NLRP3: a new therapeutic target in alcoholic liver disease

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 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.

Language: Английский

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Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 130822 - 130822

Published: March 22, 2024

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate development dextran sulfate sodium (DSS)-induced UC reflected by ameliorated pathological lesions in colon. GPs strikingly suppressed expression levels multiple cytokines, well significantly inhibited infiltration cells. Microbiota-dependent investigations virtue 16S rRNA gene sequencing, antibiotic and fecal microbiota transplantation illustrated prominently restored intestinal microbial balance predominantly through modulating relative abundance Lactobacillus. Additionally, remarkably influenced tryptophan metabolites, diminished permeability strengthened barrier integrity via inhibiting 5-HT/HTR3A signaling pathway. Taken together, promising therapeutic potential on hinges capacity to suppress cytokines influence Lactobacillus metabolites.

Language: Английский

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

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 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

Language: Английский

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

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 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.

Language: 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, Journal Year: 2024, Volume and Issue: Volume 17, P. 3225 - 3245

Published: May 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

Language: 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, Journal Year: 2025, Volume and Issue: unknown, P. 139823 - 139823

Published: Jan. 1, 2025

Language: Английский

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Pulchinenoside B4 alleviates DSS-induced colitis by inhibiting CD1d-dependent NLRP3 inflammasome activation in macrophages

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114118 - 114118

Published: Jan. 23, 2025

Language: Английский

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VANGL2 alleviates inflammatory bowel disease by recruiting the ubiquitin ligase MARCH8 to limit NLRP3 inflammasome activation through OPTN-mediated selective autophagy

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3002961 - e3002961

Published: Feb. 3, 2025

Inflammatory bowel disease (IBD) is a chronic and potentially life-threatening inflammatory of gastroenteric tissue characterized by episodes intestinal inflammation, but the underlying mechanisms remain elusive. Here, we explore role precise mechanism Van-Gogh-like 2 (VANGL2) during pathogenesis IBD. VANGL2 decreases in IBD patients dextran sulfate sodium (DSS)-induced colitis mice. Myeloid deficiency exacerbates progression DSS-induced mice specifically enhances activation NLRP3 inflammasome macrophages. NLRP3-specific inhibitor MCC950 effectively alleviates deficient Mechanistically, interacts with promotes autophagic degradation through enhancing K27-linked polyubiquitination at lysine 823 recruiting E3 ligase MARCH8, leading to optineurin (OPTN)-mediated selective autophagy. Notably, decreased peripheral blood mononuclear cells from results overt sustained inflammation. Taken together, this study demonstrates that acts as repressor inhibiting provides insights into crosstalk between inflammation autophagy preventing

Language: Английский

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Organoid, organ-on-a-chip and traditional Chinese medicine

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 12, 2025

Abstract In the past few years, emergence of organoids and organ-on-a-chip (OOAC) technologies, which are complementary to animal models two-dimensional cell culture methods can better simulate internal environment human body, provides a new platform for traditional Chinese medicine (TCM) studies. Organoids OOAC techniques have been increasingly applied in fields drug screening, assessment development, personalized therapies, developmental biology, there some application cases TCM this review, we summarized current status using organoid technologies research provide key insights future study. It is believed that will play more important roles make greater contributions innovative development TCM.

Language: Английский

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Coix Seed Oil Alleviates DSS-Induced Ulcerative Colitis via Intestinal Barrier Repair and Ferroptosis Regulation

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2557 - 2581

Published: Feb. 1, 2025

Ulcerative colitis is a chronic intestinal disease linked to barrier damage, ferroptosis and dysbiosis. Coix lacryma-jobi natural food with food-medicine homology, whose seed-derived oil (Coix seed oil, CSO) has been shown anti-inflammatory activity in vitro. Here, the effects mechanisms of CSO on ulcerative (UC) vivo are systematically investigated. Firstly, UC mice was replicated by 3% DSS, assessed efficacy observing fecal occult blood, colon length, DAI score pathological histomorphological changes tissues. The barrier-protective were observed AB staining qRT-PCR. Secondly, biological targets obtained from TCMSP database Swiss Target Prediction database, downloaded FerrDb platform, UC-related GEO intersection above three taken obtain "CSO-UC-Ferroptosis" targets, which analysed GO KEGG enrichment, GSEA analysis, immune cell infiltration validation. Finally, core genes molecular docking potential active components CSO. In order further verify effect ferroptosis, GPX4 agonist RSL-3 used stimulate vivo, levels Iron, MDA SOD measured, immunohistochemistry detect tight junction proteins protein mice. Besides, evaluated intercellular junctions tissues each group under electron microscope. addition, 16sRNA sequencing performed contents observe flora improved physiological parameters, reduced inflammation response regulated restored gut microbiota balance Bioinformatics results showed that G6PD, ABCC1 at CSO, also demonstrated similar expression DSS-induced models vivo. Our findings demonstrate for first time ameliorated regulating mice, suggesting as promising candidate treatment warranting investigation.

Language: Английский

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