A5033232177- Complement system in diseases
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Biochemical and Structural Characterization
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Sepsis Diagnosis and Treatment
- Venomous Animal Envenomation and Studies
- Insect Utilization and Effects
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Antimicrobial Peptides and Activities
- Blood Coagulation and Thrombosis Mechanisms
- Insect and Pesticide Research
- Chemical Synthesis and Analysis
- Adenosine and Purinergic Signaling
- Insect Resistance and Genetics
- Advanced Glycation End Products research
- Photoacoustic and Ultrasonic Imaging
- Renal function and acid-base balance
- Peptidase Inhibition and Analysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- COVID-19 Impact on Reproduction
- Vagus Nerve Stimulation Research
- Histone Deacetylase Inhibitors Research
- Protease and Inhibitor Mechanisms
The University of Sydney
2016-2025
The Heart Research Institute
2016-2021
The University of Queensland
2010-2020
Monash University
2017
Multiphoton fluorescence microscopy (MPM), using near infrared excitation light, provides increased penetration depth, decreased detection background, and reduced phototoxicity. Using stimulated emission depletion (STED) approach, MPM can bypass the diffraction limitation, but it requires both spatial alignment temporal synchronization of high power (femtosecond) lasers, which is limited by inefficiency probes. Here, we report that upconversion nanoparticles (UCNPs) unlock a new mode...
C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role C3aR in acute tissue injuries. deficiency worsened injury, which corresponded with increased numbers tissue-infiltrating neutrophils. Circulating neutrophils were significantly −/− mice after ischemia, and also mobilized more circulating...
The complement cascade is comprised of a highly sophisticated network innate immune proteins that are activated in response to invading pathogens or tissue injury. activation peptide, C5a, binds two seven transmembrane receptors, namely the C5a receptor 1 (C5aR1) and 2 (C5aR2, C5L2). C5aR2 non-G-protein-signalling whose biological role remains controversial. Some this controversy arises owing lack selective ligands for C5aR2. In study, library 61 peptides based on C-terminus was assayed...
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation distant organs. The mechanisms linking hemodynamic changes the gut to remote organ remain ill-defined. We demonstrate that mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These aggregates lead widespread occlusion of arteries, veins, microvasculature. A similar neutrophil-rich response occurred humans with acute respiratory distress syndrome. Intravital...
The anophelins are small protein thrombin inhibitors that produced in the salivary glands of Anopheles mosquito to fulfill a vital role blood feeding. A bioinformatic analysis anophelin sequences revealed presence conserved tyrosine residues an acidic environment were predicted be post-translationally sulfated vivo. To test this prediction, insect cell expression two proteins, from albimanus and gambiae, was performed, followed by mass spectrometry, which showed heterogeneous sulfation at...
The anaphylatoxin C5a generated by activation of the innate immunity complement system is a potent inflammatory peptide mediator through G-protein-coupled receptor C5aR (CD88) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, T and mast cells. Inflammatory cells infiltrate initiate development fibrosis chronically hypertensive heart. In this study, we have investigated whether treatment with selective antagonist prevents cardiovascular remodeling...
Significance Cardiovascular disease represents a significant health challenge, with towering economic and social costs resulting from the high levels of associated morbidity mortality. For conditions undesired blood clotting, treatment options remain limited are accompanied by side effects. Using rapid chemical ligation platform, 34 homogeneously modified variants tick anticoagulant proteins were generated. Access to this synthetic protein library enabled key structure–activity relationships...
Neutrophil infiltration to ischemic tissues following reperfusion worsens injury. A key driver of neutrophil recruitment and activation is the complement factor C5a, which signals through two receptors, C5aR1 C5aR2. In this study, we used a neutrophil-dependent mouse model intestinal ischemia-reperfusion (IR) injury investigate underexplored role C5aR2 in mobilization, recruitment, disease outcomes. We show that IR induces rapid mobilization along with concomitant reduction plasma C5a levels...
The inflammatory response is characterized by increased endothelial permeability, which permits the passage of fluid and cells into interstitial spaces. Eph/ephrin receptor ligand system plays a role in inflammation through signaling cascade, modifies Rho-GTPase activity. We hypothesized that blocking using an EphA4-Fc would result decreased tissue injury model ischemia/reperfusion (I/R) injury. Mice undergoing intestinal I/R pretreated with had significantly reduced compared to mice...
Free fatty acid 2 receptor (FFA2) is highly expressed on neutrophils and, when activated by its cognate ligand acetate, generates potent anti-inflammatory activities. The roles of FFA2 and acetate have not been explored in ischemia-reperfusion injury (IRI). We therefore examined the function therapeutic potential to reduce tissue an acute model intestinal IRI. superior mesenteric artery wild-type (WT) FFA2−/− mice was briefly occluded then reperfused following treatment with or vehicle....
Blood feeding arthropods, such as leeches, ticks, flies and mosquitoes, provide a privileged source of peptidic anticoagulant molecules. These primarily operate through inhibition the central coagulation protease thrombin by binding to active site either exosite I or II. Herein, we describe rational design novel class trivalent inhibitors that simultaneously block both exosites well site. engineered hybrids were synthesized using tandem diselenide-selenoester ligation (DSL) native chemical...
The receptor for advanced glycation endproducts (RAGE) can engage a diverse class of ligands and contribute to the immune inflammatory response infection injury. It is known be pathogenic in many diseases, including ischemia/reperfusion (IR) injuries several tissues; however, its role has not been investigated IR intestine date. Mesenteric (or intestinal) leads recruitment cells into intestinal interstitial spaces, which markedly disrupts mucosa. IR-induced mucosal injury accompanied by...
Abstract Blood feeding arthropods, such as leeches, ticks, flies and mosquitoes, provide a privileged source of peptidic anticoagulant molecules. These primarily operate through inhibition the central coagulation protease thrombin by binding to active site either exosite I or II. Herein, we describe rational design novel class trivalent inhibitors that simultaneously block both exosites well site. engineered hybrids were synthesized using tandem diselenide‐selenoester ligation (DSL) native...
Eine neue Klasse von trivalenten Thrombin-Inhibitoren wird Pedro José Barbosa Pereira, Richard J. Payne und Mitarbeitern in ihrem Forschungsartikel auf S. 5408 vorgestellt. Diese Inhibitoren wurden gezielt entworfen, indem native Sulfopeptid-Thrombin-Inhibitoren aus drei verschiedenen Wirbellosen hybridisiert wurden: Variegin der Bont-Zecke, Anophelin Anopheles-Mücke TTI Tsetsefliege. Nach Fusionierung mittels bidirektionaler Peptidsynthese Peptidligations-Technologien zeigten die...