Browsing by Subject "Dysfunction"

Now showing 1 - 5 of 5
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    Cell-Cell Communication Breakdown and Endothelial Dysfunction
    (Elsevier, 2020-04) Lee, Daniel D.; Schwarz, Margaret A.; Medicine, School of Medicine
    Guided by organ-specific signals in both development and disease response, the heterogeneous endothelial cell population is a dynamic member of the vasculature. Functioning as the gatekeeper to fluid, inflammatory cells, oxygen, and nutrients, endothelial cell communication with its local environment is critical. Impairment of endothelial cell-cell communication not only disrupts this signaling process, but also contributes to pathologic disease progression. Expanding our understanding of those processes that mediate endothelial cell-cell communication is an important step in the approach to treatment of disease processes.
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    Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction
    (MDPI, 2017-03-29) Wodicka, James R.; Chambers, Andrea M.; Sangha, Gurneet S.; Goergen, Craig J.; Panitch, Alyssa; Medicine, School of Medicine
    Endothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state. Multiple EC-SEAL variants were evaluated and the lead variant was found to preferentially bind to selectin-expressing ECs and smooth muscle cells (SMCs) and inhibit platelet binding and activation in a dose-dependent manner. In an in vivo model of DVT, treatment with the lead variant resulted in reduced thrombus formation. These results indicate that EC-SEAL has promise as a potential therapeutic in the treatment of endothelial dysfunction.
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    Longing For More Time
    (2014) Stoffer, Bridgit; Winship, Andrew
    My drawings and installations intertwine creating visual poems that allow my audience to view my inner world through shared experience and invites them to consider moments of honest vulnerability exposed in the quiet subtlety of what they witness. My narrative is always the starting point while I reflect upon and deepen an understanding of: the impact and resilience on seen and unseen realties, trying to rebuild out of brokenness, and our longing to preserve something lost. My work explores how one negative act can provoke determination and resolve. Through process and material exploration I’ve created ways that allow my art, much like an individual, to find a way to not simply endure, but navigate a path to thrive in the grim environments I create. Time is my true medium as I consider: temporality, lifespan, evolution and preservation. I use material and process to establish a passage of time so that I may reveal the way we hold on to things that are falling apart around us. I'm interested in making ephemeral objects that encapsulate a moment, holding it in place to somehow preserve something that would otherwise be lost even though they should not and cannot last. I expose this loss and our need to preserve what we can while holding on to the preciousness of the time we have that isn’t yet gone.
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    Mitochondrial quality control in alcohol-associated liver disease
    (Wolters Kluwer, 2024-10-24) Thoudam, Themis; Gao, Hui; Jiang, Yanchao; Huda, Nazmul; Yang, Zhihong; Ma, Jing; Liangpunsakul, Suthat; Medicine, School of Medicine
    Excessive alcohol consumption is a leading cause of alcohol-associated liver disease (ALD), a significant global health concern with limited therapeutic options. Understanding the key factors contributing to ALD pathogenesis is crucial for identifying potential therapeutic targets. Central to ALD pathogenesis is the intricate interplay between alcohol metabolism and cellular processes, particularly involving mitochondria. Mitochondria are essential organelles in the liver, critical for energy production and metabolic functions. However, they are particularly vulnerable to alcohol-induced damage due to their involvement in alcohol metabolism. Alcohol disrupts mitochondrial function, impairing ATP production and triggering oxidative stress, which leads to cellular damage and inflammation. Mitochondrial quality control mechanisms, including biogenesis, dynamics, and mitophagy, are crucial for maintaining optimal mitochondrial function. Chronic alcohol consumption disrupts mitochondrial quality control checkpoints, leading to mitochondrial dysfunction that impairs fatty acid oxidation and contributes to hepatic steatosis in ALD. Moreover, alcohol promotes the accumulation of damaged mitochondria and the release of proinflammatory components, exacerbating liver damage and inflammation. Preserving mitochondrial health presents a promising therapeutic approach to mitigate ALD progression. In this review, we provide a comprehensive overview of the effects of alcohol on mitochondrial function and quality control mechanisms, highlighting their role in ALD pathogenesis. Understanding these mechanisms may pave the way for the development of novel therapeutic interventions for ALD.
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    Molecular, metabolic, and functional CD4 T cell paralysis in the lymph node impedes tumor control
    (Elsevier, 2023) Guo, Mengdi; Abd-Rabbo, Diala; Bertol, Bruna C.; Carew, Madeleine; Lukhele, Sabelo; Snell, Laura M.; Xu, Wenxi; Boukhaled, Giselle M.; Elsaesser, Heidi; Halaby, Marie Jo; Hirano, Naoto; McGaha, Tracy L.; Brooks, David G.; Microbiology and Immunology, School of Medicine
    CD4 T cells are central effectors of anti-cancer immunity and immunotherapy, yet the regulation of CD4 tumor-specific T (TTS) cells is unclear. We demonstrate that CD4 TTS cells are quickly primed and begin to divide following tumor initiation. However, unlike CD8 TTS cells or exhaustion programming, CD4 TTS cell proliferation is rapidly frozen in place by a functional interplay of regulatory T cells and CTLA4. Together these mechanisms paralyze CD4 TTS cell differentiation, redirecting metabolic circuits, and reducing their accumulation in the tumor. The paralyzed state is actively maintained throughout cancer progression and CD4 TTS cells rapidly resume proliferation and functional differentiation when the suppressive constraints are alleviated. Overcoming their paralysis established long-term tumor control, demonstrating the importance of rapidly crippling CD4 TTS cells for tumor progression and their potential restoration as therapeutic targets.