Catherine Thornton

Swansea University | SWAN · Institute of Life Science "ILS"

Background: While risk of infection with SARS-CoV-2 is low to pregnant women and the fetus, there is increased risk of preterm birth and admission into ICU. The fetus is relatively protected against infection, with cases of vertical transmission being rare. Various receptors and accessory molecules which are known to regulate SARS-CoV-2 viral entry...

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, t...

Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The o...

Mandatory maternal metabolic and immunological changes are essential to pregnancy success. Parallel changes in metabolism and immune function make immunometabolism an attractive mechanism to enable dynamic immune adaptation during pregnancy. Immunometabolism is a burgeoning field with the underlying principle being that cellular metabolism underpin...

Pregnancy is characterised by metabolic changes that occur to support the growth and development of the fetus over the course of gestation. These metabolic changes can be classified into two distinct phases: an initial anabolic phase to prepare an adequate store of substrates and energy which are then broken down and used during a catabolic phase t...

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry...

Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bo...

Immune responses of neonates differ markedly to those of adults, with skewed cytokine phenotypes, reduced inflammatory properties and drastically diminished memory function. Recent research efforts have started to unravel the role of cellular metabolism in determining immune cell fate and function. For studies in humans, much of the work on metabol...

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry a...

Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia and gestational diabetes mellitus (GDM) and poses a risk to the neonate. There is a knowledge gap surrounding obesity and changes to the maternal immune system. Hypothesis: Obesity exacerbates systemic inflammation in pregnant women at 28 weeks of g...

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. H...

Preeclampsia (PE) is a common obstetric disorder typically affecting 2–8% of all pregnancies and can lead to several adverse obstetric outcomes for both mother and fetus with the greatest burden of severe outcomes in low middle-income countries (LMICs), therefore, screening for PE is vital. Globally, screening is based on maternal characteristics a...

Macrophages are key components of the innate immune system and exhibit extensive plasticity and heterogeneity. They play a significant role in the non-pregnant cycling uterus and throughout gestation they contribute to various processes underpinning reproductive success including implantation, placentation and parturition. Macrophages are also pres...

There are limited proven therapeutic options for the prevention and treatment of COVID-19. The role of vitamin and mineral supplementation or “immunonutrition” has previously been explored in a number of clinical trials in intensive care settings, and there are several hypotheses to support their routine use. The aim of this narrative review was to...

In recent years, the diagnosis of brain tumors has been investigated with attenuated total reflection ‐ Fourier transform infrared (ATR‐FTIR) spectroscopy on dried human serum samples to eliminate spectral interferences of the water component, with promising results. This research evaluates ATR‐FTIR on both liquid and air‐dried samples to investiga...

Background: Since cartilage-derived stem/progenitor cells (CSPCs) were first identified in articular cartilage using differential adhesion to fibronectin, their self-renewal capacity and niche-specific lineage preference for chondrogenesis have propelled their application for cartilage tissue engineering. In many adult tissues, stem/progenitor cel...

Introduction Thrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic H...

Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications they are being manufactured for and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches, as well as from a consumer perspective. However, despite such positives, doubts remain over the human health implications...

Introduction: Eosinophils have been long implicated in anti-parasite immunity and allergic diseases and, more recently, in regulating adipose tissue homeostasis. The metabolic processes that govern eosinophils, particularly upon activation, are unknown. Methods: Peripheral blood eosinophils were isolated for analysis of metabolic processes using...

Background: Left ventricular assist devices (LVADs) offer live-saving therapy to transplant-ineligible heart failure patients. A major limitation of the technology includes pump thrombosis, bleeding, and recurrent infection that prove difficult to predict from in vivo animal testing. Shear stress introduced by the LVAD affects more than just haemo...

Cartilage derived stem/progenitor cells (CSPCs) have been isolated from a variety of cartilage sources and are suggested to have high chondrogenic potential. However, their role in cartilage engineering has not been well described, in particular, compared to other more widely used cell types such as differentiated chondrocytes and nontissue-specifi...

Eosinophils are granular leukocytes that play a role in mediating inflammatory responses linked to infection and allergic disease. Their activation during an immune response triggers spatial reorganization and eventual cargo release from intracellular granules. Understanding this process is important in diagnosing eosinophilic disorders and in asse...

The placenta is well recognised for its role as the gateway for provision of nutrients to and removal of waste products from the foetus. The placenta also needs to protect the foetus from maternal immunological attack and provide it with rudimentary immune defence mechanisms through the passage of maternally derived immunoglobulin G in particular....

Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cells. Despite having low resting metabolic rates, nai...

White blood cell (WBC) differential counting is an established clinical routine to assess patient immune system status. Fluorescent markers and a flow cytometer are required for the current state‐of‐the‐art method for determining WBC differential counts. However, this process requires several sample preparation steps and may adversely disturb the c...

The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett’s metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes...

The umbilical cord offers a source of readily available mesenchymal stromal cells (MSCs) for use in research and ultimately therapeutic application. However, methods of isolating these cells vary between investigators, and no standard method has been adopted. The aims of this work were to (i) develop a methodology for the isolation of umbilical cor...

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible recur...

Vibrational spectroscopic techniques such as Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR) have huge potential for the analysis of biological specimens. The techniques allow the user to gain label-free, non-destructive biochemical information about a given sample. Previous studies using vibrational spectroscopy with the spec...

Heart failure (HF) remains a disease of ever increasing prevalence in the modern world. Patients with end-stage HF are being referred increasingly for mechanical circulatory support (MCS). MCS can assist patients who are ineligible for transplant and stabilise eligible patients prior to transplantation. It is also used during cardiopulmonary bypass...

The therapeutic use of ventricular assist devices (VADs) for end-stage heart failure (HF) patients who are ineligible for transplant has increased steadily in the last decade. In parallel, improvements in VAD design have reduced device size, cost, and device-related complications. These complications include infection and thrombosis which share und...

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maint...

Use of imaging flow cytometry to assess induced DNA damage via the cytokinesis block micronucleus (CBMN) assay has thus far been limited to radiation dosimetry in human lymphocytes using high end, 'ImageStream X' series imaging cytometers. Its potential to enumerate chemically induced DNA damage using in vitro cell lines remains unexplored. In the...

Ventricular assist devices (VADs) are a life-saving form of mechanical circulatory support in heart failure patients. However, VADs have not yet reached their full potential due to the associated side effects (thrombosis, bleeding, infection) related to the activation and damage of blood cells and proteins caused by mechanical stress and foreign ma...

3D bioprinting has revolutionized the field of tissue engineering. However, 3D bioprinting constructs requires an immense number of cells. Consequently, cellular expansion is one of the initial steps of the bioprinting process. The growth and expansion of cells is known to give rise to a multitude of issues that includes dedifferentiation, genomic...

Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR) and peptides presented by human leukocyte...

Ventricular assist devices (VADs) are an effective bridging or destination therapy for patients with advanced stage heart failure. These devices remain susceptible to adverse events including infection, bleeding, and thrombus; events linked to the foreign body response. Therefore, the biocompatibility of all biomaterials used is crucial to the succ...

Background: The introduction of a foreign surface and the shear stress encountered by the blood moving through a rotary pump can affect both cells and proteins with leukocytes shown to be more vulnerable to shear than erythrocytes. At high shear, viability, counts, morphology, and function have been shown to be significantly impaired. As leukocytes...

Nucleotide-binding oligomerization domain (NOD)-like receptors or NOD-like receptors (NLRs) have been implicated in several disease pathologies associated with inflammation. Since local and systemic inflammation is a hallmark of both term and preterm labour, a role for NLRs at the materno-fetal interface has been postulated. Gene expression and imm...

The common complications in heart failure patients with implanted ventricular assist devices (VADs) include hemolysis, thrombosis, and bleeding. These are linked to shear stress-induced trauma to erythrocytes, platelets, and von Willebrand factor (vWF). Novel device designs are being developed to reduce the blood trauma, which will need to undergo...

The use of manual microscopy for the scoring of chromosome damage in the in vitro micronucleus assay is often associated with user subjectivity. This level of subjectivity can be reduced by using automated platforms, which have added value of faster with high-throughput and multi-endpoint capabilities. However, there is a need to assess the reprodu...

IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1β, IL-18, IL-33, IL-1Ra...

Platelet-rich plasma (PRP) is used to stimulate the repair of acute and chronic cartilage damage even though there is no definitive evidence of how this is achieved. Chondrocytes in injured and diseased situations frequently re-express phenotypic biomarkers of immature cartilage so tissue maturation is a potential pathway for restoration of normal...

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways that yield a cytokine output in response to pathogenic stimuli have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The obj...

Inflammation is a key feature of preterm and term labour. Pro-inflammatory mediators are produced by gestation-associated tissues in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Interleukin (IL)4, IL10 and IL13 are anti-inflammatory cytokines with potential as anti-inflammatory therapi...

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsic...

Bone marrow mesenchymal stromal cells (MSCs) have shown therapeutic potential in the treatment of myocardial infarction patients. However, bone marrow requires invasive harvesting techniques. Therefore, the aim was to carry out a feasibility study of using autologous peripheral blood (PB) as a source for MSCs and platelet lysate (PL), a potential n...

Mutagens can be carcinogens, and traditionally, they have been identified in vitro using the Salmonella 'Ames' reverse mutation assay. However, prokaryotic DNA packaging, replication and repair systems are mechanistically very different to those in the humans we inevitably seek to protect. Therefore, for many years, mammalian cell line genotoxicity...

Aim: To use both a rheometer and the Calon shear device model to mimic the foreign surface and artificial shear introduced to the body by ventricular assist devices (VADs). Methods: For the rheometer model (AR-G2, TA Instruments), discs of biomaterial: diamond-like carbon coated stainless steel (DLC); single crystal sapphire (Sap); and titanium all...

Ovine and bovine blood is used heavily within the development of blood-handling medical devices, such as heart pumps (left ventricular assist devices, LVADs), for which blood cell damage needs to be monitored during in vitro testing. Hematology analyzers provide cell counts but no information about cell viability. The anthraquinone DNA dyes CyTRAK...

Introduction Improving our mechanisms of risk stratification of patients with Barrett’s oesophagus (BO) requires easily analysable, cheap and reproducable biomarkers. The PigA mutant phenotype assay is a novel flow cytometric analysis, which can be undertaken using a fingerprick test. The PigA gene codes for GPI-anchors, which tether proteins to th...

To use a rheological model to mimic the foreign surface and artificial shear introduced to the body by ventricular assist devices (VADs) in order to evaluate the effect biomaterials have on leukocyte activation in this environment.

A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or precision) medicine. Challenges to the use of biomarkers...

Small affordable automated hematology analyzers that produce rapid and accurate complete blood cell counts are a valuable tool to researchers developing blood-handling medical devices, such as ventricular assist devices, for in vitro safety assessments. In such studies, it is common to use the blood of large animals such as cattle and sheep. Howeve...