PROTECTION OF MICE AGAINST CECAL LIGATION AND PUNCTURE-INDUCED POLYMICROBIAL SEPSIS BY A FASCIOLA HEPATICA HELMINTH DEFENSE MOLECULE.

Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture model, which is considered the most clinically relevant rodent model of sepsis. In the present study, histological and biomarker multiplex analyses revealed that the cecal ligation and puncture model initiated a large-scale inflammatory response in mice by 24 h, with evidence of acute organ damage by 48-72 h.

Spatial transcriptomic characterization of pathologic niches in IPF.

Despite advancements in antifibrotic therapy, idiopathic pulmonary fibrosis (IPF) remains a medical condition with unmet needs. Single-cell RNA sequencing (scRNA-seq) has enhanced our understanding of IPF but lacks the cellular tissue context and gene expression localization that spatial transcriptomics provides. To bridge this gap, we profiled IPF and control patient lung tissue using spatial transcriptomics, integrating the data with an IPF scRNA-seq atlas.

Exploring the utility of circulating miRNAs as diagnostic biomarkers of fasciolosis.

Effective management and control of parasitic infections on farms depends on their early detection. Traditional serological diagnostic methods for Fasciola hepatica infection in livestock are specific and sensitive, but currently the earliest detection of the parasite only occurs at approximately three weeks post-infection. At this timepoint, parasites have already entered the liver and caused the tissue damage and immunopathology that results in reduced body weight and loss in productivity.

Virtual reality technology for surgical learning: qualitative outcomes of the first virtual reality training course for emergency and essential surgery delivered by a UK-Uganda partnership.

Introduction: The extensive resources needed to train surgeons and maintain skill levels in low-income and middle-income countries (LMICs) are limited and confined to urban settings. Surgical education of remote/rural doctors is, therefore, paramount. Virtual reality (VR) has the potential to disseminate surgical knowledge and skill development at low costs.

Glycan Complexity and Heterogeneity of Glycoproteins in Somatic Extracts and Secretome of the Infective Stage of the Helminth Fasciola hepatica.

Fasciola hepatica is a global helminth parasite of humans and their livestock. The invasive stage of the parasite, the newly excysted juvenile (NEJs), relies on glycosylated excreted-secreted (ES) products and surface/somatic molecules to interact with host cells and tissues and to evade the host's immune responses, such as disarming complement and shedding bound antibody. While -omics technologies have generated extensive databases of NEJs' proteins and their expression, detailed knowledge of the glycosylation of proteins is still lacking.

Fasciola hepatica antioxidant and protease-inhibitor cocktail recombinant vaccines administered five times elicit potent and sustained immune responses in sheep but do not confer protection.

Our laboratory's vaccine development strategy against the livestock parasite Fasciola hepatica centres around disrupting key biological processes by combining groups of antigens with similar/complementary functional actions into a single vaccine cocktail. In this study the focus was on antioxidant protein vaccines and a protease inhibitor vaccine aimed at disrupting the parasite's ability to defend against oxidative stress and protease-inhibitor balance, respectively. Two combinations of recombinantly expressed antioxidants were assessed, namely peroxiredoxin (rFhPrx), thioredoxin (rFhTrx) and thioredoxin-glutathione reductase (rFhTGR) (Group 1) and rFhPrx, rFhTrx, and two superoxide dismutases (rFhSOD1 and rFhSOD3) (Group 2).

The use of cathepsin L1 (FhCL1) serological ELISA in sentinel screening for liver fluke on sheep farms.

Fasciola hepatica is a parasitic helminth (worm) that poses a significant economic threat to the ruminant livestock industry worldwide. The disease, fasciolosis, can result in a range of clinical signs including anaemia, weight loss and death, with the most severe symptoms attributed to early acute infection when the parasite is migrating through the liver. Early diagnosis and intervention are essential for the control and management of the disease to prevent productivity losses.

A new multiplex SARS-CoV-2 antigen microarray showed correlation of IgG, IgA, and IgM antibodies from patients with COVID-19 disease severity and maintenance of relative IgA and IgM antigen binding over time.

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses.

In vitro evaluation of the potential use of snake-derived peptides in the treatment of respiratory infections using inhalation therapy: A proof of concept study.

Inhalation therapy using nebulisers is an attractive non-invasive route for drug delivery, particularly for the treatment of lung infections with anti-inflammatory and anti-microbial compounds. This study evaluated the suitability of three snake-derived peptides (termed Sn1b, SnE1 and SnE1-F), which we have recently shown have potent anti-inflammatory and bacteriostatic activities, for nebulisation using a vibrating mesh nebuliser (VMN). The effect of nebulisation on peptide concentration, stability and function were assessed, prior to progression to aerodynamic particle size distribution, and in vitro drug delivery in simulated adult spontaneous breathing and mechanical ventilated patient models.

Electrical Stimulation of Distal Tibial Nerve During Stance Phase of Walking May Reverse Effects of Unilateral Paw Pad Anesthesia in the Cat.

Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and the lack of this feedback results in motor deficits. We tested the hypothesis that locomotor changes caused by local unilateral anesthesia of paw pads in the cat could be reduced/reversed by electrical stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve during stance. Several split-belt conditions were investigated in four adult female cats.

Exploiting Comparative Omics to Understand the Pathogenic and Virulence-Associated Protease: Anti-Protease Relationships in the Zoonotic Parasites and .

The helminth parasites, and , are the causative agents of fasciolosis, a global and economically important disease of people and their livestock. Proteases are pivotal to an array of biological processes related to parasitism (development, feeding, immune evasion, virulence) and therefore their action requires strict regulation by parasite anti-proteases (protease inhibitors). By interrogating the current publicly available spp.

Two Distinct Superoxidase Dismutases (SOD) Secreted by the Helminth Parasite Play Roles in Defence against Metabolic and Host Immune Cell-Derived Reactive Oxygen Species (ROS) during Growth and Development.

The antioxidant superoxide dismutase (SOD) catalyses the dismutation of superoxide, a dangerous oxygen free radical, into hydrogen peroxide and molecular oxygen. Superoxide generation during the oxidative burst of the innate immune system is considered a key component of the host defence against invading pathogens. We demonstrate the presence and differential expression of two SODs in , a leaderless cytosolic (FhSOD1) and an extracellular (FhSOD3) form containing a secretory signal peptide, suggesting that the parasites exploit these enzymes in distinct ways to counteract reactive oxygen species (ROS) produced by cellular metabolism and immune defences.

Omics tools enabling vaccine discovery against fasciolosis.

In the past decade significant advances in our understanding of liver fluke biology have been made through in-depth interrogation and analysis of evolving Fasciola hepatica and Fasciola gigantica omics datasets. This information is crucial for developing novel control strategies, particularly vaccines necessitated by the global spread of anthelmintic resistance. Distilling them down to a manageable number of testable vaccines requires combined rational, empirical, and collaborative approaches.

Production of a functionally active recombinant SARS-CoV-2 (COVID-19) 3C-like protease and a soluble inactive 3C-like protease-RBD chimeric in a prokaryotic expression system.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) intracellular life-cycle, two large polyproteins, pp1a and pp1ab, are produced. Processing of these by viral cysteine proteases, the papain-like protease (PLpro) and the chymotrypsin-like 3C-like protease (3CL-pro) release non-structural proteins necessary for the establishment of the viral replication and transcription complex (RTC), crucial for viral replication. Hence, these proteases are considered prime targets against which anti-coronavirus disease 2019 (COVID-19) drugs could be developed.

Stage-specific miRNAs regulate gene expression associated with growth, development and parasite-host interaction during the intra-mammalian migration of the zoonotic helminth parasite Fasciola hepatica.

Background: MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression in organisms ranging from viruses to mammals. There is great relevance in understanding how miRNAs regulate genes involved in the growth, development, and maturation of the many parasitic worms (helminths) that together afflict more than 2 billion people.

Results: Here, we describe the miRNAs expressed by each of the predominant intra-mammalian development stages of Fasciola hepatica, a foodborne flatworm that infects a wide range of mammals worldwide, most importantly humans and their livestock.

Tuaimenal A, a Meroterpene from the Irish Deep-Sea Soft Coral , Displays Inhibition of the SARS-CoV-2 3CLpro Enzyme.

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, , were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation.

Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth .

The liver fluke is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, secretes an abundance of cathepsin peptidases but prevents excessive damage to both parasite and host tissues by co-secreting regulatory peptidase inhibitors, cystatins/stefins and Kunitz-type inhibitors. Here, we report a vaccine strategy aimed at disrupting the parasite's protease/anti-protease balance by targeting these key inhibitors.

Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins.

The complement system is a first-line innate host immune defence against invading pathogens. It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate arrays or microbial liposaccharides, respectively. The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like structure, the membrane attack complex (MAC), on the pathogen surface.

The Zoonotic Helminth Parasite Virulence-Associated Cathepsin B and Cathepsin L Cysteine Peptidases Secreted by Infective Newly Excysted Juveniles (NEJ).

Fasciolosis caused by is a major global disease of livestock and an important neglected helminthiasis of humans. Infection arises when encysted metacercariae are ingested by the mammalian host. Within the intestine, the parasite excysts as a newly excysted juvenile (NEJ) that penetrates the intestinal wall and migrates to the liver.

Pathogenicity and virulence of the liver flukes and that cause the zoonosis Fasciolosis.

Fasciolosis caused by the liver flukes and is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis.

The Impact of Lung Proteases on Snake-Derived Antimicrobial Peptides.

Respiratory infections are a leading cause of global morbidity and mortality and are of significant concern for individuals with chronic inflammatory lung diseases. There is an urgent need for novel antimicrobials. Antimicrobial peptides (AMPs) are naturally occurring innate immune response peptides with therapeutic potential.

Diagnosis of sheep fasciolosis caused by Fasciola hepatica using cathepsin L enzyme-linked immunosorbent assays (ELISA).

Fasciolosis, a global parasitic disease of agricultural livestock, is caused by the liver fluke Fasciola hepatica. Management and strategic control of fasciolosis on farms depends on early assessment of the extent of disease so that control measures can be implemented quickly. Traditionally, this has relied on the detection of eggs in the faeces of animals, a laborious method that lacks sensitivity, especially for sub-clinical infections, and identifies chronic infections only.