- |||||||||| Journal, IO biomarker: Oleoylethanolamide Protects Against Acute Liver Injury by Regulating Nrf-2/HO-1 and NLRP3 Pathways in Mice. (Pubmed Central) - Feb 5, 2021
In addition, HO-1 inhibitor ZnPP blocked the therapeutic effects of OEA on LPS/D-Gal-induced liver damage and oxidative stress, suggesting crucial role of Nrf-2/HO-1 pathway in the protective effects of OEA in acute liver injury. Together, these findings demonstrated that OEA protect against the LPS/D-Gal-induced acute liver injury in mice through the inhibition of apoptosis, oxidative stress and inflammation, and its mechanisms might be associated with the Nrf-2/HO-1 and NLRP3 inflammasome signaling pathways.
- |||||||||| Review, Journal: Mitochondrial Dysfunction in Astrocytes: A Role in Parkinson's Disease? (Pubmed Central) - Feb 5, 2021
Emerging evidence suggests that many astrocytic functions, including glutamate metabolism, Ca signaling, fatty acid metabolism, antioxidant production, and inflammation are dependent on healthy mitochondria. Here, we review how mitochondrial dysfunction impacts astrocytes, highlighting translational gaps and opening new questions for therapeutic development.
- |||||||||| Journal: Protein Kinase-Mediated Decision Between the Life and Death. (Pubmed Central) - Feb 5, 2021
Whereas, the activation process of IKK, the functions of NEMO ubiquitination, IKK-related non-canonical pathway and the nuclear transportation of NEMO and functions of IKKα are still debated in cell death. In addition, cluster of differentiation 95 (CD95)-mediated non-apoptotic signaling and CD95- death-inducing signaling complex (DISC) interactions are waiting for clarification.
- |||||||||| Journal: Dark-Side of Exosomes. (Pubmed Central) - Feb 5, 2021
On the other hand, the "inflammasome-induced" exosomes can activate inflammatory responses in recipient cells. In this chapter protein kinases-related checkpoints are emphasized considering the regulation of exosome biogenesis, secretory traffic, and their impacts on cell death, tumor growth, immune system, and obesity.
- |||||||||| glibenclamide / Generic mfg.
Preclinical, Journal: NLRP3 inhibitor glibenclamide attenuates high-fat diet and streptozotocin-induced non-alcoholic fatty liver disease in rat: studies on oxidative stress, inflammation, DNA damage and insulin signalling pathway. (Pubmed Central) - Feb 4, 2021
Immunohistochemical and immunoblotting findings showed that GLB improved the hepatic expressions of inflammatory markers (NLRP3, ASC, caspase-1, IL-1β, NF-κB), anti-oxidant markers (SOD, catalase) and insulin signalling markers (p-AKT, p-GSK-3β, p-IRS). Hepatoprotective effects of GLB was mediated by decreasing the levels of glucose, triglycerides, cholesterol, DNA damage, apoptosis and inflammatory markers, and by improving the anti-oxidant status and insulin signalling pathway in HFD fed rat.
- |||||||||| Journal: Abnormal uterine inflammation in obstetric syndromes: molecular insights into the role of chemokine decoy receptor D6 and inflammasome NLRP3. (Pubmed Central) - Feb 4, 2021
The available evidence suggests that: a) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; b) there is a role for abnormal expression and function of D6 decoy receptor at the feto-maternal interface in cases of RPL and PTD; c) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets.
- |||||||||| Review, Journal: Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality. (Pubmed Central) - Feb 4, 2021
Therefore, blocking the inflammatory arm and boosting the interferon production arm of nucleic acid-sensing pathways could facilitate early control of viral replication and dissemination, prevent disease progression, and cytokine storm development. We also discuss the rationale behind therapeutic modalities targeting these sensing pathways and their implications in the treatment of COVID-19.
- |||||||||| Review, Journal: Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies. (Pubmed Central) - Feb 4, 2021
In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.
- |||||||||| Journal: Scutellarin inhibits caspase-11 activation and pyroptosis in macrophages via regulating PKA signaling. (Pubmed Central) - Feb 4, 2021
Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.
- |||||||||| Journal: Vitamin D insufficiency increases risk of chronic pain among African Americans experiencing motor vehicle collision. (Pubmed Central) - Feb 3, 2021
Further studies are needed to assess the impact of Vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering Vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, non-opioid interventions are urgently needed to address chronic pain development following MVC.
- |||||||||| Journal: Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis Following Myocardial Infarction. (Pubmed Central) - Feb 3, 2021
Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response following myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or its downstream mediators (e.g. Nlrp3, IL-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in ACS patients.
- |||||||||| Cerebrate (pinitol) / Humanetics
Preclinical, Journal: Protective effect of D-pinitol on the experimental spinal cord injury in rats. (Pubmed Central) - Feb 3, 2021
The PN causes reduction of NLRP3, TNF-α and iNOS, with increase in caspase-1 together with modulation of MAPK mediators. It has been suggested that, D-pinitol exert protective action against SCI via inhibition of apoptosis, inflammation and oxidative stress, via modulating Bcl-2 genes and MAPK pathway.
- |||||||||| Journal: Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. (Pubmed Central) - Feb 3, 2021
Adoptively transferred alloantibody and mouse complement deposition induced IL-15/IL-15Rα expression by human ECs lining human coronary artery grafts in immunodeficient mice and enhanced intimal CD8+ T cell infiltration, which was markedly reduced by inflammasome inhibition, linking alloantibody to acute rejection. Inhibiting MAC signaling may similarly limit other complement-mediated pathologies.
- |||||||||| selenomethionine (SLM) / University of Iowa, Holden Comprehensive Cancer Center
Journal: Inhibition of Lipopolysaccharide-Induced Inflammation of Chicken Liver Tissue by Selenomethionine via TLR4-NF-κB-NLRP3 Signaling Pathway. (Pubmed Central) - Feb 2, 2021
Inflammatory factors (MyD88, NF-κB, TNF-α, IL-1β, IL-6, IL-12, IL-18, iNOS, and COX-2), heat shock proteins (HSP27, HSP60, HSP70, and HSP90), and the expression of NLRP3 and caspase-1 increased in the Con+LPS group compared with those in the Con group, while they were lower in the Se+LPS group than in the Con+LPS group. We concluded that selenomethionine inhibits the LPS-induced inflammation of liver tissue via suppressing the TLR4-NF-κB-NLRP3 signaling pathway.
- |||||||||| Journal: Genetic analysis of nucleotide-binding leucine-rich repeat (NLR) receptors in multiple sclerosis. (Pubmed Central) - Feb 2, 2021
Genotyping these variants in 2503 MS cases and 1076 healthy controls did not result in statistically significant differences between groups, and segregation analysis within MS families was largely unsupportive of co-segregation of these variants with disease. However, the identification of MS patients harboring rare homozygote variants in NLRP1 (p.Ile601Phe and p.Ser1387Ile), a variant in NLRP3 (p.Leu832Ile) resulting in the substitution of a critical amino acid for the formation of its leucine-rich repeat domain, and several MS patients with NLRC4 variants (p.Arg310Ter and p.Glu600Ter) causing protein truncations suggest that rare protein-altering variants in inflammasome-activating NLR receptors may contribute to MS risk.
- |||||||||| Journal: P2X7: An Untapped Target for the Management of Cardiovascular Disease. (Pubmed Central) - Feb 2, 2021
IL-1β and IL-18 inhibition has shown efficacy in clinical trials reducing major adverse cardiac events, including myocardial infarction, and heart failure. With several P2X7 antagonists available with proven safety margins, P2X7 antagonism could represent an untapped potential for therapeutic intervention in cardiovascular disorders.
- |||||||||| Journal: Same pollution sources for climate change might be hyperactivating the NLRP3 inflammasome and exacerbating neuroinflammation and SARS mortality. (Pubmed Central) - Feb 2, 2021
Furthermore, there are evidences relating organ inflammation caused by not only outdoor long-term but also short-term inhaled radioisotopes contained in high polluted air or in household natural radioactive background aerosols, in addition to SARS-COV-2 attached to bioaerosols, which are related with a worst evolution of severe acute respiratory syndrome patients. Reactive oxygen species (ROS) production induced by the interaction with environmental ionizing radiation contained in pollution is pointed out as a critical mechanism that predispose mainly to elder population, but not excluding young subjects, presenting previous chronic conditions of lung inflammation or neuroinflammation, which can lead to the most serious consequences.
- |||||||||| Journal: SO derivatives induce dysfunction in human trophoblasts via inhibiting ROS/IL-6/STAT3 pathway. (Pubmed Central) - Feb 2, 2021
SO derivatives exert toxic effects on trophoblasts which results in: suppressing cellular viability and intracellular ROS level, interfering with cell proliferation through arresting cell cycle, inducing cell apoptosis, disturbing inflammation-related cytokines secretion and inhibiting motility. Decreased ROS/IL-6/STAT3 levels play a role in inhibited cell viability, cell cycle arrest, apoptosis and defective motility.
- |||||||||| Review, Journal: Inflammation in Periodontal Disease: Possible Link to Vascular Disease. (Pubmed Central) - Feb 2, 2021
Some of the mechanisms underpinning the links between inflammation, diabetes, CVD and PD are also discussed. Finally, we review available epidemiological data and other reports to assess possible links between oral health and CVD.
- |||||||||| Journal: Inhibition of the NLRP3 inflammasome prevents ovarian aging. (Pubmed Central) - Feb 2, 2021
Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3 mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.
- |||||||||| Journal: The different faces of the macrophage in asthma. (Pubmed Central) - Jan 30, 2021
The prognostic value of NUD, especially when occurring in the setting of LE is not known and needs to be further investigated. The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open.
- |||||||||| Journal: A New NLRP3 Inflammasome Inhibitor, Dioscin, Promotes Osteogenesis. (Pubmed Central) - Jan 30, 2021
The increased formation of mineralized nodules after the application of dioscin further indicates that dioscin has the potential to promote osteogenesis. The above results suggest dioscin can be a potential root canal irrigation or root canal sealant for the treatment of refractory apical periodontitis.
- |||||||||| Clinical, Journal: Whole-Exome Sequencing of Patients with Posterior Segment Uveitis. (Pubmed Central) - Jan 30, 2021
A larger cohort and functional studies will help validate the pathogenicity of the mutations identified. In specific cases, whole exome sequencing can help diagnose non-syndromic uveitis patients harboring known variants for syndromic inflammatory diseases.
- |||||||||| Review, Journal: The potential involvement of P2X7 receptor in COVID-19 pathogenesis: a new therapeutic target? (Pubmed Central) - Jan 30, 2021
The most investigated is the NLRP3 inflammasome, which can be activated by various stimuli, such as the recognition of extracellular ATP by the P2X7 receptor. Based on published literature, it is shown evidence that supports the idea that the P2X7R/NLRP3 axis may be involved in the immune dysregulation caused by the SARS-CoV-2 infection.
- |||||||||| Journal: Effects of hyperbaric oxygen on NLRP3 inflammasome activation in the brain after carbon monoxide poisoning. (Pubmed Central) - Jan 30, 2021
Furthermore, HBO2 decreased NLRP3, absent in melanoma 2 (AIM2), caspase-1, and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain mRNA and protein levels, and reduced brain and serum concentrations of IL-1β and -18 and NADPH oxidase. These results indicate that HBO2 suppresses the inflammatory response after ACOP by blocking NLRP3 inflammasome activation, thereby alleviating cognitive deficits.
- |||||||||| Journal: Anti-inflammatory potential of Quercetin in COVID-19 treatment. (Pubmed Central) - Jan 30, 2021
Quercetin suppresses the NLRP3 inflammasome by affecting these regulators. Quercetin, as an anti-inflammatory, antioxidant, analgesic and inflammatory compound, is probably a potential treatment for severe inflammation and one of the main life-threatening conditions in patients with COVID-19.
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