PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

The intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents gut microbiota from lamina propria within resident mucosal immune cells to maintain homeostasis. is manifested contiguous monolayer of specialized epithelial (IEC), interconnected through tight junctions (TJs). integrity this paramount. Consequently, excessive IEC death advances permeability consequence thereof translocation bacteria into propria, subsequently triggering an inflammatory response, which underpins clinical disease trajectory bowel (IBD). A burgeoning body evidence illustrates landscape where undergoes several model programmed cell (PCD) pathophysiology pathogenesis IBD. Apoptosis, necroptosis, pyroptosis represent principal modalities PCD with intricate specific pathways molecules. Ample has revealed substantial mechanistic convergence crosstalk among these three aforementioned forms death, expanding conceptualization PANoptosis orchestrated by PNAoptosome complex. This review provides concise overview molecular mechanisms apoptosis, pyroptosis. Furthermore, based on between deaths IEC, details current knowledge regarding regulation natural products. Our objective broaden comprehension innovative underlying IBD furnish foundation for developing more drugs treatment IBD, benefiting both practitioners research workers.

Language: Английский

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Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

PANoptosis is one of several modes programmed cell death (PCD) and plays an important role in many inflammatory immune diseases. The bowel disease (IBD) currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, pathway enrichment analyses performed. LASSO regression model construction, a nomogram model, calibration curves, ROC DCA curves used to evaluate the predictive value model. Predicts transcription factors (TFs) small-molecule drugs DE-PRGs analysed. Model immuno-infiltration features IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB BAX. analysis suggested that these related TNF signalling, NF-κB, pyroptosis necroptosis. Machine learning identified three GZMB CASP5. have strong value. Immuno-infiltration revealed infiltration was increased patients with IBD, closely various cells. TFs associated RELA, NFKB1, HIF1A, TP53 SP1. In addition, Connectivity Map (CMap) database top 10 compounds, including buspirone, chloroquine, spectinomycin chlortetracycline. This study indicate good ability for IBD. Moreover, may mediate process through pyroptosis, necroptosis mechanisms. These results present new horizon research treatment

Language: Английский

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PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis

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

Published: Oct. 31, 2024

PANoptosis is a newly identified inflammatory programmed cell death (PCD) that involves the interplay of apoptosis, necrosis, and pyroptosis. However, its overall biological effects cannot be attributed to any one type PCD alone. regulated by signaling cascade triggered recognition pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs) various sensors. This triggers assembly PANoptosome, which integrates key components from other pathways via adapters ultimately activates downstream execution molecules, resulting in with necrotic, apoptotic, pyroptotic features. Autoimmune diseases are characterized reduced immune tolerance self-antigens, leading abnormal responses, often accompanied systemic chronic inflammation. Consequently, PANoptosis, as unique innate immune-inflammatory pathway, has significant pathophysiological relevance inflammation autoimmunity. most previous research on focused tumors infectious diseases, leaving activation role autoimmune unclear. review briefly outlines characteristics summarizes several PANoptosome complexes, their mechanisms, components. We also explored dual potential therapeutic approaches targeting PANoptosis. Additionally, we existing evidence for explore regulatory mechanisms involved.

Language: Английский

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Diosmin Alleviates Colitis by Inhibiting PANoptosis of Intestinal Epithelial Cells and Regulating Gut Microbiota and Metabolites

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156671 - 156671

Published: March 1, 2025

Language: Английский

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Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9751 - 9751

Published: Sept. 9, 2024

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, immune cell infiltration landscape inflamed tissues. Eight publicly available transcriptomic datasets, including non-inflamed tissues from CD UC patients were analyzed. Common differentially expressed genes (DEGs) identified through meta-analysis, revealing 180 DEGs. DEGs implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways cancer. Protein-protein interaction network cluster analysis 14 central IBD players, validated using eight external datasets. Disease module construction NeDRex platform nine out disease-associated (

Language: Английский

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Integrating Machine Learning and Bulk and Single-Cell RNA Sequencing to Decipher Diverse Cell Death Patterns for Predicting the Prognosis of Neoadjuvant Chemotherapy in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3682 - 3682

Published: April 13, 2025

Breast cancer (BRCA) continues to pose a serious risk women’s health worldwide. Neoadjuvant chemotherapy (NAC) is critical treatment strategy. Nevertheless, the heterogeneity in outcomes necessitates identification of reliable biomarkers and prognostic models. Programmed cell death (PCD) pathways serve as factor tumor development response. However, relationship between diverse patterns PCD NAC BRCA remains unclear. We integrated machine learning multiple bioinformatics tools explore association 19 prognosis within cohort 921 patients treated with from seven multicenter cohorts. A model based on PCD-related genes (PRGs) was constructed evaluated using combination 117 algorithms. Immune infiltration analysis, mutation pharmacological single-cell RNA sequencing (scRNA-seq) were conducted genomic profile clinical significance these BRCA. Immunohistochemistry (IHC) employed validate expression select (UGCG, BTG22, TNFRSF21, MYB) tissues. PRGs by signature comprising 20 DEGs forecast patients. The demonstrated excellent predictive accuracy, high concordance index (C-index) 0.772, validated across independent datasets. Our results strong developed survival prognosis, pathological features, immune infiltration, microenvironment (TME), gene mutations, drug sensitivity for Moreover, IHC studies further that certain tissues significantly associated efficacy emerged an autonomous predictor influencing outcome are first integrate bulk scRNA-seq decode various mechanisms unique model, PRGs, provides novel comprehensive strategy predicting This not only aids understanding underlying but also offers insights into personalized strategies, potentially improving patient outcomes.

Language: Английский

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PANoptosis: a potential target of atherosclerotic cardiovascular disease

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

PANoptosis is a newly discovered cell death pathway triggered by the innate immunizer, which in turn promotes assembly of PANoptosome and activates downstream effectors. As special mode, it characterized apoptosis, pyroptosis, necroptosis at same time; therefore, not feasible to inhibit suppressing single pathway. However, active ingredients targeting can effectively PANoptosis.Given importance disease, would be an important therapeutic tool. Previous studies have focused more on infectious diseases cancer, role cardiovascular field has been comprehensively addressed. While ASCVD number one killer diseases, explore new targets determine future research directions. Therefore, this review focuses PANoptosome, molecular mechanism PANoptosis, related mechanisms leading such as myocardial infarction, ischemic cardiomyopathy stroke, order provide perspective for prevention treatment ASCVD.

Language: Английский

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Integrative Gut Microbiota and Metabolomic Analyses Reveal the PANoptosis- and Ferroptosis-Related Mechanisms of Chrysoeriol in Inhibiting Melanoma

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(45), P. 25173 - 25185

Published: Nov. 4, 2024

Chrysoeriol, a natural flavonoid, has shown potential in inhibiting melanoma. However, the detailed molecular mechanisms of its action still need to be clarified. In this study, chrysoeriol showed significant suppressive effects on melanoma progression mouse model. The integrative gut microbiota and metabolomic analyses revealed that modulates multiple pathways associated with apoptosis, necroptosis, pyroptosis, ferroptosis. Morphological changes chrysoeriol-treated cells PANoptosis- ferroptosis-related characteristics. Additionally, induced altered mitochondrial membrane potential, increased ROS production, promoted also upregulated molecules linked pyroptosis Molecular-level experiments confirmed upregulation crucial proteins PANoptosis ferroptosis pathways. Inhibition by inhibitors or gene knockdown significantly attenuated inhibitory cell viability. This study provides robust evidence triggers both cells, underscoring promise as treatment option for

Language: Английский

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Cell Death Pathways in Dry Eye Disease: Insights into Ocular Surface Inflammation

The Ocular Surface, Journal Year: 2024, Volume and Issue: 34, P. 535 - 544

Published: Oct. 1, 2024

Language: Английский

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Identification of key genes in inflammatory bowel disease, characteristics of immune infiltration, and molecular mechanisms using multiomics analysis and Mendelian randomization

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Purpose: We explored the possible influence of key genes in inflammatory bowel disease (IBD) to determine if they may be targets for treating or diagnosing IBD. Patients and methods: identified associated with pathogenesis IBD through multiomics data Mendelian randomization analysis. Furthermore, we investigated role these progression, immune infiltration, underlying molecular mechanisms. Results: successfully six (Adhesion G Protein-Coupled Receptor F1 (ADGRF1), CINP Kinetochore-Binding Protein (CINP), Equatorin (EQTN), Insulin-like Growth Factor 1 (IGF1R), Poliovirus (PVR), Serpin Family A Member 9 (SERPINA9) These exhibited unique expression patterns at infiltration level. Gene set enrichment analysis revealed their multiple signaling pathways. Conclusion: Further transcription factor regulatory network single-cell sequencing results genes’ suggesting that important future treatment diagnosis Therefore, this article provides new insights into potential therapeutic

Language: Английский

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