- |||||||||| Preclinical, Journal: Kanglexin, a novel anthraquinone compound, protects against myocardial ischemic injury in mice by suppressing NLRP3 and pyroptosis. (Pubmed Central) - Jan 1, 2021
In hypoxia- or lipopolysaccharide (LPS)-treated neonatal mouse ventricular cardiomyocytes, we showed that KLX (10 μM) decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling- and propidium iodide-positive cells, and pyroptosis-related proteins. We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease.
- |||||||||| Journal: Assays for Measuring the Role of MIF in NLRP3 Inflammasome Activation. (Pubmed Central) - Jan 1, 2021
These protocols can also be applied to different cell types, such as fibroblasts, neutrophils, endothelial cells, and epithelial cells, although further optimization may be required for each. We also cover the stimulation of macrophages with established NLRP3 inflammasome activators.
- |||||||||| Kineret (anakinra) / SOBI, Affibody
Journal: Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1β-mediated colitis. (Pubmed Central) - Jan 1, 2021
Finally, we showed that BTK-deficient mice are subject to severe experimental colitis and such colitis is normalized by administration of anti-IL-β or an inhibitor of IL-1β signaling, anakinra. Together, these studies strongly suggest that BTK functions as a physiologic inhibitor of NLRP3 inflammasome activation; they thereby explain the fact that XLA patients are prone to develop Crohn's disease.
- |||||||||| Preclinical, Journal: Angiostrongylus cantonensis activates inflammasomes in meningoencephalitic BALB/c mice. (Pubmed Central) - Dec 31, 2020
In this study, we aimed to investigate the mechanism of inflammasome activation upon A. cantonensis infection in a mouse model. This study provides evidence that A. cantonensis infection can activate NLRP1B and NLRC4 inflammasomes and promote pyroptosis to cause meningoencephalitis.
- |||||||||| Journal: Could Sars-Cov2 affect MS progression? (Pubmed Central) - Dec 31, 2020
A long-term neurologic sequela arising from COVID-19 infection in multiple sclerosis (MS) patients could be related both to the increase of cytokines and the activation of NLRP3 inflammasome by the Sars-CoV2. These two mechanisms may cause a worsening of MS several months after the resolution of the infection.
- |||||||||| Review, Journal: Progress on role of extracellular ATP and its metabolite adenosine in immunoregulation: Review (Pubmed Central) - Dec 31, 2020
The change of ATP and adenosine concentration in tissue microenvironment can affect the occurrence and resolution of inflammation, which has guiding significance for exploring the prevention and treatment strategies of inflammatory diseases. In this review, we summarize that CD39/CD73 synergistically regulates the balance of extracellular ATP and adenosine, thus influencing immune cell functions through P2 receptor and P1 receptor signaling pathway.
- |||||||||| Journal: MicroRNA 223 3p Negatively Regulates the NLRP3 Inflammasome in Acute and Chronic Liver Injury. (Pubmed Central) - Dec 30, 2020
miR-223 3p disrupted the activation of the NLRP3 inflammasome by impairing the synthesis of cleaved interleukin-1β (IL-1β), mature IL-1β, and NLRP3, and the activation of caspase-1 p10 in both EAH and fibrotic NASH. Our data enlightens miR-223 3p as a post-transcriptional approach to treat acute and chronic hepatitis by silencing the activation of the NLRP3 inflammasome.
- |||||||||| OvaSave (ovalbumin) / Sangamo Therapeutics
Preclinical, Journal: Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation. (Pubmed Central) - Dec 30, 2020
In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells...Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases.
- |||||||||| Review, Journal: Evolution, role in inflammation, and redox control of leaderless secretory proteins. (Pubmed Central) - Dec 30, 2020
For example, a common feature of LLSP pathways is that they become active in response to stress and that they involve several distinct excretion mechanisms, including direct plasma membrane translocation, lysosome exocytosis, exosome formation, membrane vesiculation, autophagy, and pyroptosis. Further investigations of unconventional secretory pathways for LLSP secretion may shed light on their evolution and could help advance therapeutic avenues for managing pathological conditions such as diseases arising from inflammation.
- |||||||||| Journal: Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis. (Pubmed Central) - Dec 30, 2020
Further investigations of unconventional secretory pathways for LLSP secretion may shed light on their evolution and could help advance therapeutic avenues for managing pathological conditions such as diseases arising from inflammation. Our results indicate that wedelolactone promotes the Ser/Thr phosphorylation of NLRP3 to inhibit inflammasome activation and pyroptosis partly through potentiating PKA signalling, thus identifying its potential use for treating MSU-induced peritonitis and gouty arthritis.
- |||||||||| Clinical, Journal: COVID-19: A Case for Inhibiting NLRP3 Inflammasome, Suppression of Inflammation with Curcumin? (Pubmed Central) - Dec 30, 2020
Curcumin regulates several molecules in the intracellular signal transduction pathways involved in inflammation, including IBB, NF-kBERK1,2, AP-1, TGF-β, TXNIP, STAT3, PPARγ, JAK2-STAT3, NLRP3, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Due to anti-inflammatory and anti-inflammasome properties without any special side effects, curcumin can potentially play a role in the treatment of COVID-19 infection along with other drug regimens.
- |||||||||| Review, Journal: Role of pyroptosis in spinal cord injury and its therapeutic implications. (Pubmed Central) - Dec 29, 2020
Current investigations have documented that pyroptosis-regulated cell death plays a critical role in the pathogenesis of multiple neurological disorders as well as SCI. Our narrative article suggests that inhibiting the pyroptosis-regulated cell death and inflammasome components could be a promising therapeutic approach for the treatment of SCI in the near future.
- |||||||||| Review, Journal: Roles of Hydrogen Sulfide Donors in Common Kidney Diseases. (Pubmed Central) - Dec 29, 2020
HS donors suppress renal dysfunction by regulating autophagy, apoptosis, oxidative stress, and inflammation through multiple signaling pathways, such as TRL4/NLRP3, AMP-activated protein kinase/mammalian target of rapamycin, transforming growth factor-β1/Smad3, extracellular signal-regulated protein kinases 1/2, mitogen-activated protein kinase, and nuclear factor kappa B. In this review, we summarize recent developments in the effects of HS donors on the treatment of common renal diseases, including acute/chronic kidney disease, renal fibrosis, unilateral ureteral obstruction, glomerulosclerosis, diabetic nephropathy, hyperhomocysteinemia, drug-induced nephrotoxicity, metal-induced nephrotoxicity, and urolithiasis. Novel HS donors can be designed and applied in the treatment of common renal diseases.
- |||||||||| Journal: Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling. (Pubmed Central) - Dec 29, 2020
By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2 mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy.
- |||||||||| Review, Journal: Physiological and Pathological Roles of Mammalian NEK7. (Pubmed Central) - Dec 29, 2020
To date, the major function of NEK7 has been well documented in mitosis and NLRP3 inflammasome activation, but the detailed mechanisms of its regulation remain unclear. This review summarizes current advances in NEK7 research involving mitotic regulation, NLRP3 inflammasome activation, related diseases and potential inhibitors, which may provide new insights into the understanding and therapy of the diseases associated with NEK7, as well as the subsequent studies in the future.
- |||||||||| [VIRTUAL] DEVELOPMENT OF NLRP3 INHIBITORS FOR ALZHEIMER'S DISEASE () - Dec 24, 2020 - Abstract #ADPD2021ADPD_1029;
Chemical biology studies established that our small molecule NLRP3 inhibitors directly bind to the NLRP3 protein without interfering its ATPase activity. The newly designed NLRP3 inhibitors exhibited improved CNS drug-like properties and strongly encourage further development as potential AD therapeutics.
- |||||||||| [VIRTUAL] CIRCULATORY ADIPONECTIN INHIBITS IL1BETA SECRETION FROM MICROGLIA THROUGH NLRP3-INFLAMMASOME PATHWAY IN ALZHEIMER’S DISEASE MOUSE MODEL (On Demand Symposia A) - Dec 24, 2020 - Abstract #ADPD2021ADPD_722;
In addition, liver-specific expression of APNTri by AAV delivery increases the circulatory APN levels and improves memory functions in AD mice. AAV-APNTri treatment reduces microglia activation and IL1b levels in the brain of 5xFAD in which NLRP3, ASC and caspase-1 levels are also reduced in microglia. Conclusions Taken altogether, our study demonstrates the circulatory APN inhibits IL1β secretion from microglia through NLRP3 inhibition, suggesting that increasing periphery trimeric APN can be a potential AD therapy.
- |||||||||| [VIRTUAL] C9ORF72 DIPEPTIDES TRIGGER NEUROINFLAMMATION VIA THE NLRP3 INFLAMMASOME (On Demand Symposia C) - Dec 24, 2020 - Abstract #ADPD2021ADPD_300;
DPR-induced inflammasome activation was blocked by high concentration K+ in the media, indicating that K+ efflux from the cell is essential for this response. Conclusions We demonstrate that C9orf72 dipeptides activate the NLRP3 inflammasome, likely contributing to the neuroinflammation observed in patient brain. These findings highlight the inflammasome as a potential therapeutic target in C9orf72-linked FTD/MND.
- |||||||||| Journal: CdTe and CdTe@ZnS quantum dots induce IL-1ß-mediated inflammation and pyroptosis in microglia. (Pubmed Central) - Dec 23, 2020
This study provided two methods to alleviate the toxicity of cadmium-containing QDs, in which one is to encapsulate bare-core QDs with a shell and the other is to inhibit their toxic pathways. Since the latter way is more effective than the former one, it is significant to evaluate QDs through a mechanism-based risk assessment to identify controllable toxic targets.
- |||||||||| Journal: Inflammasome Signaling and other Factors Implicated in Atherosclerosis Development and Progression. (Pubmed Central) - Dec 23, 2020
The activities of these mature cytokines and inflammatory factors produced by other inflammatory pathways, lead to arterial inflammation and eventually arterial occlusion, which can result in life-threatening complications such as myocardial infarction and stroke. Therefore, it is essential to seek out more precise mechanisms for activation of inflammasomes and other inflammatory pathways for the development of therapeutic strategies of atherosclerosis.
- |||||||||| Review, Journal: The role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis. (Pubmed Central) - Dec 23, 2020
The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C. albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C. albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
- |||||||||| selisistat (SEN-196) / AOP Orphan Pharma
Journal: FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway. (Pubmed Central) - Dec 23, 2020
The protective roles of FNDC5 were prevented by SIRT-1 inhibitor EX527, AMPK inhibitor compound C, or integrin receptor inhibitor GLPG0187...FNDC5 deficiency deteriorated Ang II-induced oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in primary aortic VSMCs of mice, which were prevented by exogenous FNDC5. These results indicate that FNDC5 deficiency aggravates while exogenous FNDC5 alleviates the Ang II-induced vascular oxidative stress and NLRP3 inflammasome activation via the AMPK-SIRT1 signal pathway in VSMCs.
- |||||||||| Review, Journal: MicroRNAs as important regulators of the NLRP3 inflammasome. (Pubmed Central) - Dec 20, 2020
MicroRNAs have recently been recognized as crucial regulators of the NLRP3 inflammasome. In this review, we summarize the current understanding of the role of miRNAs in the regulation of NLRP3 inflammasome complexes and their impact on the pathogenesis of inflammatory disease processes.
- |||||||||| Review, Journal: Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease. (Pubmed Central) - Dec 20, 2020
In this review, we summarize the current understanding of the role of miRNAs in the regulation of NLRP3 inflammasome complexes and their impact on the pathogenesis of inflammatory disease processes. Overall, we recommend that the microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome can be a potential target for PD treatment.
- |||||||||| atorvastatin / Generic mfg.
Journal: Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells. (Pubmed Central) - Dec 20, 2020
Overall, we recommend that the microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome can be a potential target for PD treatment. These results demonstrated that atorvastatin regulated pyroptosis via the lncRNA NEXN-AS1-NEXN pathway, which provides a new insight into the mechanism of how atorvastatin promotes non-lipid-lower effects against the development of atherosclerosis and gives new directions on how to reverse atherosclerosis.
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