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  • ||||||||||  Kineret (anakinra) / SOBI, Affibody
    Journal:  Outcome of Cochlear Implantation in NLRP3-related Autoinflammatory Inner Ear Disorders. (Pubmed Central) -  Apr 22, 2021   
    DUSP14 may effectively protect against isoflurane-induced neuro-inflammation, brain damage and cognitive dysfunction, indicating that DUSP14 may be a potential predictor and therapeutic target for POCD. This is the first report to present outcome of CI among subjects with a confirmed NLRP3 genetic etiology and resultant systemic inflammation, and suggests that CI is a viable treatment option in this disease entity.
  • ||||||||||  Journal:  Immunological Aspects of Age-Related Macular Degeneration. (Pubmed Central) -  Apr 21, 2021   
    We will also assess how interactions between the immune system and infectious pathogens could potentially modulate AMD pathobiology via alterations in in immune effector mechanisms. We will conclude by reviewing the paradigm of "response to injury," which provides a means to integrate various immunologic mechanisms along with nonimmune mechanisms of tissue injury and repair as a model to understand the pathobiology of AMD.
  • ||||||||||  Review, Journal:  Potential role of mitochondria in gastric cancer detection: Fission and glycolysis. (Pubmed Central) -  Apr 21, 2021   
    The dysfunction and dysregulation of mitochondria have been associated with several ageing and degenerative diseases, as well as cancer. The present review focuses on energy metabolism and mitochondrial dynamics, and summarizes the changes in gastric carcinogenesis, the diagnosis of EGC and indicates potential targeted treatments.
  • ||||||||||  Preclinical, Journal:  Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice. (Pubmed Central) -  Apr 20, 2021   
    Treatment with PA induced ASC assembling and IL-1β secretion in macrophages, and this PA-induced IL-1β secretion was significantly suppressed in NLRP3-knockout macrophages. These results indicate that transient higher levels of PA exposure in pregnant mice activates NLRP3 inflammasome and induces placental inflammation, resulting in the incidence of absorption.
  • ||||||||||  Review, Journal:  Circadian Control of Inflammasome Pathways: Implications for Circadian Medicine. (Pubmed Central) -  Apr 20, 2021   
    Sterile inflammation is also an important driver of atherosclerosis, and targeting the production of IL-1β has proven to be a promising approach for atherosclerosis management in humans. Interestingly, the extent of injury after fulminant hepatitis or myocardial infarction is time-of-day dependent under the control of the clock, and chronotherapy represents a promising approach for the management of pathologies involving deregulation of NLRP3 signaling.
  • ||||||||||  Journal:  NLRP3 Sensing of Diverse Inflammatory Stimuli Requires Distinct Structural Features. (Pubmed Central) -  Apr 20, 2021   
    Conserved cysteines 8 and 108 appear important for inflammasome activation by sterile, but not infectious insults. Our results define common and agonist-specific regions of NLRP3 that likely mediate ligand-specific responses, discount the hypothesis that NLRP3 inflammasome activation has a unified mechanism, and implicate NLRP3 as an integrator of agonist-specific, inflammasome activating signals.
  • ||||||||||  Review, Journal:  Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease. (Pubmed Central) -  Apr 20, 2021   
    Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis. Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress.
  • ||||||||||  Clinical, Journal:  Inflammatory Responses to Monomeric and Aggregated α-Synuclein in Peripheral Blood of Parkinson Disease Patients. (Pubmed Central) -  Apr 20, 2021   
    ASC-speck expression, as well as IL-18 and caspase-1 production and LPS and I-FABP plasma concentration, was comparable in PD and HC, indicating that α-syn does not stimulate the NLRP3 inflammasome and that PD does not associate with alterations of intestinal permeability. Interestingly, though, IL-1β and IL-6 production was increased, whereas that of IL-10 was reduced in α-syn-stimulated cells of PD compared to HC, suggesting that PD-associated neuroinflammation is not the consequence of the activation of the NLRP3 inflammasome but rather of an imbalance between proinflammatory and anti-inflammatory cytokines.
  • ||||||||||  belnacasan (VX-765) / Vertex
    [VIRTUAL] KIDNEYS ON FIRE: DECIPHERING THE ROLE OF INFLAMMASOME ACTIVATION IN HUMAN CHRONIC KIDNEY DISEASE (CKD) () -  Apr 17, 2021 - Abstract #ISNWCN2021ISN-WCN_1010;    
    This IL-1β secretion was significantly attenuated in the presence of either MCC950 (a NLRP3 specific inhibitor) or VX-765 (a caspase-1 inhibitor)...Our data provide evidence that: (1) hypoxic PTEC display lipid peroxidation and secrete HMGB1, a key danger-signal; (2) ferroptosis was the predominant PTEC death pathway in a hypoxic driven model of CKD; and (3) NLRP3 inflammasome activation within DC was a primary response to hypoxic PTEC death resulting in release of the potent pro-inflammatory cytokine IL-1β in CKD. Further investigation into these key pathobiological processes may advance the identification of future targets for therapeutic intervention or diagnostic detection in CKD.
  • ||||||||||  Journal:  Compliant Substrates Enhance Macrophage Cytokine Release and NLRP3 Inflammasome Formation During Their Pro-Inflammatory Response. (Pubmed Central) -  Apr 17, 2021   
    In summary, we show that substrate stiffness modulates the pro-inflammatory response of macrophages, that the NLRP3 inflammasome is one of the components affected by macrophage mechanosensing, and a role for actomyosin contractility in this mechanosensory response. Thus, our results contribute to a better understanding of how microenvironment stiffness affects macrophage behavior, which might be relevant in diseases where tissue stiffness is altered and might potentially provide a basis for new strategies to modulate inflammatory responses.
  • ||||||||||  Review, Journal:  Mitochondrial reactive zones in antiviral innate immunity. (Pubmed Central) -  Apr 15, 2021   
    In this review, we discuss current insights regarding the fundamental phenomena of mitochondrial-related innate immune responses, and review the specific roles of various mitochondrial subcompartments in fine-tuning innate immune signaling events. We propose that specific targeting of mitochondrial functions is a potential therapeutic approach for the management of infectious diseases and autoinflammatory disorders with an excessive immune response.
  • ||||||||||  Review, Journal:  The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis. (Pubmed Central) -  Apr 14, 2021   
    Recent researches have suggested that autophagy and inflammasome have biological effect on HSC activation. Herein, we review current studies about the impact of autophagy and NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome on liver fibrosis and the underlying mechanisms.
  • ||||||||||  Preclinical, Journal:  Overexpression of Macrophage-Inducible C-Type Lectin Mincle Aggravates Proinflammatory Responses to Streptococcus pneumoniae with Fatal Outcome in Mice. (Pubmed Central) -  Apr 14, 2021   
    Together, we show that overexpression of the pattern recognition receptor Mincle triggers increased Glc-DAG-dependent Nlrp3 inflammasome activation in professional phagocytes leading to fatal pneumococcal pneumonia in mice that is amenable to Nlrp3 inhibitor treatment. These data show that ectopic expression of the Mincle receptor confers increased susceptibility rather than resistance to S. pneumoniae in mice, thus highlighting the importance of an inducible Mincle receptor expression in response to microbial challenge.
  • ||||||||||  Biomarker, Journal:  Hypoxia-Induced S100A8 Expression Activates Microglial Inflammation and Promotes Neuronal Apoptosis. (Pubmed Central) -  Apr 14, 2021   
    Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia. These results suggested that S100A8 may be an important molecule for bidirectional microglia-neuron communication and a new therapeutic target for neurological disorders caused by microglial inflammation during hypoxia.
  • ||||||||||  Review, Journal:  Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids. (Pubmed Central) -  Apr 13, 2021   
    Emerging evidence suggests a protective role for CYP450 epoxygenase metabolites of N-3 and N-6 polyunsaturated fatty acids (PUFA), epoxylipids, which modulate various aspects of the immune system and protect mitochondria. In this article, we provide insight into the potential roles N-3 and N-6 PUFA have modulating mitochondria, inflammaging and heart failure.
  • ||||||||||  Review, Journal:  The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia. (Pubmed Central) -  Apr 13, 2021   
    The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.
  • ||||||||||  Journal:  Canonical and Non-canonical Inflammasome Activation by Outer Membrane Vesicles Derived From Bordetella pertussis. (Pubmed Central) -  Apr 13, 2021   
    Moreover, we demonstrated that BpOMVs as well as transfected B. pertussis lipooligosaccharide (BpLOS) induce caspase-11 (Casp11) and guanylate-binding proteins (GBPs) dependent non-canonical inflammasome activation. Our results elucidate the mechanism by which BpOMVs trigger one central pathway of the innate response activation that is expected to skew the adaptive immune response elicited by BpOMVs vaccination.
  • ||||||||||  Review, Journal:  Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18. (Pubmed Central) -  Apr 13, 2021   
    Clinical differences in patients with NLRP3, pyrin, and NLRP1 inflammasomopathies, and the constitutive elevation of unbound free serum IL-18 that predisposes to the development of macrophage activation syndrome (MAS) in patients with gain-of function mutations in NLRC4 led to the screening and the characterization of novel diseases presenting with constitutively elevated serum IL-18 levels, and start to unravel the biology of "high IL-18 states" that translate into the use of biomarkers that improve diagnosis and monitoring of disease activity and investigations of treatments that target IL-18 and IFN-gamma which promise to improve the management and outcome of these conditions. Lastly, advances in structural modeling by cryo-electron microscopy (cryo-EM) of gasdermin, and of NLRP3- and NLRC4-inflammasome assembly, and the characterization of post-translational modifications (PTM) that regulate inflammasome activation, coupled with high-throughput screening (HTS) of libraries of inflammasome-inhibiting compounds, promise a new generation of treatments for patients with inflammasome-mediated diseases.