumatization increased, the projection of neighbouring vein and nerve structures into the sinus was found to increase as well.Öğe Bioassay-guided isolation and antiproliferative efficacy of extract loaded in chitosan nanoparticles and LC-QTOF-MS/MS analysis of Achillea magnifica(Elsevier, 2020) Taskin, Turgut; Dogan, Murat; Arabaci, TuranThis study investigated the antioxidant, anti-urease, anticholinesterase, and antiproliferative activities of different extracts of A. magnifica. The active compounds were isolated from chloroform extract, which has the strongest antiproliferative and antioxidant activities. The structures of the isolated compounds (elenolic acid, luteolin, eupatilin) were examined using spectroscopic techniques (NMR, UV, HR-MS). The antioxidant and antiproliferative effects of isolated compounds showed lower biological activity than those of the chloroform extract. Therefore, chitosan nanoparticles were prepared with this extract and characterized. The cytotoxic activities of the chitosan nanoparticles were examined, and they were found to have a strong antiproliferative activity similar to that of the chloroform extract. The ethanol extract had strong anti-urease and anticholinesterase activity compared with other extracts. Therefore, phenolic compounds that might be responsible for the biological activity were analysed by LC-QTOF-MS/MS. The ferulic acid derivative, apigenin 6 C pentoside 8 C hexoside, apigenin 6,8-di C-hexoside, vitexin, and diosmetin 8-C-glucoside (orientin 4'-methyl ether) compounds from this plant were analysed for the first time. The results showed that the chloroform-loaded chitosan nanoparticles had a strong antiproliferative activity in breast cancer cell lines (MCF-7, MDA-MB-231) and no toxic effect on normal cell lines (L-929), which suggested that this extract might be a potential candidate as a herbal medicine that can be investigated and evaluated in future cancer studies. Additionally, the potential use of ethanol extract as an anti-urease and anticholinesterase agent was revealed. (C) 2020 SAAB. Published by Elsevier B.V. All rights reserved.Öğe Design and in vitro evaluation of curcumin-loaded PLGA nanoparticle-embedded sodium alginate/gelatin 3D printed scaffolds for Alzheimer's disease(Elsevier, 2024) Yekeler, Humeyra Betul; Guler, Ece; Beato, Patricia Santos; Priya, Sushma; Abobakr, Fatima Khaled Mohammed; Dogan, Murat; Uner, BurcuBackground: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). Methods: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. Results: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/beta-catenin pathway. The gene expression level of beta-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3 beta signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. Conclusion: CNPSGS might be an effective therapeutic alternative for AD treatment.Öğe Distribution of Gene Mutations Associated with Familial Normosmic Idiopathic Hypogonadotropic Hypogonadism(TURKISH PEDIATRIC ENDOCRINOLOGY & DIABETES SOCIETY, 2012) Gurbuz, Fatih; Kotan, L. Damla; Mengen, Eda; Siklar, Zeynep; Berberoglu, Merih; Dokmetas, Sebila; Kilicli, Mehmet Fatih; Guven, Ayla; Kirel, Birgul; Saka, Nurcin; Poyrazoglu, Sukran; Cesur, Yasar; Dogan, Murat; Ozen, Samim; Ozbek, Mehmet Nuri; Demirbilek, Huseyin; Kekil, M. Burcu; Temiz, Fatih; Mungan, Neslihan Onenli; Yuksel, Bilgin; Topaloglu, Ali KemalObjective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.Öğe In Vitro Neuroprotective Effect Evaluation of Donepezil-Loaded PLGA Nanoparticles-Embedded PVA/PEG Nanofibers on SH-SY5Y Cells and AP-APP Plasmid Related Alzheimer Cell Line Model(Wiley-V C H Verlag Gmbh, 2025) Guler, Ece; Yekeler, Humeyra Betul; Uner, Burcu; Dogan, Murat; Asghar, Asima; Ikram, Fakhera; Yazir, YusufhanRecently developed nanoparticles and nanofibers present new brain-specific treatment strategies, especially for Alzheimer's disease treatment. In this study, donepezil (DO)-loaded PLGA nanoparticles (DNP) are embedded in PVA/PEG nanofibers (DNPF) produced by pressurized gyration for sublingual administration. SEM images showed produced drug-loaded and pure nanofibers, which have sizes between 978 and 1123 nm, demonstrated beadless morphology and homogeneous distribution. FT-IR, XRD, and DSC results proved the produced nanoparticles and fibers to consist of the DO and other polymers. The in vitro drug release test presented that the release profile of DO is completed at the end of the 18th day. It is released by the first order kinetic model. DNPF has an ultra-fast release profile via its disintegration within 2 sec, which proved itself to be suitable for the administration sublingually. All samples presented above approximate to 90% cell viability via their non-toxic natures on SH-SY5Y human neuroblastoma cells by using Alamar blue assay. The anti-Alzheimer effects of DO, DNP, and DNPF are evaluated on the A beta(1-42)-induced SH-SY5Y cells at 1, 5, and 10 mu M as treatment groups. The 1 mu M dosage exhibited the most significant neuroprotective effects, which showed enhanced cellular uptake and superior modulation of Alzheimer's-related proteins, including tau and A beta.Öğe Phytochemical screening and evaluation of antioxidant, enzyme inhibition, anti-proliferative and calcium oxalate anti-crystallization activities of Micromeria fruticosa spp. brachycalyx and Rhus coriaria(Elsevier, 2020) Taskin, Turgut; Dogan, Murat; Yilmaz, Beyza Nur; Senkardes, IsmailMicromeria fruticosa spp. brachycalyx species (Lamiaceae) is used as a spice and flavoring agent. Rhus coriaria (Sumac) is widely used both spice and medicinally. In this study, antioxidant, anti-urease, anticholinesterase, anti-proliferative and calcium oxalate anti-crystallization activities of different extracts from M. fruticosa spp. brachycalyx aerial parts and R. coriaria leaves were investigated. Besides, the phytochemical content of these species was analyzed qualitatively and quantitatively. R. coriaria methanol extract showed stronger antioxidant (DPPH, FRAP, CUPRAC, ARTS) and anticholinesterase (46.85%) activity than M. fruticosa spp. brachycalyx extracts. M. fruticosa spp. brachycalyx methanol extract was found to have the highest anti-urease (11.39%) and anti-proliferative (MCF-7: 53.51%) potential. It was observed that the methanol extracts of both plants had a significant inhibition effect on calcium oxalate crystallization. R. coriaria methanol extract was determined to contain high amounts of total flavonoids (0.177 mgQE/mg extract) and tannins (0.365 mg TAE/mg extract) contents. The extracts from both plants have no cytotoxic effects on the healthy cell (L-929) and have strong biological activities in parallel with traditional use, suggesting that these plants may be used as natural sources in the future.Öğe Preparation of Chitosan-Polyvinyl Prolidone (PVP) Hydrogels with Fibroblast Growth Factor (FGF) and Investigation of in Vitro Characteristics(Marmara Univ, Inst Health Sciences, 2022) Dogan, MuratObjective: In this study, it was aimed to make in vitro characterization of the formulations by preparing hydrogel formulations using chitosan, a biocompatible and natural polymer, and PVP, a synthetic polymer. In addition, the effects of hydrogels containing FGF on the proliferation of keratinocyte cells were investigated. Methods: Within the scope of the study, hydrogels with different properties were prepared and their water absorption capacity, and viscosities were examined. In addition, the hardness, adhesiveness, cohesiveness, and elasticity properties of hydrogels were investigated. The 3 - (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) test was applied to evaluate the toxicity of hydrogels on keratinocyte cell lines. Results: It was observed that hydrogel formulations have high water absorption capacity and suitable viscosity values. In addition, the mechanical characterization results showed that the hydrogels have suitable mechanical properties. According to the results of in vitro cell culture studies, it has been observed that hydrogels stimulate the proliferation of keratinocyte cells. Conclusion: Results showed that the mechanical properties of hydrogels containing FGF are suitable for application and according to the results of in vitro cell culture studies, hydrogels can be used in wound healing studies because they increase keratinocyte cell proliferation.Öğe Preparation of resveratrol containing poly (lactic-co-glycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells(Marmara Univ, 2022) Dogan, Murat; Gurgah, Fatma ZisanCancer is a complex disease involving several important changes in cell morphology that ultimately lead to tumor formulation. The biological endpoint of cancer is the uncontrolled growth and proliferation of cells. Resveratrol (RES) is a polyphenolic compound from the stilbene family, which has an important place in the treatment of cancer, which is used as a pharmaceutical and nutraceutical. Studies have shown that RES has anti-tumor effects in addition to its antioxidant, antimicrobial and anti-inflammatory effects. RES protects the body against free radicals and inhibits metabolic events that induce the proliferation of cancer cells. RES is a chemically unstable compound that has problems crossing the blood-brain barrier. Therefore, it is concluded that carrier systems containing RES should be developed in order to increase the water dispersibility of resveratrol and to increase its bioavailability when taken orally. In this way, the RES will be successfully targeted to the tumor site and the undesirable properties of the unstable, heat-sensitive RES will be improved. For this purpose, drug delivery systems prepared using synthetic polymers such as Polylactic-co-glycolic acid (PLGA) have been developed. PLGA is a biodegradable and biocompatible polymer used in areas related to human health. In this study, cell culture study of C6 glioma cells obtained from ATCC was performed and for this purpose, biocompatible nanoparticles of RES with PLGA were prepared. With the preparation of these nanoparticles, the effects of RES on cell viability and the differences in the anticancer effect on cells were evaluated with the XTT cytotoxicity study.Öğe Sublingual (3-Glucan/Vitamin C-loaded nanoparticle-embedded polyethylene oxide nanofibrous mats(Elsevier, 2024) Guler, Ece; Yekeler, Humeyra Betul; Tekinalp, Sevval Gulsah; Parviz, Gita; Dogan, Murat; Ekentok, Ceyda; Cam, Muhammet EminNutritional supplements available in various forms provide the consumer with essential molecules demanded for well-being retention. Despite the conveniences provided by oral administration, significant disadvantages such as hepatic first-pass effect, limited absorption, and age-related swallowing problems have been recognized which should be addressed appropriately. Nano-sized biomaterials, which have recently gained popularity in numerous medical fields, have the potential to resolve these problems. In this study, a drug delivery system was designed for sublingual administration and fabricated as (3-glucan/vitamin C-loaded chitosan/tripolyphosphate/polyvinylpyrrolidone (CS/TPP/PVP) nanoparticles (DNPs) embedded in polyethylene oxide (PEO) nanofibrous mats (DNFs). The optimum PNP size and DNP size for sublingual administration were obtained as 236 +/- 1 nm and 257 +/- 1 nm, respectively. The homogenous appearance of DNFs was demonstrated and measured as 783 +/- 290 nm using scanning electron microscopy. The synthesized biomaterials were analyzed chemically, 3D-wisely, and thermally. The in vitro drug release kinetics investigation concluded that the sustained drug release of DNP over 15 days proceeded based on the first-order model, and 99.30 % of vitamin C and 99.70 % of (3-glucan were released. Neither pure nor drug-loaded samples showed notable cytotoxicity in the 24-h 3-[4,5-dimethylthiazol2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the L929 cell line. Herein, it has been comprehended that DNF nutritional supplement can be a promising novel supplement dosage form with ease of use, high efficiency, and bioavailability than the conventional methods.Öğe Synthesis of Nanoparticles Loading Indenopyrazole Derivatives and Evaluation of Biological Features(Marmara Univ, Inst Health Sciences, 2022) Dogan, Murat; Kocyigit, Umit Muhammet; Gezegen, HayreddinObjective: In this study, it was aimed to prepare nanoparticle formulations using chitosan, a cationic natural polymer, and tripoly phosphate, and to perform mechanical characterization and in vitro cell culture studies. In addition, the cytotoxic effects of nanoparticles containing indenopyrazol derivatives against human glioma cells (C6) and human cervical cancer cells (HeLa) were investigated. Methods: Within the scope of the study, nanoparticles containing indenopyrazole derivative were prepared and characterization of particle size, zeta potential and morphological properties were performed. XTT cytotoxicity test was applied to evaluate the antiproliferative activities of nanoparticles containing these components. Results: Particle size, zeta potential and morphological properties of nanoparticles were observed to be suitable for application. In vitro cell culture studies showed that nanoparticles containing indenopyrazol derivatives showed better cytotoxic effects in both cell lines. Conclusion: The results showed that the mechanical properties of nanoparticles containing indenopyrazol derivatives are suitable and can be applied in anticancer activity studies.Öğe Vitamin B12-loaded chitosan-based nanoparticle-embedded polymeric nanofibers for sublingual and transdermal applications: Two alternative application routes for vitamin B12(Elsevier, 2024) Guler, Ece; Yekeler, Humeyra Betul; Parviz, Gita; Aydin, Saliha; Asghar, Asima; Dogan, Murat; Ikram, FakheraAlzheimer's disease (AD) is a neurodegeneration type that is biologically recognizable via beta-amyloid plaques and tau neurofibril tangles. Global estimation for the total count of individuals enduring AD will rise up to 131 million by 2050. Investigations suggested the existence of a direct proportion between the likelihood of AD occurrence and vitamin B12 (VB12) hypovitaminosis. Approved VB12 administrations, intramuscular and oral, each has serious defects broaching the demand for alternative routes. This work developed VB12-loaded chitosan/tripolyphosphate/polyvinyl alcohol (CS/TPP/PVA) nanoparticles (NPs) embedded in polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone/polycaprolactone (PVP/PCL) nanofibrous (NFs) produced by pressurized gyration (PG) for sublingual and transdermal routes, respectively. Biomaterials were investigated morphologically, chemically, and thermally. Moreover, degradation, disintegration, release behavior, and release kinetics were analyzed. The effectiveness and safety of nanomaterials were assessed and proven with the alamarBlue test on the A beta 1-42-induced SH-SY5Y model. The final evaluation suggested the feasibility, safety, and effectiveness of produced systems. Consequently, two alternative VB12 application routes were developed with high effectivity and low toxicity with the power of nanotechnology.
