Daniel A. Lawrence

Soluble Thrombomodulin Links Viremia and Mortality During COVID‐19: Results From the ACTIV‐4a Trial

Benjamin E. Zuchelkowski, Kyle Inman, S Mehdi Nouraie, Neeharika Beru et autres

Background COVID‐19 and other respiratory viral infections can cause cardiovascular complications. SARS‐CoV‐2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this …

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Endothelial cell-derived plasminogen activator inhibitor-1 potentiates thrombosis in antiphospholipid syndrome

Yuzhou Gan, Wenying Liang, LIU Chao, Srilakshmi Yalavarthi et autres

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays a key role in modulating fibrinolysis. However, its role in the thrombotic autoimmune disease known as antiphospholipid syndrome (APS) remains understudied. METHODS: We characterized PAI-1 expression by APS endothelial cells through single-cell RNA sequencing (scRNA-seq) of …

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A stromal PAI1-tPA axis orchestrates immunosuppression in pancreatic cancer

Tenzin Ngodup, Brynn E. Elson, Ashley M. Mello, Sean Hannifin et autres

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a dense desmoplastic stroma and an immunosuppressive tumor microenvironment that contribute to therapeutic resistance. Here, we identify plasminogen activator inhibitor 1 (PAI1) as a stroma-derived mediator of immune evasion and tumor progression in …

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A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model

Enming J. Su, Pei-Suen Tsou, Mark Warnock, Natalya M. Subbotina et autres

Systemic sclerosis (SSc) is a complex and heterogeneous condition characterized by progressive fibrosis in multiple organs. Recent studies implicate plasminogen activator inhibitor-1 (PAI-1) in the pathogenesis of SSc, and PAI-1 is considered as a potential target for therapy. Here, using single-cell and …

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Multi-parametric longitudinal imaging of cerebral biomarkers in a rodent model of Alzheimer’s disease

Tianqu Zhai, Wei Zhang, Cungen Ma, Linyu Ni et autres

This study introduces a method for longitudinally monitoring Alzheimer’s disease (AD)-related biomarkers in a rodent model utilizing a dual-modality imaging system combining photoacoustic microscopy (PAM) and confocal fluorescence microscopy (CFM). Using a cranial window transparent to both light and ultrasound, we examined …

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PAI-1 Inhibition in experimental venous thrombosis

Maxim E. Shaydakov, Cory D. Emal, Joshua P Rainey, Daniel A. Lawrence et autres

Background A novel PAI-1 inhibitor, MDI-2268, has been recently developed. The aim of the study was to evaluate the antithrombotic effects and safety of the MDI-2268 in acute venous thrombosis (VT) in vivo. Methods C57BL/6 mice, 10–12 weeks old, weighing 20–25g, were …

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Occludin acts as a dynein adaptor regulating permeability and collateral angiogenesis

Xuwen Liu, Enming J. Su, Alyssa Dreffs, John P. Gillies et autres

Previous studies of the tight junction protein occludin (OCLN) suggest that multiple phosphorylation sites on the carboxy-terminal domain contribute a regulatory role in vascular barrier properties. However, gene deletion studies failed to identify a clear functional role for OCLN, despite multiple phenotypic …

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Face Validation of an Artificial Intelligence Driven Tool for Clinical Triaging in Australian Public Oral Healthcare: A Pilot Study

Tan Minh Nguyen, Vito Carlo Alberto Caponio, Ravikumar Rajappa, Daniel A. Lawrence et autres

OBJECTIVES: The adoption of artificial intelligence (AI) technology holds significant potential to drive innovation for value-based healthcare for Victorian public oral healthcare, Australia. This pilot study compared the clinical triage decision outcome of experienced dentists in prioritizing consumers with urgent dental care …

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Immersion‐Based Clearing and Autofluorescence Quenching in Myocardial Tissue

Victoria Sturgess, Nadia K. Korovesis, Domingo Uceda, Alí Francisco Citalán‐Madrid et autres

OBJECTIVE: Recent innovations in optical microscopy and tissue preparation permit 3D visualization of complex microvascular networks. Tissue clearing techniques improve light penetration and extend imaging depth. Typically, perfusion-based approaches are used for vascular labeling and tissue clearing. However, immersion-based methodologies provide enhanced …

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Targeting Plasminogen Activator Inhibitor-1 with a Novel Small Molecule Inhibitor Attenuates Lung Fibrosis

Thomas H. Sisson, S.M. Fortier, Lam C. Tsoi, Roxann Alonzo et autres

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Targeting autophagy and plasminogen activator inhibitor-1 increases survival and remodels the tumor microenvironment in glioblastoma

Sophie Shifman, Daniel P. Radin, Aryan Sharma, Francesca Ferraresso et autres

BACKGROUND: Glioblastoma (GBM), the most common and aggressive type of primary brain tumor, engages multiple survival mechanisms, including autophagy. GBM exploits both degradative and secretory autophagy pathways to support tumor growth and limit the efficacy of standard-of-care treatments. We have previously shown …

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Occludin Acts as a Dynein Adaptor Regulating Permeability and Collateral Angiogenesis

Xuwen Liu, Enming J. Su, Alyssa Dreffs, John P. Gillies et autres

Abstract Previous studies of the tight junction protein occludin (OCLN) suggest that multiple phosphorylation sites on the carboxy-terminal domain contribute a regulatory role in vascular barrier properties. However, gene deletion studies failed to identify a clear functional role for OCLN, despite multiple …

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