Результаты поиска

Hearing Loss as the Main Clinical Presentation in NLRP3-Associated Autoinflammatory Disease.

The NLRP3 gene mutations are the cause of autosomal dominant autoinflammatory disorders (NLRP3-AID). Recently, hearing loss (HL) has been found to be the sole or major manifestation of NLRP3-AID. Here, we tested 110 autosomal dominant HL families with a custom panel of 237 HL genes and found one family carrying the NLRP3 c.1872C>G, p.Ser624Arg mutation. Functional studies revealed that this novel variant is a gain of function mutation, leading to increased activity of caspase-1 and subsequent oversecretion of proinflammatory interleukin-1β. Clinical reanalysis of the affected individuals, toge

Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis.

BACKGROUND: Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of wome … . It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as …

NLRP3+ macrophages aggravate inflammatory cystitis in diabetes.

Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3) inflammasome triggers the activation of caspase-1/IL-1β signaling cascades to mediate inflammatory response. However, it is not known whether NLRP3 activation in macrophages during cystitis may differ in normal or diabetic setting as well as the importance of it. In this study, we found that NLRP3 levels significantly increased in bladder macrophages in diabetic mice that underwent cystitis. Moreover, bladder macrophages from diabetic mi

Involvement of NF-κB/NLRP3 axis in the progression of aseptic loosening of total joint arthroplasties: a review of molecular mechanisms.

Particulate wear debris can trigger pro-inflammatory bone resorption and result in aseptic loosening. This complication remains major postoperative discomforts and complications for patients who underwent total joint arthroplasty. Recent studies have indicated that wear debris-induced aseptic loosening is associated with the overproduction of pro-inflammatory cytokines. The activation of osteoclasts as a result of inflammatory responses is associated with osteolysis. Moreover, stimulation of inflammatory signaling pathways such as the NF-κB/NLRP3 axis results in the production of pro-inflammat

Effects and underlying mechanisms of food polyphenols in treating gouty arthritis: A review on nutritional intake and joint health.

Gouty arthritis, one of the most severe and common forms of arthritis, is characterized by monosodium urate crystal deposition in joints and surrounding tissues. Epidemiological evidence indicates that gouty arthritis incidence is sharply rising globally. Polyphenols are found in many foods and are secondary metabolites in plant foods. The anti-inflammatory and antioxidant effects of food polyphenols have been extensively studied in many inflammatory chronic diseases. Research has suggested that many food polyphenols have excellent anti-gouty arthritis effects. The mechanisms mainly include (a

Идентификация NLRP3PYD Homo-Oligomerization Inhibitors с антивоспалительной активностью.

Инфламасомы представляют собой многопротеиновые комплексы, которые представляют собой важнейшие элементы подстрекательской реакции. Регулирование дискриминированного комплекса NLRP3 инфламасома связано с патогенезом таких заболеваний, как множественный склероз, тип 2 сахарный диабет, болезнь Альцгеймера и рак. Несмотря на наличие молекулярных ингибиторов, специфичных для различных компонентов воспламенительных комплексов, в настоящее время ни о каких ингибиторах не сообщается конкретно для NLRP3PYD гомо-олигомеризации. В настоящем исследовании мы описываем идентификацию QM380 и QM381 в качеств

Совпадение в полном тексте источника
… The Nod-Like Receptor family pyrin domain containing 3 (NLRP3) inflammasome comprises the NLRP3 molecular sensor, the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) adaptor protein (possessing PYD and CARD domains), and pro-caspase-1 [ 2 , 3 , 4 , 5 , 6 ]. … The NLRP3 protein contains an N-terminal pyrin domain (NLRP3 PYD ), a central NACHT domain containing a nucleotide-binding domain (NBD) (crucial for oligomerization of NLRs upon activation), and a C-terminal leucine-rich repeat (LRR) domain [ 7 , 8 ]. …

Inflammasomes as mediators of inflammation in HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1) infection is a chronic disease without a known cure. The advent of effective antiretroviral therapy (ART) has enabled people with HIV (PWH) to have significantly prolonged life expectancies. As a result, morbidity and mortality associated with HIV-1 infection have declined considerably. However, these individuals experience chronic systemic inflammation whose multifaceted etiology is associated with other numerous comorbidities. Inflammasomes are vital mediators that contribute to inflammatory signaling in HIV-1 infection. Here, we provide an overvie

Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary f

RelA/MicroRNA-30a/NLRP3 signal axis is involved in rheumatoid arthritis via regulating NLRP3 inflammasome in macrophages.

NLRP3 inflammasome plays an important role in the pathogenesis of rheumatoid arthritis (RA). However, the post-transcriptional regulation of NLRP3 expression by miRNA in synovial macrophages is still not well understood. The aim of the study is to elucidate the mechanisms of RA with the focus on miRNAs mediated post-transcriptional regulation of the NLRP3 inflammasome. Here, we used NLRP3-deficient mice (NLRP3KO) to cross with TNFα-transgenic mice (TNFTG) to generate NLRP3KO/TNFTG mice, and compared their joint phenotypes with those of their TNFTG and wild-type (WT) littermates at 5 months of

Geniposide protects against sepsis-induced myocardial dysfunction through AMPKα-dependent pathway.

Uncontrolled inflammatory response and subsequent cardiomyocytes loss (apoptosis and pyroptosis) are closely involved in sepsis-induced myocardial dysfunction. Our previous study has found that geniposide (GE) can protect the murine hearts against obesity-induced inflammation. However, the effect of GE on sepsis-related cardiac dysfunction is still unknown. Mice were exposed to lipopolysaccharide (LPS) to generate sepsis-induced myocardial dysfunction. And 50 mg/kg GE was used to treat mice for consecutive 7 days. Our results showed that GE treatment significantly improved survival rate and ca

The Nlrp3 inflammasome as a "rising star" in studies of normal and malignant hematopoiesis.

Recent investigations indicate that hematopoiesis is coregulated by innate immunity signals and by pathways characteristic of the activation of innate immunity cells that also operate in normal hematopoietic stem progenitor cells (HSPCs). This should not be surprising because of the common developmental origin of these cells from a hemato/lymphopoietic stem cell. An important integrating factor is the Nlrp3 inflammasome, which has emerged as a major sensor of changes in body microenvironments, cell activation, and cell metabolic activity. It is currently the best-studied member of the inflamma

MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts.

AIM: To investigate the effect of miR-223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs). METHODOLOGY: Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR-223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR-223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expre

Hydrogen Sulfide Plays an Important Role by Influencing NLRP3 inflammasome.

Inflammasome is a complex composed of several proteins and an important part of the natural immune system. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. It plays an important role in many diseases. Hydrogen sulfide (H2S) is an important signaling molecule that regulates many physiological and pathological processes. Recent studies indicated that H2S played anti-inflammatory and pro-inflammatory roles in many diseases through influencing NLRP3 inflammasome, but its mec

IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy.

IRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation. IRGM employs 2 parallel approaches to constrain inflammasome activation. First, IRGM directly interacts with NLRP3 and PYCARD/ASC, and mediates their SQSTM1/p62-dependent macroautophagic/autophagic degradation. Second, IRGM impedes inflammasome assembly by blocking the polymerization of NLRP3 and PYCARD. We also

The NLRP3 inflammasome - interleukin 1 pathway as a therapeutic target in gout.

The NLRP3 inflammasome is implicated in the processing of the pro-inflammatory cytokine interleukin 1β. Inflammatory disorders associated with the activation of the NLRP3 inflammasome - IL-1 axis are termed autoinflammatory diseases. Gout is an autoinflammatory disease, which is triggered by the deposition of monosodium urate crystals of precipitated uric acid. It is characterized by recurrent attacks of inflammation due to the activation of phagocytic cells that try to clear the crystals. NLRP3 inflammasome-mediated IL-1β production plays a key role in the manifestation of the disease. Curren

Muckle-Wells Syndrome: A Case Report with an NLRP3 T348M Mutation.

Autoinflammatory syndromes are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin-associated periodic syndromes are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticaria syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease. MWS is characterized by a moderate phenotype with fever, rash, arthralgia, conjunctivitis, sensorineural deafness, and potentially life-threatening amyloidosis. We report a 5-year-old girl with MWS tha

A novel redox signalling axis mediates nicotine-induced podocyte injury.

INTRODUCTION: Nicotine has been shown to induce Nlrp3 (nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome activation, thereby contributing to podocyte injury. However, the molecular mechanisms underlying nicotine-induced Nlrp3 inflammasome activation and subsequent podocyte dysfunction remain largely unknown. The present study investigated whether membrane raft (MR)-associated redox signalling plays a critical role in nicotine-induced Nlrp3 inflammasome activation and podocyte injury. METHODS AND RESULTS: Nicotine treatment induced membrane …

Dapagliflozin embedded polymeric nanomicelles for enhanced ocular drug delivery: A promising strategy for glaucoma therapy.

Glaucoma, a progressive neurodegenerative disorder, accentuates the need for a neuroprotective therapy to overcome the risk of blindness. Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing protein 3 (NLRP3) inhibitors like dapagliflozin (DAPA) may exert neuroprotective effects in the glaucoma therapy. As DAPA suffers from poor permeability and solubility challenges, it cannot be administered in the eyes. Also, invasive methods as well as retinal drug delivery suffers from compliance and safety issues. Thus, the aim was to develop and assess DAPA loaded m…

Breaking the metabolic-inflammatory vicious cycle in polycystic ovary syndrome: a comparative review of ketogenic and high-fat diets.

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic-endocrine disorder in women of reproductive age in which lipid metabolism dis … oxybutyrate, directly suppresses the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 inflammasome, remodels the gut microbiota, and attenuates nuclear factor kappa-light-chain-enhancer of activated B cells signaling, thus yielding multitarget anti-inflammatory effects. Unlike isocaloric high-fat diets, which lead to obe …

Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes.

Emerging evidence has demonstrated a strong correlation between vitamin D status and fatty liver disease. Aberrant hepatic fat infiltration … k-like CARD-domain protein (ASC), thioredoxin-interacting protein (TXNIP), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and interleukin-1β (IL-1β) involved in the NLRP3 inflammasome accompanied by caspase-1 activity and IL-1β expression were significantly suppressed by 1,25(OH)2D in PA-treated hepatocytes. Moreover, upon PA exposure, 1,25(OH)2D- …