Enteropathogenic (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis.
View Article and Find Full Text PDFHelicobacter pylori is the primary cause of gastric cancer, and there is a need to discover new molecular targets for therapeutic intervention in H. pylori disease progression. We have previously shown that spermine oxidase (SMOX), the enzyme that catabolizes the back-conversion of the polyamine spermine to spermidine, is upregulated during infection and is associated with increased cancer risk in humans.
View Article and Find Full Text PDFCystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation.
View Article and Find Full Text PDFIn solid tumours, high expression of the glycolytic enzyme, α-enolase (ENO1), predicts for poor patient overall survival (OS), and circulating autoantibodies to ENO1 correlate positively with diagnosis and negatively with advanced disease. Although ENO1 is one of the most highly expressed genes in acute myeloid leukaemia (AML), its potential role as a biomarker in AML or its precursor, myelodysplastic neoplasms (MDS), has not been investigated. A meta-analysis of nine AML online datasets (n = 1419 patients) revealed that high ENO1 expression predicts for poor OS (HR = 1.
View Article and Find Full Text PDFUsers of novel psychoactive substances (NPS) are at risk, due to limited information about the toxicity and unpredictable effects of these compounds. Wastewater-based epidemiology (WBE) has been used as a tool to provide insight into NPS use at the population level. To understand the preferences and trends of NPS use in Australia, this study involved liquid chromatography mass spectrometry analysis of wastewater collected from Australian states and territories from February 2022 to February 2023.
View Article and Find Full Text PDFThe intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium.
View Article and Find Full Text PDFDespite their impressive performance in object recognition and other tasks under standard testing conditions, deep networks often fail to generalize to out-of-distribution (o.o.d.
View Article and Find Full Text PDFBackground & Aims: The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5A) remains unknown in intestinal homeostasis. Our aim was to investigate EIF5A in the gut epithelium in inflammation and carcinogenesis.
View Article and Find Full Text PDFColorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells of patients with CRC.
View Article and Find Full Text PDFPathogenic enteric present a significant burden to global health. Food-borne enteropathogenic (EPEC) and Shiga toxin-producing (STEC) utilize attaching and effacing (A/E) lesions and actin-dense pedestal formation to colonize the gastrointestinal tract. Talin-1 is a large structural protein that links the actin cytoskeleton to the extracellular matrix though direct influence on integrins.
View Article and Find Full Text PDFAcute myeloid leukaemia (AML) is a heterogeneous disease with one of the worst survival rates of all cancers. The bone marrow microenvironment is increasingly being recognised as an important mediator of AML chemoresistance and relapse, supporting leukaemia stem cell survival through interactions among stromal, haematopoietic progenitor and leukaemic cells. Traditional therapies targeting leukaemic cells have failed to improve long term survival rates, and as such, the bone marrow niche has become a promising new source of potential therapeutic targets, particularly for relapsed and refractory AML.
View Article and Find Full Text PDFStomach cancer is a leading cause of cancer death. Helicobacter pylori is a bacterial gastric pathogen that is the primary risk factor for carcinogenesis, associated with its induction of inflammation and DNA damage. Dicarbonyl electrophiles are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules.
View Article and Find Full Text PDFExplor Target Antitumor Ther
February 2022
The importance of Ca signaling, and particularly Ca channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored.
View Article and Find Full Text PDFUnderstanding chronic pain and disability requires a consideration of the lived experience of the patient. There is limited evaluation of the content validity of patient-reported outcome measures (PROMs) in chronic pain using a comprehensive biopsychosocial view of the patient's experience. To address this gap, this study aimed to evaluate the content validity of PROMs for patients with chronic pain.
View Article and Find Full Text PDFColonization by is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage.
View Article and Find Full Text PDFAminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite , namely tyrosine RS (YRS).
View Article and Find Full Text PDFMacrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world's population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme cystathionine γ-lyase (CTH) is upregulated in humans and mice with H.
View Article and Find Full Text PDFReplay can consolidate memories through offline neural reactivation related to past experiences. Category knowledge is learned across multiple experiences, and its subsequent generalization is promoted by consolidation and replay during rest and sleep. However, aspects of replay are difficult to determine from neuroimaging studies.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2022
Curcumin is a potential natural remedy for preventing -associated gastric inflammation and cancer. Here, we analyzed the effect of a phospholipid formulation of curcumin on growth, translocation and phosphorylation of the virulence factor CagA and host protein kinase Src and in an mouse model of infection. Growth of was inhibited dose-dependently by curcumin .
View Article and Find Full Text PDFIntroduction: This research aims to understand the content and nature, and to explore the harm potential, of suspected 3,4-methylenedioxymethamphetamine (MDMA) substances circulating at music festivals in New South Wales.
Methods: Across 19 music festivals held between October 2019 and March 2020, 302 substances detected and suspected by police to contain MDMA were selected for quantitative analysis.
Results: Five percent of substances contained a drug other than MDMA (n = 13) or no drug (n = 2).
Unmanned Aerial Vehicles (UAVs) show promise in a variety of applications and recently were explored in the area of Search and Rescue (SAR) for finding victims. In this paper we consider the problem of finding multiple unknown stationary transmitters in a discrete simulated unknown environment, where the goal is to locate all transmitters in as short a time as possible. Existing solutions in the UAV search space typically search for a single target, assume a simple environment, assume target properties are known or have other unrealistic assumptions.
View Article and Find Full Text PDFBackground & Aims: Because inflammatory bowel disease is increasing worldwide and can lead to colitis-associated carcinoma (CAC), new interventions are needed. We have shown that spermine oxidase (SMOX), which generates spermidine (Spd), regulates colitis. Here we determined whether Spd treatment reduces colitis and carcinogenesis.
View Article and Find Full Text PDFCCL11, also known as eotaxin-1, is described as an eosinophil chemoattractant, which has been implicated in allergic and Th2 inflammatory diseases. We have reported that CCL11 is significantly increased in the serum of inflammatory bowel disease (IBD) patients, colonic eosinophils are increased and correlate with tissue CCL11 levels in ulcerative colitis patients, and CCL11 is increased in dextran sulfate sodium (DSS)-induced murine colitis. Here, we show that CCL11 is involved in the pathogenesis of DSS-induced colitis and in colon tumorigenesis in the azoxymethane (AOM)-DSS model of colitis-associated carcinogenesis (CAC).
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