Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Conference Object Citation - WoS: 1The Effects of Novel Telomerase Activators on Human Adipose-Derived Mesenchymal Stem Cell (had-Msc) Proliferation and Osteogenic Differentiation(Georg Thieme Verlag Kg, 2022) Kuru, G.; Küçüksolak, Melis; Pulat, G.; Karaman, O.; Bedir, Erdal[No Abstract Available]Conference Object Citation - WoS: 1Secondary Metabolites From Endophytic Fungus Penicilium Roseopurpureum and Investigation of Their Cytotoxic Activities(Georg Thieme Verlag, 2022) Dizmen, Berivan; Üner, Göklem; Küçüksolak, Melis; Ballar Kırmızıbayrak, Petek; Bedir, Erdal[No Abstract Available]Conference Object Citation - WoS: 1Phytochemical Studies on Mastic Gum of Pistacia Lentiscus Var. Chia Collected From Karaburun Peninsula and Neuroprotective Activities of the Isolates(Georg Thieme Verlag, 2022) Demir, Mehmet; Üner, Göklem; Mu, Kurt; Aygün, M.; Ballar Kırmızıbayrak, Petek; Bedir, Erdal[No Abstract Available]Conference Object Short Lecture "method Development for Pilot Production of Astragaloside Vii"(Georg Thieme Verlag, 2022) Kurt, Mustafa Ünver; Tağ, Özgür; Bedir, ErdalBased on the promising immunostimulant effect comparable to commercialized adjuvants Alum and Quillaja saponins (including QS-21) [1], [2], [3], our team has been prompted to carry out advance studies for developing Astragaloside VII (AST VII) ([Fig. 1]) as a new vaccine adjuvant or an immunotherapeutic agent. Hence, one of the most critical challenges is establishing efficient isolation and purification processes to obtain AST VII on a large scale. Thus, this study aimed to develop a production methodology for AST VII from Turkish Astragalus species.Conference Object Short Lecture Novel Neuroprotective Metabolites Produced Via Biotransformation of Cyclocephagenol by Alternaria Eureka 1e1bl1(Georg Thieme Verlag, 2022) Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalNeurodegeneration refers to the loss of structure/function of neurons leading to neurological diseases including Alzheimerʼs and Parkinsonʼs. The discovery of novel therapeutics against neurodegenerative diseases has been an area of intense research as neurodegenerative diseases are a huge burden on society and the economy [1]. Numerous studies reported that natural products have the potential to prevent and treat neurodegeneration. Among these studies, the neuroprotective activities of cycloartane-type saponins are noteworthy [2], [3]. In our preliminary studies, the neuroprotective activity of cyclocephagenol, an aglycone of cyclocephaloside I from Astragalus microcephalus [4], was screened for H2O2-induced injury in SH-SY5Y cells. Based on the promising bioactivity of cyclocephagenol, the aims of this study were: i) to perform microbial transformation studies on cyclocephagenol using Alternaria eureka followed by isolation and structural characterization of the metabolites; ii) to investigate neuroprotective activities of the metabolites; iii) to understand structure-activity relationships towards neuroprotection.Conference Object A New Iminol Derivative From Streptomyces Cacaoi in New Fermentation Conditions(Georg Thieme Verlag, 2022) Gezer, Emre; Küçüksolak, Melis; Bilgi, Eyüp; Bedir, ErdalMarine-derived organisms have varied secondary metabolism due to their adaptation to extreme conditions of marine environments. This fact has made marine-derived Actinobacteria promising sources of new/novel compounds. In addition, the expression of secondary metabolite gene clusters is typically under the control of environmental conditions that cause many of the biosynthetic gene clusters to be silent under laboratory conditions. Thus, the determination of proper fermentation conditions becomes crucial for discovering new molecules.Conference Object Citation - WoS: 1Immunomodulatory Mechanisms of Astragalus Saponins(Wiley, 2021) Yakuboğulları, Nilgün; Çağır, Ali; Bedir, Erdal; Sağ, DuyguArticle Citation - WoS: 5Citation - Scopus: 6Undescribed Polyether Ionophores From Streptomyces Cacaoi and Their Antibacterial and Antiproliferative Activities(Elsevier, 2022) Gezer, Emre; Üner, Göklem; Küçüksolak, Melis; Kurt, Mustafa Ünver; Doğan, Gamze; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.Article Citation - WoS: 12Citation - Scopus: 12New Cardenolides From Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria Eureka 1e1bl1: Characterization and Cytotoxic Activities(MDPI, 2021) Bedir, Erdal; Karakoyun, Çiğdem; Doğan, Gamze; Kuru, Gülten; Küçüksolak, Melis; Yusufoğlu, HasanMicrobial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; similar to 25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 mu M against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 mu M. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.Article Citation - WoS: 12Citation - Scopus: 12Isolation of Rosmarinic Acid and Methyl Rosmarinate as Lipoxygenase Inhibitors From Salvia Palaestina Benth. by Activity-Guided Fractionation(Elsevier, 2021) İçen, Mehmet Sina; Gürbüz, İlhan; Bedir, Erdal; Günbatan, Tuğba; Demirci, FatihSalvia palaestina aqueous and methanol extracts were prepared from the aerial parts, which were evaluated for the in vitro anti-inflammatory properties using the lipoxygenase (LO) enzyme inhibition assay. While the aqueous extract showed no activity at test concentrations, a significant (p < 0.001) lipoxygenase inhibition was detected for the methanol extract with 29% inhibition. Activity guided fractionation was carried out on the methanol extract via liquid-liquid partitioning using n-hexane, dichloromethane, ethyl acetate, and n-butanol. The ethyl acetate fraction showed statistically the best inhibition among the sub-fractions with 70% inhibition (p < 0.0001). The compounds responsible for the activity were purified, and their structures were established as rosmarinic acid, and methyl rosmarinate by spectroscopic methods. IC50 values of rosmarinic acid, and methyl rosmarinate were calculated as 0.21 and 0.02 ?M, respectively. In conclusion, the in vitro anti-inflammatory potential of S. palaestina was associated to rosmarinic acid, and methyl rosmarinate, for the first time to the best of our knowledge. © 2021 SAAB
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