Translational research : the journal of laboratory and clinical medicine
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Overactive inflammatory responses are central to the pathophysiology of many hemolytic conditions including sickle cell disease. Excessive hemolysis leads to elevated serum levels of heme due to saturation of heme scavenging mechanisms. Extracellular heme has been shown to activate the NLRP3 inflammasome, leading to activation of caspase-1 and release of pro-inflammatory cytokines IL-1β and IL-18. ⋯ Some clinical studies indicate there is a benefit to blocking the NLRP3 inflammasome pathway in patients with sickle cell disease and other hemolytic conditions. However, a thorough understanding of the mechanisms of heme-induced inflammasome activation is needed to fully leverage this pathway for clinical benefit. This review will explore the mechanisms of heme-induced NLRP3 inflammasome activation and the role of this pathway in hemolytic conditions including sickle cell disease.
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Despite significant advances and the continuous development of novel, effective therapies to treat a variety of malignancies, cancer therapy-induced cardiotoxicity has been identified as a prominent cause of morbidity and mortality, closely competing with secondary malignancies. This unfortunate limitation has prompted the inception of the field of cardio-oncology with its purpose to provide the necessary knowledge and key information on mechanisms that support the use of the most efficacious cancer therapy with minimal or no interruption while paying close attention to preventing cardiovascular related morbidity and mortality. ⋯ In this review, we focus on describing the principal mechanisms for different classes of cancer therapies that lead to cardiotoxicity involving the NLRP3 inflammasome. We also summarize current evidence of cardio-protection with inflammasome inhibitors in the context of heart disease in general, and further highlight the potential application of this evidence for clinical translation in at risk patients for the purpose of preventing cancer therapy associated cardiovascular morbidity and mortality.
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Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the world. Inflammation is often an underlying risk factor for developing CRC. Maintaining gut homeostasis and balancing inflammation is therefore critical to prevent CRC development. ⋯ Furthermore, IRF1, a key regulator of some inflammasomes and PANoptosomes, has been implicated in CRC. It is therefore critical to consider the role of inflammasomes in effector cytokine-dependent and -independent protection as well as their role in PANoptosis to modulate CRC for therapeutic targeting. Here, we discuss the mechanisms of inflammasome activation, the functions of inflammasomes in CRC, and current obstacles and future perspectives in inflammasome and CRC research.
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Case Reports
Development of Strategies for Community Engaged Research Dissemination by Basic Scientists: A Case Study.
As depicted in the translational research continuum, dissemination of research findings to past research participants and the community-at-large is integral to improving health outcomes. Blocks in translation exist in which poor dissemination is a major contributor. Limited progress has been made on how to engage basic scientists at T1 and T2 phases to meaningfully disseminate study findings to community. ⋯ Finally, we provide competencies, informed by basic scientists, needed to engage in effective, community-engaged research dissemination. The activities, reflections, and competencies can be used by basic scientists and academic institutions as models to guide their community engaged research dissemination activities. This work supports the goal to bridge the translational research gap.