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- | Journal: Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns in male rats. (Pubmed Central) - Jul 17, 2019
We conclude that after peripheral nerve injury, morphine treatment results in persistent DAMP release via TLR4, P2X7R and caspase-1, which are involved in formation/activation of NLRP3 inflammasomes. These DAMPs are responsible for maintaining persistent allodynia, which may be due to engagement of a positive feedback loop, in which NLRP3 inflammasomes are persistently activated by DAMPs signaling at TLR4 and P2X7R.
- | Journal: Depression and sterile inflammation: essential role of danger associated molecular patterns. (Pubmed Central) - Jul 17, 2019
However, the identification of the endogenous factors, referred to as danger-associated molecular patterns (DAMP) that activate these receptors remains understudied. Here we review the role of DAMPs in depression and highlight the clinical evidence for elevation of DAMP signaling in MDD patients and in pre-clinical animal stress models of depression.
- | Preclinical, Journal, IO Biomarker: Alpha-lipoamide inhibits renal inflammation and collagen 4 production in diabetic rats and its mechanism (Pubmed Central) - Jul 17, 2019
Correlation analysis showed that there was a significant positive correlation between the expressions of Notch2 and TLR4 in the DM group and ALM group, and the expression of Notch2 and NLRP3 were also significantly positively correlated. Conclusion ALM alleviates the renal inflammation and Col4 production in diabetic rats, which is related to the Notch2-induced inhibition of TLR4 and NLRP3 activation.
- | Preclinical, Journal: The LPS/D-Galactosamine-Induced Fulminant Hepatitis Model to Assess the Role of Ligand-Activated Nuclear Receptors on the NLRP3 Inflammasome Pathway In Vivo. (Pubmed Central) - Jul 17, 2019
Low doses of LPS in combination with the specific hepatotoxic agent D-galactosamine (D-GalN) promote liver injury in mice and induce the production of inflammatory cytokines associated with increased NLRP3 protein and caspase 1 activity, thus recapitulating the clinical picture of FH in humans. We provide a simple method to examine the involvement of nuclear receptors in NLRP3-driven fulminant hepatitis, consisting in the induction of FH, in the isolation of liver macrophages, and in the extraction and analysis of RNA content.
- | Preclinical, Journal: The platelet NLRP3 inflammasome is upregulated in a murine model of pancreatic cancer and promotes platelet aggregation and tumor growth. (Pubmed Central) - Jul 17, 2019
Moreover, interfering with platelet NLRP3 signaling significantly improved survival of tumor-bearing mice. Hence, the platelet NLRP3 inflammasome plays a critical role in PDA and might represent a novel therapeutic target.
- | Bystolic (nebivolol) / Allergan, Menarini
Journal: Nebivolol improves obesity-induced vascular remodelling by suppressing NLRP3 activation. (Pubmed Central) - Jul 16, 2019
Moreover, nebivolol treatment significantly increased of AMP-activated protein kinase activity and decreased of phosphorylation of the mammalian target of rapamycin. These results demonstrated that nebivolol improves obesity-induced vascular remodelling by attenuating NLRP3 inflammasome activation and restoring the antioxidant defence.
- | Preclinical, Journal, IO biomarker: Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice. (Pubmed Central) - Jul 13, 2019
Furthermore, baicalein reduced NOD-like receptor 3 (NLRP3) inflammasome activation and downstream interleukin-1β expression in a dose-dependent manner. Our study provided evidence for the first time that baicalein attenuated TNBS-induced colitis, at least in part, via inhibition of TLR4/MyD88 signaling cascade as well as inactivation of NLRP3 inflammasome.
- | Journal: Expression of Inflammasome complex mRNA and its targeted miRNA in Type II Diabetes mellitus: a possible predictor for the severity of Diabetic Nephropathy. (Pubmed Central) - Jul 13, 2019
Our study provided evidence for the first time that baicalein attenuated TNBS-induced colitis, at least in part, via inhibition of TLR4/MyD88 signaling cascade as well as inactivation of NLRP3 inflammasome. No abstract available
- | Review, Journal: NLRP3 inflammasome in colitis and colitis-associated colorectal cancer. (Pubmed Central) - Jul 13, 2019
One inflammasome in particular, NLRP3, has been analysed extensively in its contribution to colitis and has been shown to be associated with the development of colitis-associated colorectal cancer. This review will summarise the role of NLRP3 in intestinal inflammation, discuss some of the triggers of inflammation in the gastrointestinal tract such as diet and introduce some opportunities to use this inflammasome as therapeutic target for the treatment of colitis and colitis-associated colorectal cancer.
- | Journal: The relationship between caspase-1 related inflammasome expression and serum inflammatory cytokine levels during acute brucellosis. (Pubmed Central) - Jul 13, 2019
Caspase-1-related inflammasomes are sufficiently activated to induce the secretion of cytokines, such as IFN-γ and IL-18, to induce cellular immune response. Caspase-1 activation level should be investigated at different periods of disease in a group with high number of patients to understand the role of pyroptosis and caspase-1 in brucellosis.
- | Preclinical, Journal: RAGE-induced changes in the proteome of alveolar epithelial cells. (Pubmed Central) - Jul 13, 2019
The conclusions of the present work assist to unravel the molecular events that underlie the function of RAGE in alveolar epithelial cells and have implications for our understanding of RAGE signaling during lung injury. Our study was the first proteomic comparison showing the effects of RAGE activation from alveolar epithelial cells that constitutively express RAGE and these results can affect a wide field of lung biology, pulmonary therapeutics, and proteomics.
- | Review, Journal: Exploiting vita-PAMPs in vaccines. (Pubmed Central) - Jul 13, 2019
By mobilizing unique viability-associated innate responses, vita-PAMPs mobilize adaptive immunity that best elicits protection, including follicular T helper cell and antibody responses. Here, we review the molecular mechanisms that confer the unique adjuvanticity of vita-PAMPs and discuss their applications in vaccine design.
- | Journal: The toxicity of silica nanoparticles to the immune system. (Pubmed Central) - Jul 13, 2019
The main mechanisms were proinflammatory responses, oxidative stress and autophagy. Considering the toxicity of SiNPs, surface and shape modifications may mitigate the toxic effects of SiNPs, providing a new way to produce these nanomaterials with less toxic impaction.
- | Journal: Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1β production. (Pubmed Central) - Jul 13, 2019
Moreover, the process of NLRP3 inflammasome activation and IL-1β production in macrophages in response to T. pallidum infection involves K efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.
- | Preclinical, Journal: 2-BFI Provides Neuroprotection Against Inflammation and Necroptosis in a Rat Model of Traumatic Brain Injury. (Pubmed Central) - Jul 12, 2019
In addition, 2-BFI treatment markedly reduced cortical tissue loss as well as repressed TBI-induced increases in necroptosis and necroptosis-associated proteins, including receptor-interacting protein (RIP1), RIP3, and mixed linkage kinase domain-like (MLKL) in the pericontusional brain tissue. Taken together, these findings indicate that 2-BFI may be an effective neuroprotectant after brain trauma and warrants further study.
- | Journal: BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination. (Pubmed Central) - Jul 11, 2019
Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.
- | Tafinlar (dabrafenib) / Novartis
Journal: Phagocytosis of environmental or metabolic crystalline particles induces cytotoxicity by triggering necroptosis across a broad range of particle size and shape. (Pubmed Central) - Jul 11, 2019
...Deficiency of MLKL, siRNA knockdown of RIPK3, or inhibitors of necroptosis signaling e.g. RIPK-1 inhibitor necrostatin-1s, RIPK3 inhibitor dabrafenib, and MLKL inhibitor necrosulfonamide, partially protected tubular cells from crystalline particles cytotoxicity...Taken together, our data confirmed the involvement of necroptosis as one of the pathways leading to cell death in crystallopathies. Our data identified RIPK-1, RIPK3, and MLKL as molecular targets to limit tissue injury and organ failure in crystallopathies.
- | Journal: NLRP3 inflammasome is a key player in human vulvovaginal disease caused by Candida albicans. (Pubmed Central) - Jul 11, 2019
The most overexpressed SAP gene was SAP2, that correlated with neutrophils accumulation. Our data provide clinical evidence that the intracytoplasmic activation of NLRP3 inflammasome complex plays a critical, pathogenesis-relevant role in human VVC.
- | sirolimus / generics
Journal, IO Biomarker: Antiphospholipid Antibodies Inhibit Trophoblast Toll-like Receptor and Inflammasome Negative Regulators. (Pubmed Central) - Jul 11, 2019
Basal TAM receptor function and autophagy may serve to inhibit trophoblast TLR and inflammasome function, respectively. Impaired TAM receptor signaling and autophagy by anti-β2 GPI aPL may allow subsequent TLR and inflammasome activity leading to a robust inflammatory response.
- | Bay11-7082 / InvivoGen
Preclinical, Journal: Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats. (Pubmed Central) - Jul 11, 2019
NF-κB inhibitor Bay 11-7082 reduced IL-1β production induced by Mel+CA and prevented downregulation of AQP2 in IMCD cell suspension. In conclusion, Mel+CA treatment caused urine concentrating defect and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney.
- | Journal: Activation of the NLRP3 Inflammasome by Hyaboron, a new Asymmetric Boron-Containing Macrodiolide from the Myxobacterium Hyalangium minutum. (Pubmed Central) - Jul 11, 2019
Further functional studies revealed that hyaboron and other boronated natural compounds resulted in NLRP3 inflammasome dependent IL-1β maturation, which is most likely due to their ability to act as potassium ionophores. Moreover, besides its inflammasome-stimulatory activity in human and mouse cells, hyaboron (1) showed additional diverse biological activities, including antibacterial and antiparasitic effects.
- | Journal: PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation. (Pubmed Central) - Jul 11, 2019
Disruption of the interaction between NLRP3 and PtdIns4P on the dTGN blocked NLRP3 aggregation and downstream signalling. These results indicate that recruitment of NLRP3 to dTGN is an early and common cellular event that leads to NLRP3 aggregation and activation in response to diverse stimuli.
- | Journal: NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis. (Pubmed Central) - Jul 11, 2019
The disparity in spatial localization of IL-1β and NLRP3, observed only in active UC, which is characterized by a neutrophil-dominated lamina propria cell population, implies inflammasome-independent processing of IL-1β. Consistent with other acute inflammatory conditions, these results suggest that blocking both caspase-1 and neutrophil-derived serine proteases may provide an additional therapeutic option for treating active UC.
- | sirolimus / generics
Journal: Huangkui capsule alleviates renal tubular epithelial-mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling. (Pubmed Central) - Jul 11, 2019
The results of this study further indicated that HKC, different from RAP, can alleviate renal tubular EMT in the DN model rats, likely by inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling in the kidneys. Our findings thus provide the more accurate information in vivo about a clinical value of HKC, a traditional anti-inflammatory phytomedicine, in the treatment of the early DN patients.
- | Preclinical, Journal: Periostin contributes to renal and cardiac dysfunction in rats with chronic kidney disease: reduction of PPARα. (Pubmed Central) - Jul 11, 2019
In summary, our study demonstrates that POSTN negatively regulates PPARα expression. Targeting POSTN-PPARα axis may present a novel protective intervention to alleviate CKD and CKD-associated cardiac dysfunction.
- | Journal: P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis. (Pubmed Central) - Jul 11, 2019
We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.
- | Journal: Celastrol attenuates ox-LDL-induced mesangial cell proliferation via suppressing NLRP3 inflammasome activation. (Pubmed Central) - Jul 10, 2019
In summary, celastrol potently blocked ox-LDL-induced MC proliferation, possibly by inhibiting NLRP3 inflammasome activation. These findings also suggest that celastrol may be a potential drug for treating proliferative glomerular diseases related to obesity and lipid disorders.
- | Journal: An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes. (Pubmed Central) - Jul 7, 2019
Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood.
- | Kolchin (colchicine) / Incepta
Journal: Inhibitory effects of colchicine on inflammasomes. (Pubmed Central) - Jul 7, 2019
The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood. No abstract available
- | Kolchin (colchicine) / Incepta
Journal: Reply to: "Inhibitory effects of colchicine on inflammasomes". (Pubmed Central) - Jul 7, 2019
No abstract available No abstract available
- | Preclinical, Journal: Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome. (Pubmed Central) - Jul 6, 2019
In vitro, curcumin significantly inhibited anti-dsDNA+ serum induced expression of NLRP3 inflammasome in podocytes. Overall, these data demonstrate the potential use of curcumin in SLE treatment.
- | Journal: Anemoside B4 Protects Rat Kidney from Adenine-Induced Injury by Attenuating Inflammation and Fibrosis and Enhancing Podocin and Nephrin Expression. (Pubmed Central) - Jul 6, 2019
In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.
- | Journal: Reply: NLRP3 inflammasome as a mechanism linking depression and cardiovascular diseases. (Pubmed Central) - Jul 5, 2019
The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury. No abstract available
- | Journal: NLRP3 inflammasome: common nexus between depression and cardiovascular diseases. (Pubmed Central) - Jul 5, 2019
No abstract available No abstract available
- | Journal: ZIKV infection regulates inflammasomes pathway for replication in monocytes. (Pubmed Central) - Jul 5, 2019
Also, inhibition of inflammasome led to an increased transcriptional activity of IFNα, MxA and CXCL10. Based on these results we suggest that ZIKV transcription is regulated by inflammasomes.
- | Journal: Mir-21 Mediates the Inhibitory Effect of Ang (1-7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts. (Pubmed Central) - Jul 4, 2019
...In vivo, AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome...Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1-7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.
- | Journal: Cytokine Profiling of Primary Human Macrophages Exposed to Endotoxin-Free Graphene Oxide: Size-Independent NLRP3 Inflammasome Activation. (Pubmed Central) - Jul 4, 2019
Finally, these studies show that inflammasome activation is independent of the lateral dimensions of the GO sheets. These studies provide novel insights regarding the immunomodulatory properties of endotoxin-free GO.
- | Journal: Toxicological Profiling of Metal Oxide Nanoparticles in Liver Context Reveals Pyroptosis in Kupffer Cells and Macrophages Versus Apoptosis in Hepatocytes. (Pubmed Central) - Jul 4, 2019
These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1β production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.
- | Kineret (anakinra) / SOBI, Affibody
Clinical, Journal: Development and effect of antibodies to anakinra during treatment of severe CAPS: sub-analysis of a long-term safety and efficacy study. (Pubmed Central) - Jul 4, 2019
However, anakinra treatment markedly improved symptoms and was effective regardless of the presence of ADA; the annual rates of AEs were comparable between ADA-negative and ADA-positive patients. While ADA are likely to occur in CAPS patients treated with anakinra, our evidence shows that chronic daily subcutaneous treatment with anakinra is safe and effective regardless of the development and presence of ADA.
- | Clinical, Journal: A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics. (Pubmed Central) - Jul 4, 2019
This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
- | Clinical, Journal: Upregulation of proteins of the NLRP3 inflammasome in patients with periodontitis and uncontrolled type 2 diabetes. (Pubmed Central) - Jul 4, 2019
Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma. The upregulation of genes and proteins involved in the activation of the NLRP3 inflammasome components in patients with periodontitis and uncontrolled T2D suggests a possible role in the more severe pathological processes leading to destruction of periodontal tissues observed in these patients.
- | Journal: Chlorpyrifos activates cell pyroptosis and increases susceptibility on oxidative stress-induced toxicity by miR-181/SIRT1/PGC-1α/Nrf2 signaling pathway in human neuroblastoma SH-SY5Y cells: Implication for association between chlorpyrifos and Parkinson's disease. (Pubmed Central) - Jul 4, 2019
Chlorpyrifos could inhibit cell proliferation, activate cell pyroptosis and increase susceptibility on oxidative stress-induced toxicity by elevating miR-181 through down-regulation of the SIRT1/PGC-1α/Nrf2 pathway in human neuroblastoma SH-SY5Y cells. This study might give deeper insights for mechanisms of CPF induced toxicity and might give some novel research targets for PD treatment.
- | Journal: Diphenyl diselenide dietary supplementation protects against methylmercury-chloride-induced immunotoxicity in the head kidney and spleen of grass carp (Ctenopharyngodon idella) via regulation of purinergic signaling and the NLRP3 inflammasome. (Pubmed Central) - Jul 3, 2019
Based on these results, purinergic signaling in immune organs and lymphocytes can be considered a pathway linked to pro-inflammatory effects during exposure to environmental CHHgCl concentrations, which may contribute to mortality of the affected fish. Since dietary supplementation with 3 mg PhSe/kg in the feed prevented the CHHgCl-induced alterations, it can be considered a potential suitable treatment to prevent impaired immune and inflammatory responses caused by Hg.
- | Journal: Associations of interactions between NLRP3 SNPs and HLA mismatch with acute and extensive chronic graft-versus-host diseases. (Pubmed Central) - Jul 1, 2019
These results suggest the importance of certain SNP-covariate interactions in unrelated BMT. The three identified interactions may be useful for donor selection or outcome prediction.
- | Preclinical, Journal: Lutolf R, Hughes FM, Jr., Inouye BM, Jin H, McMains JC, Pak ES, Hannan JL, Purves JT. NLRP3/IL-1beta mediates denervation during bladder outlet obstruction in rats. Neurourology and urodynamics 2017. (Pubmed Central) - Jul 1, 2019
The three identified interactions may be useful for donor selection or outcome prediction. No abstract available
- | Journal: Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation. (Pubmed Central) - Jun 30, 2019
Gene expression analysis showed that BAT whitening in Atgl-deficient mice was associated to a strong inflammatory response and NLRP3 inflammasome activation. Altogether the present findings suggest that converted, enlarged brown adipocytes are highly prone to death which, by promoting inflammation in whitened BAT, may contribute to the typical inflammatory state seen in obesity.
- | Review, Journal: The Microbiota-Inflammasome Hypothesis of Major Depression. (Pubmed Central) - Jun 30, 2019
The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.
- | Review, Journal: A Novel Sex-Dependent Target for the Treatment of Postoperative Pain: The NLRP3 Inflammasome. (Pubmed Central) - Jun 28, 2019
Sex differences in the innate immune system have been shown to drive pain and sensitization through different mechanisms in inflammatory and neuropathic pain disorders, indicating that it is imperative that both sexes are studied when researchers investigate and identify new targets for pain therapeutics. This review will highlight the roles of the innate immune response, the NLRP3 inflammasome, and sex differences in neuropathic and inflammatory pain.
- | Journal: Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation. (Pubmed Central) - Jun 28, 2019
In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.
- | honokiol (HU-002) / Huons
Journal: Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway. (Pubmed Central) - Jun 28, 2019
Thus, our results demonstrate that honokiol inhibited the H2O2 induced apoptosis, oxidative stress, and inflammatory responses through the depression of TXNIP/NLRP3/caspase-1/ Interleukin -1β signaling axis and the activation of NF-kB and JNK. Honokiol possess nucleus pulposus protective properties and may be of value in suppressing the pathogenesis of IVDD.