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Öğe BIOCHEMICAL EFFECT EVALUATION OF MICROBIAL CHONDROITIN SULPHATE IN EXPERIMENTAL KNEE OSTEOARTHRITIS MODEL(Parlar Scientific Publications (P S P), 2022) Erenler, Ayse Sebnem; Karabulut, Aysun Bay; Sevimli, Resit; Geckil, Hikmet; Akpolat, Nusret; Unver, Tuba; Otlu, OnderOsteoarthritis (OA) is the most common chronic joint disease, primarily due to aging. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) commonly used to treat osteoarthritis. CS can delay the progression of pathology or reverse morphological changes in joint structure. Traditionally CS is produced from animal sources. However, due to different reasons such as contamination, ecological risk, and the possibility of infectious diseases, the trend towards microbial sources has increased because of its advantages such as purer, more antiallergic, and lower Molecular Weight (MW) than animal sources. Biochemical analysis of Microbial CS (MCS), which is a new and significant alternative as a source of CS in the OA healing process, has not been evaluated in the literature yet. This study was designed to analyze the biochemical effects of MCS produced by our team from a microbial source, with an MW value of 269 Daltons, on the osteoarthritis healing process compared to the commercial foiut. We aim to reach data that MCS has a higher antioxidant effect than animal -sourced CS, and in this way, it is a more suitable production for the treatment of osteoarthritis. In this study, knee osteoarthritis was surgically induced in experimental rabbits; and TGF113, CAT, MPO, TOS, and OSI parameters measured in blood samples before the operation and after the healing period were analyzed comparatively. After the surgical application, the rabbits were randomly divided into three groups: control, animal -sourced CS, and E. cull sourced. MCS. The standard rabbit diet was administered daily to 10 rabbits in Group 1 (control), and. CS and MCS were applied daily to the other groups as 17 mg/kg for 12 weeks. Blood samples were taken from rabbits at the 12th week after surgery, and TGF-113, CAT, MPO, TOS, and OSI parameters were biochemically evaluated. This study has confirmed that the antioxidant properties of MCS and data on its effectiveness in controlling oxidative stress compared to animal -sourced CS. Based on these results, it can be concluded that MCS has a significant potency of nutraceutical and therapeutic agents for OA treatment.Öğe Chemical composition and antimicrobial activity of an apolar extract from Lactuca serriola L. leaves(Pergamon-Elsevier Science Ltd, 2024) Unver, Tuba; Gurhan, IsmetLactuca serriola L. is an annual herbaceous plant species belonging to the Asteraceae family, called Prickly lettuce, Wild lettuce, and Jagged lettuce. L. serriola grows on grassy and rocky slopes in many regions in Europe, Asia, Australia, Africa, and North, Central and South America. The plant is used as a natural pharmaceutical agent in primary health care due to its analgesic, anti-inflammatory, antibacterial, and antioxidant properties, which are attributed to the compounds it contains. However, this is the first study demonstrating the antimicrobial activity of L. serriola essential oil. In this study, L. serriola essential oil was obtained by hydrodistillation of plant leaves and analyzed by Gas Chromatography -Mass Spectrometry (GS -MS); subsequently, antimicrobial properties of the essential oil were evaluated using agar dilution and broth microdilution methods. As a result of the GS -MS analysis, hexadecanoic acid, oleic acid, myristic acid, hexahydrofarnesyl acetone, beta-ionone, and n-tetradecyl butanoate were found as dominant components in the plant essential oil with the rate of 6.61%, 4.84%, 2.05, 1.55%, 1.3%, and 1.09% (v/v), respectively. The MIC value of L. serriola essential oil against Enterobacter aerogenes, Staphylococcus aureus , Pseudomonas aeruginosa , Candida albicans , and C andida tropicalis was found to be 0.94 mu LmL -1 , and MIC values were determined as 1.87 mu LmL -1 and 0.47 mu LmL -1 against Klebsiella pneumonia and Candida parapsilosis , respectively. These results have opened a new horizon regarding the usability of L. serriola essential oil as a pharmacological therapeutic antibacterial and antifungal agent.Öğe Comparative Analysis of Antioxidant, Anticholinesterase, and Antibacterial Activity of Microbial Chondroitin Sulfate and Commercial Chondroitin Sulfate(Wiley-V C H Verlag Gmbh, 2023) Unver, Tuba; Erenler, Ayse Sebnem; Bingul, Murat; Boga, MehmetChondroitin synthesis was performed using the recombinant Escherichia coli(C2987) strain created by transforming the plasmid pETM6-PACF-vgb, which carries the genes responsible for chondroitin synthesis, kfoA, kfoC, kfoF, and the Vitreoscilla hemoglobin gene (vgb). Then, Microbial chondroitin sulfate (MCS)'s antioxidant, anticholinesterase, and antibacterial activity were compared with commercial chondroitin sulfate (CCS). The antioxidant studies revealed that the MCS and CCS samples could be potential targets for scavenging radicals and cupric ion reduction. MCS demonstrated better antioxidant properties in the ABTS assay with the IC50 value of 0.66 mg than CCS. MCS showed 2.5-fold for DPPH and almost 5-fold for ABTS *+ (with a value of 3.85 mg/mL) better activity than the CCS. However, the compounds were not active for cholinesterase enzyme inhibitions. In the antibacterial assay, the Minimum inhibitory concentration (MIC) values of MCS against S. aureus, E. aerogenes, E. coli, P. aeruginosa, and K. pneumoniae (0.12, 0.18, 0.12, 0.18, and 0.18 g/mL, respectively) were found to be greater than that of CCS (0.42, 0.48, 0.36, 0.36, and 0.36 g/mL, respectively). This study demonstrates that MCS is a potent pharmacological agent due to its physicochemical properties, and its usability as a therapeutic-preventive agent will shed light on future studies.Öğe Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells(C M B Assoc, 2023) Unver, Tuba; Celik-Uzuner, Selcen; Erenler, Ayse SebnemCancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, cervical and breast cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of cells that form blood vessels, proteins, fibroblasts, and immune cells, is a therapeutic target for cancer therapy. As part of the extracellular matrix (ECM), glycosaminoglycan Chondroitin Sulfate (CS) is related to diverse aspects of tumor growth and metastasis depending on the CS sulfate pattern. This study analyzed the roles of Microbial CS and Commercial CS in tumor growth and metastasis using HeLa cervical cancer cells, MDA-MB-231 metastatic breast cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively. Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 breast cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.Öğe Development of microbial chondroitin sulfate-based proton exchange membranes for microbial fuel cells(Elsevier Sci Ltd, 2024) Erenler, Sebnem A.; Unver, Tuba; Ozaslan, Bahar F.; Koytepe, Suleyman; Sezer, SeldaTechnological developments have led to a significant increase in energy demand, and thus the interest in alternative energy has increased in the same direction. For this reason, fossil fuel reserves and climate-based renewable energy sources were used as alternatives in energy production, but the desired success was not fully achieved due to the decrease in fossil fuel and climate changes, and a new alternative energy source was sought. This situation has made Microbial Fuel Cells (MFC), which can directly convert chemical energy, an important alternative to renewable energy, from organic waste into electrical energy with the help of microorganisms. Therefore, in this study, microbially obtainable chondroitin, which is a non-toxic, biocompatible organic molecule that will not disrupt the ecological balance, sulfate-based proton exchange membrane was prepared for the microbial fuel cell. For this, Chondroitin was synthesized by the microbial method, chondroitin sulfate was obtained by sulfation, and chondroitin sulfate membranes were prepared by cross-linking with sulfosuccinic acid at varying molar concentrations (0.2, 0.4, 0.6, and 0.8). Firstly, the structural characterization, thermal properties, and morphological features of the prepared 20 mm thickness membranes were investigated, and then the effects of parameters such as pH change, voltage, quaternization, internal resistance, and coulomb efficiency on microbial fuel cell performance were studied. The best result was found to be that of chondroitin sulfate cross-linked with 0.8 M sulfosuccinic acid, which had an internal resistance of 0.310 omega, a power density of 30 mW/m2, and a coulomb efficiency of 70 %. Additionally, proton conductivity was measured to be 0.9919 mS/ cm, and thanks to the proton conduction efficiency of the designed Microbial chondroitin sulfate membranes, it has been determined that it has an effective proton exchange membrane potential. These developments show that microbial chondroitin sulfate-based membranes may be an alternative candidate for microbial fuel cells.Öğe Elucidating the antimicrobial and anticarcinogenic potential of methanolic and water extracts of edible Tragopogon coelesyriacus Boiss.(Wiley, 2024) Unver, Tuba; Uzuner, Ugur; Celik-Uzuner, Selcen; Gurhan, Ismet; Sivri, Nur Sena; Ozdemir, ZeynepTragopogon coelesyriacus is a pharmacotherapeutic herbaceous plant belonging to the Asteraceae family and consumed as a vegetable. Here, the methanolic and water extracts of T. coelesyriacus were obtained from its aboveground parts (stem, leaves, and flowers), and the phytochemical potentials were investigated by LC-HRMS (liquid chromatography-high resolution mass spectrometry) analysis for the first time. The antibacterial, antifungal, and anticarcinogenic activities of T. coelesyriacus extracts were investigated using experimental and in silico methods. T. coelesyriacus methanol extract revealed remarkable inhibitory activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia (MICs = 0.83, 1.67, and 1.67 mg/mL, respectively) compared to Escherichia coli and Enterobacter aerogenes (MIC = 53.3 mg/mL). Inhibitory effects of T. coelesyriacus methanolic extracts were also observed in all Candida species tested, with the highest inhibition on Candida krusei (MIC = 0.83 mg/mL), whereas no inhibitory effect was identified from the water extract. Additionally, both T. coelesyriacus methanolic (IC50 = 86 mu g/mL) and water (IC50 = 92 mu g/mL) extracts revealed significant selective anticarcinogenic effects on AR42J pancreatic cancer cells. HeLa and MDA-MB-231 cells were, however, more resilient to methanol and water extract, respectively. In silico analyses further elucidated the noteworthy antibacterial potential of keracyanin chloride on S. aureus MurB enzyme and the remarkable inhibitory potential of naringin on FYN kinase specific for pancreatic cancer (AR42J) development. In conclusion, T. coelesyriacus phytochemicals with antibacterial, antifungal, and anticancer properties were revealed for the first time, and molecular docking studies on potential targets confirmed good agreement with experimental findings. Therefore, the current studies on T. coelesyriacus provide the basis for investigating new pharmaceutical potentials of other Tragopogon members.Öğe Isorhamnetin as a promising natural bioactive flavonoid: in vitro assessment of its antifungal property(2024) Unver, TubaIsorhamnetin (3’-methylquercetin) is an important flavonoid produced as a secondary metabolite from medicinal and aromatic plants due to its pharmacological and therapeutic properties. Thus far, the anticancer, antiallergic, antiinflammatory, antioxidant, antiviral, and antimicrobial properties of isorhamnetin have been evaluated in indirect studies conducted with isorhamnetin found in plant extracts or essential oils or direct studies performed with pure isorhamnetin. However, this is the first study in the literature on the antifungal activity of 97% pure isorhamnetin against C. tropicalis, C. albicans, C. krusei, and C. parapsilosis using two assays including agar dilution and broth microdilution methods. This study showed that isorhamnetin has a significant inhibitory effect against all Candida species used. The minimum inhibitory concentration (MIC) value of isorhamnetin against C. tropicalis, C. albicans, C. krusei, and C. parapsilosis was 1.875 mg/mL, the same for all yeast strains. These results have opened a new horizon regarding the usability of isorhamnetin as a pharmacological therapeutic antifungal agent.Öğe Screening of phenolic components and antimicrobial properties of Iris persica L. subsp. persica extracts by in vitro and in silico methods(Wiley, 2024) Unver, Tuba; Uslu, Harun; Gurhan, Ismet; Goktas, BunyaminThe tendency toward natural herbal products has increased due to the antibiotic resistance developed by microorganisms and the severe side effects of antibiotics commonly used in infectious diseases worldwide. Although antimicrobial studies have been conducted with several species of the Iris genus, this study is the first in the literature to be performed with Iris persica L. subsp. persica aqueous and methanol extracts. In this study, the phenolic content of I. persica was determined by LC-MS/MS analysis, the in vitro antimicrobial activity of I. persica aqueous and methanol extracts was examined, and this study was supported by in silico analysis. Consequently, methanol and aqueous extracts were observed to have inhibitory effects against all tested microorganisms except Candida krusei. Although the MIC values of aqueous extract and methanol extract against Staphylococcus aureus and Klebsiella pneumoniae are the same (22.5 and 11.25 mg/mL, respectively), the inhibitory effect of aqueous extract is generally more potent (MIC value is 11.25 mg/mL for Candida parapsilosis and other bacterial species, and 90 mg/mL for Candida albicans and Candida tropicalis) than that of methanol extract. In silico results showed that hydroxybenzaldeyde, vanillin, resveratrol, isoquercitrin, kaempferol-3-glucoside, fisetin, and luteolin were more prone to antifungal activity. Hence, shikimic, gallic, protocatechuic, vanillic, caffeic, o-coumaric, trans-ferulic, sinapic acids, and hesperidin were more prone to antibacterial activity. In vitro and in silico results show that the antibacterial activity of our extracts may be higher than the antifungal activity. This preliminary study indicates the anti-infective potential of I. persica extracts and their usability in medicine and pharmacology.Öğe Shikimic acid, cyclohexene as a hydroaromatic intermediate, harbors potent in vitro antimicrobial activity(2024) Unver, TubaAim: Shikimic acid is a hydroaromatic intermediate in the amino acid biosynthesis pathway in bacteria, fungi, and plants. Shikimic acid is an essential agent in applied sciences, especially in pharmacy and medicine. It can be used as a reactant in organic synthesis to obtain various medicinal drugs. This study aims to evaluate the antibacterial and antifungal properties of shikimic acid comparatively and to determine the minimum inhibitory concentrations (MIC) of shikimic acid against the tested Candida and bacterial species. Materials and Methods: The inhibitory effect of pure (98.85%) shikimic acid was tested on five bacteria (two Gram-positive and three Gram-negative) and five Candida species. The broth two-fold microdilution method was used to determine the MIC values against the tested microorganisms, and the viability of microorganisms treated with shikimic acid was determined using resazurin sodium salt. Results: The MIC values of shikimic acid against Candida glabrata, Candida albicans, Candida krusei, Candida tropicalis and Candida parapsilosis were determined to be between 250 and 31.25 mg/mL. However, the MIC values against bacterial species, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter aerogenes, ranged between 15.625 and 3.906 mg/mL. Therefore, the antibacterial effect of shikimic acid is almost twenty times stronger than its antifungal effect. Conclusion: This preliminary study shows that shikimic acid is also usable as an antibacterial and antifungal as a potential therapeutic agent in addition to its p
