Stephanie Ghio

Spices and Mediterranean medicinal plants provide a rich resource for novel antiviral drug development. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic with devastating outcomes, and hence, there is a global need to search for small-molecule inhibitors that can act against this viral pathogen. This review highlights studies that have investigated the antiviral activities of spices and Mediterranean herbs, as well as their mechanism of action against SARS-CoV-2. Potential therapeutic target mechanisms addressed in this review comprise both host-directed and virus-directed therapies. Host-directed therapies include the inhibition of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Virus-directed therapies include inhibition of papain-like protease (PLpro) and the main protease, 3-chymotrypsin-like protease (3CLpro). Though numerous studies have been conducted on natural products, many of these studies have been performed in silico and require further research to verify the suggested therapeutic properties. 3CLpro has been identified as the target with the largest number of proven in vitro results, with compounds from different classes of molecules shown to inhibit this essential viral protease. In silico studies have confirmed the in vitro results, while providing additional mechanistic insights. Phytocompounds can serve as a foundation for designing new antiviral therapies.

This research study examines how lecturers at the Malta College of Arts, Science and Technology (MCAST) engage and connect with students. It analyses the impact of teacher connectedness from the educators perspective. Through an interpretivist approach that implemented phenomenography as the research method, the qualitatively different ways in which lecturers at MCAST engage with their students and how they experience teacher connectedness were analysed in order to understand the nature of student-teacher interactions. These interactions can positively affect students by guiding them towards appropriate behaviours and improved student outcomes. Three different ways in which MCAST lecturers experience teacher connectedness were identified, with a change in focus from teacher-centred to student-centred across the categories of pedagogic connectedness. Knowledge gained from this study can contribute towards the adaptation of teacher connectedness into pedagogical practices that will en...

Peer teaching is a learning strategy based on student involvement, whereby students themselves teach fellow students. If properly structured, peer teaching can be a very effective learning technique (Leung et al. 2012).Peer learning, group work, and other activities that foster peer learning are highly encouraged at the Malta College for Arts, Science and Technology (MCAST). These activities should be structured not only to fulfil the learning outcomes but also to present learners with an opportunity to learn skills and competences that go beyond such outcomes (MCAST 2020). Peer teaching, as a style of learning is most often relatively novel to the students and thus it is of interest to explore the experiences and attitudes of MCAST students with regard to peer teaching.This qualitative study explores the perceptions of the students when participating in a peer teaching session. In doing so, this research attempts to answer the overarching question of whether the phenomenon of learn...

One of the key molecular events underlying the pathogenesis of Parkinson's disease (PD) is the aberrant misfolding and aggregation of the α-synuclein (αS) protein into higher-order oligomers that play a key role in neuronal dysfunction and degeneration. A wealth of experimental data supports the hypothesis that the neurotoxicity of αS oligomers is intrinsically linked with their ability to interact with, and disrupt, biological membranes; especially those membranes having negatively-charged surfaces and/or lipid packing defects. Consequences of αS-lipid interaction include increased membrane tension, permeation by pore formation, membrane lysis and/or leakage due to the extraction of lipids from the bilayer. Moreover, we assert that the interaction of αS with a liquid-disordering phospholipid uniquely enriched in mitochondrial membranes, namely cardiolipin (1,3-diphosphatidyl-sn-glycerol, CL), helps target the αS oligomeric complexes intracellularly to mitochondria. Binding mediated by CL may thus represent an important pathomechanism by which cytosolic αS could physically associate with mitochondrial membranes and disrupt their integrity. Impaired mitochondrial function culminates in a cellular bioenergetic crisis and apoptotic death. To conclude, we advocate the accelerated discovery of new drugs targeting this pathway in order to restore mitochondrial function in PD.

Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes and mitochondria are increasingly recognised as key targets of oligomer toxicity, we investigated the damaging effects of aggregates of HypF-N on mitochondrial membranes. Essentially, we found that HypF-N oligomers characterised by high surface hydrophobicity (type A) were able to trigger a robust permeabilisation of mito-mimetic liposomes possessing cardiolipin-rich membranes and dysfunction of isolated mitochondria, as demonstrated by a combination of mitochondrial shrinking, lowering of mitochondrial membrane potential and cytochrome c release. Furthermore, using single-channel electrophysiology recordings we obtained evidence that the type A agg...

The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive compounds to protect mitochondrial membranes against insult by oligomeric aggregates of the amyloidogenic proteins amyloid-β (Aβ), α-synuclein (α-syn) and tau, which are currently considered to be major targets for drug discovery in Alzheimer’s disease (AD) and Parkinson’s disease (PD). We show that PPE manifested a significant inhibitory effect against swelling of isolated mitochondria exposed to the amyloid oligomers, and attenuated the release of cytochrome c from the mitochondria. Using cardiolipin-enriched synthetic lipid membranes, we also show that dye leakage from fluorophore-loaded vesicles and formation of channel-like pores in plan...

A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the via...