Результаты поиска

A 4-Benzene-Indol Derivative Alleviates LPS-Induced Acute Lung Injury Through Inhibiting the NLRP3 Inflammasome.

Acute lung injury (ALI) is a common complication of critical illness that could frequently lead to acute respiratory distress syndrome and other serious clinical consequences. Sepsis is one of the major and most common inducements among all causes of ALI. Due to its high incidence and mortality rate and also the complexity in treatment, sepsis-related ALI has become an urgent clinical problem waiting to be solved effectively. At present, only the protective ventilation strategy, restrictive fluid management, and antibiotics application are measures that can improve the prognosis with evidence-

The effect of valproic acid and furosemide on the regulation of the inflammasome complex (NLRP1 and NLRP3 mRNA) in the brain of epileptic animal model.

OBJECTIVES: This study aimed to explore the effect of concomitant use of Furosemide (FRS) and Valproic acid (VPA), demonstrating anti-inflammation efficacy, on epilepsy, and its underlying mechanism. METHODS: Twenty-five adult male Wistar rats were divided into five groups including, Group 1: (Normal) rats received no drugs, Group 2: (E): rats were administered with a single dose of kainic acid (stereotaxic surgery), Group 3: (E + VPA): rats received Valproic acid (200 mg/kg/day/orally), Group 4: (E + FRS): rats received a single dose of Furosemide (100 mg/kg/I.P.) 30 min before epilepsy indu

Linear ubiquitination of LKB1 activates AMPK pathway to inhibit NLRP3 inflammasome response and reduce chondrocyte pyroptosis in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common chronic disease. It is characterized by high levels of clinical heterogeneity and low inflammation. Therefore, elucidation of the mechanisms that regulate gene expression is critical for developing effective OA therapies. This study aimed to explore the role of LKB1/AMPK in the progression of OA. METHODS: Anterior cruciate ligament transection (ACLT) was performed on Sprague Dawley (SD) rats right knee to construct OA model, followed by AICAR [AMP-activated protein kinase (AMPK) activator] treatment. The level changes [AMPK, IL-10, IL-13, IL-

Ciclopirox inhibits NLRP3 inflammasome activation via protecting mitochondria and ameliorates imiquimod-induced psoriatic inflammation in mice.

The maturation and secretion of interleukin-1β (IL-1β) mediated by NLRP3 inflammasome activation plays an important role in the progression of many inflammatory diseases. Inhibition of NLRP3 inflammasome activation may be a promising strategy to treat these inflammation-driven diseases, such as psoriasis. As a broad-spectrum antifungal agent, ciclopirox (CPX) is widely used in the treatment of dermatomycosis. Although CPX has been reported to have anti-inflammatory effects in many studies, there has been little research into its underlying mechanisms. In our study, CPX reduced lipopolysacchari

Rutin ameliorates gout via reducing XOD activity, inhibiting ROS production and NLRP3 inflammasome activation in quail.

Gout is a metabolic disease affected by monosodium urate (MSU) deposition, which is directly related to hyperuricemia. Recent reports on the prevalence and incidence of gout have been widely circulated worldwide. Currently, the anti-gout drugs in clinical practice are mainly small-molecule synthetic drugs, and the effectiveness and safety are limited. Reducing uric acid and inhibiting inflammation are the focused areas of drug research and development on gout. Rutin, a natural flavonoid, has been reported to alleviate inflammation in various diseases. However, whether rutin exerts protective e

Обнаружение нового и мощного ингибитора с дифференциально-видовым воздействием на NLRP3 и AIM2 инфламасомного пироптоза.

В патологическом процессе различных человеческих заболеваний, таких, как множественный склероз, тип NLRP3, который регулировал запрограммированную на профанфламационную форму смерти клеток, называемую пироптозом. 2 диабет и болван. Таким образом, соединения, препятствующие активации NLRP3, могут стать перспективным средством лечения этих заболеваний. В этом исследовании мы провели фенотипический скрининг против NLRP3-dependent Пироптоз и обнаруженное соединение 1, который продемонстрировал умеренную антипироптотивную активность. Химические усилия по повышению эффективности 1 В результате появи

Совпадение в аннотации оригинала
The NLRP3 inflammasome, which regulated a proinflammatory programmed cell death form termed pyroptosis, is involved in the pathological proc … which is worthy of further research to understand the differential regulation of the NLRP3 and AIM2 inflammasomes in humans and mice.

Clozapine Induces an Acute Proinflammatory Response That Is Attenuated by Inhibition of Inflammasome Signaling: Implications for Idiosyncratic Drug-Induced Agranulocytosis.

Although clozapine is a highly efficacious schizophrenia treatment, it is under-prescribed due to the risk of idiosyncratic drug-induced agranulocytosis (IDIAG). Clinical data indicate that most patients starting clozapine experience a transient immune response early in treatment and a similar response has been observed in clozapine-treated rats, but the mechanism by which clozapine triggers this transient inflammation remains unclear. Therefore, the aim of this study was to characterize the role of inflammasome activation during the early immune response to clozapine using in vitro and in viv

Co-activation of Caspase-1 and Caspase-8 in CMV-induced SGN death by inflammasome-associated pyroptosis and apoptosis.

Cytomegalovirus (CMV) infection causes newborn deafness, and the death of the spiral ganglion neurons (SGNs) is crucial in determining the degree of CMV-related hearing loss. Therefore, understanding the psychopathology of CMV-related SGN loss is important for identifying targets and exploring treatment strategies. In this study, we found that pyroptosis and apoptosis, two inflammasome-related programmed cell death pathways, are involved in CMV-induced SGN death and are mainly regulated by activated caspase-1 and caspase-8. Moreover, suppressing inflammasome assembly by blocking apoptosis-asso

Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.

Rickettsia species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits. Although our understanding of Rickettsia cell biology and pathogenesis is evolving, the mechanisms by which pathogenic Rickettsia spp. evade host innate immune detection remain elusive. Here, we show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typ

Loganin alleviates sepsis-induced acute lung injury by regulating macrophage polarization and inhibiting NLRP3 inflammasome activation.

Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treate

Topical calcitriol application promotes diabetic corneal wound healing and reinnervation through inhibiting NLRP3 inflammasome activation.

Vitamin D (VD) deficiency delays corneal wound healing in those with diabetes, which cannot be rescued with supplemental diet. Here, we employed topical calcitriol application to evaluate its efficiency in corneal wound healing and reinnervation in diabetic mice. Type 1 diabetic mice were topically administrated calcitriol, or subconjunctivally injected with NLRP3 antagonist MCC950 or IL-1β blocking antibody after epithelial debridement. Serum VD levels, corneal epithelial defect, corneal sensation and nerve density, NLRP3 inflammasome activation, neutrophil infiltration, macrophage phenotypes

Cerebroprotection by dioscin after experimental subarachnoid haemorrhage via inhibiting NLRP3 inflammasome through SIRT1-dependent pathway.

BACKGROUND AND PURPOSE: Dioscin has multiple biological activities and is beneficial for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of dioscin against subarachnoid haemorrhage and the molecular mechanisms involved. EXPERIMENTAL APPROACH: Dioscin was administered after subarachnoid haemorrhage induced in rats. MCC950, a potent selective nod-like receptor pyrin domain-containing 3 (NLRP3) inhibitor, was used to suppress NLRP3 and EX527 (selisistat) was used to inhibit sirtuin 1 (SIRT1). KEY RESULTS: In vivo, dioscin inhibited acute inflammatory

Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway.

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant syste

H2S alleviates aortic aneurysm and dissection: Crosstalk between transforming growth factor 1 signaling and NLRP3 inflammasome.

BACKGROUND: Vascular remodeling and inflammation are involved in aortic aneurysm (AA) and aortic dissection (AD). TGF-β1 signaling is involved in tissue fibrosis, extracellular matrix remodeling and inflammation, which are linked with AA and AD. The inhibition of NLRP3 inflammasome suppresses AA and AD. Hydrogen sulfide (H2S) exerts anti-vascular remodeling and anti-inflammatory properties, but little is known about its action on AA and AD progression. METHODS: The effect of H2S on AA and AD formation was investigated in Sprague-Dawley (SD) rat fed a normal diet supplemented with 0.25% β-amin

Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice.

BACKGROUND: Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4'-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain. METHODS: A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate

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

Exposure to Dengue Envelope Protein Domain III Induces Nlrp3 Inflammasome-Dependent Endothelial Dysfunction and Hemorrhage in Mice.

Typically occurring during secondary dengue virus (DENV) infections, dengue hemorrhagic fever (DHF) causes abnormal immune responses, as well as endothelial vascular dysfunction, for which the responsible viral factor remains unclear. During peak viremia, the plasma levels of virion-associated envelope protein domain III (EIII) increases to a point at which cell death is sufficiently induced in megakaryocytes in vitro. Thus, EIII may constitute a virulence factor for endothelial damage. In this study, we examined endothelial cell death induced by treatment with DENV and EIII in vitro. Notably,

Dengue Virus Envelope Protein Domain III Induces Nlrp3 Inflammasome-Dependent NETosis-Mediated Inflammation in Mice.

Abnormal immune responses and cytokine storm are involved in the development of severe dengue, a life-threatening disease with high mortality. Dengue virus-induced neutrophil NETosis response is associated with cytokine storm; while the role of viral factors on the elicitation of excessive inflammation mains unclear. Here we found that treatments of dengue virus envelope protein domain III (EIII), cellular binding moiety of virion, is sufficient to induce neutrophil NETosis processes in vitro and in vivo. Challenges of EIII in inflammasome Nlrp3-/- and Casp1-/- mutant mice resulted in less inf

Differential inflammasome activation predisposes to acute-on-chronic liver failure in human and experimental cirrhosis with and without previous decompensation.

OBJECTIVE: Systemic inflammation predisposes acutely decompensated (AD) cirrhosis to the development of acute-on-chronic liver failure (ACLF). Supportive treatment can improve AD patients, becoming recompensated. Little is known about the outcome of patients recompensated after AD. We hypothesise that different inflammasome activation is involved in ACLF development in compensated and recompensated patients. DESIGN: 249 patients with cirrhosis, divided into compensated and recompensated (previous AD), were followed prospectively for fatal ACLF development. Two external cohorts (n=327) (recomp

Genetic disruption of the inflammasome adaptor ASC has minimal impact on the pathogenesis of Duchenne muscular dystrophy in mdx mice.

AIM: Up-regulation of inflammasome proteins was reported in dystrophin-deficient muscles. However, it remains to be determined whether inflammasome activation plays a role in the pathogenesis of Duchenne muscular dystrophy. This study was therefore set out to investigate whether genetic disruption of the inflammasome pathway impacts the disease progression in mdx mice. MAIN METHODS: Mice deficient in both dystrophin and ASC (encoded by Pycard [PYD And CARD Domain Containing]) were generated. The impact of ASC deficiency on muscular dystrophy of mdx mice were assessed by measurements of serum