Serap Demir

Extended‐spectrum β‐lactamase‐producing Klebsiella pneumoniae in paediatric wards: A nested case‐control study

Aim:  A high rate (48.6%) of extended spectrum beta‐lactamase production among Klebsiella pneumoniae (ESBL‐KP) clinical isolates in the paediatric wards of our hospital prompted the introduction of enhanced infection control measures, and after the implementation of these measures, we instituted a prospective surveillance programme, with a nested case‐control study to determine the risk factors for rectal colonisation by ESBL‐KP.

Immobilization of α-amylase onto poly(glycidyl methacrylate) grafted electrospun fibers by ATRP

In this study, novel α-amylase immobilized poly(vinyl alcohol) (PVA) nanofibers were prepared. The PVA nanofiber surfaces were functionalized with 2-bromoisobutyryl bromide (BiBBr) and followed by surface initiated atom transfer radical polymerization (SI-ATRP) of glycidyl methacrylate (GMA). The morphology of the poly(glycidyl methacrylate) (PGMA) grafted PVA nanofibers was characterized by scanning electron microscopy (SEM). Also PGMA brushes were confirmed by X-ray photo electron microscopy (XPS). α-Amylase was immobilized in a one step process onto the PGMA grafted PVA nanofiber. The characteristic properties of the immobilized and free enzymes were examined. The thermal stability of the enzyme was improved and showed maximum activity at 37 °C by immobilization. pH values of the maximum activity of the free and immobilized enzymes were also found at 6.0 and 6.5, respectively. Free enzyme lost its activity completely within 15 days. The immobilized enzyme lost only 23.8% of its activity within 30 days.

Synthesis of selected 3- and 4-arylcoumarin derivatives and evaluation as potent antioxidants

A series of hydroxyl-, methoxy-, and acetoxy-substituted 3- and 4-arylcoumarins were synthesized. All title compounds were screened for their antioxidant capacity, ability to scavenge the 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical, and ability to chelate iron ions. Furthermore, all derivatives were assessed using molecular properties prediction and drug likeness using Molinspiration. It was found that all studied derivatives were potential candidates for further research, as they complied with Lipinski’s rule of five for drug likeness. 3- or 4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 4h, 5b, h, and 6a, had remarkable half-maximal effective concentration (EC50) for radical scavenging, with better performance than known antioxidants in DPPH and metal-chelating assays. In addition, the cupric-reducing antioxidant capacity and ferric-reducing antioxidant power of the synthesized compounds were investigated for antioxidant activity. Among them, 5g, h and 6a, b showed significantly better Trolox equivalent antioxidant capacity (TEAC) than standard compounds. The results demonstrate that the compounds with dihydroxyl groups at 6- and 7-positions of the benzopyrone ring of the arylcoumarin structure are the most active of the series as antioxidants. On the basis of these findings, these new coumarin derivatives are potential therapeutic candidates for pathogenesis of many diseases characterized by free-radical overproduction.

QSAR models for antioxidant activity of new coumarin derivatives

This study presents 37 new antioxidant coumarin derivatives and strategies for structural modification to improve their antioxidant activities, the main ferric-reducing antioxidant power (FRAP) assay used to evaluate their antioxidant properties and the generation of validated quantitative structure–activity (antioxidant activity) relationship (QSAR) models. In an attempt to generate QSAR models, structures of all coumarin derivatives in the data set were fully optimized by semi-empirical PM6 method using SPARTAN 10 software. Descriptors were calculated by DRAGON 6.0 software. Multiple linear regression (MLR) models were developed with different training/test set combinations using QSARINS 2.2.1 software. Robustness, reliability and predictive power of the models were tested by internal and external validations. Applicability domain of the best two-descriptor model (nTR = 30; r2 = 0.924; RMSETR = 0.213; nTEST = 7; r2ext = 0.887; RMSEext = 0.255; CCCext = 0.939) was determined. Descriptors appeared in the model revealed that complexity, H-bond donor and lipophilic character are important parameters in describing the antioxidant activity. Apart from the compounds in the data set, we also designed 31 new antioxidant coumarin derivatives and predicted their antioxidant activity using the best two-descriptor model. Most of these compounds are promising antioxidants

Covalent immobilization of acetylcholinesterase on a novel polyacrylic acid-based nanofiber membrane

In this study, polyacrylic acid‐based nanofiber (NF) membrane was prepared via electrospinning method. Acetylcholinesterase (AChE) from Electrophorus electricus was covalently immobilized onto polyacrylic acid‐based NF membrane by demonstrating efficient enzyme immobilization, and immobilization capacity of polymer membranes was found to be 0.4 mg/g. The novel NF membrane was synthesized via thermally activated surface reconstruction, and activation with carbonyldiimidazole upon electrospinning. The morphology of the polyacrylic acid‐based membrane was investigated by scanning electron microscopy, Fourier Transform Infrared Spectroscopy, and thermogravimetric analysis. The effect of temperature and pH on enzyme activity was investigated and maxima activities for free and immobilized enzyme were observed at 30 and 35°C, and pH 7.4 and 8.0, respectively. The effect of 1 mM Mn2+, Ni2+, Cu2+, Zn2+, Mg2+, Ca2+ ions on the stability of the immobilized AChE was also investigated. According to the Michaelis–Menten plot, AChE possessed a lower affinity to acetylthiocholine iodide after immobilization, and the Michaelis–Menten constant of immobilized and free AChE were found to be 0.5008 and 0.4733 mM, respectively. The immobilized AChE demonstrated satisfactory reusability, and even after 10 consecutive activity assay runs, AChE maintained ca. 87% of its initial activity. Free enzyme lost its activity completely within 60 days, while the immobilized enzyme retained approximately 70% of the initial activity under the same storage time. The favorable reusability of immobilized AChE enables the support to be employable to develop the AChE‐based biosensors.

Preparation, characterization, and in vitro evaluation of isoniazid and rifampicin‐loaded archaeosomes

The ability of Archaea to adapt their membrane lipid compositions to extreme environments has brought in archaeosomes into consideration for the development of drug delivery systems overcoming the physical, biological blockades that the body exhibits against drug therapies. In this study, we prepared unilamellar archaeosomes, from the polar lipid fraction extracted from Haloarcula 2TK2 strain, and explored its potential as a drug delivery vehicle. Rifampicin and isoniazid which are conventional drugs in tuberculosis medication were loaded separately and together in the same archaeosome formulation for the benefits of the combined therapy. Particle size and zeta potential of archaeosomes were measured by photon correlation spectroscopy, and the morphology was assessed by with an atomic force microscope. Encapsulation efficiency and loading capacities of the drugs were determined, and in vitro drug releases were monitored spectrophotometrically. Our study demonstrates that rifampicin and isoniazid could be successfully loaded separately and together in archaeosomes with reasonable drug‐loading and desired vesicle‐specific characters. Both of the drugs had greater affinity for archaeosomes than a conventional liposome formulation. The results imply that archaeosomes prepared from extremely halophilic archaeon were compatible with the liposomes for the development of stable and sustained release of antituberculosis drugs.

Amine functional magnetic nanoparticles via waterborne thiol–ene suspension photopolymerization for antibody immobilization

The modification of magnetic nanoparticles (MNPs) via different routes for biomolecule binding is an attractive area of research. Waterborne thiol-ene suspension photopolymerization (TESP) can be a useful method for preparing functional MNPs. In this study, for the very first time waterborne TESP was performed in the presence of MNPs. Neat MNPs were coated and in situ functionalized with amine groups by using thiol-ene chemistry. Engrailed-2 (EN2) protein, a potential biomarker for various cancers such as prostate cancer, bladder cancer, breast cancer and ovarian cancer, is known to be a strong binder to a specific DNA sequence (50-TAATTA-30) to regulate transcription. Anti-EN2 antibodies were immobilized onto these MNPs by physical adsorption and covalent bonding methods, respectively. The amount of the physically immobilized antibodies (0.54 mg/g) were found to be lower than the loading of the covalently bonded antibodies (1.775 mg/g). The biomarker level in the artificial solutions prepared was determined by enzyme-linked immunosorbent assay. Coated MNPs were characterized by FTIR, TGA, SEM and STEM. After TESP, the average diameter of the neat magnetite nanoparticles increased from ∼15 nm to ∼32 nm.

Proteomic changes in the cortex membrane fraction of genetic absence epilepsy rats from Strasbourg

Epilepsy is a serious neurodegenerative disorder with a high incidence and a variety of presentations and causes. Studies on brain from various animal models including chronic models: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are very useful for understanding the fundamental mechanisms associated with human epilepsy. Individual regions of the brain have different protein composition in different conditions. Therefore, proteomic analyses of the brain compartments are preferred for the development of new therapeutic targets in different pathophysiological conditions like neurodegenerative disorders. In this study, we describe a proteomic profiling of membrane fraction of cortex tissue from epileptic GAERS and non-epileptic Wistar rat brain by two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption/ionization mass spectroscopy. Comparing the optical density of spots between groups, we found that one protein expression was significantly down-regulated (guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1) and one protein expression was significantly up-regulated (14-3-3 protein epsilon isoform) in GAERS group. Our results indicate that these proteins might have played a significant role in epilepsy and may be considered as valuable therapeutic targets in the absence of epilepsy.