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The pivotal roles of the NOD-like receptors with a PYD domain, NLRPs, in oocytes and early embryo development†.

Nucleotide-binding oligomerization domain (NOD)-like receptors with a pyrin domain (PYD), NLRPs, are pattern recognition receptors, well recognized for their important roles in innate immunity and apoptosis. However, several NLRPs have received attention for their new, specialized roles as maternally contributed genes important in reproduction and embryo development. Several NLRPs have been shown to be specifically expressed in oocytes and preimplantation embryos. Interestingly, and in line with divergent functions, NLRP genes reveal a complex evolutionary divergence. The most pronounced diffe…

Acute adrenal cortex injury during cardiopulmonary bypass in a canine model.

OBJECTIVE: Cardiopulmonary bypass (CPB) might induce systemic inflammatory responses that cause acute injuries to multiple organs. However, … s. Steroidogenic enzymes and the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome pathway were detected using quantitative polymerase chain reaction and Western blot analysis. RESULTS: During CPB, serum interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α, cortisol, and aldosterone levels were signific …

Baicalin exerts neuroprotective effects via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway in a rat model of depression.

Chronic stress can provoke depressive-like behaviors through activation of inflammation and apoptosis, leading to a reduction of neurons. An … ynthase kinase-3 (GSK3) β/Nuclear factor-κB (NF-κB)/Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) signal pathway. Taken together, these results indicate that BA could promote neuronal maturation and rescue neurons from apoptosis via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway that is known to be associa …

Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity.

Acute respiratory distress syndrome (ARDS) is a common and devastating disorder. Alcohol use disorders (AUDs) increase ARDS risk and worsen outcomes through mechanisms that may include enhancement of pulmonary oxidative stress. Alcohol consumption increases activity of the enzyme xanthine oxidoreductase (XOR) that contributes to production of both reactive oxygen species (ROS) and uric acid, a damage-associated molecular pattern. These by-products have the potential to modulate proinflammatory pathways, such as those involving cyclooxygenase (COX)-2, and to activate the nucleotide-binding doma

Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats.

The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin …

A survey of host range genes in poxvirus genomes.

Poxviruses are widespread pathogens, which display extremely different host ranges. Whereas some poxviruses, including variola virus, displa … rosis factor receptor II homologs, apoptosis inhibitor T4-related proteins, Bcl-2-related proteins, pyrin domain-containing proteins, cellular serine protease inhibitors (serpins), short complement-like repeats containing proteins, KilA-N/RING domain-containing proteins, as well as inhibitors of the double-stranded RNA-activated protein kinase PKR. We conducte …

NLRP7, a nucleotide oligomerization domain-like receptor protein, is required for normal cytokine secretion and co-localizes with Golgi and the microtubule-organizing center.

A hydatidiform mole (HM) is a human pregnancy with hyperproliferative placenta and abnormal embryonic development. Mutations in NLRP7, a mem … nd demonstrate that this inhibitory function is abolished by protein-truncating mutations after the Pyrin domain. Within peripheral blood mononuclear cells, NLRP7 co-localizes with the Golgi and the microtubule-organizing center and is associated with microtubules. This suggests that NLRP7 mutations may affect cytokine secretion by interfering, directly or ind …

Decoding neuroinflammation: the critical role of NLRP3 inflammasome in Alzheimer's disease.

The hallmarks of Alzheimer's disease (AD), a progressive neurodegenerative disease, include tau tangles, amyloid-β (Aβ) plaques, cognitive impairment, and severe neuroinflammation. A key molecular mediator linking immunological activation and neurological pathology in AD is the NLRP3 inflammasome. This review explains the intricate role of the NLRP3 inflammasome in AD, including its structure, activation mechanisms, and regulatory signaling pathways. The pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) that activate NLRP3 include oxidative stress,

NLRP3 inflammasomes at the ARDS-cancer interface: mechanisms and translational hypotheses.

Acute respiratory distress syndrome (ARDS) and cancer share common pathogenetic mechanisms that involve immune dysregulation and inflammatory responses. Inflammasomes, part of the initial innate immune response to infection and injury, play a pivotal role in both carcinogenesis and ARDS. Here we review the role of inflammasomes in ARDS and cancer and, in doing so, we find a set of commonalities that allow the proposal of a conceptual framework for their potential intersection that could inform therapeutic development for both conditions. We highlight the importance of understanding how chronic

Is Gout an Autoinflammatory Disease?

PURPOSE OF REVIEW: This review recognizes gout as an autoinflammatory disease rather than a solely metabolic condition. It provides an overview of autoinflammatory diseases, the NOD-, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and how soluble and crystalline forms of uric acid (UA) act as inflammatory triggers, prompting NLRP3 inflammasome formation and activation. It also highlights the genetics associated with the autoinflammatory features of gout and discusses NLRP3 inflammasome-targeted treatments. RECENT FINDINGS: Autoinflammatory diseases result from hyperactivity o…

Importance of the inflammasome in gut-brain axis: from pathological driver to therapeutic target.

The inflammasome, a supramolecular complex, plays important role in the gut-brain axis (GBA), acting as a sensor of cellular stress and danger signals. It activates inflammatory responses, and its dysregulation has been implicated in neurological diseases. Various inflammasomes, such as NLRP3, NLRC4, and AIM2, contribute to disease progression by promoting inflammation, tissue damage, and oxidative stress. These inflammasomes recognize and get activated by different stimuli, such as ATP, fluctuations in ion fluxes, nucleic acids, and molecular signatures associated with pathogens, eventually r

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odd

NLRP3 inflammasome activation in PCOS: A novel target for managing insulin resistance and metabolic dysregulation.

In this comprehensive narrative review, we systematically examine the role of the NLRP3 inflammasome in the pathogenesis of polycystic ovary syndrome (PCOS) and evaluate its potential as a therapeutic target for managing insulin resistance. We performed literature searches in PubMed, Scopus, and Web of Science up to April 2025, using keywords including "PCOS," "NLRP3 inflammasome," "insulin resistance," and "reproductive dysfunction." Only peer-reviewed studies directly addressing inflammasome activation in PCOS were included, while articles lacking mechanistic or clinical relevance were exclu

[Avitinib suppresses NLRP3 inflammasome activation and ameliorates septic shock in mice].

OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intrace

Glial Cells in the Early Stages of Neurodegeneration: Pathogenesis and Therapeutic Targets.

Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest sta…

NLRP3 воспаление в нейро-воспалении и заболеваниях центральной нервной системы.

Нейроинфламмация играет важную роль в патогенезе различных заболеваний центральной нервной системы (КНС). NLRP3 является важным внутриклеточным многопротеиновым комплексом, состоящим из врожденного иммунного рецептора NLRP3, адаптационного белка ASC и протеза каспе-1. Активация NLRP3 испарения может вызвать пироптоз и высвобождение проинфламамина IL-1β и IL-18, тем самым играя центральную роль в иммунной и подстрекательской реакции. Недавние исследования показали, что воспаление NLRP3 активируется в мозгу, с тем чтобы вызвать нейроинфламму, что приводит к дальнейшим нейронным повреждениям и фу

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… NLRP3 (NOD-like receptor family pyrin domain containing 3) is a representative pattern recognition receptor that is widely expressed in microglia and astrocytes and forms an inflammasome to promote neuroinflammation upon sensing stress or damage. … LPS lipopolysaccharide, PAMPs pathogen-associated molecular patterns, DAMPs damage-associated molecular patterns, TLR4 toll-like receptor 4, NF-κB nuclear factor-κB, ROS reactive oxygen species, mtDNA mitochondrial DNA, NLRP3 NOD-, LRR- and pyrin domain-containing protein 3, IL-1β interleukin 1β, IL- …

Nanoparticle-mediated co-delivery of inflammasome inhibitors provides protection against sepsis.

The NLRP3 inflammasome, a multiprotein complex responsible for triggering the release of pro-inflammatory cytokines, plays a crucial role in inducing the inflammatory response associated with sepsis. While small molecule inhibitors of the NLRP3 inflammasome have been investigated for sepsis management, delivering NLRP3 inhibitors has been accompanied by several challenges, primarily related to the drug formulation, delivery route, stability, and toxicity. Many existing inflammasome inhibitors either show higher liver toxicity or require a high dosage to efficiently impede the inflammasome comp

Exogenous hydrogen sulfide ameliorates diabetes-associated cognitive dysfunction by regulating the nrf-2/HO-1 axis and the NLRP3 inflammasome pathway in diabetic rats.

Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus that leads to an increased risk of cognitive impairment and dementia. However, the molecular mechanism underlying DACD has not been elucidated, and a promising therapy for this disease remains to be established. Hydrogen sulfide (H2S), a significant antioxidative and anti-inflammatory gasotransmitter, has emerged as a neuroprotective agent. In this study, we investigated the protective effects of H2S on DACD in a streptozotocin (STZ)-induced diabetic rat model. We applied the Morris water maze to evaluate s

Renal transplantation in patients with cryopyrin-associated periodic syndrome: A case report and literature review.

BACKGROUND: The cryopyrin-associated periodic syndrome (CAPS) is a rare autosomal dominant hereditary inflammatory disease clinically characterized by three overlapping types and associated with interleukin (IL)-1β.We reported a rare case of CAPS in a patient with accompanying symptoms such as growth retardation and urticaria-like rash. These clinical manifestations were caused by mutations in the NALP3 gene. CASE PRESENTATION: A 28-year-old male patient, with a height of 1.3 m and a weight of 33.4 kg. He began to experience fever, rash, joint swelling and pain, as well as recurrent cerebral

Review on the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway in diabetes: mechanistic insights and therapeutic implications.

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1β and interleukin-18, driving insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. These pr