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  • ||||||||||  Journal:  Novel aspects of the assembly and activation of inflammasomes with focus on the NLRC4 inflammasome. (Pubmed Central) -  Jun 15, 2019   
    Recent biochemical studies of pro-caspase-1 and an adapter protein known as ASC suggest that inflammasomes act to initiate self-generating effector filaments responsible for activating caspase-1 and initiating downstream signaling. These studies have suggested a model of molecular events from sensor activation to inflammasome formation that may describe processes that are universal to inflammasome formation.
  • ||||||||||  Journal:  USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation. (Pubmed Central) -  Jun 7, 2019   
    Using CRISPR/Cas9 in the macrophage cell line THP-1, we show that inflammasome activation is reduced when both USP7 and USP47 are knocked down. Altogether, these data reveal a new post-transcriptional role for USP47 and USP7 in inflammation by regulating inflammasome activation and the release of the pro-inflammatory cytokines IL-1β and IL-18, and implicate dual USP7 and USP47 inhibitors as potential therapeutic agents for inflammatory disease.
  • ||||||||||  Journal:  Allicin attenuated chronic social defeat stress induced depressive-like behaviors through suppression of NLRP3 inflammasome. (Pubmed Central) -  Jun 7, 2019   
    Finally, allicin supplementation inhibited the Nucleotide-binding oligomerization domain containing 3 (NLRP3) inflammasome hyperactivity, and the expressions of inflammasome components, such as ACS, caspase-1, and IL-1β in the hippocampus of CSDS mice. Allicin attenuated depressive-like behaviors of CSDS mice through reducing neuroinflammation, ameliorating iron abnromal accumulation, balacing oxidative stress, and attenuation neuronal apoptosis in the hippocampus via suppression of NLRP3 inflammasome.
  • ||||||||||  Journal:  Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis. (Pubmed Central) -  Jun 7, 2019   
    More importantly, the inhibition of pyroptosis restored the bone formative property, attenuated the aberrant activation of osteoclast in vitro and reversed bone injury in vivo. Our study identified pyroptosis as a key pathway in osteomyelitis and elaborated that the inhibition of pyroptosis could attenuate S. aureus-induced bone destruction in osteomyelitis, providing a potential treatment target to osteomyelitis.
  • ||||||||||  Journal:  O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells. (Pubmed Central) -  Jun 6, 2019   
    Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction. Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
  • ||||||||||  Journal:  Desiccating stress worsens alkali burn injury by magnifying caspase-8-induced imbalance of NLRP3 and NLRP6. (Pubmed Central) -  Jun 5, 2019   
    Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells. We reveal novel discoveries of an innate immune pathway mediated by the imbalanced activation of NLRP3 and NLRP6 promoted by caspase-8 activation in AB and secondary dry eye and create new intervention strategies to treat inflammatory diseases.
  • ||||||||||  Clinical, Journal:  Association of NLRP3 single nucleotide polymorphisms with ulcerative colitis: A case-control study. (Pubmed Central) -  Jun 5, 2019   
    We reveal novel discoveries of an innate immune pathway mediated by the imbalanced activation of NLRP3 and NLRP6 promoted by caspase-8 activation in AB and secondary dry eye and create new intervention strategies to treat inflammatory diseases. Despite no significant association between three investigated SNPs and disease, "GG" and "CG" genotypes of rs10754558 have been significantly associated with disease.
  • ||||||||||  Journal:  Leishmania donovani evades Caspase 1 dependent host defense mechanism during infection. (Pubmed Central) -  Jun 4, 2019   
    Further, siRNA mediated knock-down of caspase 1 in macrophage cells (THP-1) resulted in significantly higher parasitic burden validating the importance of caspase 1 in the host defense mechanism. Taken together, our data suggests that the parasite inhibits caspase 1 activation to evade the inflammatory nature of pyroptosis.
  • ||||||||||  Journal:  HYPOTHYROIDISM INCREASES EXPRESSION OF STERILE INFLAMMATION PROTEINS IN RAT HEART TISSUE. (Pubmed Central) -  Jun 3, 2019   
    In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.
  • ||||||||||  PMX205 / Teva
    Journal:  Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis. (Pubmed Central) -  May 31, 2019   
    ...The C5a receptor 1 (C5aR1) was inhibited with the C5a receptor antagonist PMX205 (1.5 mg/kg)...In contrast, inhibition of C5aR1-mediated inflammation diminished expression of major pro-inflammatory mediators, but unlike C6 inhibition, it did not stop progression of neurological disability completely. Our study suggests that MAC is a key driver of neuroinflammation in this model, thereby MAC inhibition might be a relevant treatment for chronic neuroinflammatory diseases.
  • ||||||||||  Journal:  A role of inflammasomes in the pathogenesis of neurological and mental diseases (Pubmed Central) -  May 31, 2019   
    The review discusses the involvement of NLRP3 inflammasome and other their types in the development of the traumatic brain injury, ischemic and hemorrhagic stroke, brain tumors, CNS infections, Alzheimer's and Parkinson's diseases, epilepsy, amyotrophic lateral sclerosis, depressiver, and consequences of alcohol abuse. The elucidation of molecular mechanisms and signaling pathways controlled by inflammasomes will allow the development of new therapeutic measures for diseases, in which neuroinflammation plays a leading pathogenetic role.
  • ||||||||||  Review, Journal:  The Role of Calcium in Inflammation-Associated Bone Resorption. (Pubmed Central) -  May 30, 2019   
    We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.
  • ||||||||||  Review, Journal, Heterogeneity:  A Novel Insight on Endotyping Heterogeneous Severe Asthma Based on Endoplasmic Reticulum Stress: Beyond the "Type 2/Non-Type 2 Dichotomy". (Pubmed Central) -  May 30, 2019   
    Consistent with these findings, recent clinical data from a large European severe asthma cohort, in which molecular phenotyping as well as diverse clinical and physiological parameters from severe asthmatic patients were incorporated, suggest a brand new framework for endotyping severe asthma in relation to ER-associated mitochondria and inflammasome pathways. These findings highlight the view that ER stress-associated molecular pathways may serve as a unique endotype of severe asthma, and thus present a novel insight into the current knowledge and future development of treatment to overcome corticosteroid resistance in heterogeneous severe asthma.
  • ||||||||||  Kolchin (colchicine) / Incepta
    Review, Journal:  The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. (Pubmed Central) -  May 30, 2019   
    It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability. In this review, we describe the role of monocytes/macrophages and neutrophils in atherosclerosis, outline mechanisms of activation of the NLRP3 inflammasome in the setting of atherosclerosis-associated inflammation and discuss potential therapies that specifically target the NLRP3 inflammasome and/or its downstream mediators in atherosclerosis, with a particular focus on the emerging role of colchicine.
  • ||||||||||  glucopyranosyl lipid A (G100) / Merck (MSD)
    Clinical, Journal:  Effective Combination Adjuvants Engage Both TLR and Inflammasome Pathways To Promote Potent Adaptive Immune Responses. (Pubmed Central) -  May 29, 2019   
    ...The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation to induce strong adaptive responses...These data thus demonstrate that GLA-SE adjuvanticity acts through TLR4 signaling and NLRP3 inflammasome activation to promote robust Th1 and B cell responses to vaccine Ags. The findings suggest that engagement of both TLR and inflammasome activators may be a general paradigm for induction of robust CD4 T cell immunity with combination adjuvants such as GLA-SE.
  • ||||||||||  Clinical, Journal:  NLRP3 inflammasome activation in liver cirrhotic patients. (Pubmed Central) -  May 29, 2019   
    Plasma IL-1β and IL-18 levels were higher in plasma in patients with liver cirrhosis than in control subjects, and plasma IL-18 levels were significantly positively associated with Child-Pugh classification and IL-1β levels. In addition, NLRP3 and cleaved caspase-1 expression were increased in the livers of patients with cirrhosis.
  • ||||||||||  Journal:  Roles of the inflammasome in the gut‑liver axis (Review). (Pubmed Central) -  May 29, 2019   
    Therefore, further investigation of the molecular mechanisms underlying the inflammasome, involved in the gut‑liver axis, may provide important insights into the identification of a potential therapeutic target for the treatment of liver and gut diseases. The present review discusses the roles of the inflammasome in the gut‑liver axis, and the emerging associations between the inflammasome and the intestinal microbiota or the bile acids in the gut‑liver axis.