Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 3033 - 3033

Опубликована: Фев. 3, 2023

Immunogenic cell death (ICD) is a form of programmed with strong sense inflammatory detection, whose powerful situational awareness can cause the reactivation aberrant immunity. However, role ICD in pathogenesis severe acute pancreatitis (SAP) has yet to be investigated. This study aims explore pivotal genes associated SAP and how they relate immune infiltration short-chain fatty acids (SCFAs), order provide theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from Gene Expression Omnibus (GEO). The use differentially expressed gene (DEG) analysis; weighted co-expression network analysis (WGCNA) least absolute shrinkage selection operator (LASSO) regression allowed us identify total three ICD-related hub (LY96, BCL2, IFNGR1) SAP. Furthermore, single sample set enrichment (ssGSEA) demonstrated that are closely specific cells, activation pathways metabolism SCFAs (especially butyrate). These findings were validated through expression patterns both clinical patients rat animal models In conclusion, first concept was proposed our study. important implications future investigations into pro-inflammatory mechanisms mediated by damage-associated molecular (DAMPs) late stages

Язык: Английский

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Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

Microbiology Spectrum, Год журнала: 2023, Номер 11(4)

Опубликована: Июнь 20, 2023

The pivotal roles of gut microbiota in severe acute pancreatitis-associated lung injury (SAP-ALI) are increasingly revealed, and recent discoveries the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used clinical to treat However, underlying mechanisms remain be fully elucidated. Herein, by using caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model antibiotics (Abx) cocktail-induced pseudogermfree model, we tried uncover administration QYD explored its possible mechanisms. Immunohistochemical results showed that severity intestinal barrier functions could affected relative depletion bacteria. composition was partially recovered after treatment with decreased Firmicutes/Bacteroidetes ratio increased abundance short-chain fatty acids (SCFAs)-producing Correspondingly levels SCFAs (especially propionate butyrate) feces, gut, serum, lungs were observed, generally consistent changes microbes. Western-blot analysis RT-qPCR indicated AMPK/NF-κB/NLRP3 signaling pathway activated oral QYD, which found possibly related regulatory effects on intestine lungs. In conclusion, our study provides new insights into through modulating has prospective practical value use future. IMPORTANCE Gut affects function. During SAP, significant increase pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) observed. At same time, pathogenic bacteria SCFAs-producing (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). addition, mediated along may play an essential role preventing pathogenesis SAP-ALI, allows reduced systemic inflammation restoration barrier.

Язык: Английский

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Exploring immune-related pathogenesis in lung injury: Providing new insights Into ALI/ARDS

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116773 - 116773

Опубликована: Май 21, 2024

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a significant global burden of morbidity mortality, with being the primary cause death in affected patients. The pathogenesis injury, however, remains complex issue. In recent years, role immune system has attracted extensive attention worldwide. Despite advancements our understanding various subtypes, limitations persist both prevention treatment. This review investigates immunopathogenesis ALI/ARDS, aiming to elucidate pathological processes mediated by dendritic cells (DCs), natural killer (NK) cells, phagocytes, neutrophils. Furthermore, article expounds on critical contributions gut microbiota, inflammatory pathways, cytokine storms development ALI/ARDS.

Язык: Английский

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Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 23, 2023

Background A number of recent observational studies have indicated a correlation between the constitution gut microbiota and incidence pancreatitis. Notwithstanding, are unreliable for inferring causality because their susceptibility to confounding, bias, reverse causality, causal relationship specific pancreatitis is still unclear. Therefore, our study aimed investigate four types Methods An investigative undertaking encompassing genome-wide association (GWAS) comprising 18,340 participants was undertaken with aim discerning genetic instrumental variables that exhibit associations microbiota, The aggregated statistical data pertaining acute (AP), alcohol-induced AP (AAP), chronic (CP), CP (ACP) were acquired from FinnGen Consortium. two-sample bidirectional Mendelian randomization (MR) approach utilized. Utilizing Inverse-Variance Weighted (IVW) technique as cornerstone primary analysis. Bonferroni analysis used correct multiple testing, In addition, sensitivity methodologies, MR-Egger intercept test, Cochran’s Q MR polymorphism residual outlier (MR-PRESSO) leave-one-out performed evaluate robustness findings. Results total 28 intestinal microflora ascertained significant diverse outcomes Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p 0.008) has strong ACP after Bonferroni-corrected in order assess potential causation effects, we exposure variable scrutinized its impact on outcome variable, this revealed 30 distinct microflora. implementation test lack substantial heterogeneity among various single nucleotide polymorphisms (SNP). Conclusion Our first systematic provides evidence taxa may be causally associated disease. This discovery contribute biomarkers conducive preliminary, non-invasive identification Pancreatitis. Additionally, it could present viable targets therapeutic interventions disease’s treatment.

Язык: Английский

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Altered gut microbiota in the early stage of acute pancreatitis were related to the occurrence of acute respiratory distress syndrome

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Март 6, 2023

Acute respiratory distress syndrome (ARDS) is the most common cause of organ failure in acute pancreatitis (AP) patients, which associated with high mortality. Specific changes gut microbiota have been shown to influence progression pancreatitis. We aimed determine whether early alterations related and could predict ARDS occurrence AP patients.In this study, we performed 16S rRNA sequencing analysis 65 patients 20 healthy volunteers. The were further divided into two groups: 26 AP-ARDS 39 AP-nonARDS based on during hospitalization.Our results showed that exhibited specific composition function as compared subjects group. Higher abundances Proteobacteria phylum, Enterobacteriaceae family, Escherichia-Shigella genus, Klebsiella pneumoniae, but lower Bifidobacterium genus found group groups. Random forest modelling revealed Escherichia-shigella was effective distinguish from AP-nonARDS, patients.Our study admission after hospitalization, indicating a potential predictive pathogenic role development patients.

Язык: Английский

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Preventive Effect of the Total Polyphenols from Nymphaea candida on Sepsis-Induced Acute Lung Injury in Mice via Gut Microbiota and NLRP3, TLR-4/NF-κB Pathway

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4276 - 4276

Опубликована: Апрель 12, 2024

This study aimed to investigate the preventive effects of total polyphenols from Nymphaea candida (NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate tissue pathological as well wet/dry ratio MPO activities (p < 0.05). decrease blood leukocyte, neutrophil, monocyte, basophil, eosinophil amounts LPS contents ALI compared with model group 0.05), improving lymphocyte Moreover, group, TNF-α, IL-6, IL-1β levels 0.05) downregulate protein expression TLR4, MyD88, TRAF6, IKKβ, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB NLRP3, ASC, Caspase1 tissues Furthermore, inhibit ileum histopathological injuries, restoring tight junctions by increasing ZO-1 occludin. Simultaneously, reverse gut microbiota disorder, restore diversity microbiota, increase relative abundance Clostridiales Lachnospiraceae, enhance content SCFAs (acetic acid, propionic butyric acid) feces. These results suggested that has ALI, mechanism is related regulation SCFA metabolism, TLR-4/NF-κB NLRP3 pathways.

Язык: Английский

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Cordyceps militaris solid medium extract alleviates lipopolysaccharide-induced acute lung injury via regulating gut microbiota and metabolism

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Acute lung injury (ALI) is a common respiratory disease, Cordycepin has been reported to reduce ALI, which an effective component in Cordyceps militaris solid medium extract (CMME). Therefore, we aimed explore the alleviating effect and mechanism of CMME on ALI. This study evaluated lipopolysaccharide (LPS)-induced ALI mice by analyzing intestinal flora metabolomics its potential mechanism. We assessed pulmonary changes, inflammation, oxidative stress, macrophage neutrophil activation levels, then analyzed gut microbiota through 16S rRNA profile UPLC-QTOF/MS. The results showed that treatment improved injury, reduced inflammatory factors stress decreased recruitment. revealed significantly increased richness diversity abundance Bacteroides compared with Mod group significantly. Metabolic analysis indicated reversed levels differential metabolites may ameliorate purine metabolism, nucleotide bile acid (BA) did reverse changes BA mice, were associated flora. improve regulating correcting metabolic disorders, providing new insights into action.

Язык: Английский

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Chaihuang Qingyi Huoxue granule ameliorates severe acute pancreatitis by modulating gut microbiota and repairing the intestinal mucosal barrier

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Фев. 18, 2025

During severe acute pancreatitis (SAP), damage to the intestinal mucosal barrier and translocation of pathogenic bacteria are key mechanisms that accelerate disease progression SAP. Chaihuang Qingyi Huoxue Granule (CH) is a herbal formula used in clinical treatment This study aims investigate role CH regulating gut microbiota SAP rats. Sodium taurocholate (3.5%) was retrogradely perfused into biliopancreatic duct establish model (4.4 g/kg) administered by gavage. Serum amylase, lipase, endotoxin levels were measured. Hematoxylin-eosin (HE) staining observe morphological changes pancreas colon. The expression zona occludens-1 (ZO-1) occludin colon examined immunohistochemistry (IHC) western blot. 16S rDNA gene sequencing analyze content short-chain fatty acids (SCFAs) contents rats determined gas chromatography-mass spectrometry (GC-MS). reduced serum rats, alleviated pathological colon, restored ZO-1 occludin. Moreover, dysbiosis with diversity structure. At phylum level, relative abundance Firmicutes Bacteroidetes increased, while Proteobacteria decreased. genus Ruminococcus 1, Parabacteroides, Prevotellaceae UCG-001, Lachnospiraceae NK4A136 group, Lactobacillus Escherichia-Shigella, Enterococcus, Enterobacter In addition, increased SCFAs ameliorates maintaining homeostasis microbiota, increasing SCFAs, repairing barrier.

Язык: Английский

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Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 2173 - 2193

Опубликована: Апрель 1, 2024

The pathogenesis of severe acute pancreatitis-associated lung injury (SAP-ALI), which is the leading cause mortality among hospitalized patients in intensive care unit, remains incompletely elucidated.The intestinal mucosal immune barrier a crucial component epithelial barrier, and its aberrant activation contributes to induction sustained pro-inflammatory responses, paradoxical intercellular communication, bacterial translocation.In this review, we firstly provide comprehensive overview composition pivotal roles SAP-ALI.Secondly, mechanisms crosstalk with gut microbiota, called gut-lung axis, effect on SAP-ALI were summarized.Finally, number drugs that could enhance exhibit potential anti-SAP-ALI activities presented, including probiotics, glutamine, enteral nutrition, traditional Chinese medicine (TCM).The aim offer theoretical framework based perspective protect against SAP-ALI.

Язык: Английский

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Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

The FASEB Journal, Год журнала: 2024, Номер 38(8)

Опубликована: Апрель 23, 2024

Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum L-arginine-induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up-regulated. Increased Pck1 expression intestinal epithelial cells (IECs) further validated and duodenum patients. mice, level positively correlated with pancreatic ileal histopathological scores, serum amylase activity, permeability (serum diamine oxidase (DAO), D-lactate, endotoxin). patients, had a positive correlation Ranson white blood cell count C-reactive protein. Inhibition by 3-Mercaptopicolinic acid hydrochloride (3-MPA) alleviated injuries mice. + 3-MPA showed improved permeability, including less apoptosis, increased tight junction proteins (TJPs) expression, decreased DAO, endotoxin, FITC-Dextran levels, reduced bacteria translocation. Lysozyme secreted Paneth mucin2 (MUC2) secretion goblet were also partly restored Meanwhile, inhibition immune response during AP, elevation M2/M1 macrophages ratio secretory immunoglobulin A (sIgA) reduction neutrophils infiltration. vitro, administration dramatically ameliorated inflammation enteroids treated LPS. conclusion, IECs might alleviate via modulating homeostasis.

Язык: Английский

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