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result(s) for
"McClean, Stephen"
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Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes
by
Gault, Victor A
,
McClean, Stephen
,
Coulter-Parkhill, Aimee
in
Biological activity
,
Biological products
,
Diabetes
2021
The therapeutic potential of venom-derived drugs is evident today. Currently, several significant drugs are FDA approved for human use that descend directly from animal venom products, with others having undergone, or progressing through, clinical trials. In addition, there is growing awareness of the important cosmeceutical application of venom-derived products. The success of venom-derived compounds is linked to their increased bioactivity, specificity and stability when compared to synthetically engineered compounds. This review highlights advancements in venom-derived compounds for the treatment of diabetes and related disorders. Exendin-4, originating from the saliva of Gila monster lizard, represents proof-of-concept for this drug discovery pathway in diabetes. More recent evidence emphasises the potential of venom-derived compounds from bees, cone snails, sea anemones, scorpions, snakes and spiders to effectively manage glycaemic control. Such compounds could represent exciting exploitable scaffolds for future drug discovery in diabetes, as well as providing tools to allow for a better understanding of cell signalling pathways linked to insulin secretion and metabolism.
Journal Article
Making room for interactivity: using the cloud-based audience response system Nearpod to enhance engagement in lectures
2017
Active and collaborative learning provides distinct advantages for students in higher education, yet can often be hampered by the barrier of large class sizes. Solutions that combine a 'bring your own device culture' with cloud-based technologies may facilitate a more interactive learning experience. In this pilot study, we describe the use of one such technology, Nearpod, to enhance interactivity in lectures delivered to pharmacy and bioscience students at Ulster University. Existing material in PowerPoint or Keynote format is uploaded to the instructor area of Nearpod, interactive elements are added, and the lecture is then broadcasted via the internet to student devices. The lecturer may choose to share polling responses or examples of submissions from the drawing tool or open-ended questions, thereby providing instant feedback on learning. Students commented favourably on the interactivity and engagement afforded by Nearpod. Most students were happy to use their own electronic devices (smartphones, tablets and laptops) for such activities with a minority expressing concern over problems with connecting to the institutional Wi-Fi. Nearpod and similar products represent a new class of feature-rich audience response systems that have potential to transform learning even in large classes.
Journal Article
Biological Activity and Antidiabetic Potential of C-Terminal Octapeptide Fragments of the Gut-Derived Hormone Xenin
by
McClean, Stephen
,
Parthsarathy, Vadivel
,
Hasib, Annie
in
Amino Acid Sequence
,
Amino acids
,
Analysis
2016
Xenin is a peptide that is co-secreted with the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), from intestinal K-cells in response to feeding. Studies demonstrate that xenin has appetite suppressive effects and modulates glucose-induced insulin secretion. The present study was undertaken to determine the bioactivity and antidiabetic properties of two C-terminal fragment xenin peptides, namely xenin 18-25 and xenin 18-25 Gln. In BRIN-BD11 cells, both xenin fragment peptides concentration-dependently stimulated insulin secretion, with similar efficacy as the parent peptide. Neither fragment peptide had any effect on acute feeding behaviour at elevated doses of 500 nmol/kg bw. When administered together with glucose to normal mice at 25 nmol/kg bw, the overall insulin secretory effect was significantly enhanced in both xenin 18-25 and xenin 18-25 Gln treated mice, with better moderation of blood glucose levels. Twice daily administration of xenin 18-25 or xenin 18-25 Gln for 21 days in high fat fed mice did not affect energy intake, body weight, circulating blood glucose or body fat stores. However, circulating plasma insulin concentrations had a tendency to be elevated, particularly in xenin 18-25 Gln mice. Both treatment regimens significantly improved insulin sensitivity by the end of the treatment period. In addition, sustained treatment with xenin 18-25 Gln significantly reduced the overall glycaemic excursion and augmented the insulinotropic response to an exogenous glucose challenge on day 21. In harmony with this, GIP-mediated glucose-lowering and insulin-releasing effects were substantially improved by twice daily xenin 18-25 Gln treatment. Overall, these data provide evidence that C-terminal octapeptide fragments of xenin, such as xenin 18-25 Gln, have potential therapeutic utility for type 2 diabetes.
Journal Article
Nutrition Education and Community Pharmacy: A First Exploration of Current Attitudes and Practices in Northern Ireland
by
Douglas, Pauline L.
,
McClean, Stephen
,
Gallagher, Alison M.
in
Attitudes
,
community pharmacists
,
Dietary supplements
2019
Community pharmacist is one of the most prominent and accessible healthcare professions. The community pharmacists’ role in healthcare is evolving, with opportunities being taken to reduce pressure on primary care services. However, the question remains of how well community pharmacists are equipped for this changing role. This was a sequentially designed study using a mix of methods to explore nutrition education among community pharmacists in Northern Ireland. It consisted of two phases. Phase 1 was a cross-sectional exploration to map the attitudes and practice of Northern Ireland (NI) pharmacists towards diet-related health promotion and disease prevention. An online questionnaire with open and closed questions to gain both quantitative and qualitative responses was developed and distributed to community pharmacists practising in NI. A total of 91% considered nutrition important in reducing the global burden of disease. While the majority (89%) believed patients would value nutritional advice from a pharmacist, 74% were not confident in providing advice to a patient with diabetes. From the consensus gained in Phase 1 a nutrition education intervention (Phase 2) for pre-registration pharmacists was developed using the Hardens 10 question system. The training programme was advertised to pre-registration pharmacy students in NI. It was delivered by nutrition experts who have education qualifications. The intervention was evaluated using a before and after questionnaire that assessed knowledge, attitudes, and practice (KAP). Phase 2 did find sustained improvement from the baseline in KAP but there was a decline from immediately post-training to three months post-training. This suggests the need to further embed nutrition education. The education programme was found to be effective for the target population and sets the stage for the development of an implementation strategy for a wider roll-out with evaluation.
Journal Article
Microbial rhamnolipid production: a critical re-evaluation of published data and suggested future publication criteria
by
Irorere, Victor U.
,
McClean, Stephen
,
Marchant, Roger
in
20th century
,
Agricultural production
,
Analysis
2017
High production cost and potential pathogenicity of
Pseudomonas aeruginosa
, commonly used for rhamnolipid synthesis, have led to extensive research for safer producing strains and cost-effective production methods. This has resulted in numerous research publications claiming new non-pathogenic producing strains and novel production techniques many of which are unfortunately without proper characterisation of product and/or producing strain/s. Genes responsible for rhamnolipid production have only been confirmed in
P. aeruginosa
,
Burkholderia thailandensis
and
Burkholderia pseudomallei
. Comparing yields in different publications is also generally unreliable especially when different methodologies were used for rhamnolipid quantification. After reviewing the literature in this area, we strongly feel that numerous research outputs have insufficient evidence to support claims of rhamnolipid-producing strains and/or yields. We therefore recommend that standards should be set for reporting new rhamnolipid-producing strains and production yields. These should include (1) molecular and bioinformatic tools to fully characterise new microbial isolates and confirm the presence of the rhamnolipid
rhl
genes for all bacterial strains, (2) using gravimetric methods to quantify crude yields and (3) use of a calibrated method (high-performance liquid chromatography or ultra-performance liquid chromatography) for absolute quantitative yield determination.
Journal Article
Quorum sensing as a potential target for increased production of rhamnolipid biosurfactant in Burkholderia thailandensis E264
by
McClean, Stephen
,
Kwiencien, Michal
,
Banat, Ibrahim M.
in
Bacterial Proteins - genetics
,
Bacterial Proteins - metabolism
,
Biomedical and Life Sciences
2019
Burkholderia thailandensis
E264 is a potential non-pathogenic substitute for producing rhamnolipid biosurfactant, replacing the pathogenic
Pseudomonas aeruginosa
. However, it has low rhamnolipid production and longer fermentation time. We have earlier suggested that media supplementation with exogenous quorum sensing (QS) molecules could lead to early onset of biosynthesis and increased rhamnolipid yield. Here, we assessed the effect of single, double or triple mutations in the various QS systems of
B. thailandensis
on rhamnolipid production, with the view to see which system(s) have the most impact on rhamnolipid yield and subsequently use the QS molecule to potentially increase yield in the wild-type
B. thailandensis
. The triple mutant strain had a rhamnolipid yield of 4.46 ± 0.345 g/l at 240 h of fermentation which was significantly higher than that of the wild type (0.94 ± 0.06 g/l), an unexpected outcome. To gain more insight as to how this might occur, we studied substrate metabolism and energy storage in the form of polyhydroxyalkanoate (PHA) by both the triple mutant and the wild type. We observed increased glycerol metabolism and reduced PHA production in the triple mutant compared with the wild type. Glycerol concentration at 240 h and maximum PHA productivity (g/gDCB) were 8.76 g/l or 16.19 g/l and 21.80% or 31.4% in either the triple mutant or the wild type respectively. Complementation of the triple-mutant cultures with exogenous QS molecules restored rhamnolipid production to similar levels as the wild type. QS therefore is a potential target for increased rhamnolipid production in
B. thailandensis
.
Journal Article
Fatty acid synthesis pathway provides lipid precursors for rhamnolipid biosynthesis in Burkholderia thailandensis E264
by
Cobice, Diego
,
Banat, Ibrahim M
,
Smyth, Thomas J
in
Biosynthesis
,
Burkholderia
,
Burkholderia thailandensis
2018
Rhamnolipid production was monitored for a period of 216 h using different substrates in Pseudomonas aeruginosa PAO1 and Burkholderia thailandensis E264 which showed comparable crude yields attained by both after 216 h. The crude yield for P. aeruginosa, however, was significantly higher at the early stages of fermentation (72 or 144 h). Additionally, P. aeruginosa produced rhamnolipid with odd and even carbon chain lipid moieties using odd carbon chain fatty acid substrates (up to 45.97 and 67.57%, respectively). In contrast, B. thailandensis produced rhamnolipid with predominantly even carbon chain lipid moieties (up to 99.26). These results indicate the use of the fatty acid synthesis (FAS II) pathway as the main source of lipid precursors in rhamnolipid biosynthesis by B. thailandensis. Isotope tracing using 0.25% stearic acid – d35 + 1% glycerol as carbon substrate showed a single pattern of deuterium incorporation: with predominantly less than 15 deuterium atoms incorporated into a single Di-C14-C14 rhamnolipid molecule. This further indicates that the FAS II pathway is the main source of the lipid precursor in rhamnolipid biosynthesis by B. thailandensis. The pathogenicity of these strains was also assessed, and results showed that B. thailandensis is significantly less pathogenic than P. aeruginosa with an LC50 at 24 h > 2500, approximately three logs higher than P. aeruginosa using the Galleria mellonella larva model.
Journal Article