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Öğe (18)FDG conjugated magnetic nanoparticle probes: synthesis and in vitro investigations on MCF-7 breast cancer cells(Springer, 2013) Ozkaya, Feriha; Unak, Perihan; Medine, E. Ilker; Sakarya, Serhan; Unak, Gulcan; Timur, Suna(18)FDG conjugated magnetic iron oxide nanoparticles (MNPs) were synthesized as PET-MR hybrid imaging agent. Synthesized and characterized NPs were then applied to MCF-7 human breast cancer cells. (18)FDG conjugated MNPs exhibited the cell incorporation ratio up to 30 %. As well as the characterization studies, apoptotic effects were observed depending on the cellular incorporations by the time. In conclusion, synthesized structures could have a potential as hybrid imaging agent in PET-MR imaging systems besides apoptotic effect on cancer cells.Öğe (18)FDG conjugated magnetic nanoparticle probes: synthesis and in vitro investigations on MCF-7 breast cancer cells(Springer, 2013) Ozkaya, Feriha; Unak, Perihan; Medine, E. Ilker; Sakarya, Serhan; Unak, Gulcan; Timur, Suna(18)FDG conjugated magnetic iron oxide nanoparticles (MNPs) were synthesized as PET-MR hybrid imaging agent. Synthesized and characterized NPs were then applied to MCF-7 human breast cancer cells. (18)FDG conjugated MNPs exhibited the cell incorporation ratio up to 30 %. As well as the characterization studies, apoptotic effects were observed depending on the cellular incorporations by the time. In conclusion, synthesized structures could have a potential as hybrid imaging agent in PET-MR imaging systems besides apoptotic effect on cancer cells.Öğe 4-aminothiophenol-intercalated montmorillonite: Organic-inorganic hybrid material as an immobilization support for biosensors(Elsevier Science Sa, 2020) Yilmaz, Yahya Yasin; Yalcinkaya, Esra Evrim; Demirkol, Dilek Odaci; Timur, SunaHybrid materials containing organic and inorganic structures are very important because they have the advantages of each of their components. Intercalation of the organic molecule to inorganic structures such as clay allows the preparation of multifunctional new immobilization matrices that contain both the strength properties of the clays and the properties of the organic molecule such as its functional groups (amine, carboxyl or hydroxyl etc.). in this study, 4-aminothiophenol intercalated montmorillonite (4ATP-Mt) was prepared and used as an immobilization layer for the pyranose oxidase (PyOx) enzyme on a glassy carbon (GC) electrode. Firstly, 4ATP intercalation of Mt was carried out, and the success of intercalation was proven using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffractometer (XRD), and Thermogravimetric Analysis (TGA) techniques. Then PyOx was immobilized using 4ATP-Mt, BSA and glutaraldehyde as a cross-linker on the surface of GC electrodes. To show the coating steps for the preparation of 4ATP-Mt/PyOx biosensors, cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques were applied, and surface morphology was visualized by scanning electron microscopy (SEM). After optimization of working conditions, analytical performance parameters were determined for glucose detection. the 4ATP-Mt/PyOx biosensor exhibited a wide linear concentration range between 0.01 and 0.5 mM (LOD: 1.0 mu M) for glucose. Additionally, the fabricated 4ATP-Mt/PyOx was assayed for the analysis of glucose in artificial body fluids and drinks.Öğe An acetylcholinesterase biosensor based on a conducting polymer using multiwalled carbon nanotubes for amperometric detection of organophosphorous pesticides(Elsevier Science Sa, 2014) Kesik, Melis; Kanik, Fulya Ekiz; Turan, Janset; Kolb, Marit; Timur, Suna; Bahadir, Muefit; Toppare, LeventA novel amperometric biosensor based on a conducting polymer using multi walled carbon nanotube modified electrode was developed for detection of organophosphorus pesticides. Acetylcholinesterase (AChE) was successfully immobilized by covalent linkage on the modified graphite electrode. Carbon nanotubes were functionalized by electrochemical treatment. A conducting polymer; poly(4-( 2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine) (poly( SNS-NH2)) was synthesized via electropolymerization to examine its matrix properties for biomolecule immobilization. This strategy enhanced electron transfer rate at a lower potential (+100 mV vs. Ag reference) and catalyzed electrochemical oxidation of acetylthiocholine effectively. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), contact angle measurements and electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) techniques were used to monitor changes in surface morphologies and electrochemical characterizations. The proposed biosensor design offered a fast response time (6 s), a wide linear range (0.05 mM and 8.00 mM) and a low detection limit (0.09 mM) with a high sensitivity (24.16 mu AmM-1 cm(-2)) for acetylthiocholine. The inhibition responses of paraoxon, parathion and chlorfenvinphos on the enzymatic activity of AChE were detected. The fabricated biosensor was tested for the detection of pesticides in fortified tap water samples. The results were found to be in good agreement with the ones determined by HPLC/DAD technique. (C) 2014 Elsevier B.V. All rights reserved.Öğe Alcohol Biosensing by Polyamidoamine (PAMAM)/Cysteamine/Alcohol Oxidase-Modified Gold Electrode(Wiley, 2010) Akin, Mehriban; Yuksel, Merve; Geyik, Caner; Odaci, Dilek; Bluma, Arne; Hoepfner, Tim; Beutel, Sascha; Scheper, Thomas; Timur, SunaA highly stable and sensitive amperometric alcohol biosensor was developed by immobilizing alcohol oxidase (A OX) through Polyamidoamine (PAMAM) dendrimers on a cysteamine-modified gold electrode surface. Ethanol determination is based on the consumption of dissolved oxygen content due to the enzymatic reaction. The decrease in oxygen level was monitored at -0.7 V vs. Ag/AgCl and correlated with ethanol concentration. Optimization of variables affecting the system was performed. The optimized ethanol biosensor showed a wide linearity from 0.025 to 1.0 mM with 100 s response time and detection limit of (LOD) 0.016 mM. In the characterization studies, besides linearity some parameters such as operational and storage stability, reproducibility, repeatability, and substrate specificity were studied in detail. Stability studies showed a good preservation of the bioanalytical properties of the sensor, 67% of its initial sensitivity was kept after 1 month storage at 4 degrees C. The analytical characteristics of the system were also evaluated for alcohol determination in flow injection analysis (FIA) mode. Finally, proposed biosensor was applied for ethanol analysis in various alcoholic beverage as well as offline monitoring of alcohol production through the yeast cultivation. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 26: 896-906, 2010Öğe alpha-glucosidase based bismuth film electrode for inhibitor detection(Elsevier Science Bv, 2007) Timur, Suna; Anik, UelkueA biosensing system based on (alpha-glucosidase (AG) activity was developed by using bismuth film modified glassy carbon electrode (BiFE). AG enzyme was immobilized on the BiFE by means of gelatin membrane and the activity was measured by the following of liberated 4-nitrophenol from the 4-nitrophenyl-alpha-D-glucopyranoside (PNPGP) which is the synthetic substrate of the enzyme at the working potential of -950 mV. The proposed system was used as an AG based biosensing system. Experimental data showed that the response current of 4-nitrophenol obtained at the BiFE was linear in concentration range between 0.033 and 0.33 mM of PNPGP. Before examining the analytical characteristics, pH optimization of the AG-biosensor was also performed. Furthermore, the proposed method was applied to analyze two different AG inhibitors (Amaryl and Acorbose) which are important in Noninsulin-dependent diabetes mellitus (NIMM). (C) 2007 Elsevier B.V. All rights reserved.Öğe Amine intercalated clay surfaces for microbial cell immobilization and biosensing applications(Royal Soc Chemistry, 2013) Demir, Bilal; Seleci, Muharrem; Ag, Didem; Cevik, Serdar; Yalcinkaya, Esra Evrim; Demirkol, Dilek O.; Anik, Ulku; Timur, SunaTrimethylamine (TM) intercalated montmorillonite (Mont) clay was prepared and characterized using X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential and thermal gravimetric measurements. Gluconobacter oxydans cells were immobilized on the micro-structured matrix and used in microbial sensor applications. Sensor responses were based on the respiratory activity of the cells and the consumption of oxygen was monitored at 20.7 V (vs. Ag/AgCl and platinum electrodes) by using glucose as a substrate. Stabilization of the bacteria was performed on the Mont using glutaraldehyde. Optimization of the TM-Mont/G. oxydans sensor and examination of the electrochemical mechanism were carried out in a batch system. Measurements concerning analytical characteristics, operational stability, repeatability and substrate specificity depending on the carbon source in the culture were investigated in a flow injection analysis (FIA) system. Linear ranges were found between 0.15 and 5.0 mM for the batch mode and 0.1 and 5.0 mM for the FIA system, respectively. Finally, real samples were analyzed and were compared with the results of a spectrophotometric method as reference.Öğe Amine intercalated clay surfaces for microbial cell immobilization and biosensing applications(Royal Soc Chemistry, 2013) Demir, Bilal; Seleci, Muharrem; Ag, Didem; Cevik, Serdar; Yalcinkaya, Esra Evrim; Demirkol, Dilek O.; Anik, Ulku; Timur, SunaTrimethylamine (TM) intercalated montmorillonite (Mont) clay was prepared and characterized using X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential and thermal gravimetric measurements. Gluconobacter oxydans cells were immobilized on the micro-structured matrix and used in microbial sensor applications. Sensor responses were based on the respiratory activity of the cells and the consumption of oxygen was monitored at 20.7 V (vs. Ag/AgCl and platinum electrodes) by using glucose as a substrate. Stabilization of the bacteria was performed on the Mont using glutaraldehyde. Optimization of the TM-Mont/G. oxydans sensor and examination of the electrochemical mechanism were carried out in a batch system. Measurements concerning analytical characteristics, operational stability, repeatability and substrate specificity depending on the carbon source in the culture were investigated in a flow injection analysis (FIA) system. Linear ranges were found between 0.15 and 5.0 mM for the batch mode and 0.1 and 5.0 mM for the FIA system, respectively. Finally, real samples were analyzed and were compared with the results of a spectrophotometric method as reference.Öğe Amine-intercalated montmorillonite matrices for enzyme immobilization and biosensing applications(Royal Soc Chemistry, 2012) Seleci, Muharrem; Ag, Didem; Yalcinkaya, Esra Evrim; Demirkol, Dilek Odaci; Guler, Cetin; Timur, SunaClay based biosensors were developed using montmorillonite (Mont) modified with methyl (M) and dimethylamine (DM). X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential and thermal gravimetric measurements were used to characterize the modified clays. After immobilization of glucose oxidase (GOx) via clay on the glassy carbon electrode, its application as a glucose biosensor was investigated in detail. The best response characteristics were obtained by DM-Mont and optimization of enzyme amount, reproducibility of biosensor fabrication, repeatability of measurements and operational stability were all evaluated. The optimized biosensor showed a very good linearity between 0.05 mM and 1.0 mM, a 7 s response time and a limit of detection to glucose of 0.038 mM. Also, kinetic parameters and stabilities were determined. Apparent K-m and I-max values were found as 0.73 mM and 2.955 mu A, respectively. As well as batch configuration, the DM-Mont/GOx biosensor was successfully applied in the flow injection analysis mode. Finally, the performance of the DM-Mont/GOx biosensor to analyze glucose in a wine sample was compared with HPLC.Öğe Amino acid intercalated montmorillonite: electrochemical biosensing applications(Royal Soc Chemistry, 2014) Demir, Filiz; Demir, Bilal; Yalcinkaya, Esra E.; Cevik, Serdar; Demirkol, Dilek Odaci; Anik, Ulku; Timur, SunaThe present work is the first that includes the use of glycine (Gly), lysine (Lys) and glutamic acid (Glu) modified clay mineral matrices in the biosensors. For this purpose, initially, Gly, Lys and Glu were intercalated with montmorillonite (Mt), thus, various modified Mts were obtained. These modified materials were then characterized via X-ray diffraction, Fourier transform infrared spectroscopy, zeta potential and thermal gravimetric analysis (TGA/DTG) and scanning electron microscopy (SEM). In order to investigate the applicability of amino acid modified clay minerals in biosensor areas, glucose oxidase (GOx) was selected as the model enzyme and a GOx based biosensor was prepared. After immobilizing the enzyme with amino acid modified Mt onto a glassy carbon electrode, working conditions like pH and modifier type were optimized. Among the modified Mts, Gly-Mt was the optimum clay mineral type and pH 4.0 was the optimum pH value. Then analytical characteristics were examined under optimum experimental conditions. The linear range of optimum sensor design was 0.1-1.0 mM within the kinetic parameters of an immobilized enzyme K-m(app) m = 0.7 mM, I-max = 107.8 nA. Finally, the developed biosensor was applied to real samples where the results were compared with a spectrophotometric reference method.Öğe An amperometric acetylcholine biosensor based on a conducting polymer(Elsevier, 2013) Kanik, Fulya Ekiz; Kolb, Marit; Timur, Suna; Bahadir, Muefit; Toppare, LeventAn amperometric acetylcholine biosensor was prepared by the generation of the conducting polymer poly(4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine) (poly(SNS-NH2)) on graphite electrodes. For pesticide detection, the enzymes acetylcholinesterase (AChE) and choline oxidase (ChO) were co-immobilized onto the conducting polymer poly(SNS-NH2) films using covalent binding technique. Electrochemical polymerization was carried out using a three-electrode cell configuration via cyclic voltammetry. Characterization of resulting acetylcholine biosensor was done in terms of optimum pH, enzyme loading, range of linear response and shelf-life. Linear range was 0.12-10 mM and shelf-life 4 weeks. Sensitivity was calculated as 2.19 mu A mM(-1) cm(-2). The designed biosensor was tested for the determination of paraoxon-ethyl in spiked tap water samples. The results were compared with a conventional quantification method using HPLC-DAD. Linear correlation of the quantification results with both methods (R-2=0.998) was obtained. (C) 2013 Elsevier B.V. All rights reserved.Öğe Amperometric biosensors for detection of sugars based on the electrical wiring of different pyranose oxidases and pyranose dehydrogenases with osmium redox polymer on graphite electrodes(Wiley-V C H Verlag Gmbh, 2007) Tasca, Federico; Timur, Suna; Ludwig, Roland; Haltrich, Dietmar; Volc, Jindrich; Antiochia, Riccarda; Gorton, LoElectrical wiring of different types of pyranose oxidase (P20) (fungal wild type, recombinant wild type with a hexahistidine tag, mutant form E542K with a hexa-histidine tag) from Trametes multicolor, and recombinant P20 from Coriolus sp. overexpressed in Escherichia coli as well as of pyranose dehydrogenase (PDH) from Agaricus meleagris and Agaricus xanthoderma with an osmium redox polymer (poly(1-vinylimidazole)(12)-[Os(4,4'-dimethyl-2,2'-dipyridyl)(2)Cl2+/+) on graphite electrodes was carried out. After optimization studies using glucose as substrate, the biosensors, which showed the best characteristics in terms of linear range, detection limit and sensitivity were selected, viz. wild type P20 from T multicolor and PDH from A. meleagris. These two enzymes were used and investigated for their selectivity for a number of different sugars.Öğe Antibacterial Acrylamide Hydrogels Containing Silver Nanoparticles by Simultaneous Photoinduced Free Radical Polymerization and Electron Transfer Processes(Wiley-V C H Verlag Gmbh, 2009) Uygun, Mustafa; Kahveci, Muhammet U.; Odaci, Dilek; Timur, Suna; Yagci, YusufAg-nanoparticle-containing hydrogels were successfully prepared by in situ reduction of silver nitrate in the presence of citrate molecules as stabilizing agent during photoinduced copolymerization of AAm and BAAm. Swelling-de swelling behavior and thermal properties of the synthesized hydrogels were investigated. The interior morphology of the gels exhibit continuity, which is a common feature for hydrogel networks. Antimicrobial activities of the hydrogels were also investigated against pathogenic E. coli O157:H7, S. aureus, and non-pathogenic E. coli K-12, which are model microorganisms for testing bactericidal properties. The hydrogels containing well-dispersed Ag NPs showed significant antibacterial activity.Öğe Antibacterial Acrylamide Hydrogels Containing Silver Nanoparticles by Simultaneous Photoinduced Free Radical Polymerization and Electron Transfer Processes(Wiley-V C H Verlag Gmbh, 2009) Uygun, Mustafa; Kahveci, Muhammet U.; Odaci, Dilek; Timur, Suna; Yagci, YusufAg-nanoparticle-containing hydrogels were successfully prepared by in situ reduction of silver nitrate in the presence of citrate molecules as stabilizing agent during photoinduced copolymerization of AAm and BAAm. Swelling-de swelling behavior and thermal properties of the synthesized hydrogels were investigated. The interior morphology of the gels exhibit continuity, which is a common feature for hydrogel networks. Antimicrobial activities of the hydrogels were also investigated against pathogenic E. coli O157:H7, S. aureus, and non-pathogenic E. coli K-12, which are model microorganisms for testing bactericidal properties. The hydrogels containing well-dispersed Ag NPs showed significant antibacterial activity.Öğe Antibody-Conjugated Electrospun Nanofibers for Electrochemical Detection of Methamphetamine(Amer Chemical Soc, 2023) Atik, Gozde; Kilic, Nur Melis; Horzum, Nesrin; Odaci, Dilek; Timur, SunaMultifunctional electrospunnanofibers (ENs) with improved propertieshave increased attention nowadays. Their insoluble forms in waterwith decreased hydrophobicity are desired for the immobilization ofbiological molecules. Also, the addition of functional groups on thebackbone provides the conjugation of biomolecules onto the surfaceof ENs via covalent bonds to increase their stability. Here, poly-(vinylidenefluoride) (PVDF) was chosen to prepare a platform, which is insolublein water, and polyethylenimine (PEI) was used to add amine groupson the surface of ENs to bind biological molecules via covalent conjugation.So, PVDF-PEI nanofibers were prepared on a glassy carbon electrodeto immobilize an antimethamphetamine antibody (Anti-METH) as a modelbiomolecule. The obtained PVDF-PEI/Anti-METH was used for the bioelectrochemicaldetection of methamphetamine (METH), a common illicit drug. Bioelectrochemicaldetection of METH on PVDF-PEI/Anti-METH-coated electrodes was carriedout by voltammetry in the range of 2.0-50 ng/mL METH. Moreover,the effect of dansyl chloride (DNC) derivatization of METH on thesensitivity of PVDF-PEI/Anti-METH was tested. Finally, METH analysiswas carried out in synthetic body fluids. The obtained results showedthat PVDF-PEI ENs can be adopted as an immobilization matrix for thebiorecognition elements of biobased detection systems, and the derivativeof METH (METH-DNC) increased the sensitivity of PVDF-PEI/Anti-METH.Öğe Application of Biofunctionalized Magnetic Nanoparticles Based-Sensing in Abused Drugs Diagnostics(Amer Chemical Soc, 2020) Sanli, Serdar; Ghorbani-Zamani, Faezeh; Moulahoum, Hichem; Gumus, Zinar Pinar; Coskunol, Hakan; Demirkol, Dilek Odaci; Timur, SunaReal-time detection of substance use is an approach of high interest leading to the optimization of behavioral interventions and drug abuse intervention. the current methods in use suffer many limitations and need high logistical and laboratory requirements. Biosensors have shown a great potential in overcoming these limitations. in the present study, the electrochemical biosensor composed of a screen-printed electrode (SPE) was designed for the detection of synthetic cannabinoid (SC). Antibody-immobilized magnetic nanoparticles were also used to create a surface on the transducer with magnetic interactions in order to detect JWH-073 as a SC model. the use of immobilized magnetic nanoparticles to create working surfaces makes the electrode a reusable SPE which can be reutilized after the cleansing. To examine and observe any possible changes on the surface due to its interaction with the analyte, different electrochemical techniques such as differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectrometry were applied. Based on the obtained results, the linearity of the biosensor was found between 5 and 400 ng/mL, and the detection limit was calculated as 22 ng/mL (n = 6) using the 3 Sb/m formula. the biosensor functionality was studied in the presence of some related interferents that showed lower responses than JWH-073, thus demonstrating the good selectivity of the prepared biosensor. Finally, the sensory platform was used to test synthetic urine sample, and the results were compared with obtained results from liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), which showed that the proposed method could be utilized to identify abuse drugs.Öğe Application of Centri-voltammetry to Cytosensors: Cyto-centrivoltammetry(Pergamon-Elsevier Science Ltd, 2016) Tepeli, Yudum; Barlas, Firat Baris; Timur, Suna; Anik, UlkuIn this work, a centri-voltammetric cytosensor suitable for the for detection of folate receptor positive cervical cancer (HeLa) cells was developed for the first time. In order to see the effect of centrifugation, developed cytosensor's performance was compared in terms of analytical characteristics values, in the presence and absence of centri-voltammetry. As a result, in the absence of centri-voltammetry, the linear range was found between 75 cells/mL and 10(6) cells/mL with limit of detection (LOD) value as 75 cells/mL and with R.S.D value of 3.5% (for 5.0 x 10(4) HeLa cells/mL (n = 3)). Meanwhile in the presence of centri-voltammetry, the linear range was found between 8.0 cells/mL and 5 x 10(6) cells/mL and LOD value was calculated as 8 cells/mL with R.S.D value of 4.7% for the same concentration. (C) 2016 Elsevier Ltd. All rights reserved.Öğe An aptamer folding-based sensory platform decorated with nanoparticles for simple cocaine testing(Wiley, 2017) Guler, Emine; Bozokalfa, Guliz; Demir, Bilal; Gumus, Zinar Pinar; Guler, Bahar; Aldemir, Ebru; Timur, Suna; Coskunol, HakanThe consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD). For the fabrication of AFSD, QDs were initially immobilized onto the poly-L-lysine coated -well surfaces. Then, the AuNP-aptamer conjugates were bound to the QDs. The addition of cocaine or BE caused a change in the aptamer structure which induced the close interaction of AuNPs with the QDs. Hence, quenching of the fluorescence of QDs was observed depending on the analyte amount. The linearity of cocaine and BE was 1.0-10 nM and 1.0-25M, respectively. Moreover, the limits of detection for cocaine and BE were calculated as 0.138 nM and 1.66M. The selectivity was tested by using different interfering substances (methamphetamine, bovine serum albumin, codeine, and 3-acetamidophenol). To investigate the use of AFSD in artificial urine matrix, cocaine/BE spiked samples were applied. Also, confirmatory analyses by using high performance liquid chromatography were performed. It is shown that AFSD has a good potential for testing the cocaine abuse and can be easily adapted for detection of various addictive drugs by changing the aptamer according to desired analytes. Copyright (c) 2016 John Wiley & Sons, Ltd.Öğe Aptasensors for Small Molecule Detection(Verlag Z Naturforsch, 2012) Walter, Johanna-Gabriela; Heilkenbrinker, Alexandra; Austerjost, Jonas; Timur, Suna; Stahl, Frank; Scheper, ThomasAptamers are single-stranded oligonucleotides composed of RNA or DNA that are able to bind their corresponding targets via molecular recognition. Thus, aptamers can be thought of as nucleic acid-based alternatives to antibodies and have attracted attention as receptors in biosensors. Aptamers seem to be ideal biological recognition elements, since they enable the design of intelligent sensors based on their specific properties. Especially the fact that most aptamers undergo conformational changes during the binding of the target and their oligonucleotide nature can be used to rationally design novel sensing strategies. This review focuses on aptasensors for the detection of small molecules. In the first part, aptamers, their generation and their properties are briefly described. In the second part, different design strategies for aptasensors are reviewed, and examples for the detection of small molecules are given.Öğe Artemisia alleviates AGE-induced liver complications via MAPK and RAGE signaling pathways modulation: a combinatorial study(Springer, 2022) Moulahoum, Hichem; Ghorbanizamani, Faezeh; Khiari, Zineb; Toumi, Mohamed; Benazzoug, Yasmina; Tok, Kerem; Timur, SunaArtemisia herba-alba (AHA) is a traditionally used plant to treat various diseases, including diabetes and metabolic dysfunctions. Plant extracts are generally explored empirically without a deeper assessment of their mechanism of action. Here, we describe a combinatorial study of biochemical, molecular, and bioinformatic (metabolite-protein pharmacology network) analyses to elucidate the mechanism of action of AHA and shed light on its multilevel effects in the treatment of diabetes-related advanced glycation end-products (AGE)-induced liver damages. The extract's polyphenols and flavonoids content were measured and then identified via LC-Q-TOF-MS/MS. Active compounds were used to generate a metabolite-target interaction network via Swiss Target Prediction and other databases. The extract was tested for its antiglycation and aggregation properties. Next, THLE-2 liver cells were challenged with AGEs, and the mechanistic markers were measured [TNF-alpha, IL-6, nitric oxide, total antioxidant capacity, lipid peroxidation (LPO), and caspase 3]. Metabolite and network screening showed the involvement of AHA in diabetes, glycation, liver diseases, aging, and apoptosis. Experimental confirmation showed that AHA inhibited protein modification and AGE formation. Additionally, AHA reduced inflammatory mediators (IL-6, TNF alpha), oxidative stress markers (NO, LPO), and apoptosis (Caspase 3). On the other hand, cellular total antioxidant capacity was restored to normal levels. The combinatorial study showed that AHA regulates AGE-induced liver damages through MAPK-AKT and AGE-RAGE signaling pathways. This report highlights the combination of experimental and network pharmacology for the exact elucidation of AHA mechanism of action as a multitarget option in the therapy of diabetes and AGEs-related diseases.
