2D Cobalt Oxyhydroxide Nanozymes Inhibit Inflammation by Targeting the NLRP3 Inflammasome

Advanced Functional Materials, Год журнала: 2023, Номер 33(27)

Опубликована: Апрель 19, 2023

Abstract Nucleotide‐binding domain and leucine rich repeat family pyrin containing 3 (NLRP3) inflammasomes are implicated in diverse inflammatory diseases, so their activation needs to be tightly controlled. Over generation of reactive oxygen species (ROS) is a key factor NLRP3 inflammasome activation. Consequently, nanozymes with ROS scavenging ability potential inhibitors promising therapeutic agents for related diseases. Herein, type 2D cobalt hydroxide oxide nanosheets (Co NSs), nanozyme excellent multienzyme‐like activity, possessing peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) activities, exhibits superior properties protects cells from oxidative damage. Density functional theory (DFT) calculations further reveal these enzyme‐like catalytic reactions eliminating spontaneous CAT dominant under physiological conditions. Performing multienzyme properties, Co NSs present anti‐inflammation activity by blocking oligomerization ASC speck formation, thereby inhibiting assembly Importantly, treatment attenuates the severity LPS‐induced systemic inflammation DSS‐induced colitis. This study highlights successful strategy utilizing cobalt‐based scavenge provides valuable insights into underlying mechanism, demonstrating effects prevention NLRP3‐associatied

Язык: Английский

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NLRP3: a new therapeutic target in alcoholic liver disease

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 13, 2023

The liver is in charge of a wide range critical physiological processes and it plays an important role activating the innate immune system which elicits inflammatory events. Chronic ethanol exposure disrupts hepatic mechanism leads to release proinflammatory mediators such as chemokines, cytokines activation inflammasomes. fibrosis/cirrhosis involve NLRP3 inflammasome, leading destruction hepatocytes subsequent metabolic dysregulation humans. In addition, increasing evidence suggests that alcohol intake significantly modifies epigenetics, promoting development alcoholic disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, DNA methylation are crucial alcohol-evoked cell signaling affects gene expression system. Though we at beginning stage without having entire print epigenetic signature, time focus more on inflammasome modifications. Here review novel aspect ALD pathology linking inflammation highlighting modification associated with how could be therapeutic target ALD.

Язык: Английский

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Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 5, 2024

Abstract Background Osteoporosis is characterized by an imbalance in bone homeostasis, resulting the excessive dissolution of minerals due to acidified microenvironment mediated overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential reversing osteoporosis inhibiting osteoclast-mediated resorption. The limited water solubility and lack targeting specificity hinder effective accumulation within pathological environment osteoporosis. Results Osteoclasts’ microenvironment-responsive nanoparticles are prepared incorporating with amorphous calcium carbonate (ACC) coated glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing drug delivery efficiency as well therapeutic effect. obtained smart nanoparticles, coined OAPLG, could instantly neutralize release extracellular combination ACC synergistically inhibits osteoclast formation activity, leading significant reversal systemic loss ovariectomized mice model. Conclusion work highlights intelligent nanoplatform based on for spatiotemporally controlled lipophilic drugs, illustrates prominent promise against

Язык: Английский

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Natural compounds target programmed cell death (PCD) signaling mechanism to treat ulcerative colitis: a review

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Ulcerative colitis (UC) is a nonspecific inflammatory bowel disease characterized by abdominal pain, bloody diarrhea, weight loss, and colon shortening. However, UC difficult to cure due its high drug resistance rate easy recurrence. Moreover, long-term inflammation increased severity can lead the development of cancer in some patients. Programmed cell death (PCD) gene-regulated process that includes apoptosis, autophagy, necroptosis, ferroptosis, pyroptosis. PCD plays crucial role maintaining body homeostasis organs tissues. Abnormal signaling observed pathological UC, such as activating apoptosis pathway promote progression UC. Targeting may be therapeutic strategy, natural compounds have shown great potential modulating key targets treat For instance, baicalin regulate alleviate infiltration damage. This review focuses on specific expression interaction with multiple pathways, NF-κB, Nrf2, MAPK, JAK/STAT, PI3K/AKT, NLRP3, GPX4, Bcl-2, etc., elucidate targeting for treatment used (ulcerative colitis) (programmed death) (natural products) keywords search related studies PubMed Web Science, CNKI database past 10 years. work retrieved 72 (65 from 5 years 7 years), which aims provide new strategies patients serves foundation drugs.

Язык: Английский

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PANoptosis and Autophagy-Related Molecular Signature and Immune Landscape in Ulcerative Colitis: Integrated Analysis and Experimental Validation

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 3225 - 3245

Опубликована: Май 1, 2024

Background: Ulcerative colitis (UC) is an autoimmune inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), including PANoptosis and autophagy, plays roles in inflammation immunity. This study aimed to investigate molecular signature immune landscape PANoptosis- autophagy-related differentially expressed genes (DEGs) UC. Methods: Analyzing UC dataset GSE206285 yielded DEGs. Differentially were identified using DEGs relevant gene collections. Functional pathway enrichment analyses conducted. A protein-protein interaction (PPI) network was established identify hub genes. TRRUST database predicted transcription factors (TFs), pivotal miRNAs, drugs interacting with Immune infiltration analysis, UC-associated single-cell sequencing data construction a competing endogenous RNA (ceRNA) for Machine learning key candidate genes, evaluated diagnostic value via receiver operating characteristic (ROC) curves. mice model verified expression Results: Identifying ten PANoptosis-related four associated them chemotaxis, wound healing positive MAPK cascade regulation. analysis revealed increased immunocyte patients, closely linked various infiltrations. five TIMP1, TIMP2, TIMP3, IL6, CCL2, strong performance. At level, these exhibited high fibroblasts (IAFs). They showed significant differences colon mucosa both patients model. Conclusion: validated novel signatures autophagy UC, potentially influencing dysregulation healing, thus opening avenues future research therapeutic interventions. Keywords: ulcerative colitis, PANoptosis, infiltration, fibroblasts, bioinformatics

Язык: Английский

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CaGA nanozymes inhibit oxidative stress and protect mitochondrial function in ulcerative colitis therapy

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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N-acetyltransferase 10 impedes EZH2/H3K27me3/GABARAP axis mediated autophagy and facilitates lung cancer tumorigenesis through enhancing SGK2 mRNA acetylation

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 139823 - 139823

Опубликована: Янв. 1, 2025

Язык: Английский

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Metformin Ameliorates Ulcerative Colitis Through Inhibiting NLRP3 Inflammasome Activation

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 1773 - 1786

Опубликована: Фев. 1, 2025

Purpose: Metformin (Met) is widely used to treat a variety of diseases, but its role in ulcerative colitis (UC) has not been fully elucidated. This study aimed clarify the effect Met on UC, exploring relationship with NLRP3 inflammasome and elucidating potential mechanisms. Methods: C57BL/6J mice were administrated DSS solution establish UC model. Disease Activity Index (DAI) hematoxylin eosin staining (HE) performed evaluate impact Enzyme-linked immunosorbent assay (ELISA), Reverse transcription - quantitative polymerase chain reaction (RT-qPCR), Western blotting (WB), immunohistochemistry, immunofluorescence detect activation vivo. Furthermore, vitro, bone marrow-derived macrophages (BMDMs) selected underlying Results: In vivo, could significantly inhibit development characterized by decreased DAI, increased body weight colorectal length, repair damaged tissue. also block macrophage infiltration subsequently reduced level IL-1β, NLRP3, Caspase-1 tissue, which mainly expressed macrophages. addition, IL-1β serum was remarkedly down-regulated Met. dampen maturation pro-caspase-1 pro-IL-1β. Moreover, simultaneously suppress NF-κB/p65 signaling pathway disrupt formation ASC speck. At last, exhibited an anti-oxidant effect, along upregulating UCP2 NCF1. Conclusion: ameliorated inhibiting The mechanisms only involved inhibition NF-κB (first signal), associated up-regulation NCF1 levels thus repression ROS generation (second signal). Keywords: metformin, NF-κB, inflammasome, ROS,

Язык: Английский

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Natural products modulate NLRP3 in ulcerative colitis

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Окт. 2, 2023

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) complex composed multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) induce maturation secretion mediators such as interleukin (IL)-1β IL-18, promoting development responses. Recent studies have shown NLRP3 associated with UC susceptibility, it maintains stable intestinal environment by responding wide range pathogenic microorganisms. The mainstay treatment for control inflammation relieve symptoms. Despite certain curative effect, there are problems easy recurrence after drug withdrawal many side effects long-term medication. serves core link in response. If relationship between gut microbes inflammation-associated factors can be analyzed concerning its related signaling pathways, expression status well specific mechanism course IBD elucidated further considered clinical diagnosis IBD, expected lead compounds targeting inflammasome developed IBD. Research into prevention UC, which has become hotbed research recent years, natural products rich therapeutic means, multi-targets, fewer adverse effects. Natural promise treating numerous basic trials over past few years. This paper describes regulatory role against provides reference this disease.

Язык: Английский

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Ononin alleviates DSS‐induced colitis through inhibiting NLRP3 inflammasome via triggering mitophagy

Immunity Inflammation and Disease, Год журнала: 2023, Номер 11(2)

Опубликована: Фев. 1, 2023

Abstract Background: Ononin, a flavonoid isolated from Astragalus membranaceus root, is the active ingredient of A. and has potential anti‐inflammatory properties, but its effect on colitis unclear. Aims: This study aimed to explore anticolitis Ononin by establishing model in mice induced dextran sulfate sodium (DSS). Methods: Male C57BL/6 were provided DSS, then treated with (10, 20, 40 mg/kg) or 5‐ASA (40 mg/kg). The symptoms observed, disease activity index (DAI) score recorded daily, colonic inflammation was evaluted histopathological scoring. expression cytokines, inflammatory mediators, mitophagy/NLRP3 inflammasome‐related proteins measured. Results: significantly alleviated weight loss colon shortening ( p < .01). Moreover, decreased production cytokines mediators associated .05). In addition, inhibited macrophages infiltration reduced caspase‐1 activation mice. Caspase‐1 closely related NLRP3 inflammasome. Therefore, we investigated inflammasome vitro. relevant results confirmed that mitochondrial damage Further studies revealed through triggering mitophagy Conclusion: alleviates DSS‐induced activating inhibit

Язык: Английский

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