Archivum Immunologiae et Therapiae Experimentalis最新文献

{"title":"Ectromelia Virus Reprograms the Noncanonical NF-κB Signaling Pathway in HeLa Epithelial Cells.","authors":"Justyna Struzik, Lidia Szulc-Dąbrowska, Michał Koper, Małgorzata Gieryńska","doi":"10.2478/aite-2026-0025","DOIUrl":"https://doi.org/10.2478/aite-2026-0025","url":null,"abstract":"<p><p>The noncanonical nuclear factor κB (NF-κB) pathway regulates adaptive immune responses and antiviral innate immunity. Orthopoxviruses, including the human pathogen variola virus and zoonotic viruses such as vaccinia virus and monkeypox virus, have evolved multiple strategies to suppress host antiviral signaling. Our previous work using <i>in vitro</i> immune cell models demonstrated that the mouse-specific orthopoxvirus ectromelia virus (ECTV) inhibits the noncanonical NF-κB signaling pathway. Here, we investigated the impact of ECTV on noncanonical NF-κB signaling in human epithelial HeLa cells. Tumor necrosis factor superfamily ligands were used to activate or modulate noncanonical NF-κB signaling. Using fluorescence microscopy and immunoblot analyses, we found that ECTV reduced LIGHT (TNFSF14)- and lymphotoxin α₁β₂ (LTα₁β₂)-induced nuclear accumulation of the NF-κB subunits RelB and p52. ECTV infection alone increased whole-cell RelB and NF-κB2/p100 levels but did not significantly alter nuclear RelB levels. In TNF-α-stimulated cells, ECTV reduced levels of cellular inhibitor of apoptosis protein 2 (cIAP2), whereas in LTα₁β₂-stimulated cells, ECTV reduced levels of TNF receptor-associated factor 3 (TRAF3). RT-qPCR analysis revealed that ECTV upregulated <i>RELB</i>, <i>NFKB2</i>, and <i>CHUK</i> expression. Viral infection also increased expression of <i>TNFAIP3</i> and <i>OTUD7B</i>, genes encoding regulators of noncanonical NF-κB signaling. Moreover, infected cells exhibited increased expression of selected RelB-responsive genes, including <i>FBRS</i>, <i>CCR10</i>, and <i>TNFRSF6B</i>. Together, these findings indicate that ECTV modulates components associated with noncanonical NF-κB signaling in epithelial cells <i>in vitro</i>, without evidence of constitutive pathway activation.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Killer Cells in Kidney Transplantation: Dual Role in Allograft Injury and Immune Adaptation.","authors":"Anna Skotny, Paweł Poznański, Katarzyna Kościelska-Kasprzak, Dorota Bartoszek, Marcelina Żabińska, Dorota Kamińska, Magdalena Krajewska","doi":"10.2478/aite-2026-0026","DOIUrl":"https://doi.org/10.2478/aite-2026-0026","url":null,"abstract":"<p><p>Kidney transplantation is the optimal treatment for end-stage renal disease, yet long-term graft survival remains limited by allograft rejection. While T and B cells and donor-specific antibodies (DSA) have been the main focus, accumulating evidence indicates that natural killer (NK) cells play a significant dual role in both graft injury and immune adaptation, including in DSA-negative rejection. This narrative review summarizes current knowledge on the dual role of NK cells in kidney transplantation, with emphasis on antibody-independent mechanisms, adaptive NK-cell subsets, and their potential as biomarkers of graft outcome. NK cells are highly heterogeneous, consisting of CD56^bright and CD56^dimCD16 subsets. Cytomegalovirus infection promotes expansion of adaptive NKG2C⁺CD57⁺ cells with memory-like features. In rejection, NK cells act through both antibody-dependent cellular cytotoxicity and antibody-inde-pendent pathways, such as \"missing-self\" recognition via killer immunoglobulin-like receptors (KIR)/human leukocyte antigen (HLA) mismatch and release of the killer-specific secretory protein of 37 kDa (Ksp37). Specific NK subsets are associated with microvascular inflammation and graft loss even in the absence of DSA. In contrast, NK cells support tolerance by killing donor dendritic cells and activated T cells, producing interleukin (IL)-10 and transforming growth factor-β (TGF-β), and undergoing reeducation, gradually shifting from a cytotoxic to a regulatory phenotype. NK cells exert a dual, often opposing role in kidney transplantation, mediating both allograft injury and immune tolerance. Better understanding of their plasticity may enable new biomarkers and NK-targeted therapies to improve long-term graft survival.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.","authors":"Dorota Kamińska, Paweł Poznański, Wojciech Tański, Anna Skotny","doi":"10.2478/aite-2026-0024","DOIUrl":"10.2478/aite-2026-0024","url":null,"abstract":"<p><p>Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nimbolide Reduces Inflammation and Oxidative Stress to Inhibit Disease Progression in Septic Acute Kidney Injury Mice.","authors":"Yihua Yu, Yangling Li, Ying Gong","doi":"10.2478/aite-2026-0023","DOIUrl":"https://doi.org/10.2478/aite-2026-0023","url":null,"abstract":"<p><p>The study investigates the protective role of Nimbolide, a natural limonoid, against sepsis-associated acute kidney injury (SA-AKI) and its underlying molecular mechanisms. A murine sepsis model was established via cecal ligation and perforation. Renal histopathological changes were evaluated by hematoxylin and eosin staining, and renal function was assessed based on serum creatinine (Scr) and blood urea nitrogen (BUN) levels. The levels of inflammatory cytokines (interleukin-6 [IL-6], interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α]) in serum and renal homogenates were quantified by ELISA. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) in renal tissue were measured using commercial assay kits. Renal cell apoptosis was detected by transferase dUTP nick end labeling (TUNEL) assay. Also, the protein expression and phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and STAT3 in renal tissues were analyzed by Western blotting. Nimbolide treatment markedly attenuated tubular vacuolization and inflammatory cell infiltration, and improved renal function, as demonstrated by reduced serum Scr and BUN levels. Nimbolide also suppressed the levels of the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in both serum and renal tissue. Furthermore, Nimbolide decreased MDA levels, increased SOD activity and GSH content, and inhibited renal apoptosis. Mechanistically, these protective effects were associated with the inhibition of NF-κB p65 and STAT3 phosphorylation in the kidneys. Nimbolide protects against SA-AKI by inhibiting activation of the NF-κB/STAT3 pathway, thereby attenuating inflammation, oxidative stress, and apoptosis.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sEV-Enriched Serum Preparations From Healthy Individuals Protect Against Acute Pancreatitis-Induced Intestinal Barrier Dysfunction Through miR-579-3p/ANXA3-Mediated Inhibition of NLRP3 Inflammasome Pyroptosis (DOI: 10.2478/aite-2026-0018).","authors":"","doi":"10.2478/aite-2026-0022","DOIUrl":"https://doi.org/10.2478/aite-2026-0022","url":null,"abstract":"","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isovitexin can Alleviate Fracture-Related Infection, Promote Osteogenesis, and Inhibit Activation of the NF-κB Signaling Pathway.","authors":"Yaping Gu, Ping Xu","doi":"10.2478/aite-2026-0021","DOIUrl":"https://doi.org/10.2478/aite-2026-0021","url":null,"abstract":"<p><p>Fracture-related infection is a challenging aspect of orthopedic care, as it leads to prolonged inflammation and impaired bone healing. Although isovitexin is a naturally occurring flavonoid with anti-inflammatory properties, its effects on fracture-related infection remain unclear. A rat fracture infection model was established and randomly divided into four groups: control, model, Vancomycin, and isovitexin. Tissue staining was used to assess bone healing. In contrast, enzyme-linked immunosorbent assay and biochemical kits were used to measure the levels of inflammatory factors and bone metabolism-related indicators. The expression of proteins associated with osteogenesis and the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway was examined using Western blot. When compared to the model group, isovitexin treatment more effectively reduced inflammatory cell infiltration in bone tissue and promoted callus formation than the Vancomycin group. In addition, isovitexin improved the imbalance of bone metabolism and promoted the expression of osteogenesis-related proteins Bone Morphogenetic Protein 2 (BMP2), Osteopontin (OPN), and Runt-related Transcription Factor 2 (RUNX2). It also decreased the levels of pro-inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of the anti-inflammatory factor IL-10. Mechanistic studies showed that isovitexin significantly inhibited the activation of the NF-κB signaling pathway. Isovitexin can promote bone metabolism and healing, suppress the NF-κB signaling pathway, and reduce the inflammatory response associated with fracture-related infection. This study suggests that isovitexin may be a viable therapy option for fracture-related infections.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heteronemin, a Scalarane Sesterterpenoid, Activates Apoptosis and Non-Apoptotic Ferroptosis and Inhibits Cytoprotective Autophagy in Oral Cancer Cells.","authors":"Rovelyn Gallego, Chun-Tzu Hung, Sheng-Kai Hsu, Yi-Hua Chang, Ciao-Ping Chen, En-De Shu, Ching-Ming Chien, Mei-Chin Lu, Ching-Chung Ko, Chien-Chih Chiu","doi":"10.2478/aite-2026-0016","DOIUrl":"10.2478/aite-2026-0016","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) ranks 16th worldwide as the most common type of malignancy in head and neck cancer globally, and addressing it has been an ongoing but difficult pursuit, as treatment resistance is commonly reported. Hence, employing multiple cell death pathways is an emerging strategy in overcoming treatment resistance in OSCC. We investigate here the effect of heteronemin, a marine sesterterpenoid isolated from sponges, for its anti-cancer potential, hypothesizing that it can induce non-apoptotic cell death pathways to overcome apoptosis-resistant cells and elucidate the underlying mechanisms involved. Our results show that heteronemin significantly kills cancer cells via the induction of the intrinsic apoptotic pathway. It also triggers ferroptosis, down-regulating glutathione peroxidase 4 (GPX4) and upregulating markers of lipid peroxidation such as 4-hydroxynonenal and malondialdehyde. We demonstrate that increasing reactive oxygen species generation plays a central role in triggering these pathways. ensuring the death of the cancer cells despite a compensation attempt via inducing autophagy and modulating Nrf2. Our study is the first to demonstrate the complex but interesting role of heteronemin in killing OSCC cells: inducing apoptosis and switching to ferroptosis as the cells attempt to survive. It also inhibits protective autophagy, leaving OSCC cells incapable of protecting themselves from imminent death. This complex mechanism adds to the existing knowledge on the mechanism of heteronemin as a strong therapeutic compound to treat OSCC cells.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP25 Promotes Glycolysis of Acute Myeloid Leukemia Cells and Enhances Tumor Immunity.","authors":"Nianxue Wang, Can Yang, Ruya Zhang, Wei Ren, Biao Shen","doi":"10.2478/aite-2026-0020","DOIUrl":"https://doi.org/10.2478/aite-2026-0020","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an incursionary hematopoietic tumor with frequent relapses and an unfavorable prognosis. Ubiquitin-specific peptidase 25 (USP25) mediates the progression of various cancers, but its role in AML remains uncharted. The expression of USP25 in AML was analyzed <i>in silico</i>, <i>in vitro,</i> and <i>in vivo</i> through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. The function of USP25 in proliferation, apoptosis, glycolysis, and immunity in AML was addressed through cell counting kit-8 (CCK-8), flow cytometry, detection of glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR), immunohistochemistry, immunofluorescence, and Western blot. The mechanism of USP25 in AML was explored via co-immunoprecipitation (Co-IP), ubiquitination, cycloheximide, and Western blot. Upregulation of USP25 indicated a poor overall survival in AML patients. Knock-in and knock-down results revealed that USP25 enhanced viability, the level of glucose consumption, lactate production, ECAR, and the level of anti-glucose transporter type 1 (GLUT1) and hexokinase-2 (HK2), but reduced the apoptosis rate and the OCR level. Mechanically, USP25 directly bound and deubiquitinated c-Myc. An upregulation of c-Myc and programmed cell death ligand 1 (PD-L1) was found in AML. Knockdown of c-Myc decreased USP25-induced cell viability, glucose consumption, and lactate production level. <i>In vivo</i>, knockdown of USP25 decreased tumor volume and weight, the ki-67 expression, and the levels of c-Myc and PD-L1, but elevated the levels of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). USP25 facilitated proliferation, glycolysis, and immunity through deubiquitinating c-Myc in AML. The results identified USP25 as a possible target for AML treatment.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCR1 and NCR3 Expression and Genetic Polymorphism are Associated with CMV Infection after Allogeneic Haematopoietic Stem Cell Transplantation.","authors":"Sylwia Biały, Piotr Łacina, Jagoda Siemaszko, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-Kubik","doi":"10.2478/aite-2026-0019","DOIUrl":"10.2478/aite-2026-0019","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality due to the compromised immune system after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are pivotal in the immune response following HSCT, as these cells regenerate early and play a crucial role in detecting and eliminating infections. In the present study, we analyzed expression and single nucleotide polymorphisms (SNPs) of genes coding for NK cell Natural Cytotoxicity Receptors (NCRs). Expression was studied on the mRNA level and on the protein level, using flow cytometry to examine NCR-positive NK cell populations. Our study revealed significant higher expression of <i>NCR1</i> and <i>NCR3</i> in HSCT recipients with CMV infection compared to those without complications. Additionally, expression of both receptors correlated with expression of IFN-γ. Changes over time after HSCT were observed in the proportion of NCR1+ NK cells. SNPs genotyping identified associations of <i>NCR1</i> rs1433097 and <i>NCR3</i> rs11575836 genotypes with increased risk of CMV infection, as well as of <i>NCR3</i> rs11575836 with post-HSCT overall survival. These results underscore the crucial role of NCRs in the prevention of infection and the development of post-HSCT complications, highlighting their potential as therapeutic targets to improve transplant outcomes.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sEV-Enriched Serum Preparations From Healthy Individuals Protect Against Acute Pancreatitis-Induced Intestinal Barrier Dysfunction Through miR-579-3p/ANXA3-Mediated Inhibition of NLRP3 Inflammasome Pyroptosis.","authors":"Huiyuan Gu, Chenyue Tang, Yuqi Shi, Jiaqing Shen, Chunfang Xu","doi":"10.2478/aite-2026-0018","DOIUrl":"10.2478/aite-2026-0018","url":null,"abstract":"<p><p>Acute pancreatitis (AP) frequently triggers intestinal barrier dysfunction, yet the underlying molecular mechanisms remain poorly understood. This study investigated whether small extracellular vesicle (sEV)-enriched serum preparations from healthy individuals protect against AP-induced intestinal barrier dysfunction through microRNA-mediated regulation of pyroptosis. sEV-enriched preparations were isolated from 10 AP patients (AP-sEV) and 10 healthy controls (HC-sEV) using ExoQuick precipitation followed by ultracentrifugation. A murine AP model was established using cerulein and lipopolysaccharide, and human intestinal epithelial cells were stimulated with lipopolysaccharide for <i>in vitro</i> studies. HC-sEV preparations significantly ameliorated AP-induced tissue damage, restored tight junction proteins (claudin-1, occludin, ZO-1), reduced intestinal permeability, and suppressed inflammatory cytokines (TNF-α, IL-6, IL-1β) and pyroptosis-related proteins including NLRP3, gasdermin D, and cleaved caspase-1. Conversely, AP-sEV preparations exacerbated barrier dysfunction. Bioinformatics analysis identified miR-579-3p as significantly downregulated in AP-sEV. Inhibition of miR-579-3p reversed HC-sEV protective effects. ANXA3 was validated as a direct miR-579-3p target, and ANXA3 overexpression counteracted miR-579-3p-mediated protection. These findings demonstrate that HC-sEV preparations protect against AP-induced intestinal barrier dysfunction through miR-579-3p delivery targeting ANXA3 to suppress NLRP3 inflammasome-mediated pyroptosis. The miR-579-3p/ANXA3/NLRP3 axis represents a novel therapeutic target for preserving intestinal barrier integrity during acute pancreatitis.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"74 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}