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Scientific Publications
Hepatic cell junctions: Pulling a double-duty
24/10/2024Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in the structural and functional organization of multicellular tissues, including in liver. Specifically, hepatic cell junctions mediate intercellular adhesion and communication between liver cells. The establishment of the hepatic cell junction network is a prerequisite for normal liver functioning. Hepatic cell junctions indeed support liver-specific features and control essential aspects of the hepatic life cycle
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The role of Pannexin1 channels in cardiac ischemia/reperfusion injury
04/06/2024Pannexin1 (Panx1) is a broadly expressed glycoprotein forming heptameric channels in the plasma membrane that allow for the controlled release of ATP from cells. Extracellular ATP is a crucial signaling molecule during inflammation and injury responses, and by stimulating purinergic (P2) receptors it amplifies NLRP3 inflammasome activation, enhances leukocyte infiltration, and provides a positive feedback loop in T lymphocytes, leading to their sustained activation. Extracellular ATP is rapidly converted to adenosine through the action of CD39 and CD73 ectonucleotidases, which dampens inflammation and promotes the resolution of tissue injury.
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Determination of structural features that underpin the pannexin1 channel inhibitory activity of the peptide 10Panx1
03/06/2024Pannexin1 channels facilitate paracrine communication and are involved in a broad spectrum of diseases. Attempts to find appropriate pannexin1 channel inhibitors that showcase target-selective properties and in vivo applicability remain nonetheless scarce. However, a promising lead candidate, the ten amino acid long peptide mimetic 10Panx1 (H-Trp1-Arg2-Gln3-Ala4-Ala5-Phe6-Val7-Asp8-Ser9-Tyr10-OH), has shown potential as a pannexin1 channel inhibitor in both in vitro and in vivo studies.
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Structure-Based Design and Synthesis of Stapled 10Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases
03/06/2024Following a rational design, a series of macrocyclic (“stapled”) peptidomimetics of 10Panx1, the most established peptide inhibitor of Pannexin1 (Panx1) channels, were developed and synthesized. Two macrocyclic analogues SBL-PX1-42 and SBL-PX1-44 outperformed the linear native peptide
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Nanobody-based pannexin1 channel inhibitors reduce inflammation in acute liver injury
13/10/2023The opening of pannexin1 channels is considered as a key event in inflammation. Pannexin1 channel-mediated release of adenosine triphosphate triggers inflammasome signaling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases
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Pannexin1 channels in the liver: an open enemy
29/07/2023Pannexin1 proteins form communication channels at the cell plasma membrane surface, which allow the transfer of small molecules and ions between the intracellular compartment and extracellular environment. In this way, pannexin1 channels play an important role in various cellular processes and diseases.
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Pannexin1 channels-a potential therapeutic target in inflammation
28/12/2022An exaggerated inflammatory response is the hallmark of a plethora of disorders. ATP is a central signaling molecule that orchestrates the initiation and resolution of the inflammatory response by enhancing activation of the inflammasome, leukocyte recruitment and activation of T cells.
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Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods
28/12/2022One of the major mechanisms of drug-induced liver injury includes mitochondrial perturbation and dysfunction. This is not a surprise, given that mitochondria are essential organelles in most cells, which are responsible for energy homeostasis and the regulation of cellular metabolism.
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Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals
28/12/2022Drug-induced liver injury, including cholestasis, is an important clinical issue and economic burden for pharmaceutical industry and healthcare systems. However, human-relevant in vitro information on the ability of other types of chemicals to induce cholestatic hepatotoxicity is lacking. This work aimed at investigating the cholestatic potential of non-pharmaceutical chemicals using primary human hepatocytes cultured in 3D spheroids.
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Osteoarthritis: Mechanistic Insights, Senescence, and Novel Therapeutic Opportunities
10/10/2022Osteoarthritis (OA) is the most common joint disease. In the last years, the research community has focused on understanding the molecular mechanisms that led to the pathogenesis of the disease, trying to identify different molecular and clinical phenotypes along with the discovery of new therapeutic opportunities. Different types of cell-to-cell communication mechanisms have been proposed to contribute to OA progression, including mechanisms mediated by connexin43 (Cx43) channels or by small extracellular vesicles.
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