13 results on '"Gwenin C"'
Search Results
2. Attitudes of the general public and professional health care staff in Wales towards cancer treatment: the influence of age, quality of life, survival and side effects.
- Author
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Brewster AE, Morrison V, Branston L, Hackett P, White-Gwenin C, Price P, Robbe IJ, O'Mahony S, and Maughan TS
- Published
- 2006
Catalog
3. Iridium oxide-modified reference screen-printed electrodes for point-of-care portable electrochemical cortisol detection.
- Author
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Ji T, Ye W, Xiao W, Dawson G, Dong Q, and Gwenin C
- Subjects
- Point-of-Care Systems, Humans, Limit of Detection, Gold chemistry, Biosensing Techniques methods, Hydrocortisone analysis, Electrodes, Iridium chemistry, Electrochemical Techniques instrumentation, Electrochemical Techniques methods
- Abstract
Cortisol is a well-known stress biomarker; this study focuses on using electrochemical immuno-sensing to measure the concentration of cortisol selectively and sensitively in artificial samples. Anti-cortisol antibodies have been immobilised on polycrystalline Au electrodes via strong covalent thiol bonds, fabricating an electrochemical bio-immunosensor for cortisol detection. IrO
x was then anodically electrodeposited as a reference electrode on a commercial screen-printed electrode and electrochemical impedance spectrometry (EIS) studies were used to correlate the electrochemical response to cortisol concentration and the induced changes in charge transfer resistance (Rct ). A linear relationship between the Rct and the logarithm of cortisol concentration was found in concentrations ranging from 1 ng/mL to 1 mg/mL with limit of detection at 11.85 pg/mL (32.69 pM). The modification of the reference electrode with iridium oxide has greatly improved the reproducibility of the screen-printed electrode. The sensing system can provide a reliable and sensitive detection approach for cortisol measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.) more...- Published
- 2024
- Full Text
- View/download PDF
4. The dinitrobenzamide mustard prodrugs, PR-104A and SN27686, for use in a novel MNDEPT cancer prodrug therapy approach.
- Author
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Ball P, Thompson E, Anderson S, Gwenin V, Ashoorzadeh A, Smaill J, and Gwenin C
- Subjects
- Humans, Antineoplastic Agents, Alkylating, Prodrugs metabolism, Prodrugs pharmacology, Nitrogen Mustard Compounds metabolism, Neoplasms, Antineoplastic Agents metabolism
- Abstract
Directed enzyme prodrug therapy is a highly promising anti-cancer strategy. However, the current technology is limited by inefficient prodrug activation and the dose-limiting toxicity associated with the prodrugs being tested; to overcome these limitations, the dinitrobenzamide mustard prodrugs, PR-104A and SN27686, have been developed. The present study will assess both of these prodrugs for their potential uses in a novel magnetic-nanoparticle directed enzyme prodrug therapy strategy by determining their kinetic parameters, assessing the products formed during enzymatic reduction using HPLC and finally their ability to cause cell death in the ovarian cancer cell line, SK-OV-3. It was shown for the first time that the dinitrobenzamide mustard prodrugs are able to be reduced by the genetically modified nitroreductases, NfnB-cys and YfkO-cys, and that these enzyme/prodrug combinations can induce a significant cell death in the SK-OV-3 cell line, highlighting the potential for both enzyme/prodrug combinations for use in magnetic-nanoparticle directed enzyme prodrug therapy., (© 2023 The Author(s).) more...
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- 2023
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5. The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach.
- Author
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Ball P, Hobbs R, Anderson S, Thompson E, Gwenin V, Von Ruhland C, and Gwenin C
- Abstract
The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy. One such enzyme that has proved promising is the YfkO nitroreductase from Bacillus Licheniformis. Upon investigation, the YfkO nitroreductase was shown to have a much lower Km (below the maximum dosage) than that of NfnB as well as the fact that when reacting with the prodrug it produces a much more favourable ratio of enzymatic products than NfnB, forming more of the desired 4-hydroxylamine derivative of CB1954. more...
- Published
- 2021
- Full Text
- View/download PDF
6. Development of Electrochemical DNA Biosensor for Equine Hindgut Acidosis Detection.
- Author
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Davies J, Thomas C, Rizwan M, and Gwenin C
- Subjects
- Animals, DNA, DNA Probes, Electrochemical Techniques, Electrodes, Firmicutes, Gold, Horses, Nucleic Acid Hybridization, Streptococcus bovis, Acidosis, Biosensing Techniques
- Abstract
The pH drop in the hindgut of the horse is caused by lactic acid-producing bacteria which are abundant when a horse's feeding regime is excessively carbohydrate rich. This drop in pH below six causes hindgut acidosis and may lead to laminitis. Lactic acid-producing bacteria Streptococcus equinus and Mitsuokella jalaludinii have been found to produce high amounts of L-lactate and D-lactate, respectively. Early detection of increased levels of these bacteria could allow the horse owner to tailor the horse's diet to avoid hindgut acidosis and subsequent laminitis. Therefore, 16s ribosomal ribonucleic acid (rRNA) sequences were identified and modified to obtain target single stranded deoxyribonucleic acid (DNA) from these bacteria. Complementary single stranded DNAs were designed from the modified target sequences to form capture probes. Binding between capture probe and target single stranded deoxyribonucleic acid (ssDNA) in solution has been studied by gel electrophoresis. Among pairs of different capture probes and target single stranded DNA, hybridization of Streptococcus equinus capture probe 1 (SECP1) and Streptococcus equinus target 1 (SET1) was portrayed as gel electrophoresis. Adsorptive stripping voltammetry was utilized to study the binding of thiol modified SECP1 over gold on glass substrates and these studies showed a consistent binding signal of thiol modified SECP1 and their hybridization with SET1 over the gold working electrode. Cyclic voltammetry and electrochemical impedance spectroscopy were employed to examine the binding of thiol modified SECP1 on the gold working electrode and hybridization of thiol modified SECP1 with the target single stranded DNA. Both demonstrated the gold working electrode surface was modified with a capture probe layer and hybridization of the thiol bound ssDNA probe with target DNA was indicated. Therefore, the proposed electrochemical biosensor has the potential to be used for the detection of the non-synthetic bacterial DNA target responsible for equine hindgut acidosis. more...
- Published
- 2021
- Full Text
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7. Cortisol level dysregulation and its prevalence-Is it nature's alarm clock?
- Author
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Jones C and Gwenin C
- Subjects
- Animals, Biomarkers blood, COVID-19 epidemiology, COVID-19 physiopathology, Cardiovascular Diseases epidemiology, Cardiovascular Diseases physiopathology, Cytokines blood, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 physiopathology, Humans, Hypothalamo-Hypophyseal System physiopathology, Inflammation epidemiology, Inflammation physiopathology, Inflammation Mediators blood, COVID-19 blood, Cardiovascular Diseases blood, Circadian Rhythm, Diabetes Mellitus, Type 2 blood, Hydrocortisone blood, Hypothalamo-Hypophyseal System metabolism, Inflammation blood, Stress, Physiological
- Abstract
This review examines the stress hormone cortisol which plays an important role in regulating and supporting different bodily functions. Disruption in cortisol production has an impact on health and this review looks at a wide range of papers where cortisol has been indicated as a factor in numerous chronic conditions-especially those which are classed as "noncommunicable diseases" (NCDs). Timely detection, screening, and treatment for NCDs are vital to address the growing problem of NCDs worldwide-this would have health and socioeconomic benefits. Interestingly, many of the papers highlight the pro-inflammatory consequences of cortisol dysregulation and its deleterious effects on the body. This is particularly relevant given the recent findings concerning COVID-19 where pro-inflammatory cytokines have been implicated in severe inflammation., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.) more...
- Published
- 2021
- Full Text
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8. Evaluation of two xenobiotic reductases from Pseudomonas putida for their suitability for magnetic nanoparticle-directed enzyme prodrug therapy as a novel approach to cancer treatment.
- Author
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Ball P, Halliwell J, Anderson S, Gwenin V, and Gwenin C
- Subjects
- Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Bacterial Proteins genetics, Bacterial Proteins metabolism, Bacterial Proteins pharmacology, Cell Survival drug effects, Drug Evaluation, Preclinical, Flavoproteins genetics, Flavoproteins metabolism, Flavoproteins pharmacology, Humans, Neoplasms drug therapy, Oxidoreductases genetics, Oxidoreductases metabolism, Oxidoreductases pharmacology, Prodrugs chemistry, Prodrugs metabolism, Prodrugs pharmacology, Pseudomonas putida chemistry, Pseudomonas putida genetics, Antineoplastic Agents chemistry, Bacterial Proteins chemistry, Flavoproteins chemistry, Magnetite Nanoparticles chemistry, Oxidoreductases chemistry, Pseudomonas putida enzymology
- Abstract
Directed enzyme prodrug therapy (DEPT) is a cancer chemotherapy strategy in which bacterial enzymes are delivered to a cancer site before prodrug administration, resulting in prodrug activation at the cancer site and more localized treatment. A major limitation to DEPT is the poor effectiveness of the most studied enzyme for the CB1954 prodrug, NfnB from Escherichia coli, at concentrations suitable for human use. Much research into finding alternative enzymes to NfnB has resulted in the identification of the Xenobiotic reductases, XenA and XenB, which have been shown in the literature to reduce environmentally polluting nitro-compounds. In this study, they were assessed for their potential use in cancer prodrug therapy strategies. Both proteins were cloned into the pET28a+ expression vector to give the genetically modified proteins XenA-his and XenB-his, of which only XenB-his was active when tested with CB1954. XenB-his was further modified to include a cysteine-tag to facilitate direct immobilization on to a gold surface for future magnetic nanoparticle DEPT (MNDEPT) treatments and was named XenB-cys. When tested using high-performance liquid chromatography (HPLC), XenB-his and XenB-cys both demonstrated a preference for reducing CB1954 at the 4-nitro position. Furthermore, XenB-his and XenB-cys successfully induced cell death in SK-OV-3 cells when combined with CB1954. This led to XenB-cys being identified as a promising candidate for use in future MNDEPT treatments., (© 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.) more...
- Published
- 2020
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9. Development of Solid-Phase RPA on a Lateral Flow Device for the Detection of Pathogens Related to Sepsis.
- Author
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Heeroma AJ and Gwenin C
- Subjects
- Anti-Bacterial Agents, Gram-Negative Bacteria, Gram-Positive Bacteria, Humans, Sepsis diagnosis
- Abstract
Population extended life expectancy has significantly increased the risk of septic shock in an ageing population. Sepsis affects roughly 20 million people every year, resulting in over 11 million deaths. The need for faster more accurate diagnostics and better management is therefore paramount in the fight to prevent these avoidable deaths. Here we report the development of a POC device with the ability to identify a broad range of pathogens on a lateral flow platform. Namely Gram-positive and Gram-negative bacteria. The simple to use laboratory device has the potential to be automated, thus enabling an operator to carry out solid-phase lysis and room temperature RPA in situ, providing accurate results in hours rather than days. Results show there is a potential for a fully automated device in which concepts described in this paper can be integrated into a lateral flow device. more...
- Published
- 2020
- Full Text
- View/download PDF
10. Time dependent HPLC analysis of the product ratio of enzymatically reduced prodrug CB1954 by a modified and immobilised nitroreductase.
- Author
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Ball P, Thompson E, Anderson S, Gwenin V, and Gwenin C
- Subjects
- Chromatography, High Pressure Liquid, Oxidation-Reduction, Antineoplastic Agents chemistry, Aziridines chemistry, Hydroxylamine chemistry, Nitroreductases chemistry, Prodrugs chemistry
- Abstract
Directed enzyme prodrug therapy is a chemotherapy strategy that utilises prodrug-activating enzymes to activate prodrugs at the tumour location, thus reducing off-target effects. The most commonly investigated enzyme for use with the CB1954 prodrug is the NfnB nitroreductase from E. coli. Literature states that CB1954 is reduced by NfnB at the 2- or 4-position at a 1:1 ratio; deviation from this ratio has been observed in the literature, but not further investigated. The kinetic parameters for the genetically-modified enzymes; NfnB-his, NfnB-cys and AuNP-NfnB-cys were assessed and HPLC analysis was used to determine the hydroxylamine product ratios formed when reacted with CB1954. Time-dependent HPLC studies were carried out to assess how this ratio changes over time. It was shown that the hydroxylamine ratio formed by the reduction of CB1954 by a nitroreductase changes over time and that this change in ratio relates directly to the kinetics of the reaction. Thus, the hydroxylamine ratio measured using HPLC at a given time point was not a true indication of the preference of the nitroreductase enzymes during catalysis. These results question how nitroreductases are evaluated in terms of the hydroxylamine ratio and it is suspected that this phenomenon may also apply to other enzyme/prodrug combinations., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2019
- Full Text
- View/download PDF
11. Botulinum neurotoxin serotypes detected by electrochemical impedance spectroscopy.
- Author
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Savage AC, Buckley N, Halliwell J, and Gwenin C
- Subjects
- Botulinum Toxins chemistry, Dielectric Spectroscopy, SNARE Proteins chemistry, Serogroup, Biosensing Techniques, Botulinum Toxins analysis
- Abstract
Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A-E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins. more...
- Published
- 2015
- Full Text
- View/download PDF
12. A label free colorimetric assay for the detection of active botulinum neurotoxin type A by SNAP-25 conjugated colloidal gold.
- Author
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Halliwell J and Gwenin C
- Subjects
- Animals, Clostridium botulinum metabolism, Electrophoresis, Polyacrylamide Gel, Lactose chemistry, Mice, Serum Albumin chemistry, Botulinum Toxins, Type A chemistry, Botulinum Toxins, Type A isolation & purification, Colorimetry methods, Gold Colloid chemistry, Synaptosomal-Associated Protein 25 chemistry
- Abstract
Botulinum neurotoxins are one of the most potent toxins known to man. Current methods of detection involve the quantification of the toxin but do not take into account the percentage of the toxin that is active. At present the assay used for monitoring the activity of the toxin is the mouse bioassay, which is lengthy and has ethical issues due to the use of live animals. This report demonstrates a novel assay that utilises the endopeptidase activity of the toxin to detect Botulinum neurotoxin in a pharmaceutical sample. The cleaving of SNAP-25 is monitored via UV-Visible spectroscopy with a limit of detection of 373 fg/mL and has been further developed into a high throughput method using a microplate reader detecting down to 600 fg/mL of active toxin. The results show clear differences between the toxin product and the placebo, which contains the pharmaceutical excipients human serum albumin and lactose, showing that the assay detects the active form of the toxin. more...
- Published
- 2013
- Full Text
- View/download PDF
13. The orientationally controlled assembly of genetically modified enzymes in an amperometric biosensor.
- Author
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Gwenin CD, Kalaji M, Williams PA, and Jones RM
- Subjects
- Electrochemistry, Escherichia coli genetics, Genetic Engineering, Substrate Specificity, Biosensing Techniques methods, Enzymes, Immobilized chemistry, Explosive Agents analysis, Nitroreductases chemistry
- Abstract
A novel, nitroreductase (NTR) containing a sequence of six cysteine amino acids, enabling strong thiolate bonds to form on a gold electrode surface without the loss of enzyme activity, was genetically engineered. The enzyme was directly immobilised at a gold electrode without the need for pre-treatment of the surface with a self-assembled monolayer or a conducting polymer. The ensemble was used to develop an amperometric biosensor for the detection of explosives containing nitroaromatic compounds. Preliminary results demonstrate detection levels down to 100 parts per trillion, signifying tremendous promise towards an in situ sensor for the detection of explosives. more...
- Published
- 2007
- Full Text
- View/download PDF
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