Articles - Department of Pharmaceutical Sciences and Biotechnology
https://research.thea.ie/handle/20.500.12065/2436
2024-03-29T10:48:07ZAssociation of feed efficiency with organ characteristics and fatty liver haemorrhagic syndrome in laying hens
https://research.thea.ie/handle/20.500.12065/4502
Association of feed efficiency with organ characteristics and fatty liver haemorrhagic syndrome in laying hens
Anene, Doreen Onyinye; Akter, Yeasmin; Groves, Peter John; Horadagoda, Neil; Liu, Sonia Yun Liu; Moss, Amy; Hutchison, Christine; O'Shea, Cormac John
Poor feed efficiency (FE) in hens impacts body weight (BW) and may reflect suboptimal health. Fatty Liver Haemorrhagic Syndrome (FLHS) is mostly observed in laying hens and affects egg production and hen performance. The aim of this study was to investigate the relationships of FE and BW with organ characteristics, liver composition and incidence of FLHS of 150 individually housed ISA Brown hens ranked on the basis of feed conversion ratio (FCR) attained from early lay. At 45 weeks, 10 birds per FE group (HFE—High feed efficient; MFE—medium feed efficient; LFE—low feed efficient) were randomly selected and euthanized. Hen BW was positively associated with feed intake and FCR. The HFE hens had a lower abdominal fat pad and liver weight compared to LFE hens. FLHS lesion score was higher (worse) in the LFE than HFE hen group and was moderately positively associated with BW and abdominal fat pad, but strongly positively associated with liver weight. Liver pathology of LFE hens showed hepatocytes with abnormal retention of lipids causing distended cytoplasmic vacuoles compared to the HFE hens. Hens which exhibited poorer FE in early lay had heavier abdominal fat pads, heavier, fatter livers and were more prone to FLHS.
2023-04-11T00:00:00ZIn silico screening of phytochemicals from Dissotis rotundifolia against Plasmodium falciparum Dihydrofolate Reductase.
https://research.thea.ie/handle/20.500.12065/4467
In silico screening of phytochemicals from Dissotis rotundifolia against Plasmodium falciparum Dihydrofolate Reductase.
Adams, Latif; Afiadenyo, Michael; Kwofie, Samuel; Wilson, Michael D.; Kusi, Kwadow Asamoah; Obiri-Yeboah, Dorcas; Moane, Siobhan; McKeon-Bennett, Michelle
Background: Malaria remains a major health concern in developing countries with high morbidity and mortality,
especially in pregnant women and infants. A major obstacle to the treatment of malaria is a low effectiveness and
an increase resistance of the parasite to antimalarial drugs. As a result, there is an ongoing demand for new and
potent antimalarial drugs. Medicinal plants remain a potential source for the development of new antimalarial
drugs. Amongst them is Dissotis rotundifolia is an ethnomedical important plant used in West Africa to treat
malaria.
Purpose: This study aimed at identifying new potential antifolates by virtually screening phytochemicals characterized
from the whole plant methanolic extract of D. rotundifolia against Plasmodium falciparum Dihydrofolate
Reductase (PfDHFR).
Methods: LC-ESI-Q-TOF-MS analysis was employed to identify the phytochemicals present in the whole plant
methanolic extract of D. rotundifolia. These phytochemicals were docked against the catalytic site of PfDHFR. The
docking protocol was evaluated using the Area Under the Curve (AUC) of a Receiver Operating Characteristic
(ROC) curve. The binding mechanisms and the drug-likeness of the phytochemicals were characterized. A 100 ns
Molecular Dynamics (MD) simulation and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA)
calculations were utilized to analyze the stability, the energy decomposition per residue and the binding free
energy of the potential leads.
Results: Twenty nine phytochemicals were characterized and docked against PfDHFR. Dimethylmatairesinol,
flavodic acid, sakuranetin, and sesartemin were identified as potential leads with binding affinities of -8.4, -8.9,
-8.6, and -8.9 kcal/mol respectively, greater than a stringent threshold of -8.0 kcal/mol. The potential leads also
interacted hydrophobically with critical residue Phe58. A novel critical residue, Leu46 was identified to be
crucial in the catalytic activity of PfDHFR. The potential leads were also predicted to be anti-protozoal with a
probability of active (Pa) value ranging from 0.319 to 0.537.
Conclusion: This study elucidates the potential inhibition of PfDHFR by dimethylmatairesinol, flavodic acid,
sakuranetin and sesartemin present in D. rotundifolia. These compounds are druglike, do not violate Lipinski’s
rule of five, have a high binding affinity to PfDHFR, and interact with crucial residues involved in the catalytic
activity PfDHFR. Dimethylmatairesinol, flavodic acid, sakuranetin
2023-04-01T00:00:00ZEffectiveness of front line and emerging fungal disease prevention and control interventions and opportunities to address appropriate eco-sustainable solutions
https://research.thea.ie/handle/20.500.12065/4066
Effectiveness of front line and emerging fungal disease prevention and control interventions and opportunities to address appropriate eco-sustainable solutions
Garvey, Mary; Meade, Elaine; Rowan, Neil J.
Fungal pathogens contribute to significant disease burden globally; however, the fact that fungi are eukaryotes has greatly complicated their role in fungal-mediated infections and alleviation. Antifungal drugs are often toxic to host cells and there is increasing evidence of adaptive resistance in animals and humans. Existing fungal diagnostic and treatment regimens have limitations that has contributed to the alarming high mortality rates and prolonged morbidity seen in immunocompromised cohorts caused by opportunistic invasive infections as evidenced during HIV and COVID-19 pandemics. There is a need to develop real-time monitoring and diagnostic methods for fungal pathogens and to create a greater awareness as to the contribution of fungal pathogens in disease causation. Greater information is required on the appropriate selection and dose of antifungal drugs including factors governing resistance where there is commensurate need to discover more appropriate and effective solutions. Popular azole fungal drugs are widely detected in surface water and sediment due to incomplete removal in wastewater treatment plants where they are resistant to microbial degradation and may cause toxic effects on aquatic organisms such as algae and fish. UV has limited effectiveness in destruction of anti-fungal drugs where there is increased interest in the combination approaches such as novel use of pulsed-plasma gas-discharge technologies for environmental waste management. There is growing interest in developing alternative and complementary green eco-biocides and disinfection innovation. Fungi present challenges for cleaning, disinfection and sterilization of reusable medical devices such as endoscopes where they (example, Aspergillus and Candida species) can be protected when harboured in build-up biofilm from lethal processing. Information on the efficacy of established disinfection and sterilization technologies to address fungal pathogens including bottleneck areas that present high risk to patients is lacking. There is a need to address risk mitigation and modelling to inform efficacy of appropriate intervention technologies that must consider all contributing factors where there is potential to adopt digital technologies to enable real-time analysis of big data, such as use of artificial intelligence and machine learning. International consensus on standardised protocols for developing and reporting on appropriate alternative eco-solutions must be reached, particularly in order to address fungi with increasing drug resistance where research and innovation can be enabled using a One Health approach.
2022-08-21T00:00:00ZInsights into the mechanisms of Cronobacter sakazakii virulence
https://research.thea.ie/handle/20.500.12065/4035
Insights into the mechanisms of Cronobacter sakazakii virulence
Phair, Katie; Gonçalves Pereira, Sónia; Kealey, Carmel; Fanning, Séamus; Brady, Damien B.
Cronobacter species have adapted to survive harsh conditions, particularly in the food manufacture environment, and can cause life-threatening infections in susceptible hosts. These opportunistic pathogens employ a multitude of mechanisms to aid their virulence throughout three key stages: environmental persistence, infection strategy, and systemic persistence in the human host. Environmental persistence is aided by the formation of biofilms, development of subpopulations, and high tolerance to environmental stressors. Successful infection in the human host involves several mechanisms such as protein secretion, motility, quorum sensing, colonisation, and translocation. Survival inside the host is achieved via competitive acquisition and utilization of minerals and metabolites respectively, coupled with host immune system evasion and antimicrobial resistance (AMR) mechanisms. Across the globe, Cronobacter sakazakii is associated with often fatal systemic infections in populations including neonates, infants, the elderly and the immunocompromised. By providing insight into the mechanisms of virulence utilised by this pathogen across these three stages, this review identifies current gaps in the literature. Further research into these virulence mechanisms is required to inform novel mitigation measures to improve global food safety with regards to this food-borne pathogen.
2022-06-01T00:00:00Z