A novel non-enzymatic glucose sensor based on nickel (II) oxide electrospun nanofibers

A new enzymeless glucose sensor has been fabricated via electrospinning technology and subsequent calcination. The morphology and structure of the as-prepared nanofibers have been characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The electrocatalytic oxidation of glucose in alkaline medium at nickel oxide modified glassy carbon electrodes has been investigated. The modified electrodes offer excellent electrocatalytic activity toward the glucose oxidation at low positive potential (0.3 V). Glucose has been determined chronoamperometrically at the surface of NiO nanofibers modified electrode in 0.5 mM NaOH. Under the optimized condition, the calibration curve is linear in the concentration range of 2 × 10−3 mM∼1 mM, and 1 mM∼9.5 mM. The detection limit (signal-to-noise 3) and response time are 3.394 × 10−6 M and 2 s, respectively. The NiO electrospun nanofibers is easy to prepare and feasible in economy. The modified electrode is steady and can be used repeatedly, so it is reasonable to expect its broad use in non-enzymatic glucose sensor.

Metabolism and transport of oxazphosphorines and the clinical implications

The oxazaphosphorines including cyclophosphamide (CPA), ifosfamide (IFO), and trofosfamide represent an important group of therapeutic agents due to their substantial antitumor and immuno-modulating activity. CPA is widely used as an anticancer drug, an immunosuppressant, and for the mobilization of hematopoetic progenitor cells from the bone marrow into peripheral blood prior to bone marrow transplantation for aplastic anemia, leukemia, and other malignancies. New oxazaphosphorines derivatives have been developed in an attempt to improve selectivity and response with reduced toxicity. These derivatives include mafosfamide (NSC 345842), glufosfamide (D19575, β-D-glucosylisophosphoramide mustard), NSC 612567 (aldophosphamide perhydrothiazine), and NSC 613060 (aldophosphamide thiazolidine). This review highlights the metabolism and transport of these oxazaphosphorines (mainly CPA and IFO, as these two oxazaphosphorine drugs are the most widely used alkylating agents) and the clinical implications. Both CPA and IFO are prodrugs that require activation by hepatic cytochrome P450 (CYP)-catalyzed 4-hydroxylation, yielding cytotoxic nitrogen mustards capable of reacting with DNA molecules to form crosslinks and lead to cell apoptosis and/or necrosis. Such prodrug activation can be enhanced within tumor cells by the CYP-based gene directed-enzyme prodrug therapy (GDEPT) approach. However, those newly synthesized oxazaphosphorine derivatives such as glufosfamide, NSC 612567 and NSC 613060, do not need hepatic activation. They are activated through other enzymatic and/or non-enzymatic pathways. For example, both NSC 612567 and NSC 613060 can be activated by plain phosphodiesterase (PDEs) in plasma and other tissues or by the high-affinity nuclear 3'-5' exonucleases associated with DNA polymerases, such as DNA polymerases and ε. The alternative CYP-catalyzed inactivation pathway by N-dechloroethylation generates the neurotoxic and nephrotoxic byproduct chloroacetaldehyde (CAA). Various aldehyde dehydrogenases (ALDHs) and glutathione S-transferases (GSTs) are involved in the detoxification of oxazaphosphorine metabolites. The metabolism of oxazaphosphorines is auto-inducible, with the activation of the orphan nuclear receptor pregnane X receptor (PXR) being the major mechanism. Oxazaphosphorine metabolism is affected by a number of factors associated with the drugs (e.g., dosage, route of administration, chirality, and drug combination) and patients (e.g., age, gender, renal and hepatic function). Several drug transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated proteins (MRP1, MRP2, and MRP4) are involved in the active uptake and efflux of parental oxazaphosphorines, their cytotoxic mustards and conjugates in hepatocytes and tumor cells. Oxazaphosphorine metabolism and transport have a major impact on pharmacokinetic variability, pharmacokinetic-pharmacodynamic relationship, toxicity, resistance, and drug interactions since the drug-metabolizing enzymes and drug transporters involved are key determinants of the pharmacokinetics and pharmacodynamics of oxazaphosphorines. A better understanding of the factors that affect the metabolism and transport of oxazaphosphorines is important for their optional use in cancer chemotherapy.

High torsional energy disulfides : relationship between cross-strand disulfides and right-handed staples

Redox-active disulfides are capable of being oxidized and reduced under physiological conditions. The enzymatic role of redox-active disulfides in thiol-disulfide reductases is well-known, but redox-active disulfides are also present in non-enzymatic protein structures where they may act as switches of protein function. Here, we examine disulfides linking adjacent β-strands (cross-strand disulfides), which have been reported to be redox-active. Our previous work has established that these cross-strand disulfides have high torsional energies, a quantity likely to be related to the ease with which the disulfide is reduced. We examine the relationship between conformations of disulfides and their location in protein secondary structures. By identifying the overlap between cross-strand disulfides and various conformations, we wish to address whether the high torsional energy of a cross-strand disulfide is sufficient to confer redox activity or whether other factors, such as the presence of the cross-strand disulfide in a strained β-sheet, are required.

Microbial lipases : at the interface of aqueous and non-aqueous media: a review

In recent times, biotechnological applications of microbial lipases in synthesis of many organic molecules have rapidly increased in non-aqueous media. Microbial lipases are the working horses' in biocatalysis and have been extensively studied when their exceptionally high stability in non-aqueous media has been discovered. Stability of lipases in organic solvents makes them commercially feasibile in the enzymatic esterification reactions. Their stability is affected by temperature, reaction medium, water concentration and by the biocatalyst's preparation. An optimization process for ester synthesis from pilot scale to industrial scale in the reaction medium is discussed. The water released during the esterification process can be controlled over a wide range and has a profound effect on the activity of the lipases. Approaches to lipase catalysis like protein engineering, directed evolution and metagenome approach were studied. This review reports the recent development in the field of non-aqueous microbial lipase catalysis and factors controlling the esterification/transesterification processes in organic media.

Enrichment of cellulosic waste hemp (Cannabis sativa) hurd into non-toxic microfibres

In this study a largely available lignocellulose feedstock hemp (Cannabis sativa), obtained as an industrial waste, was used for cellulose extraction. The extraction of cellulose microfibres from hemp biomass was conducted by alkaline treatment and an acidification process. The extracted cellulose microfibres were characterised using Fourier-transformed infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and X-ray diffraction (XRD).The viability of the study was determined by growing human fibroblasts on the preparation which resulted in being non-toxic; indicating its potential in preparing biological scaffolds. Upon enzymatic hydrolysis of the cellulose microfibre using cellulase from Trichoderma reesei, a maximum of 909 mg/g of reducing sugars were obtained, which endorses its suitability for biofuel production.