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Deep Learning Enhanced Near Infrared-II Imaging and Image-Guided Small Interfering Ribonucleic Acid Therapy of Ischemic Stroke.

Small interfering RNA (siRNA) targeting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as a promising therapeutic strategy to mitigate infarct volume and brain injury following ischemic stroke. However, the clinical translation of siRNA-based therapies is significantly hampered by the formidable blood-brain barrier (BBB), which restricts drug penetration into the central nervous system. To address this challenge, we have developed an innovative long-circulating near-infrared II (NIR-II) nanoparticle platform YWFC NPs, which is meticulously engineered to…

Non-covalent mTOR inhibition suppresses NLRP3-GSDMD inflammasome-mediated pyroptosis.

Pyroptosis is an inflammatory form of programmed cell death primarily driven by activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which triggers caspase-1-dependent cleavage of gasdermin D (GSDMD) and subsequent release of pro-inflammatory cytokines. The mechanistic target of rapamycin (mTOR) signaling pathway has emerged as a critical regulator of pyroptosis, yet its precise role in inflammasome activation remains to be incompletely understood. Here, we report that compound CD25, a novel non-covalent small-molecule inhibitor, suppresses NLRP3 inflammas…

Коннексин и Panexin Hemichannels: широкополосные игроки в нейроинфламаторном сигнатуре.

Коннексины и гемиханели, полученные с помощью аннексина, стали центральными усилителями нейроинфламма. При физиологическом стресс-деполяризации, перегрузке Ca2+, переключении на рентгенокс или цитокиновом воздействии эти крупные поры выделяют аденозиновый трифосфат, глютамат и другие опасные сигналы, которые активируют рецепторы P2X/P2Y и N-метил-D-аспертат, возгорают семейный пирин NLR, содержащий (NLRP) 3 и распространяют волна Ca2+/реактивный вид кислорода между мачтовыми клетками, микроглией, астроцитами, олигодендроцитами, нейронами и мозговым эндотелием. Данные, полученные с помощью моде

Совпадение в аннотации оригинала
Connexin- and pannexin-formed hemichannels have emerged as pivotal, upstream amplifiers of neuroinflammation. Under physiological stressors- … nd other danger signals that activate P2X/P2Y and N-methyl-D-aspartate receptors, ignite NLR family pyrin domain containing (NLRP) 3 inflammasome, and propagate Ca2+/reactive oxygen species waves between mast cells, microglia, astrocytes, oligodendrocytes, neurons, and brain endothelium. Evidence across acute (e.g., stroke, trauma, seizure, and sepsis) and chr …

Understanding the Role of NLRP3 Inflammasome in Acute Pancreatitis.

Acute pancreatitis (AP) remains a serious clinical condition, with current treatment options being largely supportive. The discovery of inflammasomes, particularly the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, has significantly advanced our knowledge regarding many inflammatory diseases' pathogenesis, including AP. The NLRP3 inflammasome is central in mediating the inflammatory process in AP through its diverse activation mechanisms and its involvement in multiple signal transduction pathways. This has made NLRP3 an appealing target for novel therapeutic strategi…

The mechanism of Shoutai Wan in the treatment of recurrent spontaneous abortion - A review.

Recurrent spontaneous abortion (RSA) is a prevalent pregnancy complication with a complex and poorly understood pathogenesis. Shoutai Wan (S … eme oxygenase-1, JAK kinase 1/Signal transducer and activator of transcription 3, NOD-like receptor pyrin domain-containing protein/Caspase-1/Gasdermin D, Human Leukocyte Antigen G, Mitogen-activated protein kinase, and Serum and glucocorticoid-regulated kinase 1/Epithelial sodium channel. This review provides a theoretical reference for the clinical applicati …

Ornithine lipid is a partial TLR4 agonist and NLRP3 activator.

Gram-negative bacterial lipopolysaccharides (LPSs) trigger inflammatory reactions through Toll-like receptor 4 (TLR4) and prime myeloid cells for inflammasome activation. In phosphate-limited environments, bacteria reduce LPS and other phospholipid production and synthesize phosphorus-free alternatives such as amino-acid-containing lipids like the ornithine lipid (OL). This adaptive strategy conserves phosphate for other essential cellular processes and enhances bacterial survival in host environments. While OL is implicated in bacterial pathogenicity, the mechanism is unclear. Using primary m

YOD1 protects against MRSA sepsis-induced DIC through Lys33-linked deubiquitination of NLRP3.

Disseminated intravascular coagulation (DIC) is considered to be the most common and lethal complication of sepsis. NLR-family pyrin domain-containing-3 (NLRP3) inflammasome plays an important role in host defense against microbial pathogens, and its deregulation may cause coagulation cascade and should be strictly managed. Here, we identified the deubiquitinase YOD1, which played a vital role in regulating coagulation in a NLRP3 inflammasome-dependent manner in sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA). YOD1 interacted with NLRP3 to remove K33-linked ubiquitination …

Mesenchymal stem cells (MSCs) and MSC-derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome.

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a multimeric protein complex that is engaged in the innate immune system and plays a vital role in inflammatory reactions. Activation of the NLRP3 inflammasome and subsequent release of proinflammatory cytokines can be triggered by microbial infection or cellular injury. The NLRP3 inflammasome has been implicated in the pathogenesis of many disorders affecting the central nervous system (CNS), ranging from stroke, traumatic brain injury, and spinal cord injury to Alzheimer's disease, Parkinson's disease, epilepsy, mu…

Recent Advances in Microbiota-Associated Metabolites in Heart Failure.

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney failure and death. The gut microbiota and … ear factor kappa-light-chain-enhancer of activated B cells, Bcl-2 interacting protein 3, NLR Family Pyrin Domain Containing inflammasome, and Protein kinase RNA-like endoplasmic reticulum kinase. We have also highlighted the beneficial role of other gut metabolites in heart failure and other cardiovascular and metabolic diseases.

TRPV4-mediated mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via the Drp1-HK2 axis.

Osteoarthritis (OA) is an age-related chronic degenerative disease with complex pathophysiological mechanisms. Accumulating evidence indicates that nod-like receptor pyrin domain 3 (NLRP3) inflammasome-mediated pyroptosis of chondrocytes plays a crucial role in the OA progression. Transient Receptor Potential Vanilloid 4 (TRPV4), described as a calcium-permeable cation channel, isassociated with proinflammatory factors and pyroptosis. In this study, we studied the potential functions of TRPV4 in chondrocyte pyroptosis and cartilage degradation. We found that lipopolysaccharides(LPS)-induced mi…

Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications.

Absent in melanoma 2 (AIM2), a member of the Pyrin and HIN domain protein family, is a cytoplasmic receptor that recognizes double-stranded DNA. AIM2 exhibits limited expression under physiological conditions but is widely expressed in many human diseases, including autoimmune diseases, and plays an essential role in the immune response. Rheumatoid arthritis (RA) is an autoimmune disease that poses a severe threat to physical and mental health, and is caused by several genetic and metabolic factors. Multiple immune cells interact to form a complex inflammatory network that mediates inflammator

Pharmacological suppression of NLRP3 inflammasome attenuated the development of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbe…

Galectin-9 Targets NLRP3 for Autophagic Degradation to Limit Inflammation.

NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been implicated in a variety of inflammatory disorders, and its activation should be tightly controlled to avoid detrimental effects. NLRP3 protein expression is considered as the rate-limiting step for NLRP3 inflammasome activation. In this study, we show that galectin-9 (encoded by lgals9) attenuated NLRP3 inflammasome activation by promoting the protein degradation of NLRP3 in primary peritoneal macrophages of C57BL/6J mice. Lgals9 deficiency enhances NLRP3 inflammasome activation and promotes NLRP3-dependent inflamm…

MerTK inhibits the activation of the NLRP3 inflammasome after subarachnoid hemorrhage by inducing autophagy.

The NLR family pyrin domain-containing 3 (NLRP3) multiprotein complex is associated with neuroinflammation and poor prognosis after subarachnoid hemorrhage (SAH). Accumulating evidence shows that Mer tyrosine kinase (MerTK) alleviates inflammatory responses via a negative feedback mechanism. However, the contribution and function of MerTK in SAH remain to be determined. In this study, we explored the role of MerTK during microglial NLRP3 inflammasome activation and evaluated its contribution to the outcome of SAH in mice. Activating MerTK with growth arrest-specific 6 (Gas6) alleviated brain e…

Toxoplasma gondii GRA9 Regulates the Activation of NLRP3 Inflammasome to Exert Anti-Septic Effects in Mice.

Dense granule proteins (GRAs) are essential components in Toxoplasma gondii, which are suggested to be promising serodiagnostic markers in toxoplasmosis. In this study, we investigated the function of GRA9 in host response and the associated regulatory mechanism, which were unknown. We found that GRA9 interacts with NLR family pyrin domain containing 3 (NLRP3) involved in inflammation by forming the NLRP3 inflammasome. The C-terminal of GRA9 (GRA9C) is essential for GRA9-NLRP3 interaction by disrupting the NLRP3 inflammasome through blocking the binding of apoptotic speck-containing (ASC)-NLRP…

H 2S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome.

Hydrogen sulfide (H 2S) is an important messenger for its strong anti-inflammatory effects, which may be involved in multiple cardiovascular … MCP1 were also significantly reduced by GYY4137. Mechanically, GYY4137 suppressed the activation of pyrin domain containing protein 3 (NLRP3) inflammasome in diabetes-accelerated atherosclerosis conditions. Upon knockdown of NLRP3, the increase of ICAM1 and VCAM1 caused by high glucose and oxLDL could be reversed, indicating that H 2S protected the endothelium …

Melatonin inhibits endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in lipopolysaccharide-induced endometritis in mice.

Endometritis, an inflammatory response of the uterus tissue, is characterized by the production of inflammatory cytokines and migration of n … atonin also inhibited LPS-induced thioredoxin-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) activation, reactive oxygen species (ROS) production, and endoplasmic reticulum (ER) stress. Furthermore, melatonin was found to increase AMPK activity. In conclusion, our results …

MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are autoimmune, inflammatory diseases with substantial genetic contributions. Matrix metalloproteinase (MMP)-2, tumor necrosis factor (TNF)-α and NLR family pyrin domain-containing 1 (NLRP1) play important roles in the immune response. We studied the MMP-2 rs243865 C/T, TNF-α rs1800629 A/G, NLRP1 rs878329 C/G and NLRP1 rs6502867 C/T polymorphisms in a Chinese cohort of 520 patients with RA, 100 with AS and 520 controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Using the…

Familial Mediterranean Fever in Crete: a genetic and structural biological approach in a population of 'intermediate risk'.

Familial Mediterranean Fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent and short attacks of fever with serosal inflammation that are caused by mutations in MEFV gene that encodes pyrin protein. To date, more than 70 disease-associated mutations have been identified, almost all of them representing missense nucleotide changes. FMF is very common among patients with Mediterranean ancestry, although the exact prevalence is not yet known, Greeks are considered to be at 'intermediate risk'. In the present study, we studied FMF patients in natives of Crete, a p

Molecular characterization and preliminary functional analysis of the NLRP3 inflammasome in golden pompano (Trachinotus ovatus) in response to Streptococcus agalactiae infection.

Golden pompano (Trachinotus ovatus) is an economically important marine fish in southern China, but intensive aquaculture has increased the risk of bacterial diseases, especially streptococcosis caused by Streptococcus agalactiae. As a key component of innate immunity, the NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3 inflammasome) regulates inflammatory responses through caspase-1 (Cysteine-aspartic acid protease 1) activation and the maturation of IL-1β (Interleukin-1β) and IL-18 (Interleukin-18). In this study, five core genes associated with the NLRP3 inflammasome…